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THE SILENT
BATTLE
WITHIN
A PATIENT’S VIEW OF
PROSTATE CANCER (PC)
BY
DALE HOLLENBECK
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
1
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER (PC)
BY DALE HOLLENBECK
COPYRIGHT © 2012 DALE HOLLENBECK, ALL RIGHTS RESERVED.
A PUBLICATION OF KNOWINGHELPS CORP.
See knowinghelps.com
Reproduction, sharing, translation, or transmission of this work, in whole or in part, without the expressed
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addressed to owner of the copyright. Third party illustration contributions herein are reused with
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copyright owner of the work.
Released in pdf format, last updated December 2012.
Library and Archives Canada Cataloguing in Publication Data is available on request.
ISBN:
978-1-927768-03-7
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
2
Table of Contents
Title
Page
Cover
1
Front matter
2
Table of Contents
Preface
The Eye opener
Chapter 1 Terrain and the Enemy
Prostate
Organs, Musculature and Nerves of the male Pelvic Area
Lymphatic System
Cytology
The Genome
Normal Cell Life Cycle and the Phases of Cell Division
Abnormal condition of the Prostate
Benign Growth, Condition and Presentation
Dysplasia and the Cancer Cell
Malignant Growth, Condition and Presentation
3
6
13
17
16
20
23
27
28
31
37
38
39
39
Chapter 2 Symptoms, Examinations & Opinions
44
Symptoms
Prostate Self-Examination (PSE)
Clinical Prostate Examination (CPE)
Ultrasound Imaging
CT Scan
Molecular Imaging (PET/CT Scan)
MRI
Near Infrared Scanning
Biopsy
Pathology
43
46
50
52
53
54
56
61
61
62
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
3
Invasiveness and Staging
Survivability Statistics
Relative Survival Rates for Prostate Cancer
ECG (Electrocardiograph)
Second Opinion
Archives
Chapter 3 Surgical Treatment and Therapy
Surgeons and Surgical Teams
Preparation for Surgery
Prostate Surgical Procedure
Prostatectomy
Orchiectomy
Prostate Conserving Surgery
Laparoscopic Procedure
Robotic Surgery
Surgical Options for Advanced Metastasis
Surgical Risk
After the Surgery
Infection and Antibiotics
Post-Operative Condition and Rehabilitation
Post-Operative Pathology Report
Lymphedema
Long-term surgical outcome
Spousal and family reaction to hard times
Chapter 4 Non-Surgical Treatment and Therapy
Oncologists and Oncology Staff
Clinical Testing
Chemotherapy
Non-Conventional Chemotherapy
Radiation Therapy
Recurrence following Treatment
Quality of Life
High Intensity Focused Ultrasound Therapy
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
64
70
71
73
73
75
76
80
81
82
82
84
85
85
89
91
93
95
98
103
106
107
108
108
110
113
116
119
129
136
139
141
141
4
Chapter 5 Alternative Strategy & Prevention
Diet
Sugar, Starch and other things Sweet
Toxic Contamination and Organic Produce
Metronomics
Attitude and Environnent
Exercise
Acupuncture
Early Recognition and Screening
Prevention
Follow Up
Miscellaneous and Promising Research
Patient Support
Praying and Belief
Cancer Foundations
142
147
150
153
155
160
164
168
172
174
175
176
177
179
179
Glossary of Terms
181
References and Notes
189
Index
209
Third party Illustration Permission & Agreements
213
Acknowledgements
215
Disclaimer
216
Synopsis
217
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
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Preface
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
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It was about twenty years ago that I recall my Uncle Wellington made one of his
rare visits to my parent’s place out in the country. He didn’t usually travel or visit much
and lived in the city about an hour and a half away. So when I wandered in to my parent’s
kitchen about a month later and saw Uncle Wellington again I made a “note to self” to
ask Mom if everything was Okay. It was then I found out that Uncle Wellington had
cancer.
At the time I chalked it up to yet another relative with cancer, but this time it was
not someone who was a heavy smoker. In fact, Uncle Wellington did not smoke at all as
far as I knew. Nor did he have any wild or uncontrolled habits. He didn’t drink and I
never thought of him being anything but peaceful. It all made no sense. Here was a lean,
strapping, quiet man who always looked fifteen years younger than his age. A man that
was as pleasant as one could ever be. In my whole life I never heard him so much a raise
his voice or say anything stronger than “gese”, “by golly” or “son of a gun”. He always
seemed to have a smile on his face and loved to listen to music. I always thought Uncle
Wellington strangely articulate for someone who had only high school education and
drove a delivery truck. I assumed he must have spent his time reading and listening. He
had a small house in the suburbs, raised two children and put them through university,
and worked his “blue collar” job until he took early retirement at the company’s request.
The only “out of the ordinary” thing that I knew about him was that he had divorced,
which was unusual for the times.
Prostate Cancer (PC), sometimes there is no pain and no dire symptoms just
invasive metastasis silently making its way from tumor and into everything else even
after it has been diagnosed. A disease that respected the serene surface of a man like
Uncle Wellington while reeking complete havoc with his insides.
Oh, Uncle Wellington seemed optimistic enough at the beginning about the
possible success of surgery and treatment; but, as much as I gather, his condition was too
far along and nothing at that time was successful in halting the migration of his disease.
Over the course of about three years Uncle Wellington fought his “silent battle within”
and lost.
Every year hundreds of thousands of men worldwide are diagnosed with Prostate
Cancer. To me, Uncle Wellington’s battle was the one that really brought home the
message that this disease can strike any man no matter what their apparent physical wellbeing or habits and become fatal.
In the year 2008, according to the World Health Organization (WHO) Prostate
Cancer (PC) was the number one cancer diagnosed of men in developed countries.
Accompanying this fact is a marked increase in the number of reported instances of PC;
however, mortality from PC is generally decreasing.1 Overall, PC is the most prevalent
cancer for males in 111 countries worldwide. 2
In the United States based on rates for 2007-2009 SEER (Surveillance,
Epidemiology, and End Results) data it is estimated that roughly 16% of men born today
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
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will be diagnosed with cancer of the prostate during their lifetime. This is like saying that
if six random men stand in a room together from that country, one of them will be
diagnosed with Prostate Cancer during the course of their life.3
In the United States the National Cancer Institute reports that as of January 1,
2009 there were 2,496,784 men alive with a history of Prostate Cancer! Further
consideration of the patients and their profiles, it is obvious that Prostate Cancer
incidence is most common in older men. The statistics indicate that 67.1% of all
diagnosis occurs in the age group between 55 to 74 years. In addition, it has been
reported that men of Black descent have a rate of incidence 52% higher than all other
races; and a death rate that is more than double the rate for all other races in that
country. Also be aware that death rate due to PC in all races begins to rise after 45 years
of age.4 These are all facts to consider and cater to when you have your annual physicals.
Since the early 1990’s PC awareness has become much more prevalent. This is in
no small way due to the efforts of private research, as well as, the intervention of major
world and governmental health organizations, foundations, and cancer societies. Adding
to this list are those individuals who have stood in the celebrity limelight who graciously
share their personal experience with this disease.
As I sit here poised in front of my keyboard I suppose I should qualify just who I
am to be writing what some would regard as a quick reference handbook on Prostate
Cancer (PC). I am not a health worker or a medical researcher. I do not pretend to know
all the answers in order to prevent, recover from or cope with the disease. I, like many of
you, have had what seems an unending line of relatives afflicted by cancer of one sort or
another. Beyond this, my interest in cancer is one that was spurred as a cancer patient.
Mine was a different cancer than what is discussed in this book and by the time it was
discovered I was at Stage III. For those of you not yet “in the know” of the jargon of
oncology (the study of cancer) I will let you know that for my cancer Stage III is
considered an advanced cancer. Stage IV is the final or end stage of any cancer. I
underwent surgery and adjuvant (post-surgical) treatment and am presently in remission.
Being able to recover to a state of remission is my good luck. I get my inspiration
to write this from the actor and philanthropist Paul Newman who lost his battle to lung
cancer several years ago. This was a man who, in a very low key and gracious way,
touched the lives of many through charity from what he called his “good luck”. He made
the point that he, in his life, was lucky and that there are a lot of people out there that are
not; and, that those who are lucky should help those that are not. I agree.
In my experience with cancer one of the things I found about being a patient was
just how difficult it was to make any sense out of the mountain of information on my
disease. So I did my research and took notes which eventually became a book on
colorectal cancer. That book was the first in this “series” that I am writing which deals
with cancer information that caters more to a patient’s perspective. In this book I will
also recount some of the recollections and view of my friend and colleague, Tony, who is
a Prostate Cancer survivor. I believe it is important to have the benefit of a patient’s
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
8
perspective on the disease. It adds to the clarity of interpreting the literature, as well as
events and outcome of treatment.
The literature surrounding the cause and effect of Prostate Cancer is extensive and
spans more than a half of century in modern medicine in research, diagnostic pathology,
surgery and treatment. The variables that go in the progression of such a disease are
numerous and are hypothesized to carry over in everything from host “genetic make-up”,
to habit, to environmental exposures, diet, exercise and attitude. No one has the same
combination of the variables that conspire to cause disease. As such; how one arrives in
the line of being diagnosed and treated for Prostate Cancer is different for each patient.
Prostate Cancer is a man’s disease. This is because women in their anatomical
development have an equivalent structure often referred to as the Skene’s glands that is
rarely affected by this cancer.
Socially the prostate is not one of those areas of the anatomy that surfaces over
light discussion at the dinner table. Of course, there may be a “haw- haw and a tee-hee”
when one refers to the snap of a rubber glove at an annual physical, but that is usually the
extent of the conversation. In this way it can be said that PC is not a “popular” cancer, in
as much as there is no general and obvious awareness of it especially if you are relatively
young. This is a disease that can run its course with no more than a “burble” or two until
it is too late for the host to do anything about it if you don’t make a point of having
yourself checked as you get older. My point is that you must be aware and take
measures that will both harden your resistance to Prostate Cancer, and, afford early
detection, diagnosis and treatment. Three of the simplest things you can do to raise your
guard against PC is to:
1) Be aware of the anatomy involved;
2) Know the symptoms of PC and get checked if you have any of those
symptoms;
3) Know your lifetime risk category for PC and begin screening in accordance
with your risk category; which involves a blood sample for a PSA (ProstateSpecific Antigen) test and a DRE (Digital Rectal Exam) annually.
The symptoms of Prostate Cancer when they do occur are not easy to ignore;
however, it is easy to think that they are related to some other “not so serious” affliction
such as prostatitis. Prostatitis is a disease that causes the prostate to inflame. Pain in the
area of the urinary system, abnormal frequency or difficulty urinating, or upset sexual
function are some of the symptoms for both afflictions.
Since the prostate is basically encased in the pelvic area it is possible to have
referred pain in areas that do not seem related. Places like the rectum, penis, hips, groin,
back, thighs and even the head. Some of this is because there are a number of nerves that
radiate to and around the prostate. When these nerves are impinged upon by abnormal
growth they can cause considerable pain in areas that one would not normally associate
with the prostate. It is the predominant theory that Prostate Cancer generally proliferates
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
9
(grows) slowly and takes years to develop. Along with this slow proliferation of the
cancer can be an equally gradual build-up of symptoms and discomfort. Even advanced
Prostate Cancer, like most cancer, may be asymptomatic (without symptoms). Advanced
stage Prostate Cancer may only present with one or two of the symptoms listed below. In
short, it is important to have regular medicals and report any of the following symptoms
if they are persisting. It is also important to start paying attention to how your
“plumbing” and health are doing. It is important to start taking care of yourself. The
following are signs and symptoms that are can be brought on by Prostate Cancer:
•
•
•
•
•
•
•
•
•
need to urinate often (especially at night);
intense need to urinate (urgency);
difficulty in starting or stopping the urine flow;
inability to urinate;
weak, decreased or interrupted urine stream;
a sense of incompletely emptying the bladder;
burning or pain during urination;
blood in the urine or semen;
painful ejaculation 5
This list is not all of the symptoms, but it does have some of the most common
ones. Having symptoms does not mean that you have Prostate Cancer. It could be
something else that is the cause. If; however, you have any of these, GO SEE A
DOCTOR and find out the cause. Also, it is time to start exercising if you don’t already;
stay away from tobacco smoke, and eat better. Eating better will be discussed later in the
discussion so you will know what that means in terms of a Prostate Cancer strategy.
A person’s lifetime risk of Prostate Cancer can be assessed by a medical
evaluation, so have this done. The risks that make someone more susceptible to
developing Prostate Cancer are as follows:
o Middle or Advanced Age (PC is unusual in young men);
o Family (first degree male relatives) history of PC;
o Race (Men of Black descent have a much higher risk of PC incidence and
mortality);
o Consuming a diet high in animal fat;
o Having a high intake of dairy products and calcium;
o Excessive use of multivitamins;
o Exposure to cadmium which is one of the cancer causing agents in tobacco
smoke;
o Topical exposure to dioxin such as agent orange.6
A quick prostate cancer risk calculator is available on line at the link:
http://sunnybrook.ca/content/?page=OCC_prostateCalc
To use this risk calculator you will have had to undergone a clinical prostate exam
because this risk calculator requires the following basic prostate information:
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
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- the presence of urinary symptoms as measured by the eight question International
Prostate Symptom Score (for the questionnaire see ww.urospec.com/uro/Forms/ipss.pdf);
- your total PSA value;
- your Free (PSA not bound to other proteins) to total PSA ratio value; and,
- your DRE of prostate results from your physician.
Provide this information to the risk calculator when prompted and select the “Evaluate
Prostate Cancer Risks” push button for the risk result.
Screening is the testing for a disease before symptoms are present. Screening,
when done correctly, affords early detection of any cancer. The debate is ongoing in the
mainstream medical community as to the value of early detection of Prostate Cancer. As
is the case with other cancers there is no harmonized approach to PC screening.
Conflicting reports continue to allow medical policy makers to circumvent the common
sense need to have men checked.
For example, a recently published study involving 76,693 men reported that after
7 to 10 years of follow up, the death rate from Prostate Cancer was very low and that
there was no significant difference between the group who had undergone screening with
annual PSA testing and DRE (Digital Rectal Examination) versus the group who had
not.7 The results of this study are in sharp contrast to those reported in another study
involving 182,000 men. Researchers in that study reported that PSA based screening
reduced the death rate from Prostate Cancer by 20% but was associated with a high
risk of over diagnosis and overtreatment.8
In any case, there are basically two common ways that Prostate Cancer is
screened for. One involves the testing for the level of PSA (Prostate-Specific Antigen)
which is a simple blood test; the other involves a clinical exam (CE) where the attending
physician checks the prostate via the rectum using a finger. This is called a DRE (Digital
Rectal Examination). General practitioners, as well as, urologists will be able to conduct
such an exam. My personal view is that a urologist should be involved since this is their
area of expertise.
The facts of PC are that incidence and mortality are predominant with men in
their later years. The National Cancer Institute has summarized Prostate Cancer
screening generally practiced in the mainstream medical community and point out that
screening advisory groups are saying that there are pros and cons of PSA testing; and,
that a detailed discussion between patient and doctor should occur before using the test.
The concern revolves around PSA results that could prompt “unnecessary” biopsy
resulting in complications including incontinence (unable to control bladder); bowel
disruption; erectile dysfunction; and, infection.9 These concerns coupled with a relative
high survival rate among those diagnosed with PC have seen recommendations to begin
screening of men beginning at 50 years old being “backed away from”.
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
11
Cancer research, screening and treatment costs money. In countries where there
is no social medical coverage the repercussion of paying for healthcare can be devastating
to those trying fight the disease.
In a place like Canada, where there is a relatively comprehensive social medical
system, there are nevertheless inconsistencies in provision for cancer screening. For
example, in the provinces of Ontario, Quebec and British Columbia, the medical system
does not cover the cost of routine PSA testing. To make things more difficult, one cannot
even get a PSA test at an independent laboratory without a doctor’s referral! It’s bad
enough to try to get a man into a doctor to get his “plumbing checked”; but, the principle
of having to pay for a what seems an essential medical service; the cost of having to pick
up the bill when there may not be funds to do so, especially if living solely on a senior
citizen’s pension; and, the fact that a lot of men do not even have a family practitioner
available to write them a referral are all completely inconsistent with what should be
basic medical coverage and early PC detection.
Nevertheless, my attitude is, if you can afford it, stay on top of your health with
regular examination, immediate diagnosis and timely treatment. Much as agencies, such
as the U.S. Preventative Services Task Force, call attention to the statistics that PSA
testing does not save lives,10 someone should point out that early detection of PC is not
just about saving lives. It is about finding better ways to address a disease that can
emasculate even before advanced stage.
Having interviewed Tony, I found his experience an “eye opener” in terms of
expectation, consideration, processing, resource, and relief. In addition, it is obvious that
there are mistakes that should be and could be avoided if only we were all made a bit
more aware.
This discussion is a layman’s interpretation and overview of the literature that is
available for anyone’s review on the topic. The diagrams and tables in this document may
not be the most definitive or current and are referenced only as example to support the
discussion. They are the better part of what I found to become informed of this cancer
and the medical jargon belonging to it. Most of the information herein is found on the
internet in a number of sources that are openly available to the public. It is where I went
in order to make sense out of my own cancer condition so I could have an idea of the key
issues and questions to ask of my physicians. The remainder is derived from a patient’s
first-hand experience in addressing this disease from within.
To be clear, this discussion is not intended as a solution to replace qualified
medical professionals or their opinion. It is meant to give you a footing in the topic so
you can have an informed dialogue with your medical team. This way you are better able
to understand the issues and options so as to be more comfortable making decisions
relating to your condition.
These are my words in hopes of spurring a bit of awareness. If you find that when
you are reading the description of PC symptoms they seem oddly familiar to what you or
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
12
someone you know are experiencing, I strongly suggest immediate follow up with the
appropriate medical visits and referrals.
No one wants the CANCER sign hung around their neck, but burying ones head
in the sand and counting on PC progressing slowly is not going to improve on your
situation.
The Eye Opener
I interviewed my friend Tony while having coffee at Tim Horton’s on a cold day
in January. He told the story of how he was diagnosed with PC at the age of 61. Tony
was a corporate pilot then and since the age of forty had to pass a Transport Canada
aeromedical twice a year to stay current in his licencing and be able to fly. Tony’s
employer made allowances to include PSA testing for their pilot staff; and so, he did this
at the same time as his aeromedical. After one aeromedical in the winter, Tony’s doctor
did not say what the results were in the post-medical debrief. Tony really did not pay
much attention to this until he showed up for his next medical in the summer. After
questioning the lack of results on a PSA test it was discovered that his results had
somehow been “misplaced”. When they were eventually found, a review of those PSA
results detailed levels that were alarmingly higher than the results on his previous PSA
done the summer before.
Tony immediately followed up and his urologist who conducted a DRE, as well
as, biopsies. The pathology report stated that three of the tissue samples showed
malignancy and Tony was given the choice of three courses of action. These were:
1) Do nothing [known as the “Watchful Waiting” approach]; or,
2) Undergo hormone treatment (Androgen Deprivation Therapy); or,
3) Undergo a surgical procedure called radical prostatectomy.
After a bit of consideration he elected to have the radical which also involved a
possible lymph node dissection. Tony seemed to recall that his lymph nodes were
sampled in the same session as the radical prostatectomy (RP) and the results came back
negative (no lymph node involvement) while the RP was still being performed. This
would have been unusual surgical undertaking for the times. In any case, he was certain
that a complete lymph node dissection was not done. The post-surgical pathology report
was something that Tony did not see. In fact, neither did he see the preliminary
pathology report before surgery. He thinks his condition was diagnosed at Stage III
although he was not sure.
Five days after surgery Tony was sent home with a catheter still installed. His
recovery involved some physiotherapy with exercise including “Kegles” to strengthen his
pelvic floor muscles. As for follow up Tony had no adjuvant (post-surgical) treatment;
for the first year he had PSA testing every 3 months; then, PSA testing every six months
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
13
up to five years; and, no imaging of any kind. It has been 13 years since initial diagnosis
and Tony is still in remission.
Had it not been for his career choice (which made mandatory medicals every six
months a part of Tony’s normal life) along with the relative frequency of PSA testing that
he had arranged, the PC probably would not have been discovered until it had spread to
other parts of his body. Had it not been for Tony’s insistence on knowing his missing
PSA results from his winter 1998 testing, his condition could have been allowed to
progress even further than it had.
Tony reflected on a colleague he knew at the time who was as well diagnosed
with PC. He recalled that they discussed each other’s choice of treatment. The other
man elected to not have the radical surgery and instead opted for Androgen Deprivation
Therapy. Within a couple of years, that man ended up contributing to the mortality
figures of PC.
All to say, do not assume that you can just fall into a hospital or doctor’s office
and trust that your best interests are being taken care of. You have to become informed.
You have to ask the right questions and know the reasonable response. You have the
right to see your file and have apt explanation. You have to understand the facts and your
options. If you can’t understand or remember what is being said, have someone with you
that can.
When it comes to your own cancer condition, YOU are your best manager of your
own case and health. Remember, in the course of a day the doctor(s) and administrators
that you are relying on see dozens of patients. It doesn’t matter how smart you believe
them to be OR that their procedures and protocols should be able to make sure you are
handled correctly and in a timely manner; it is an easy thing to miss something important
when you are faced with the patient load that these medical professionals have to contend
with. In the grand scheme of things forgetting or failing to properly diagnose a condition
doesn’t have much of an effect on their overall patient outcome, but for you it could be
devastating.
For those of you who want to do nothing and deny a high lifetime risk or the signs
of a cancerous prostate condition, I will tell you right now that your inaction is exactly
what this disease needs to become advanced to the point that it can have grave
repercussions on your quality of life. It can even kill.
For the others who are diagnosed with PC and are fortunate enough to find a state
of remission, know that cancer is not a bruise or cut or a broken bone that repairs and is
all better. The conditions for cancer have already proven to be hospitable in your body.
You would do well to consider what you can do to make those conditions less likely to
cause a relapse. Relapse in Prostate Cancer can revisit your prostate (if it was not
removed in whole); tissues in the vicinity of where your prostate used to be; seminal
vesicles; nearby muscles and organs such as the rectum, bladder or pelvic wall; or, other
distant organs including the bones.
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
14
You may find some parts of the following chapters as either too much or not
enough information. They reflect the scope I think would be needed to lend a better
understanding for most of your questions.
Time now to begin your fight, and it starts with information on the enemy, the
occupied terrain and mechanisms involved.
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
15
Chapter 1
Terrain and the Enemy
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
16
I assume most of you have not studied biology, physiology or anatomy at all, so I
will review the pertinent details of the prostate as the area hosting cancer. Be aware that
in stage IV the cancer has traveled and resides in distant parts of the body not necessarily
covered by this discussion.
Prostate
Common understanding is that the prostate gland is an organ exclusive to males.
In terms of human anatomy the notion that females and males all have the same
fundamental anatomical parts makes sense because both genders actually start out as
female in the womb. It is only as foetus develops in the womb that the genetic
instructions cause some aspects of the human anatomical blueprint to be more or less
emphasized. The result of this developmental emphasis is the departure from a strictly
female outcome into one that is male.
There are other obvious examples of this kind of gender related “emphasis”;
however, what it all amounts to, in simplistic terms, is that the prostate has a female
equivalent occupying roughly the same place that features differences in size, shape and
role. Nevertheless, this organ exists and it is with this understanding more recent study
and research supports the contemporary view that the female urogenital anatomy has a
smaller variant of the prostate organ typical to males and that has, in the past, been
referred to by a number of names including the Skene’s glands; lesser vestibular;
periurethral; or, the paraurtheral glands. In 2002 the Federative International
Committee on Anatomical Terminology officially renamed the Skene’s gland the female
prostate. In reviewing the literature it is clear that PC is a man’s disease as is duly
reflected in the data; however, there exist very rare cases reported in females.
A simplified illustration of the male urogenital anatomy and the organs and
structure that surround it is at Figure 1. In it you see the prostate located in close
association with the bladder and the seminal vesicle.
Androgens are hormones and include, for example, testosterone and 5alphadihydrotestosterone. In males testosterone is produced in the testes. In females it is
produced in the ovaries. Both sexes, as well, have lesser production of testosterone in the
adrenal glands. The balance between androgens and other hormones in a man’s body is
fundamental to the health of his prostate. The prostate size varies but is generally about
the size of a chestnut. It weighs in at anywhere between 10 to 20 grams (near or less than
a half an ounce). It is made up of several types of tissue including:
- glandular which forms the pouch-like structures where a liquid component of
semen is made;
- epithelial which lines the canals, terminal vesicles and ducts of the glands that
open into the prostatic portion of the urethra;
- muscle and connective tissues forming the body of the organ;
- venous providing veins and arties supplying the prostate; and,
- nervous composing the nerves that radiate from the pelvic plexus.11
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
17
The prostate’s role in men is to produce, store and release a clear alkaline
somewhat viscous fluid that contributes to semen. Alkaline means that it has a pH closer
to a base (like baking soda) than to an acid (like vinegar). The prostate fluid comprises
the largest part of the volume released during ejaculation. The remainder of the male
mixture comes from secretions made by the Cowper’s gland and the seminal vesicles. In
terms of fertilization, the characteristic alkaline pH of the prostate fluid serves to help
lower acidity levels that are naturally found in the man’s urethra (urinary tract) and the
receiving vagina. Without the contribution of this prostate excretion, the sperm would
have much lower survival rate and fertilization would become much less likely.
Figure 1. The male pelvic area including the prostate
source: http://en.wikipedia.org/wiki/File:Male_anatomy.png [modified]
Originator: http://www.luckymojo.com/faqs/altsex/penis.html
Figure 2 is an illustration detailing the anatomy of a woman’s pelvic area and
location of the female prostate or Skene’s glands. Like the male counterpart, this gland
releases a clear fluid when stimulated. It is in the area commonly referred to as the “gspot” and, is in close association with the base of bladder above it. These would be the
glands involved in a female case of Prostate Cancer.
Figure 2. The female pelvic area detailing Skene’s glands.
source: http://en.wikipedia.org/wiki/File:Female_anatomy.svg [modified]
originator: Tsaitgaist
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In pathology reports the prostate will most be referred to in terms of zones. There
are four zones that are based on distinct glandular regions of the organ namely the:
-
Peripheral zone (PZ) which is the largest of the four zones and includes
the posterior aspect of the prostate gland that surrounds the distal urethra;
-
Central zone (CZ) which is the zone that surrounds the ejaculatory ducts;
-
Transition zone (TZ) which surrounds the proximal urethra. This is the
region that grows throughout life; and, the
-
Anterior fibro-muscular zone which is usually devoid of glandular
components and composed of muscle and fibrous tissues.
Figure 3 is a cross-section of the male prostate illustrating the zones with the
approximate percentage that each zone occupies in the gland. The magenta (pink) portion
in the middle represents the urethra and is the major duct that goes through the middle of
the prostate from the bladder to exit from the penis.
Figure 3. Lateral cross -section of the male prostate detailing the prostate zones. Pink center is the
urethra.
source: http://en.wikipedia.org/wiki/File:Illu_prostate_zones.jpg
originator: http://training.seer.cancer.gov/ss_module02_prostate/unit02_sec03_anatomy.html
In a pathology report you may encounter the notion of exceeding the prostate
“capsule” when detailing cancer spread. Prostate capsule in this case refers to what is
known as the prostate parenchyma or the glandular tissue that makes up the majority of
the prostate.
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Organs , Musculature and Nerves of the male Pelvic area
The next few illustrations are to ensure a more comprehensive understanding of
the location of the prostate and its surrounding anatomy. This will allow you to better
understand the issues involved in any surgical procedures that may be used to address a
prostate condition. Figure 4 illustrates the muscles in the male pelvic floor.
Figure 4. The male pelvic floor musculature.
source: http://en.wikipedia.org/wiki/File:Gray406.png
originator: Henry Gray (1825–1861). Anatomy of the Human Body. 1918
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Figure 5 illustrates the location of the prostate in a male beneath the pelvic floor
musculature. The prostate is shown here with the base of the bladder behind it. When
considering the jargon used to describe the orientation of the prostate the part closest to
the bladder is called the base; and, the part further downstream towards the penis is called
the apex.
Figure 5. The prostate and associated organs of the male [pelvic floor view].
source: http://en.wikipedia.org/wiki/File:Gray543.png
originator: Henry Gray (1825–1861). Anatomy of the Human Body. 1918
Figure 6 more clearly illustrates the prostate and the associated urogenital
structures that converge on it. In pathology this organ is often referred to by lobes (left
and right sides) and the diagram shows the prostate split down the middle into left and
right lobes to make this point and also shows the canals that run through the surrounding
lobes.
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Figure 6. The prostate and its component parts with cutaway views of 1- vas deferens; 2- Seminal
vesicle; 3- Base of prostate; 4- Apex of the prostate; 5- Prostatic urethra (leading to the penis) .
source: http://en.wikipedia.org/wiki/File:Illu_quiz_prostate01.jpg
originator: http://training.seer.cancer.gov/ss_module02_prostate/unit02_sec05_quiz_match01.html
Figure 7 illustrates the major nerves associated with the male urogenital area.
Disruption of area nervous tissue by abnormal growth or by surgical procedure can result
in chronic pain or erectile dysfunction, for example.
Figure 7. Nerves serving the male urogenital area.
source: http://en.wikipedia.org/w/index.php?title=File:Pudendal_nerve.svg&page=1
originator: Mikael Häggström
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Lymphatic System
The lymphatic system is a network of vessels or conduits that stem from head to
toe throughout the body. Associated with these lymphatic vessels are nodes. A node is a
“bean shaped” filter in a lymphatic vessel. There are approximately 500 to 600 lymph
nodes in the human body and they are clustered in areas such as the neck, armpits,
abdomen and groin. At Figure 8, the diagram details some of the major components of
the lymphatic system. This diagram is a simplified view of the very complex lymphatic
network.
Figure 8. The Lymphatic System
source: http://humanphysiology2011.wikispaces.com/06.+Cardiology
The lymphatic system has three major roles:
Firstly, consider that the average adult human is composed of 55 to 60% water. Some of
this water circulates in the form of blood. Some of this water resides in cells. Some of
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water lies in the fluid between the cells. The fluid between the cells is called interstitial
fluid. The lymphatic system is responsible for the filtration of this interstitial fluid. The
filtered fluid is called lymph and is eventually returned to the circulatory system (blood).
As such the lymphatic system is a player in the distribution and balancing of fluid in the
body;
Secondly, the lymphatic system absorbs lipids, for example fat, from the intestine. So the
lymph also transports lipids to the blood stream; and,
Thirdly, in the lymph nodes there are a number of cells that respond in the event of
disease or injury. These cells are the “workers” that make up the body’s repair and
defence or immune response. Their purpose is to recognize, trap and absorb infection
called immunogens. Among such cells are the B cells, T cells and Natural Killer (NK
cells). B and T cells are specialized white blood cells called lymphocytes.
These lymphocytes make their way from the circulatory system to the lymphatic
system in response to a signal released when there is infection or injury. To do this the
white blood cells actually excrete an enzyme that allows them to escape through the wall
of their closed circulatory system into the surrounding interstitial fluid. Then they are
picked up by the lymphatic system and migrate along specific paths that direct them to
the point of injury or infection.
Typically when a lymph node encounters an immunogen (invading foreign body
that is not supposed to be there) it becomes enlarged. This is primarily because of B cell
migration occurring in that node in response to the infection. When nodes are infected
with cancer they usually become inflamed. Sometimes; however, they do not. This is one
of the reasons why it is so difficult for the surgeon and pathologist to determine exactly
how far the cancer may have traveled within the lymphatic system.12
The lymph is not pumped through the body like blood. In fact, the lymphatic
system has no recognized pump at all. Throughout the lymphatic system there exists the
equivalent of “one way” valves so that lymph does not tend to flow backwards. Cancer
cells can make their way to other parts of the body through the lymphatic system if they
manage to get picked up by the lymphatic system then somehow survive its defenses and
get dumped into the bloodstream with the returning lymph.13
The rate and extent of flow of lymph through the lymphatic system is a matter that
is not completely understood and is still under investigation by researchers. The lymph
fluid is picked up and generally moves slowly through the lymphatic network by the
action of local skeletal muscle movement, local arterial expansion and contraction, and,
by peristalsis in the case of the larger lymphatic vessels. It is thought that sometimes the
movement of the lymph fluid actually “skips” at a much faster rate than the described
slow progression. As such; this becomes a problem in the certainty of just how far any
surviving cancer cells have moved towards the circulatory system once in the lymphatic
network. 14
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As the lymph from the prostate area is drained it is transported through an array of
lymphatic vessels and ducts and eventually makes its way to the blood stream. The blood
stream then distributes the lymph all over the body. Sentinel nodes is a term used to
describe the lymph nodes that are first in line to receive the draining lymph of the
prostate on its way to being returned to the blood. These nodes are often sampled
(biopsied) to determine if the cancer has spread from the prostate via the lymphatic
system.
Classic anatomical theory for the drainage of the prostate gland lymph is basically
that the vessels of the prostate have drainage to the periprostatic node; internal iliac
nodes; sacral nodes; and, external iliac node. These are considered the regional lymph
nodes for the prostate. 15 Pathology reports often refer to regional lymph nodes as a way
to determine metastasis (spread) of the cancer. Figure 9 is a side view of some of the
prostate regional lymph nodes and how they are situated with respect to each other. In
this illustration the intestinal tract has been “left out” so that the prostate lymph system
structures are more obvious. The lymph tissue is detailed in blue. The bean-like
structures are nodes and are referred to as glands in the diagram.
Figure 9. Lymphatics of the prostate (sagittal view).
source: http://en.wikipedia.org/wiki/File:Gray619.png
originator: Henry Gray (1825–1861). Anatomy of the Human Body. 1918
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The collected lymph then passes into the lateral aortic nodes and eventually
makes its way to the thoracic duct via the abdominal confluence of lymph ducts or the
cisterna chyli (see Figure 8). Figure 10 is a front view illustration as though facing
someone and looking down into their pelvic area lymph node distribution. This shows
the left and right lateral aortic nodes.
Figure 10- Lymphatics of the pelvis. (frontal view).
source: http://en.wikipedia.org/wiki/File:Gray611.png
originator: Henry Gray (1825–1861). Anatomy of the Human Body. 1918
Recent investigation involving whole body scans using a form of imaging called
SPECT/CT (Single Photon Emission Computed Tomography/CT) has shown that
patients can exhibit variable prostate drainage patterns and that those patterns can be
mapped using SPECT/CT imaging techniques to better identify sentinel and secondary
lymph nodes that may be harboring microscopic metastasis (cancer spread). This may
be a way to assist in addressing the estimates that speak of 50% relapse for those patients
with high risk PC following definitive treatment.16
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The SPECT/CT is basically a “doubled up” approach to traditional CT imaging
involving a gamma camera combined with an inline CT scanner (which will be discussed
later). Such imaging greatly improves capture of detail that allows the technicians and
physicians a more accurate understanding of disease spread. Definitive treatment is what
is regarded as the best way to address a patient’s disease after all of the options have been
considered.
When cancer goes undetected and is allowed to develop it eventually exceeds the
bounds of its originating site and then passes beyond the prostate. When this happens the
cancer cells can find their way into the surrounding interstitial fluid where they are
moved into the lymphatic system. When they arrive at a node in the lymphatic system
they are attacked by body’s immune system. If the immune response is successful then
the “migrating” cancer cells are destroyed. If the response is unsuccessful then the cancer
cells will, in time, proceed through the lymphatic system to other lymph nodes and
eventually into the circulatory system and other organs. This process of cancer spread
from its original site to other parts of the body is called metastasis.17
The lymphatic system is not the only way through which metastasis occurs.
Prostate Cancer, like any other cancer, may spread through a number of ways.
To summarize, spread occurs:
1) Directly [Direct extension] - this means the cancer spreads and grows in more
than one place within the organ of origin;
2) Trans-coelomically - Once the cancer exits through its originating organ it
gains access to the fluid between cells. This means it may migrate in the body
cavity through the fluid there;
3) Via Blood circulation - Tumors are a group of cells and cells need blood to
live. Tumors build their own circulatory networks that are connected to the
rest of the body’s blood circulation. When this happens blood that is
circulating through cancer cells is moved throughout the rest of the body as
well; and,
4) Via Implantation - What implantation most commonly refers to is “tumor
spillage” that occurs due to unintentional contamination of the surrounding
area with cancer cells during the process of surgery.18
Cytology
For those of you not familiar, cytology is the study of cells. In order to
understand the process of cancer, as well as the “why and how” of the way it is treated,
one has to have a bit of an understanding of cell division and structure. A cell is the
building block of life. It is the smallest unit that can be considered living. Although you
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may not have been aware, an example of a single cell is a chicken egg. Of course, not all
cells are this large. In fact, most cells can only be viewed under a microscope. Some
organisms are made up of only one cell. Humans are made up of many cells and so we
are a multi-cellular organism. In a human there are approximately 60 to 100 trillion cells.
These cells do not all look or behave the same. They as well have complex signalling
and communication processes that, for the most part, defy our present scope of medical
understanding. Some cells can repair or regenerate. Some cannot. Some last the life of
the person, for example, brain and nervous tissue cells. Others last only a few days and
are replaced.
The Genome
The location, structure and function of any cell are coded in the organism’s
genome. The genome is the complete package of genetic material that each of us contain.
This genetic material is our entire blueprint of life. The genome is made up of
individual genes. There are approximately 50,000 to 100,000 genes in the human
genome. Genes are made from large molecules called DNA and RNA.
There are two types of genetic material. One is called DNA (deoxyribonucleic
acid). The other is RNA (ribonucleic acid). This genetic material is arranged in long
“spaghetti-like” complex molecules and these molecules are located in the cells. DNA is
packed in a double helix molecule format (see Figure 11). RNA is transcribed from the
DNA and does not feature the double helix packing.
Figure 11. Segments of DNA molecule packed in three helical formats. From left to right A, B and Z
variants respectively
source: http://en.wikipedia.org/wiki/File:A-DNA,_B-DNA_and_Z-DNA.png
originator - Richard Wheeler (Zephyris) at en.wikipedia
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DNA’s main role is the long term storage of an organism’s genetic information.
RNA, on the other hand, is involved in carrying information and translating it into
proteins. DNA and RNA are made up of smaller parts called nucleotides. Nucleotides
are the small building blocks that make up DNA and RNA.
To simplify, there are five primary nucleotide bases. Each of the nucleotides can
attract its matching group of nucleotide. For example, the nucleotide Thymine attracts
Adenine; and, Guanine attracts Cytosine. After bonding with each other the order that
nucleotide pairs are arranged and replicated is unique and specific to each life form. The
packing and storage of this genetic material is contained in the form of chromosomes.
Humans have 46 chromosomes.
A human made by normal sexual reproduction receives half of their genetic
material from the mother which is stored in her egg, and, the other half from the father
which is stored in each individual sperm. Upon fertilization the genetic material in the
egg and sperm combine and form chromosomes. As stated, in a healthy human genome
there are 46 distinct chromosomes. The genetic material of the mother and father
combine to make 23 pairs of chromosomes.
Figure 12 is an example of a full complement of 23 chromosome pairs for a
human male. The only difference between the male genome and the female is at the final
pair there is an X/Y for males and X/X for females. That means an additional X (female)
half is in place of the shorter Y half to form the X/X pair.
Figure 12. The 23 paired chromosome compliment of a normal human male
source: http://commons.wikimedia.org/wiki/File:DNA_human_male_chromosomes.gif
originator: National Human Genome Research Institute
http://www.genome.gov/Images/EdKit/bio1c_large.gif
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Somewhere embedded in our 46 chromosomes are the instructions that allow
cancer cells to be made and multiply. So you can say that we all have the built in
capacity to “self-destruct”. Similarly, instructions to turn off the cancer are as well
embedded in this genetic material. Where exactly any of these instructions are in the
genetic code is a matter of ongoing research. How and when this cancer code becomes
active is, as well, under investigation.
The study of genetics and unravelling the secrets of this genetic code will result in
being able to better understand and control cell behaviour. This understanding will
eventually give us the ability to address disease, deformation, mutation and even aging.
The hopes are that there are actual strands of genetic code that can be identified then
removed or modified so as to affect a cure for a disease such as Prostate Cancer (PC).
In 2011 a collaborative effort involving two teams of researchers managed to
sequence the entire genome of a prostate tumor. In comparing this sequencing to healthy
prostate sequencing they discovered that the prostate tumors had entire “chunks” of their
DNA sequencing that appeared to be cut out and inserted to another location in the
genome. These chunks of DNA that had been relocated contained genes that help drive
cancer progression; and, they were moved to areas in the genome where they may be
most active.19 How this exactly takes place is still a matter of investigation; however,
being able to identify these changes may soon afford a clinical method to better diagnose
and treat prostate malignancy.
In May 2012 the same researchers have identified what appear to be at least two
distinct sub-types of Prostate Cancer based on those that have ETS fusion genes and
another subtype that has mutations to a protein called SPOP. Apparently ETS fusion
genes such as TMPRSS2-ERG occur in approximately 50% of Prostate Cancer and have
so far not be found in tumors featuring the SPOP mutation. Prostate Cancer with SPOP
mutations were observed in approximately 6-15% of the study’s Prostate Cancer. 20 In
any case, the mechanisms involved are so far not understood and a matter of promising
ongoing research.
In the literature it is suggested that certain inherited gene mutations may increase
the risk of familial PC which is also referred to as HPC (Heredity Prostate Cancer).
Some of these mutations are found on chromosome 1; and others are located on
chromosomes 8; 17; 20; and, X.21 None of these mutations have been reported to reliably
signal the inheritance of PC. With the exception of PC in a family with evidence of
heredity breast /ovarian cancer syndrome (HBOC) a clinical test to determine genetic
predisposition to PC is so far unavailable.22 HCOC is a syndrome associated with
mutations on the BRCA1 and BRCA2 genes. BRCA stands for BReast CAncer.
Everyone has the genes in question. Usually the genes are in a normal unchanged
state; however, some people have inherited genes in a mutated or variant state. Carrying
any one of these genes in a mutated or variant state does not necessarily mean that you
will get Prostate Cancer. It only means that you may be more at risk to get Prostate
Cancer.
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Identifying those more likely to inherit PC is looking at the family history of
Prostate Cancer combined with genetic analysis. Criteria detailed by the researcher B.
Isaac and his team at the James Buchanan Brady Urological Institute consider certain
characteristics that suggest which mutation a family may have. HPC can be also be
passed through either the father’s or mother’s side of the family and can involve mutated
genes on different chromosomes.23
For the present we are still bound by a relatively poor understanding of how
cancer cells are directed due to the complexity, variability and microscopic nature of the
processes and genetics involved. While the research continues, medical treatment of
cancer in terms of chemotherapy and radiotherapy, is aimed more at interrupting or
disrupting the cycle and processes of quickly replicating cancer cells. To do this the
strategy is to take advantage of key weaknesses of cancer cell cycle.
Normal Cell Life Cycle and the Phases of Cell Division
From conception onwards a human is one big bundle of cellular and chemical
activity. The cells in a body are in a constant state of dynamic process. Such dynamic
process includes the “making of cells” referred to as cell Replication; the exchange and
use of energy called metabolic process; and, programmed cell death (PCD). This cell
activity is all arranged to support our specific design, function and needs as a biological
organism. These cell processes are the essence of life and death.
Replication is part of the “cell cycle”. When a normal cell replicates it divides into
two halves called daughter cells. When daughter cells are formed, each daughter cell
takes half of the sequenced genetic information of the normal parent cell. Figure 13
shows a normal cell dividing into daughter cells. Notice the “shared” genetic information
being pulled to opposite poles in each daughter cell on strands called microtubules.
Figure 13. A cell dividing into two daughter cells during M or Mitotic phase.
source: http://en.wikipedia.org/wiki/File:Anaphase_IF.jpg
originator- Delta Vision Roy van Heesbeend
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Daughter cells are formed in a phase of the cell cycle called the Mitotic phase.
The Mitotic phase is only a small part of a cells life cycle. The other phase is called
Interphase and represents the remainder of the cells life.
To visualize this sharing of genetic information, think of a common garment
zipper. When the zipper is “zipped up” both sides are joined together. If you hold the
zipper at both ends and twist in opposite directions you now have made a helix. This is
basically how the DNA is packaged as complete strands in a normal cell.
During daughter cell formation the complete DNA strands or helix is “unzipped”
into halves. Each half is now called a template. The “unzipping’ occurs at each bond
between two joined nucleotides. Remember the nucleotides are the building blocks that
are paired and arranged in sequence in a DNA molecule. They are like the teeth on a
zipper except, unlike the teeth on a conventional zipper, there are different types of
nucleotides that are designed to bond only with nucleotides from a matching group.
Rebuilding and preserving the order of the DNA sequence in the daughter cells is a
matter of respecting the order of nucleotides on the template and joining template
nucleotides with the correct free nucleotide they are normally attracted to.
Figure 14 demonstrates the unzipping of nucleotide pairs in a DNA strand into
two separate templates. Notice that each side of the strand keeps its nucleotide sequence
intact so it can later attract free floating nucleotides of the correct type to complete
(replicate) two new DNA strands with exactly the same order of nucleotides.
Figure 14. DNA unzipping into two templates during Mitotic (M) phase
source: http://commons.wikimedia.org/wiki/File:DNA_replication_split.svg
originator – Madprime
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Figure 15 demonstrates how each unzipped template becomes a blueprint in
assisting the replication of a complete DNA strand bound for each daughter cell.
Figure 15. DNA rebuilding during Interphase.
source: http://commons.wikimedia.org/wiki/File:DNA_replication_split.svg
originator - Madprime
The sequence of the genetic information is specific to the form and function of a
human. Mistakes in the copying of DNA, if made, may occasionally go undetected and
so get passed on to the next generation of cells. These are called mutations.
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Mutations are not supposed to occur. If DNA copying mistakes occur, the cell
has internal mechanisms that recognize most of these errors. If the error cannot be
corrected, it usually results in the cell “self-destructing”. This way the genetic sequence
or code is preserved and errors are not passed on through replication. Unfortunately,
cellular mechanisms to recognize mistakes in the genetic code are not perfect and
sometimes mistakes go undetected.
A cell’s life follows a set of phases. As stated, Mitotic phase is when the cell
splits into two daughter cells. After this the daughter cells must rebuild the shared
genetic information into complete DNA strands and go on to reproduce, or, live out their
cycle as mature cells. This is done in the next stage that is called Interphase.
Interphase can be divided into four distinct sub-phases and these sub-phases must
follow in order, otherwise, the cell cycle is interrupted and the cell will likely die. The
sub-phases are:
G1 or Gap 1 occurs immediately after the Mitotic phase. In G1 one of the important
things to occur is the production of enzymes involved in DNA synthesis. Without these
enzymes the cell will not be able to rebuild DNA and so
will not proceed to the next
cell sub-phase;
S or Synthesis phase is the next sub-phase. This is when the DNA is actually rebuilt or
replicated. During S phase the templates provide the nucleotide sites that attract and bind
to matching “loose” nucleotides within the daughter cell. The result is complete DNA
strands or helices. When DNA synthesis is complete the S phase is done;
G2 or Gap 2 is the next sub-phase. During G2 the cell manufactures proteins
used to
build the microtubules that act like cables and draw the shared DNA to opposite daughter
cells in the M phase. If protein synthesis is interrupted in G2, the cell will not proceed to
the Mitotic phase and so the replication process stops. For cancer cells, which tend to
replicate quickly, upsetting G2 protein synthesis is a tactic used by some types of
chemotherapy to halt or slow down replicating cancer cells.
When the cell does not replicate and instead proceeds to its normal duties directly from
G1 it enters into the sub-phase called G0. Cells that go into this sub-phase can stay in
this sub-phase for the remainder of their life or, at some later date, re-join the cycle of cell
replication.
Depending on the cell type and condition, the age of a cell varies. Red blood cells
last only a very short amount of time (days) then are removed and replaced by new red
blood cells. Comparatively brain and nervous tissue cells, if treated nicely, last the life of
the person they belong to.
Figure 16 shows a simple schematic of the cell cycle. In reality, the length of
each phase or sub-phase varies. So the duration of each phase is not accurately reflected
in the diagram. The order of each phase; however, is accurate and the diagram should be
considered in a clockwise sequence. This means that a cell will not skip, back up or
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proceed to any other phase out of sequence. The circle of the schematic shows the
phases of Mitosis (M) and Interphase (I) with its sub-phases G1, G0, S and G2.
Although this pie diagram implies timeframe you should know that time frame varies
substantially between different cell types. So this diagram only represents the rough
notion of cell phase duration to example the element of accumulating timeframe to the
reader.
Figure 16. Schematic of Cell cycle involving mitotic division.
source: http://en.wikipedia.org/wiki/File:Cell_Cycle_2-2.svg
Originator- Zephyris
The initiation, pace, and, duration of cell replication is regulated by instructions
that are guided by proteins within a cell’s genetic material. In adults, there are two rules
that define the way a normal cell behaves.
These rules are:
1) Normal cells should not reproduce unless they are trying to repair or replace
damaged cells; and,
2) A normal cell is not allowed to stay alive if the damage to it is too extensive, it is
replaced.
Further, damage does not just mean trauma, it can also mean mistakes in the cells genetic
code. As stated; should the mistake go undetected then it becomes part of the DNA
sequence that can be passed on and replicated. A mutation is a permanent change in a
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gene’s code resulting from a mistake in the original DNA sequence. Such mutations can
change the end result of what is being replicated, as well as its functional ability. It is
theorized that such mutation opens the door for changes that can eventually progress into
cancer cells. Generally speaking, cancer is caused by mistakes or mutations in
protein production and particularly, mutations in enzyme production.24
Mutations can be caused by copying errors, breakages or overlaps in the DNA,
and exposure to agents called mutagens. CIGARETTE SMOKE, either first or second
hand, is an example of a mutagen. So is radiation. Mutations also occur when precancerous cells lose their identity as differentiated cells. When a cell loses its identity as a
differentiated cell this means the cell loses its capacity and structure to behave, resemble
and integrate with normal cells that reside in the same area.
Figure 17A illustrates this notion of normal cell division and how mutations that
give rise to a cancer cell typically results in the death of the mutant cell. Figure 17B
shows what happens when the mutation resulting in cancer is not handled correctly by the
body’s defenses and the cell is allowed to replicate.
Figure 17. A - A cell division Mutation giving rise to a cancer cell that dies; B- Surviving Cancer cell
division.
Source: http://en.wikipedia.org/wiki/File:Normal_cancer_cell_division_from_NIH-2.svg
originator - Normal_cancer_cell_division_from_NIH.png
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When one considers cancer cells, the initiation, pace and the extent of this
replication is not like normal cells. Cancer cells do not abide by the two rules of normal
cells. This lends to a signature that is common, either in whole or in part, to all cancer.
The cancer signature includes:
a) The ability of the cancer cell to function independent of the chemical signals (in the
form of proteins) that tell the surrounding normal, healthy cells how to behave;
b) The resistance or refusal of the cancer cell to self-destruct, also known as a resistance
to apoptosis. This allows the cancer cells, which are basically non-standard or damaged
cells, to thrive and proliferate with apparent immortality;
c) The ability of cancer cells to form their own network of blood vessels; and,
d) The ability to reproduce without any normal reason resulting in the proliferation of the
cancer cells and the subsequent invasion of surrounding tissue and body systems.25
Active cancer cells generally multiply quickly. They can overgrow surrounding
cells and can migrate. If left untreated the cancer cells will continue to develop until their
host is overgrown to the point where normal biological function and process are so
burdened or interrupted that it is inconsistent with life.
Abnormal condition of the Prostate
Occasionally the prostate becomes host to growth resulting in feature or condition
not normally associated with a pristine organ. Cysts; 26 inflammation (prostatitis); painful
condition resulting from abnormal nerves or muscles in the region (prostatodynia);
benign prostate enlargement (prostatomegaly); as well as, PC are examples of conditions
that a prostate may host. Unfortunately, when such condition or growth occurs there is
often not much by way of symptoms that indicate any change or problem until these
abnormalities become quite advanced.
These conditions are either benign or malignant (cancerous). Sometimes
abnormal structure can harbour what is called pre-cancerous cells. It is thought that if
pre-cancerous cells are left unattended for a substantial period of time they can eventually
develop into cancer. As much as I gather, the mechanism of how or when such a change
happens is not understood. Neither is how long it actually takes for PC to develop.
Abnormality should, at the very least, be monitored closely especially if it is regarded to
be in a precancerous state or if you are moderate to high life time risk based on your
history and profile.
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37
Benign (Non-Cancerous) Growth, Condition and Presentation
Prostatomegaly (enlarged prostate) is a common occurrence especially as men
grow older. This can be due to a number of conditions which include:
1) Benign prostatic hyperplasia (BHP) is enlargement of the prostate due to the increase
the number of cells of the prostate.28 Another name that finds its way under the title of
BHP in the literature is adenofibromyomatous hyperplasia;
2) Benign prostatic hypertrophy (BPH) is enlargement of the prostate due to the increased
size of the prostate cells. This condition is common in elderly men and occurs usually
in the peripheral zone of the prostate. Its cause is not known; however, there is evidence
to suggest it is hormonally mandated; 29
3) Benign cystic hyperplasia involves irregular and abnormal prostate enlargement
caused by an increase in the reproduction rate of cells related to benign cyst development.
A cyst is basically a fluid filled sac. Paraprostatic cysts are an example of a type of cyst
found connected to the prostate by thin stalks;
4) Squamous metaplasia is a benign condition where prostate cells start changing into a
squamous (plate-like) form. It also mimics a cancerous condition called squamous
carcinoma although no there is no clear understanding that this benign condition leads to
a malignant condition;
5) Prostatitis is a group of prostate disorders that are sub-divided into four categories.
- Bacterial prostatitis is usually caused by urinary tract pathogens (foreign
bacteria) and can be either acute or chronic. Prostate abscess is a complication
associated with acute bacterial prostatitis;
- Non-bacterial prostatitis can be inflammatory or non-inflammatory the cause of
which is not really known. It is thought that it could be related to elevated urinary
pressure triggering an inflammatory response in the prostate OR increased pelvic
autonomic (immune system) activity leading to chronic pain (prostatodynia).30
6) Prostatodynia is a term for pain that emanates from the prostate. Described as a deep
burning or aching pain, it often radiates to the rectum; which sometimes causes it to be
misdiagnosed as proctalgia, a more generalized term referring to pain in the rectum.
Prostatodynia can be formative to a syndrome called PPOD (pelvic pain and organic
dysfunction) which can manifest into a wide range of bladder, bowel and sexual
dysfunctions.31
Prostatomegaly, if left unchecked, will likely advance and create more
pronounced problems as the prostate enlarges. It must not be ignored and requires
medical attention.
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38
Dysplasia and the Cancer Cell
Sometimes in a pathology report you may encounter the word dysplasia. As I
have been told, dysplasia is the earliest form of pre-cancerous lesion that a pathologist
can recognize. Dysplasia can be low grade or high grade. It is thought that the risk of low
grade dysplasia transforming into high grade dysplasia and then into cancer is low simply
because the process of cells changing to feature cancer-like behavior can take a very long
time if it happens at all. It is proposed that for the cells of the low grade dysplasia to turn
into cancer a series of undetected random mutations have to occur. However unlikely it
may be, when a lesion is typed as low grade dysplasia the cells therein could be in the
beginning Initiation phase of cancer. Following this Initiation phase is the phase of
Promotion.
The Promotion phase is when the cancer becomes robust through successive
mutations. In theory this phase can last for many years before the cancer transitions to
the next phase called Progression.
High grade dysplasia represents a more advanced trend towards malignant or
cancerous transformation. Carcinoma in situ, (CIS) means the cancer is restricted to the
surface on which it resides. Lesions of this type essentially have cells that undergo no
maturation. They are said to have lost their ability to differentiate into a recognizable
healthy cell. As such; these CIS cells have lost their tissue identity and have assumed
what is considered a primitive cell form that grows rapidly and without regulation.
Further to this, it is thought that the lack of maturation generally results in associated
changes in the genome since irregular cell growth generally results in incorrect
replication and/or mutation of the genetic code. This is the essence of cancer-like cell
behavior.
Progression is the phase when the cancer invades the local tissue (in this case the
prostate elements) and eventually moves throughout the rest of the body. Invasive
carcinoma is the final step in this sequence. It is cancer which has metastasized or
invaded beyond the original tissue layers and has spread. Invasive cancer can usually be
treated but not always successfully; however, if it is left untreated it is certain to be fatal
with time.
Malignant Growth, Condition and Presentation
Generally the longer cancer goes undetected and untreated the more chance of it
exceeding the membranes of its original site and becoming invasive. It is important to
catch any cancer before it has become invasive. The timeframes involved in the
development and progression of the different types of Prostate Cancer in humans remain
unclear. The staging of Prostate Cancer will be discussed more thoroughly in a later
chapter.
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39
As stated, the prostate requires androgens to function and the balance between
androgens and other hormones is fundamental to the health of the organ. Considerable
research is ongoing to investigate the impact of this balance and its role in activating and
promoting PC.
It has long since been reported that Prostate Cancer development is initially
steroid hormone dependent. Androgen receptors (ARs), Estrogen receptors (ERs), and,
Progesterone receptors (PRs) with their matching hormones are all participants in normal
and malignant prostate cell activity and growth. Research is focused on the processes of
how these assorted receptors of hormones change; and in so doing, activate and promote
PC.
It has been reported that PC cells have marked differences from normal prostate
cells in that two of the three Estrogen α receptors (types ERα-A and ERα-B) are often
found to be deactivated.32 It is not clear when exactly this deactivation of ERα receptors
occurs. Nor is it clear if this deactivation is in fact causative to PC initiation or simply a
feature of PC promotion.
In the past one of the strategies in addressing PC was castration (removal of the
testes). As stated, the testes produce most of an adult male’s hormone called
testosterone. Testosterone is one of the androgens that contribute to male hormone
levels. It is also made at much lower levels in the adrenal glands. As well, adult women
produce testosterone but also much lower levels than in an adult male. Prostate cells need
androgen; the idea was that by removing the testes the associated reduction in a man’s
ability to produce androgen hormones would either stop or significantly slow the PC.
This worked on some PCs; however, it has since been known that there is “castrate
resistant” PC (CRPC) that can grow despite medical interventions [surgical and
therapeutic] aimed at reducing androgen hormone levels.
CRPC continues to challenge and confound treatment regimens. It is reported that
90% of men with CRPC develop bone metastases which can lead to significant pain
fractures, spinal cord compression and bone marrow failure.33
Overall, it can be said that there is much more to discover as to how and why
hormones affect PC cells.
At times the term neo-plastic will be used to describe a tumor. Neo-plasticity
means that an abnormal tissue mass has developed as a result of uncontrolled cell growth
occurring usually after a genetic mutation. Neo-plastic tumors do not always progress
(get worse), but sometimes they do. Neo-plastic tumors can be benign, pre-cancerous or
cancerous.
High Grade prostatic intraepithelial neoplasia (HGPIN) is believed to precede the
development of prostate adenocarcinoma. Figure 18 shows a microscopic view of
HGPIN. Grading will be discussed in a later chapter.
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
40
Figure 18. Micrograph of High Grade prostatic intraepithelial neoplasia (HGPIN). Lesion (HPIN at
left of image) progressively changes to a solid cord of tumor cells (pointed to by arrows). N (top
right) is used in the photograph to mark a normal prostate cell.
source: http://openi.nlm.nih.gov/detailedresult.php?img=3177701_PC2011-249290.002&query=human
Prostate carcinoma
&fields=all&favor=none&it=none&sub=none&uniq=0&sp=none&req=4&npos=42&prt=
originator – R.B Nagle and Cress, A.E.
The following is a brief overview of the types of Prostate Cancer and tumors:
Acinar Adenocarcinoma (also known as glandular Prostate Cancer) – this disease
accounts for more than 90% of all newly diagnosed Prostate Cancer.34 It begins when
normal semen secreting gland cells mutate into cancer cells most commonly in the
prostate’s peripheral tissues. Figure 19 shows a microscopic view of prostate acinar
adenocarcinoma;
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41
Figure 19. Micrograph of prostate acinar adenocarcinoma with Gleason pattern 4.
source: http://en.wikipedia.org/wiki/File:Prostate_cancer_with_Gleason_pattern_4_low_mag.jpg
originator - Nephron
The remaining 10% of those diagnosed have a number of different types of PC
including:
Adenoid cystic carcinomas (AdCC) – can be associated with distant metastasis;
Basal cell carcinomas (BCC) and carcinoid tumors – are rare prostatic neoplasms with
unfavorable clinical outcomes;
Carcinosarcomas and sarcomatoid carcinomas - are biphasic tumors that progress (grow)
rapidly;
Lymphoepithelioma-like carcinomas - are poorly differentiated carcinomas with a
syncytial growth pattern and adverse clinical behavior;
Mucinous carcinomas – rarely respond to hormonal therapy and often cause bone
metastases;
Prostatic duct carcinomas- originate in the larger dilated central ducts of the prostate
gland and typically are low to intermediate aggressiveness.
-
Endometrioid adenocarcinomas are included in this ductile PC group;
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42
Prostatic transitional cell carcinomas – arise from the periurethral glandular epithelium
OR from metaplastic prostatic epithelium; and, often develop aggressive tumors that are
not responsive to hormonal therapy;
Signet-ring cell carcinoma – is a clinically aggressive PC;
Small cell and neuroendocrine carcinomas – are associated with poor prognosis;
Squamous and adenosquamous carcinomas - may develop following radiation therapy or
after conventional adenocarcinoma has been treated with estrogens; 35 and,
Transitional cell carcinoma (TCC) – rarely develops as a primary cancer in the prostate
instead is derived from primary tumors present in the bladder. As a primary cancer of the
prostate it difficult to detect until it is advanced. In advanced condition its prognosis is
unfavorable.36
Notes to clarify the jargon used in the above PC descriptions [in order of appearance]:
- Carcinoma means cancer of the epithelial tissue (in this case, thin tissue that
covers the outside or lines the insides of the prostate);
either
- Sarcoma means cancer of connective tissue such as bone, cartilage and fat;
- Basal cell is one of two types of cells that make up the epithelial tissue of the
prostate. The other type of cell in the epithelial tissue is called luminal cells;
- Biphasic means it occurs in two different phases;
- Syncytial refers to cytoplasm (the contents normally inside a cell where metabolic
activity and cell division occurs) that is not separated into cells;
-Mucinous means it is related to or covered with mucous;
-Metaplastic means the transformation of cells from a normal to abnormal state;
- Signet ring cell is an unusually malignant cell containing clear cytoplasm that
into a signet (flat cookie) shape;
flattens
- Neuroendocrine means relating to or involving both nervous system stimulation and
endocrine system secretion;
- Squamous means characterized or covered with scales.
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43
Chapter 2
Symptoms, Examination & Opinions
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44
Diagnosis is the medical determination of disease or syndrome performed by a
physician. The focus is on the disease process and the physical, genetic, or environmental
cause of that process.37
Symptoms
As outlined in the previous chapter, the symptoms associated with the range of
prostate related condition and ailments have striking similarity. These symptoms can be
obvious, missing or masked by other condition or disease. In the end, correct diagnosis
of normal, benign or malignant prostate condition must rely on proper medical
examination and testing. It is important to be aware of what the symptoms of PC are. A
doctor should be consulted and follow up should be done with the appropriate tests if any
of the following symptoms are observed.
To reiterate, some of the common symptoms are:
•
need to urinate often (especially at night);
•
intense need to urinate (urgency);
•
difficulty in starting or stopping the urine flow;
•
inability to urinate;
•
weak, decreased or interrupted urine stream;
•
a sense of incompletely emptying the bladder;
•
burning or pain during urination;
•
blood in the urine or semen;
•
painful ejaculation.
Additionally, symptoms of more advanced PC can be any one or combination of the
following:
•
Bone pain (back, hips, thighs and neck);
•
Weight loss;
•
Fatigue;
•
Anemia (low red blood cell count);
•
Weakness or numbness in the legs or feet;
•
Loss of bladder or bowel control. 38
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
45
These symptoms are all obvious aspects that can be detected by any one hosting
them then brought to the attention of medical staff. All that is required is to apply your
knowledge.
Prostate Self-Examination (PSE)
It has long since been known that those who conduct breast self-examination
(BSE) and are proficient in their technique may reduce the risk of death from breast
cancer through earlier detection.39 Since I only recently finished writing a book on
Breast Cancer, by logical extension I went about in search of reputable reference for
proficient Prostate Self Examination (PSE) technique and studies reporting on the impact
of such technique with respect to the incidence or mortality of Prostate Cancer.
Unbelievably, I found nothing in this regard in the literature.
I did find a number of opinions on why PSE is not even considered. Most of
which I consider invalid since DRE (digital rectal exam) used to be the gold standard for
PC detection and remains an integral part of prostate Clinical Examination and is often
used to give context to a patient’s screening PSA test results.40 So it is not like the DRE
has been abandoned by the mainstream medical community.
In fact, the American Cancer Society recommends that for those who have had an
informed discussion with their physician and elect to participate in prostate screening; a
DRE in conjunction with PSA testing should be done for men of:
o average lifetime risk beginning at the age of 50;
o high lifetime risk beginning at the age of 45 which includes AfricanAmerican men and those with first degree relatives (father, brother or son)
already diagnosed with PC at an early age;
o highest lifetime risk beginning at the age of 40 which includes those with
more than one first degree relative diagnosed with PC at an early age.
All of this as part of a strategy promoting early detection of PC.41
Given the ongoing use of DRE, it is my view that if a Clinician can be taught to
perform DRE in a way that promotes earlier detection of PC; then similarly, so can a
patient. So then what aspects have to be overcome in order to have proficient PSE
technique?
First, it must be understood that any such technique would not be a substitute for
clinical examination where DRE is performed by a trained medical clinician in
accordance with a patient’s risk and proposed screening regimen. PSE could be used
like BSE (breast self- exam) to maintain a regular check on the status of an area that is
within reach and amenable to a patient’s palpable review. Palpable review means
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46
figuring out the health or status of something by feeling it; in this case, with a finger.
Those that have been properly trained and regularly practice PSE would know the
palpable areas of their prostate better than anyone. With this, any palpable abnormality
could then be brought to the attention of the patient’s physician or urologist in a more
timely way.
Second, most people are really uncomfortable with the notion of having what
amounts to a total stranger stick a finger up their butt and probe around; even if it is only
for a few seconds. Several years ago I recall hearing the former Surgeon General of the
United States, Antonia Novello, M.D. speak on pressing health issues in her country.
Addressing a room filled mostly with men, she raised eyebrows by stating that men are
afraid of losing their “anal virginity”. After a great silence in the room along with a
couple of solitary coughs she clarified by making the recommendation that everyone
should consider the statistics on colon cancer and go get a colonoscopy as they get older.
Her comments spoke volumes on the psyche that leads to advanced cancer in those parts
of the body that folks consider private or otherwise “off limits”. I know having gone
through surgery and treatment for advanced colon cancer the notion of “off limits” is a
non-issue as soon as you show up to a medical facility with cancer. Everyone can do
themselves a great favor by being sensible about their body when it comes to keeping
track of abnormality and possible cancer. In terms of PSE, I think it may be a way to
begin being aware of your prostate status while respecting your need for a bit of privacy
without any “surprises”. After all, I am sure most men never have a clinical prostate
exam. Those that do go for a clinical exam probably do so once every five years and start
late when they are in their fifties, for example. What about all of that time in between
check-ups? The lack of monitoring is precisely what PC needs to develop into invasive
condition.
Third, PSE is basically self-practiced DRE after one has been properly trained. It
is a way to increase the chances of early detection which can be a valuable addition to
screening for those with moderate to high lifetime risk of developing PC. Training can
be found by asking your urologist or physician. They should be able to accommodate
your request. If not, then go find another who will.
Fourth, there are those who say that self-practiced DRE can’t be done because of
the difficultly of correct hand placement. This is absolute nonsense if you have
appendages (arms, hands and legs) that are developed and function within the norm of
our species. If one bends one’s knees so as to crouch to the floor in a full squat resting
on your feet then slide the preferred hand between the onside hamstring and lower calf,
not only can you position your hand in exactly the correct position over the anus; but as
well, your leg has a firm grip on your forearm and provides a rock steady platform from
which your hand can be leveraged and maneuvered without physical exhaustion during
PSE. I would suggest holding onto something solid with the other hand to maintain your
balance.
Fifth, the technique for DRE is not rocket science. In fact, it is considered an easy
technique to learn given a sound understanding of the prostate’s anatomy, the knowledge
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
47
of what to feel for, and, a bit of practice. Medical students learn the technique in a
number of ways. Some these ways involve prostate examination simulators; others
involve practicing on other students or volunteer patients.42 The bottom line is that real
proficiency comes with training and practice.
So the question is what is involved in a DRE that would make it amenable to selfexamination? To reply, the following is a brief description of some of the practical
considerations in clinical DRE:
- The patient usually assumes a knees bent position on the examination table. This is the
equivalent of the full squat position discussed above;
- Preparation for the examination is simply that the patient evacuates the bowel (i.e. has a
bowel movement) before doing the exam and then washing the area. This will normally
afford a sufficient void in the colorectal complex to conduct the exam;
- Using a hand dressed in a latex glove to avoid the transfer of bacteria, the physician or
urologist applies lubrication (like KY jelly) and gently accesses the prostate via the
rectum using a finger. The same can be done by a patient. General rule, don’t put
anything up your anus that you would not put in your mouth (for example baby oil or
Vaseline are made for external application only);
- Finger palpation will not allow the entire prostate to be examined. In fact, only about
40% to 50% of the prostate is accessible using a finger because of the anatomy of the
prostate and the length of a finger.43 This shortcoming is the same for a clinician as it is if
the patient is conducting a self-DRE;
-
When a clinician conducts this examination they are feeling and looking for any
irregularities that may be symptomatic of PC. These include abnormal prostate size,
shape, nodules (bumps); ulcers; bleeding; unusual hardness or sponginess; and, pain for
example. As well, the prostate is being felt through the colon wall so there has to be a
regard so as not to injure either organ during the examination. In addition, one must be
aware that any discovery could be the related to the colorectal tissue harboring abnormal
condition instead of the prostate;
- The prostate is small and a DRE done by a seasoned clinician usually takes less than ten
seconds. The clinician uses their experience with other patients as a basis of comparison.
A patient conducting self-DRE on the other hand knows their own prostate; so any
changes may be more immediately obvious. As well, the examination can be conducted
more slowly in a relaxed atmosphere so that a more thorough understanding of
abnormality can be had. Patients can also monitor any changes over much shorter
intervals;
- DRE technique involves using an index finger to sweep from the top of the prostate
laterally back and forth over each lobe while being vigilant for any palpable
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
48
abnormality.44 This can be done by anyone who is properly versed in the technique,
including the patient;
- According to J.M. White et al, “the clinical significance of careful examination of the
prostate gland is highlighted by the observation that approximately one-third of those
above age 60 will have some symptoms or findings that can be referable to the
prostate”;45
- The risks of DRE are minimal in terms of causing injury or infection so long as the
examination involves accustomed DRE technique and protocol. For the patient this
means get some training; cut your fingernails so that there is less risk of causing injury
during the DRE; wash; wear a latex glove on the examining hand; be gentle; use common
sense as to the interval between self-DRE; don’t use “accessories” to extend reach, even
if they are from what is advertised as an approved kit; and, bring any concerns to the
attention of your clinician.
Overall I see no reason why proficient self-practice DRE cannot be done given
training, common sense, and, some open communication with your physician or
urologist. Some prostate patients have pointed out that DRE can similarly be conducted
by a willing “significant other”. In my view, whatever you are comfortable with; as long
as they have proper training and exercise the same considerations as discussed. Figure
20 is an illustration of the area the DRE accesses.
Figure 20. The DRE (Digital Rectal Exam).
source: http://visuals.nci.nih.gov/details.cfm?imageid=4351
originator: National Cancer Institute, Alan Hoofring (illustrator)
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49
Clinical Prostate Examination (CPE)
Clinical Prostate Exam (CPE) is an examination of your prostate by a medical
professional usually done as part of a screening regimen. Unfortunately, even with the
obvious recognition of the need for better screening techniques; there remains a complete
lack of harmonization of screening recommendation using the present technology within
the mainstream medical community.
The American Cancer Society, the Canadian Urological Association, and, the
American Urological Association all have prostate screening recommendation.46 In
contrast; the US Preventative Service Task Force unbelievably has issued statement in
2008 saying that for men younger than 75 years the balance of harms and benefits of
prostate screening cannot be determined. Effectively, they have no recommendation
except to say that for men over 75 they do not recommend prostate screening.47
Nevertheless, CPE can be done as part of your annual physical examination; or, in
accordance with a specific schedule associated with your PC lifetime risk; or, in response
to concern brought to your physician as a patient.
CPE can include a number of tests and examination; however, more commonly, it
involves a DRE; a PSA test; and a thorough review of your profile including family
history of PC. In the case of high levels of prostate specific antigen (PSA) a trans-rectal
ultrasound (TRUS) may as well be done. The findings of the CPE are not conclusive to
any diagnosis. Further testing involving more blood work, imaging and biopsy may be
required if the physician feels it is merited. In short, CPE is very much a preliminary
examination that assists the physician in determining the merit and need for further
investigation of suspected abnormal prostate condition, as well as the emphasis and
direction of that investigation.
One of the problems of examinations, tests and imaging is that sometimes the
results are interpreted “incorrectly”. This could involve failing to find or report abnormal
growth resulting in the patient being sent home with the condition untreated. This is
called false negative results. It can also involve calling some types of imaging artifact
“abnormal” growth when it is not. This can result in unnecessary follow up and/or
surgical procedure such as biopsy. This is called false positive results.
Ideally, it is best if results from tests or imaging are reviewed twice. This way the
reviewing specialists can compare their findings. A second review lowers the risk of
review error. Unfortunately, this is costly and health facilities in North America do not
necessarily provide this service as commonly as those in Europe. To address this, a
number of technologies are now used. One such technology is called Computer Aided
Detection (CAD). It is another way to have a more thorough review of your images.
CAD is a program that analyses the images for high probability areas of abnormal
growth. The program then “marks” the high probability area so that it can be looked at by
the radiologist. CAD programs can be found on X-ray, CT and MRI imaging, for
example. Figure 21 shows an example of TRUS image with CAD markings and Color
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50
Doppler enhancements to point out areas where the blood flow pattern is suspicious and
may be the result of malignancy. Consider how difficult it would be to identify
suspicious tissue in this type of ultrasound imaging without the benefit of CAD.
Figure 21. TRUS images of a prostate lesion in a 45 year old man. A – band like lesion (arrows)
with regular outline at outer peripheral zone; B- CAD enhanced Color Doppler US shows
prominent hypervascularity (arrows) indicating likelihood of malignancy;
source: http://openi.nlm.nih.gov/detailedresult.php?img=2672179_kjr-10-244-g001&query= Prostate
Cancer tumor &fields=all&favor=none&it=u&sub=none&uniq=0&sp=none&req=4&simResults=f0a0c121
f0a1c6 f0a2c133 f0a3c60 f0a4c9 f1a0c347 f1a1c244 f1a2c3 f2a0c146 f3a0c141 f3a1c134 f3a2c138 f3a3c3
f3a4c3 f3a5c6 f4a0c94&npos=12&prt=2
originator: H.Y. Lee et al.
One of the larger problems is trying to address the processing of the 5-10 million
cores from the 1,000,000 or so prostate biopsy procedures that occur annually just in the
United States. The traditional efficiency of reviewing these cores on micrograph slides
and finding cancer is only about 20%. HistoCAD is a CAD program able to review such
micrograph slides and provide analysis and grading of Prostate Cancer with near 100%
reproducibility.48 The biggest problem with this technology, apart from it not being
available in most medical facilities, is having sufficient storage to bank all of the
additional information that is processed in reviewing biopsy tissue at a microscopic level
with CAD. Still, it is a tool that would greatly improve a pathology clinician’s ability to
identify PC and render accurate PC prognosis.
After your clinical prostate exam, protocol and process is such that in most
facilities the results take time before being released to you. If you have not received
your results and it has been two weeks since the exam, follow up with a call to either
the facility or to your overseeing physician. Find out why. This is important to do
because sometimes results get misplaced. Delaying disclosure of the results makes for
unnecessary anxiety; and in the case of disease, can ultimately delay diagnosis of any
abnormality you may have. This is unacceptable. You must be aware that a clinical
exam will not necessarily provide a solid diagnosis of your prostate condition. In the
case of abnormality that has been confirmed by imaging, you can expect to undergo a
biopsy before diagnosis.
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Ultra Sound Imaging
Ultrasound or sonography (USG) is a technology that sends high frequency sound
waves through tissues and captures the signature of those sound waves. Tissues all have
different reflective qualities because of structure and their physical properties and it is
this sound reflection and absorption that is captured and compiled to create an image of
the area and organ(s) being scanned.
The prostate trans-rectal ultrasound is a procedure that involves the patient lying
on their back on an examination table with their knees bent and legs open. The
examination table may or may not have stirrups to assist in maintaining the patient’s
station during the examination. The technician conducts the examination using ½”
diameter wand-like probe (called a transducer) that is inserted via the anus to the prostate
area. Several adjustments to the probe’s angle and position may be required to ensure
adequate “sounding coverage” allowing the capture and imaging of the area of interest.
Apart from some slight discomfort, the examination is totally painless. It takes about 15
to 20 minutes to perform.
Sometimes the TRUS may be used as “real time” guidance of a core biopsy of the
prostate. In this case, a sedative and anti-biotic are administered to the patient before the
biopsy needle is inserted into the prostate and core samples taken.
Figure 22 shows TRUS image with CAD markings and color Doppler
enhancement. As stated, the Doppler enhancement is able to detect the movement of
blood. A cancer tumor typically has a congested network of veins serving its needs of
circulation. This type of congestion is obvious when the ultrasound has Doppler
enhancement.
Figure 22. TRUS images of a prostate lesion. E – lesion (arrows) mostly located in peripheral zone;
F- Color Doppler shows vascularity (arrows) in lesion.
source: http://openi.nlm.nih.gov/detailedresult.php?img=2672179_kjr-10-244-g001&query= Prostate
Cancer tumor &fields=all&favor=none&it=u&sub=none&uniq=0&sp=none&req=4&simResults=f0a0c121
f0a1c6 f0a2c133 f0a3c60 f0a4c9 f1a0c347 f1a1c244 f1a2c3 f2a0c146 f3a0c141 f3a1c134 f3a2c138 f3a3c3
f3a4c3 f3a5c6 f4a0c94&npos=12&prt=2
originator: H.Y. Lee et al.
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CT Scan
Advancement to X-ray or radiographic technology has seen the arrival and use of
the CT (computed tomography) scan. The CT scan uses the same ionizing radiation as an
X-ray to make an image. The CT is the modern version of the old CAT scan which could
only take images in an axial plane (2D). So the CT is essentially an X-ray that is taken
over multiple cross sections and then be recompiled into a 3D image by computer.
Again like the X-ray, this type of imaging is best suited to tissue or structure composed of
calcium or carbon; so, in the case of the prostate, it is not as useful an imaging solution as
for example an MRI; and, therefore it is not so commonly used for imaging the prostate.
Nevertheless, CT is used for imaging organs and vessels.
Figure 23 is a picture of a spiral CT scanner. For the scan the patient lies down
on the platform and they are then passed through the opening of the scanner. While the
scanner is taking the image the patient will be asked to remain still. The beam emitter
inside the scanner then “spirals” the patient while taking numerous images that are
collected and to later render a 3D projection. Other than a little discomfort in having to
lie still on a platform, the whole procedure is totally painless. The time frame varies
according to the extent of the condition being imaged. Generally, the imaging session
only takes a few minutes to complete once begun; however, the preparation for the CT if
contrast agents are involved will take about an hour since the contrast agent has to be
delivered to the patient they adequately absorbed by the tissues before the CT is began.
Figure 23. Spiral CT Scanner.
source: http://commons.wikimedia.org/wiki/File:Ct-scan.jpg
Originator: NithinRao
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Contrast agents are used to enhance the CT image allowing for structure to be
more easily determined. These agents are delivered to the patient either orally or by
intravenous injection. IV injection of contrast agents will likely cause you to feel tingly
and warm shortly after the IV is started as was my experience with IV contrast agents.
CT imaging is less likely to have artefacts caused by patient movement.
Molecular Imaging (PET/CT scan)
It is known that cancer cells generally multiply quickly. To do this cancer needs
fuel. The fuel that it uses to drive its energy needs is a basic sugar, which I will discuss
in Chapter 5. As the cancer cells grow the tissue that is formed requires a circulation
network to supply oxygen and fuel, and remove waste. Fortunately, because cancer
tissue grows without any “plan” the associated circulation network generally becomes
congested and “choked” much like a bowl of spaghetti. This makes for circulation that is
typically not very good or dependable in delivering oxygen to the cancer tissues. In
short, the cancer basically resides in an oxygen deprived (anaerobic) environment and
adopts a way of processing fuel, called glycolysis, which is inefficient and requires much
more sugar than normal cells do in order to satisfy the energy requirements. Uptake and
processing of fuel by a cell is called metabolism or metabolic activity. When cancer cells
exist they are typically associated with areas of high metabolism or hypermetabolism.
With these facts, imaging specialists have developed techniques that attach a
“label” to molecules that are introduced to the bloodstream by IV then consumed and
concentrated in cancer cells. The technology then “sees” the label and a better picture of
the malignant area of activity is the result. This approach to viewing cancer is called
molecular imaging.
A common label used during molecular imaging in oncology is fluorine-18.
Fluorine-18 is combined with glucose (sugar) molecules then introduced to the patient by
IV for the purpose of the scan. The labeled molecule is called 18F-floro-2-deoxy-Dglucose which is abbreviated as FDG in the literature. Most cancer cells have increased
uptake of FDG compared to normal cell tissue.
The imaging that can see these labeled molecules is called Positron Emission
Tomography or PET. FDG-PET scans show the distribution of tumor deposits based on
their metabolic activity. The relative intensity of FDG uptake gives an idea of cancer cell
activity. If a patient is being treated for cancer, the effectiveness of the treatment can be
monitored using FDG-PET. Decreases in FDG uptake, for example, indicate that the
patient is responding to the selected therapy.49
PET is combined with computed tomography (PET/CT) and used as a diagnostic
tool for determining aspects such as the stage, response and recurrence of cancer. Recent
data is indicating that there are possible advantages of using FDG-PET in whole body
imaging in order to earlier detect cancer spread or recurrence.50
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Figure 24 shows a PET/CT scan with areas of concern throughout the thorax and
pelvic area from a cancer that originated in the colon. Crosshairs on the image clearly
point out a tumor in the right lung in front, sagittal and plan views of the patient.
With this type of imaging used in a screening capacity, early detection of prostate
metastasis to distant parts of the body is made much more likely. As such; proposed
treatment can be more accurately tailored to address the patient’s actual condition.
Figure 24. PET/CT of a staging exam of colon carcinoma - Tumor in the crosshairs on right side of
body is a lung nodule. Numerous other tumors are visible in thorax and pelvic area.
source: http://commons.wikimedia.org/wiki/File:RectalCancerStagingInPETCT%2Barrow.jpg
originator: Hg6996
In 2006 it was reported that the contrast agent 11C-Choline combined with
PET/CT accumulates preferentially within Prostate Cancer tissue. As such; PC can be
located and imaged precisely. In addition, this type of imaging can differentiate
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55
between malignant and benign tissue within the prostate. 51 In 2011 these findings were
supported by investigators reviewing this type of imaging and who also encouraged
training of technical readers in the specifics of 11C-Choline uptake and its distribution in
the body as a way to minimize false positive and false negative occurrence in the
interpretation of 11C-Choline PET/CT scans.52 This type of imaging has significant
clinical implications both in the screening and diagnosis of PC.
MRI
Magnetic resonance imaging is another totally painless procedure that takes
between 20 to 45 minutes to do for the pelvic area. As the patient lies flat on the platform
they are passed through what looks like a big donut (see Figure 25).
The MRI machine creates a very strong magnetic field that induces mini magnetic
emissions in the body’s hydrogen nuclei which can be captured and stored by the MRI
system. Successive pictures or “slices” of these emissions are made at different angles
and planes. These are then compiled by computer to make the 3D image of the area
scanned. Since every tissue and structure has a distinct magnetic imprint, the reviewing
surgeon can clearly see the abnormal outline and growth in the pelvic area before they
ever operate. This allows the surgeon to operate with more confidence that they are
addressing the problem area(s).
Figure 25. Example of an MRI scanner.
source: http://commons.wikimedia.org/wiki/File:MRI-Philips.JPG
originator : Jan Ainali
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MRI is well suited for cases when a patient is to undergo the exam several times
successively in the short term because, unlike X-ray and CT scan, it does not expose
the patient to the hazards of ionizing photon radiation.
A small inconvenience of the MRI is that the patient must be still during image
capture. If they are not, the image becomes unclear. This is called motion artifact. As a
result, MRI scanners are equipped with speakers that tell the patient when to hold their
breath as they are being scanned and when they can breathe after. This again only
happens for a few seconds at a time. During the pelvic imaging, the patient is positioned
on the platform and can be administered a sedative to keep them from moving
excessively from discomfort or pain during the scan.
There are some risks in using MRI that have to be considered. As I have been
told the magnetic pulse generated by this machine is about 60,000 times the pull of
earth’s gravity. As a result, patients are briefed not to wear any ferrous (steel or iron)
type jewellery. The problem is twofold. First, the ferrous object can be attracted to the
center of the magnetic field (not good). In addition, severe thermal burns can occur as
the metal heats in response to the magnetic pulse.
If the patient has any kind of steel prosthetic implant it becomes problematic. As
well, vagus nerve stimulators, implantable cardioverter-defibrillators, loop recorders,
insulin pumps, cochlear implants, deep brain stimulators all may be susceptible to
thermal heating or failure if exposed to MRI pulse. Patients with integrated hardware of
this nature should always give complete information (manufacturer, model, serial number
and date of implantation) about all implants to both the referring physician and to the
radiologist or technologist before entering the room for the MRI scan.
The ability of MRI to detect PC metasis is well documented in the literature;
however, sometimes the MRI scan produces image where the abnormal growth is not so
obvious. Techniques using organic complexes of metals like Gadolinium or Manganese
can be introduced intravenously to patients to enhance image contrast while the magnetic
pulse is being applied. When the MRI pulse ends these metals do not retain any magnetic
field. These organic compounds then deteriorate and leave the patient’s system via the
urinary tract. It is important to take in a lot of fluids following this type of scan to ensure
quick purging of the enhancement compound.
Figure 26 a, b and c is a series of side-by-side images taken over the period of 6
months on a patient with Castration Resistant Prostate Cancer (CRPC) comparing full
body MRI to sagittal (side) view imaging of the vertebrae of the same patient using 11CCholine PET/CT. The accuracy and ability of MRI and PET/CT imaging to detect
metastasis well in advance of traditional radiological methods such as bone scan (BS)
involving the non-specific uptake of the nuclear enhancement agent 99mTC with plain Xray raises the question of whether the era of traditional method of bone scanning is
over.53
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Figure 26a. Initiation scan of patient with Castrate Resistant PC (CRPC) with full body MRI image
on left and sagittal view 11C-Choline PET/CT on right.
source: http://openi.nlm.nih.gov/detailedresult.php?img=3195676_AU2012-893193.002&query= 11CCholine PET/CT&fields=all&favor=none&it=none&sub=none&uniq=0&sp=none&req=4&npos=3&prt=
originators – B. Tombal and F. Levouvert
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Figure 26b. Scan of patient with Castrate Resistant PC (CRPC) with full body MRI image on left
and sagittal view 11C-Choline PET/CT on right at three months. Arrow on right image points to
obvious metastasis in vertebrae. Similar metasis can be seen in the MRI.
source: http://openi.nlm.nih.gov/detailedresult.php?img=3195676_AU2012-893193.002&query= 11CCholine PET/CT&fields=all&favor=none&it=none&sub=none&uniq=0&sp=none&req=4&npos=3&prt=
originators – B. Tombal and F. Levouvert
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Figure 26c. Scan of patient with Castrate Resistant PC (CRPC) with full body MRI image on left
and sagittal view 11C-Choline PET/CT on right at six months. Arrows on right image points to
progressive metastasis in vertebrae. Similar metasis can be seen in the MRI.
source: http://openi.nlm.nih.gov/detailedresult.php?img=3195676_AU2012-893193.002&query= 11CCholine PET/CT&fields=all&favor=none&it=none&sub=none&uniq=0&sp=none&req=4&npos=3&prt=
originators – B. Tombal and F. Levouvert
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Near Infrared Scanning
Advancements in imagery have given rise to the development of other
technologies in search of more economical ways to better screen for Prostate Cancer.
Near Infrared Scanning is one such technology that is in development. The technology
involves a portable rectal scanner that is able to detect emission from a bio-dye that has
been delivered and absorbed by the PC. The scanner records differences and patterns of
laser absorption by the prostate tissue then displays it in a 3D image.54
Biopsy
After prostate abnormality has been discovered, there remains a question as to
whether or not it is benign or malignant. The common procedure used to determine this
is a biopsy. The tissue taken during a biopsy is sent to the laboratory for analysis.
At this point, imaging and biopsy are considered clinical evidence of malignant
growth. There are several types of biopsy procedure used on the prostate. The one used
depends largely on the location of the growth, its properties and the availability of
technology.
These days, the “gold standard” for prostate biopsy is the use of real time (see it
as it is happening) TRUS radiographic guidance of the surgical tool to perform multiple
sampling of suspect prostate tissue. The actual sampling of the prostate tissue, in this
strategy, is done with a spring loaded coring needle. In preparation the patient is usually
given a local anesthetic, as well as, an antibiotic. The coring needle is part of the TRUS
probe and the clinician positions the point of the transducer wand then takes a sample.
This is repeated between 8 and 18 times! The procedure lasts about 10 minutes. Blood
in the semen and urine as well as light bleeding from the rectum may occur for several
weeks following the procedure. One of the comments that will come back from the
pathologist’s report after analysis of the cores is the percentage of cores that actually
have cancer in them. 55
Manual needle placement is a major limitation of the accuracy with which a
prostate biopsy can be taken using conventional methods. As well, the relatively poor
imaging associated with traditional use of TRUS guidance is problematic. To
compensate for this “less than ideal” combination, multi-samples of the prostate tissues
using needle coring is done during biopsy. This method is inaccurate; traumatic to
benign tissues that are erroneously sampled; and, imposes an extraordinary burden on
pathology lab resources in having to process millions of unnecessary samples annually.
To improve on the conventional “the gold standard” for prostate biopsy, a team of
researchers at Brigham and Women’s Hospital developed an MRI-guided transperineal
prostate biopsy approach that allows for targeted sampling of suspected abnormalities. 56
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The use of MRI significantly improves image quality allowing the clinician to
guide 3D slicing tools of the robotic surgical system with pinpoint precision to sample
suspicious tissue. Nevertheless, TRUS imaging, manual positioning and manipulation of
coring biopsy needle, and multiple coring of the prostate remains the pre-dominant
method in use to date. Figure 27 illustrates the TRUS core needle biopsy.
Figure 27. TRUS core needle biopsy.
source: http://www.cancer.gov/PublishedContent/MediaLinks/432903.html
Illustration: ©2005 Terese Winslow, U.S. Govt. has certain rights
Pathology
Pathology is the laboratory based study of disease. It is a discipline that uses
microscopic techniques to determine the state of disease in tissue, organs and bodily
fluids. Diagnosis of Prostate Cancer is only as good as the technique and resource
available. In a modern and well equipped laboratory the tests and techniques available
are substantial. Nevertheless, new techniques and diagnostic machines are constantly
developing and the burden of acquiring and being trained with the “latest and greatest” is
a constant financial and medical concern for every institution.
The personnel performing the analysis in pathology labs are trained technicians
and medical doctors. Their backgrounds include such disciplines as microbiology,
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62
biochemistry and genetics, to name a few. The physician will perform the clinical
examination and take note of the patient’s physical symptoms. If merited, usually due to
elevated levels of PSA, biopsy of the suspect tissue will be performed and forwarded to
the laboratory for analysis. The laboratory then takes these samples and processes them
to determine the state of the sample tissue or fluids. The results of this analysis can take
a few days to a few weeks to receive, depending on the efficiency of your health system
or chosen institution.
During this analysis of the sample tissue if cancer cells are discovered the report
reflects where in the tissue these cells were located. As well, the grading of the cancer
and percentage of the biopsy cores involved will be detailed. Recommendations are also
made as to the prudent follow up that should occur in order to address the malignancy
with sufficient margin and possible invasiveness (metastasis). Margin is the distance
between the healthy and infected tissue.
When tissue is removed during surgical procedure it, as well, is analyzed in the
pathology lab to determine the margin. Negative margin means there is a comfortable
“buffer zone” of healthy cells between where the cancer ends and the edge of the
removed tissue. Positive margin means that the cancer cells extend right out to the very
edge of the tissue taken. Close margins means there are healthy cells between where the
cancer ends and the edge of the removed tissue BUT the distance is not substantial.
Generally, if positive or close margins are found further treatment may be required.
Bodily fluids of the patient, such as the blood and urine are also analysed for other
possible signs of tumor and immune response to cancer.
Tumor markers are specific proteins in the blood and urine that may occur as a
result of different types of cancer. So far, the levels of these specific proteins in bodily
fluids are not a reliable way to diagnose any cancer. This is because most patients can
have low levels of tumor marker in their fluids even if they do not have cancer. As well,
some patients do not necessarily have elevated levels of the tumor marker even if their
cancer is advanced.57
The use of PSA (prostate specific antigen) testing is widespread and clinically
recommended and accepted as one of the most useful indicators of the presence and
outcome of Prostate Cancer. It is also useful in monitoring patients with a Prostate
Cancer diagnosis and evaluating their response to therapeutic interventions; and,
detecting tumor relapse. This is despite the fact that PSA it is not a cancer specific
marker. In other words, elevated PSA levels can be the result of benign prostate
condition as well as PC. 58
PSA is made within the prostate epithelial tissues. If the prostate is completely
removed there should be no PSA in the blood.
Pre-diagnosis PSA testing is done by taking a sample of the blood before DRE or
any procedure that could disrupt the prostate. The test results are detailed in terms of total
PSA, as well as, Free PSA (fPSA) in a pathology report. Free PSA is the portion of the
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total PSA that is not bound to its usual carrier molecule and is expressed as a percentage
of the total PSA. Total PSA is expressed in micrograms (millionth of a gram) per liter.
The symbol for a microgram per liter is µg/l. Total PSA is the sum of circulating fPSA
and that part of the PSA bound as a stable complex called PSA-ACT. 59
In the reviewing the literature on PSA testing an ongoing debate exists as to when
total PSA levels should merit further testing and biopsy of a patient. Again there is no
consensus between major health organizations as to the level that would best detect PC in
early stage while keeping the number of unnecessary biopsies to a minimum. Metaanalysis suggests that when total PSA is < (less than) 10 µg/l the % fPSA and DRE
results should also be considered to make a decision on whether to proceed with biopsy.60
On a pathology report a PSA value of “X” may be remarked. This means that the PSA
value cannot be determined.
The next generation of Prostate Cancer markers are undergoing evaluation. In
the meantime PSA testing remains the predominant and preferred marker used by
clinicians.
Invasiveness and Staging
Invasiveness describes the way that cancer cells of a tumor or lesion make their
way beyond the organ of origin to other parts of the body as the disease progresses. The
factors that influence the rate and extent of invasiveness are numerous and not well
understood. Invasiveness remains a matter of continuing research and redefinition.
The extent of invasiveness is measured by staging conventions that describe the
degree and extent the cancer is considered to have advanced in a patient. Clinical staging
is based on information available to the physician before any treatment and is used to
define treatment options. Pathological staging is based on clinical information AND
surgery whereby a more comprehensive analysis of the suspect tissue has been done and
is detailed in a post-surgical pathology report. There are several standard staging
conventions used by physicians for PC. These are the TNM; and, the Whitmore-Jewett
conventions. Please note, interpretation of your pathology report must be done with
your attending physician as classification is sometimes applied differently between
medical facilities.
From what I have reviewed in the literature, the TNM system seems the most
precise and descriptive of the staging conventions. It was the one used on my pathology
reports for Colorectal Cancer. It is the system accepted by the American Joint
Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC).
The following is my understanding of the alpha-numeric combinations commonly found
in the pathology reports describing the stage of Prostate Cancer with TNM. In places I
have simplified the text and use different language so that it can be more easily
understood. For the comprehensive and exact wording of TNM definition based on the
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64
latest 7th Edition of TNM staging go to this site and click on the Prostate large poster:
http://www.cancerstaging.org/staging/index.html
The latest Prostate Cancer TNM convention is detailed in AJCC TNM 7th edition
which came into effect January 2010. For those diagnosed before then, the alphanumeric combinations found in your earlier pathology report(s) is based on previous
AJCC TNM convention that is similar but not exactly the same.
The TNM convention covers 3 key factors of Prostate Cancer staging as detailed
below. On any pathology report each of the three factors will be commented on in this
alpha-numeric expression. The convention makes further distinction of how the factor
was arrived at by clinical or pathological means. To simplify, clinical assignment
basically means the factor is based on imaging or non-excisional biopsy; and,
pathological assignment involves excision or biopsy sometimes beyond the prostate such
as the lymph nodes, for example.
The T factor describes the tumor. It notes the size and extent of spread within the
prostate and nearby tissues. Clinically detected T factor will be designated as cT or T and
pathologically detected T factor will be designated as pT. By progressive order the
following is what the assorted T factors mean in edition seven:
ClinicalTx: the primary tumor cannot be assessed;
T0: there is no evidence of primary tumor;
T1: Clinically unapparent tumor neither palpable nor visible by imaging:
T1a: the tumor is incidental (small) in less than 5% of the tissue resected
(removed by surgery);
T1b: the tumor is incidental (small) in more than 5% of the tissue
resected;
T1c: the tumor identified by needle biopsy.
T2: the tumor is confined within the prostate:
T2a: the tumor involves one half of one lobe or less;
T2b: the tumor involves more than one half of one lobe but not both
lobes;
T2c: the tumor involves both lobes.
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T3: the tumor extends through the prostate capsule:
T3a: the tumor has extra-capsular extension (unilateral or bilateral);
T3b: the tumor has invaded the seminal vesicle(s).
T4: a tumor is fixed or invades adjacent structure other than the seminal vesicles.
Pathological – There is no pT0 or pT1 designation.
pT2: the tumor is confined to the prostate:
pT2a; the tumor is confined to one half of one side of the prostate or less;
pT2b: the tumor is confined to one side of the prostate and involves more
than half of that side;
pT2c: the tumor is on both sides of the prostate.
pT3: the tumor has extended beyond the prostate:
pT3a: the tumor has microscopic invasion of the bladder neck;
pT3b: the tumor has invaded the seminal vesicle (s).
pT4: the tumor has invaded parts of the body other than the seminal vesicle(s).
The N factor describes whether or not the cancer has spread (metastasized) to
nearby lymph nodes and, if so, how many lymph nodes are involved. Clinically detected
N factor will be designated as cN or N and pathologically detected N factor will be
designated as pN. By progressive order the following is what the assorted pathological N
factors mean in edition seven:
Clinical Nx: the regional lymph nodes were not assessed;
N0: there is no evidence of regional lymph node metastasis;
N1: there is metastasis in the regional lymph nodes.
Pathological pNx: the regional lymph nodes were not sampled.
pN0: No regional lymph node involvement was found.
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pN1: Metastases in the regional lymph nodes was found.
M factor stands for Metastasis and indicates whether or not the cancer has spread
to distant organs such as the bone, liver, lungs, or brain. By progressive order the
following is what the assorted M factors mean in edition seven:
M0: No evidence of distant spread.
M1: Distant spread is present:
M1a: spread involves the non-regional lymph nodes;
M1b: spread involves the bone;
M1c: spread involves other site(s) with or without bone disease;
pM1c: when more than one site of distant metastasis is present. This is
the M factor describing the most advanced condition of spread.
In addition to factors of the TNM nomenclature being preceded by the small case
letters c or p; you may encounter y or r (for example rTNM). In such cases the letter y
identifies a factor after the patient has undergone neoadjuvant (before surgery)
pretreatment; and, the r refers to factor that has occurred after relapse from a disease free
period.
Although it is not reflected as a prognostic stage in this 7th edition of Prostate
Cancer TNM; Stage 0 is cancer in the earliest stage. This stage is also known as
Carcinoma In Situ (CIS). CIS cells have already lost their tissue identity and have
reverted back to a primitive cell form (less or poorly differentiated) that grows rapidly
and without regulation. Further to this lack of maturation generally results in associated
changes in the genome since irregular cell growth inevitably results in incorrect
replication of the genetic code.
After the T, N, and M factors are determined. The three factors are combined and
the patient‘s samples are taken in context of total PSA and Gleason grade (as available)
then staged. The stage is expressed in Roman numerals from stage 0 (the earliest and
least advanced form) to stage IV (the most advanced). Some stages are further
subdivided with letters, for example IIA and IIB.
Table 1 is an overview of how the TNM factors are combined and anatomic
stage/prognostic groups are arrived at derived from the latest 7th Edition of AJCC TNM.
It has some simplification and change in language so that it can be more clearly
understood. For the original wording go to the following link and click on the Prostate
large poster – http://www.cancerstaging.org/staging/index.html.
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Note- the following signs are used in the next table: < (less than);
to); > (greater than); ≥ (greater than or equal to).
M
Total PSA
Stage/Prognostic T
N
Group
factor factor factor µg/l
≤ (less than or equal
Gleason
M0
< 10
≤6
N0
M0
< 10
≤6
T1-2a
N0
M0
X
X
Any
T1
N0
M0
< 20
7
or
Any
T1
N0
M0
≥ 10 ≤ 20
≤6
or
T2a
N0
M0
≥ 10 ≤ 20
≤6
or
T2a
N0
M0
< 20
7
or
T2b
N0
M0
< 20
≤7
or
T2b
N0
M0
X
T2c
N1
M0
>0
≥2
or
T1-2
N0
M0
≥ 20
≥2
or
T1-2
N0
M0
>0
≥8
III
Any
T3
N0
M0
>0
≥2
IV
T4
N0
M0
>0
≥2
or
Any
T
N1
M0
>0
≥2
or
Any
T
Any
N
M1
>0
≥2
Any
T1
N0
or
T2a
or
I
IIA
IIB
X
Table 1. TNM Prostate Cancer Autonomic Stage/Prognostic group derived from AJCC 7th Edition.
source: http://www.cancerstaging.org/staging/index.html
The longer cancer cells are allowed to duplicate, the farther away they become in
appearance and structure from the cells of the surrounding healthy prostate tissue. This is
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the aspect of the cancer cells becoming “less or poorly differentiated” than their
surrounding normal tissue cells. The departure from any recognizable healthy cell type
of cell is graded. Grading gives an indication of how closely the cancer cells resemble
normal surrounding prostate tissue when looked at under a microscope. It is also used as
an indicator of prognosis. Generally speaking; higher grade Prostate Cancer means a
worse prognosis for the patient.
Grading of Prostate Cancer is usually done with a system called Gleason grading.
Gleason grading provides a score between 2 and 10 which is the result of adding the two
most prominent tissue patterns seen by the pathologist when examining the prostate
tissue samples from biopsy or surgery under a microscope. A Gleason score of “X”
means that the score cannot be determined.
Tissue patterns are rated between 1 and 5. For example, pattern 1 means the
cancerous cells closely resemble normal prostate tissue. In the most advanced pattern 5
the tissue does not have recognizable glands and, there are often sheets of cells
throughout the surrounding tissue. Figure 28 illustrates the cell patterns referred to in
the Gleason grading.
Figure 28. Prostate Cancer cell patterns according to Gleason grading system.
source: http://en.wikipedia.org/wiki/File:Gleasonscore.jpg
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Survivability Statistics
One of the facts that Prostate Cancer patients have to address is that the disease
does have an impact on a patient’s survivability. Intervention with treatment is effective
for most Prostate Cancer and greatly improves overall patient survivability statistics. Care
must be taken when reviewing the statistics associated with survivability. To set things
into perspective you should consider the following when looking at any study’s statistics
on patient survivability for Prostate Cancer.
First, make sure that the statistics you are looking at come from a reputable
source. Reputable sources are usually those that publish in refereed medical and
biological journals or government sites. Refereed means that there are a panel of experts,
associated with the journal, that review the researcher’s submission and makes sure it is
scientifically valid before allowing it to be published. If you have doubt as to whether or
not you are viewing a reputable source, the easiest thing to do is to call or go to any
University or Hospital library and ask their reference desk for an opinion on that source.
The size of the sample or actual number of patients that were involved in the
study is a significant aspect of the validity of the statistics. Beware of study statistics that
have small sample sizes. The idea of statistics is to draw conclusions that would be valid
and apply to the Prostate Cancer population as a whole. If you look at the number of
patients involved in the data of the National Cancer Institute’s SEER (Surveillance,
Epidemiology, and End Results) statistics you see that the number is in the thousands.
Generally, the larger the sample size of patients, the more likely the data gives a reliable
picture of what to expect overall.
Watch out for studies that are conducted over a relatively short period of time.
The best studies on any biological or medical related theme are those that last years not
weeks. This way the weight of the results can be better seen over the long term. It is the
long term that one must consider in survivability. As well, consider that diagnostic
method and treatment schemes for PC evolve all the time. Data for long terms studies
take a bit of time to gather and compile into a meaningful analysis. Sometimes this takes
years. If so, the methods and treatments used 5 or 10 years ago are quite likely improved
upon or no longer used at all. So the survivability statistics for present treatment regimens
are likely even better than statistics based on timeframes from a half to full decade before
the present date.
Next, it is important to know what kinds of patients were used in the study. This
is called patient profile. If you are 40 years old, athletic, fit, non-smoker and have been
operated on for a Stage III Prostate Cancer, it is difficult to have a meaningful
comparison to your case if the study you are looking at has an average age was 75, are
generally inactive, and 50% of the sample size are smokers. As well, remember the
numbers of environmental and genetic variables that usher each patient to the point of
being affected by Prostate Cancer are numerous. No one really knows the exact impact
of these variables on each patient or how to weigh these differences. So there will always
be unaccountable differences between individuals in a study. In short, if you are looking
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for survivability statistics that are meaningful in your case ideally the closer those study’s
patients are to your profile the better and more meaningful the results.
Be aware of who paid or funded the study. It is sad to say, but, studies can have a
tendency of “propping up” the desired result in favour of the funding body. The funding
body justifies spending money on such studies because they are great marketing tools.
The researchers skew their research in a way that is supporting to the funding body so
that they can be sure to receive continued funding. The bottom line is that independent
studies are a rare thing. Almost every researcher has to contend with finding and
maintaining continued funding for their work even if they are an academic conducting
research under the flag of a university. Studies put out by the government generally have
less concern with funding so the published results tend to be less biased in that regard. At
the end of most reputable studies is a commentary or column that denotes any “conflict of
interest”. In this column the ideal is to see the word “none”.
Finally, look at the results of many studies and get a general feel for survivability
as it pertains to your profile. This way you get around bias introduced by the wrong
patient profile, the influence of funding bodies, evolving treatment schemes and
researchers who have ran their statistical analysis using inappropriate statistical method.
Remember one thing; statistics of any sort are a tool to give someone a rough idea of
probability to support theory, policy and decision making. They likely do not define
exactly how your individual response is going to be or what your “chances” are.
Relative Survival Rates for Prostate Cancer
The focus on survival rates is done to be able to help answer, among other things,
the question of prognosis of a patient. Some say that prognosis is just a fancy word that
means the “best guess” as to how a patient will do given their profile, the state of the
disease and the proposed treatment regimen. Statistics is the science of probability.
Probability of an event happening involves collecting data from a defined population then
analyzing the trends in the data with mathematical method. It is not a certainty; but
rather a probability that events will play out according to the statistics. Prognosis
considers the statistics but is not that simple. Ultimately it is the doctor’s experience,
understanding of the facts of your particular case, disease and profile that result in the
prognosis. As well, it should be understood that five year survival rates do not address
what happens after the five year period. Living for 5 years following diagnosis does not
necessarily mean a patient is cured and will never experience PC relapse.
A standard 5-year survival rate refers to the percentage of patients who live at
least 5 years after their cancer is diagnosed. Sometimes a study will include people with
PC who died of other causes, such as heart disease, during the timeframe of the study.
The conclusions from a study carry more weight if such mortality (death) is excluded
from the end figures on five year survival. This brings us to relative survival rates.
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Relative survival rates are quoted because patients that participate in the study
sometimes expire due to causes that do not have anything to do with PC. So the
researchers take this into consideration and produce what is called a relative survivability
quotient so as to remove this unrelated mortality from the data.
The statistics below come from a study of the SEER database, looking at United
States patients diagnosed with Prostate Cancer between 1975 and 2009. Note that the
study involves hundreds of thousands of men with Prostate Cancer; and, the period over
which the data was collected is in excess of 30 years. PC mortality (death) has been on a
steady, small percentage decline since the early 1990s. The incidence of PC has as well
been on a small percentage decrease of approximately 1.9% between 2000 and 2009.61
In review of the SEER results between 2002 and 2008, we find that the average 5
year relative survivability for Prostate Cancer that is local [confined to primary site] is
100%; Regional [spread to regional lymph nodes] is as well 100%; and, Distant [spread
to the body] is only 27.8%.62
Table 2 summarizes the 5 year Relative Survival between 2002- 2008 and details
the distribution of stages for Prostate Cancer during that period.
Stage
Stage Distribution
(%)
Local [confined to primary site ]
81
Regional [spread to regional lymph
nodes]
12
Distant [spread to the body]
4
Relative 5-year Survival
Rate
100.0%
100.0%
27.8%
Table 2. Relative 5 year survival rate SEER Prostate Cancer All races, Males by stage 2002-2008.
source: http://seer.cancer.gov/statfacts/html/prost.html
As you can see, the 5 year relative survival for local and regional PC is as good as
it gets. As soon as the PC invades parts of the body other than the regional lymph nodes
the 5 year relative survival tumbles significantly to where roughly only 1 in 4 men make
it to 5 years. These figures speak to the importance of making sure that Prostate Cancer
is caught early and not allowed to progress to advanced stage.
After the initial pathology results from biopsy are received a course of action is
formed to address the condition either by monitoring or by treatment. In the event of
cancer, a number of considerations go into the next step including the PC type; the size of
the mass; location of the tumor(s); progression of the disease, your overall state of health,
age, preferences, and the medical institution’s resource.
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If surgery is required and the growth is substantial, treatment to reduce the growth
may be proposed before surgery. In which case, your next appointment will be with an
oncologist. An oncologist is the specialist who deals with treatment specific to your
cancer. This may delay the surgery for several months. Alternatively, surgery may be
appropriate immediately. In any event, your specialist will discuss the matter with you
and if surgery is the next step then the surgeon will request a standard pre-operative work
up which usually includes blood and urine analysis, chest X-ray (if not already done),
ECG (electro-cardiograph) and an MRI or CT (if not already done or sufficiently
current).
ECG (Electrocardiograph)
The electrocardiograph (ECG) is given to a patient prior to surgery as a
precautionary measure to determine the state and relative health of the patient’s heart.
Surgery imposes stresses on the body and if the patient proceeds to surgery with an
unknown heart condition it could result in complications and even death. Identifying
hidden heart problems in advance allows the surgeon and anaesthesiologist to make the
appropriate modifications to their procedure and so avoid any related complications
during surgery.
If you have not already experienced an ECG it is a totally painless procedure that
takes a technician or nurse about 15 minutes to do. You simply lie flat on an examination
table and the probes of the ECG are attached to your chest, wrist and ankles with a light
adhesive. Some of the new generation machines only require attachment of probes to the
chest. Then a recording of your heart beat is sampled and graphed for the cardio
specialist to review. That’s it, unless a problem is discovered. In which case, a better
understanding of your cardiac condition will have to be had.
If a problem is discovered you may have to go through a stress test. The stress
test is a cardiac examination designed to assess heart performance during exercise. To do
this, probes are connected to the patient and the patient is put through a monitored routine
to make the heart “work” harder. Then the results are reviewed by a cardiologist and a
determination of your suitability for surgery is made. Occasionally, if a patient’s heart is
too weak, the risk of surgery may be too great. If so, then alternative treatment and
strategy to address the prostate condition may be made.
Second opinion
Sometimes what is being told to you in terms of explanation of your symptoms
and condition may seem to not make any sense. Sometimes you may not trust the
individual who is delivering the initial opinion because you may not know them or they
may not be that experienced or they just don’t seem to be behaving as expected. Maybe
you are not comfortable with the methods or equipment being used at a particular facility.
Sometimes you may just be grappling with the idea that you are sick and can’t believe it.
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Your option is to get a second opinion. Seeking out the opinion of other urological
experts can be a valuable exercise, even if you end up staying with the medical staff that
you started with.
The biggest problem most patients encounter when seeking a second opinion is
that they do not know who to ask or how to ask it. Medical specialists are usually
referred to by another physician. If you are not happy with the specialist that you have
been “directed to” then you can always go back to your referring physician and ask he
find someone else for you.
Doctors understand the concept of a second opinion and they do understand that it
is important that you are comfortable with those who are going to treat you. Be aware
that referring doctors tend to use specialists they know of. It is their way of sending you
off to where they think your treatment will be satisfactory. Saying you want a second
opinion is asking them to rethink their initial recommendation. Nevertheless, do not be
shaken from getting a second or third or fourth opinion if that is what is required to
satisfy your concerns and make you comfortable. Sometimes the referring physician will
ask if you have a particular specialist you would like to be referred to. As such; ask
around. You may be surprised the specialists who are in some way linked to network of
acquaintances.
Know that the medical profession has a tendency to respect the “insight” of their
colleagues. One of the first things I was asked when I sought a second opinion was who
was the specialist handling my file and what did they say. What followed, however, was a
careful review of the imaging and reports in my file and a very calm and professional
discussion to support the opinion that the results were inconclusive and that a
laparoscopic procedure was appropriate.
Also know that most physicians and specialists in a social health system are
already having difficulty dealing with their own case load. In short, they simply do not
have enough hours in the day. So their administrators have to prioritize the workload.
From this, getting an appointment for a second opinion may not be so easy because the
administrator may consider that providing second opinions to some other specialist’s
patient may not merit disrupting pressing schedule and case load. In a system where you
pay for the medical service, those specialists renowned for their work in the field are as
well highly in demand. They too usually have a very heavy case load and getting to them
for a second opinion in a timely way can be near impossible unless you are in some way
connected. All I can say is you must politely insist that you need their insight and
assistance.
Lastly, in speaking to friends and relatives, I have found that most people uphold
the premise that they have to unquestionably trust the health system when it comes to
disease and treatment. Patients are not usually in the habit of questioning their doctors. I
have heard stories of old school doctors who actually discourage patients from asking
questions. This is not acceptable. Sometimes patients are not so well informed as to be
asking the right questions. Those patients that have good questions sometimes get a bit
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intimidated by the fact that they do not necessarily have sufficient command of the
medical jargon and techniques to understand the response. My solution to this is to “read
on” and get acquainted. Then start believing and insisting that you are the user of a
service and, in the case of PC, your life and quality of life depends on timely, well
directed and executed medical attention. If that means you have to go to a facility out of
your district then seriously consider that option. It could mean the difference between a
favorable outcome of treatment or not.
One of the things that you must do before you arrange a second opinion is to get
your hands on the results of what has been done and diagnosed to date in your file. Make
sure these are as complete as possible and include the preliminary pathology reports, CDs
or DVDs of any scans or imaging. When you contact the doctor that you are going to use
for a second opinion they will often ask that they be faxed your file in advance of any
appointment. Make sure that the doctor of second opinion clearly understands the
timings of what is being proposed by the medical staff presently handling your case. This
way the appointment can hopefully be scheduled in such a way as to afford to you the
option of resorting to alternative staff and treatment.
After you have discussed your file and received a second opinion the decision
now becomes yours to make a choice as to how best to proceed. I suggest that you
choose the one that you have the most confidence in and are comfortable with. Consider
the treatment, your recovery, and, the impact to your quality of life during and after
treatment.
Archives
If you have not realized it by now I will tell you that you should be keeping a
personal record on your condition. The progress of your condition, schedule and details
of treatment can become quite involved over a period of time. It is easy to lose track of
what and when things were done, and, what progress was made. If you keep a running
record on things you will be able to avoid or minimize the fog that typically blankets a
lengthy monitoring or treatment regimen. Prostate Cancer can have lengthy monitoring
or treatment regimens that span over many years particularly if recurrency occurs. Even
if your treatment regimen is relatively short, you will be monitored for the rest of your
life. So it is good to have something to refer to and refresh your memory ten years after
surgery if, for example, new medical staff takes over the role of monitoring you.
To get a copy of your records you can either ask your doctor’s administrative
assistant or, if you are in a hospital or clinic, go to the department of archives and make
the request. Both may charge a small administrative fee for the copies. So have some
cash on you when you do this. I found it best to make a phone call first and let the
administrator know what you need. Then ask for the best time for you to pick it up. If
possible, go in person. Otherwise, the request may get “lost in the shuffle” and not be
forwarded to you for a long time.
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Chapter 3
Surgical Treatment and Therapy
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Surgical prostate procedures are done to address benign and malignant growth. If
there is doubt as to the state of disease, the general tact for any kind of mass in the
prostate is to biopsy. Then, an analysis of the extracted tissue can be done to determine
whether or not cancer cells exist within those tissues. Biopsy procedures are most times
scheduled for “Out Patient” surgery. This means that you arrive at the hospital on the
day of your surgery, have the procedure done then leave that same day. Local or general
anaesthetic will be administered for the procedure and most medical institutions will not
release you unless someone is with you to ensure that you are “Okay”. For more
complex surgery you will be admitted.
Whether or not surgery is appropriate for a particular Prostate Cancer condition is
a matter to be discussed between the patient and their doctors. There are times when the
cancer is not operable. For these conditions the options may involve Radiotherapy (RT),
chemotherapy or combination approaches instead. Treatment facilities have protocols
(guidelines) to help determine when a condition in operable or not. This coupled with the
specialist’s experience, and, the patient’s or family’s wishes are normally the determinant
factors of proceeding with certain surgery or not. Once the surgery has begun the
surgeon will use their discretion as to exactly what tissues ought to be removed to
achieve the best prognosis for the patient.
When surgery is appropriate lymphatic node dissection, resection surgery on the
prostate and other organs infected by metastatic PC may be performed. Such surgical
procedures may be done as “stand alone” or in combination with regimens of
chemotherapy and/or radiotherapy depending on the state of invasiveness. Sometimes
the initial surgery has not been done with sufficient margin so additional surgery has to
be done at the primary site. Sometimes surgery may be delayed pending shrinkage of
tumor tissue by chemotherapy or radiotherapy. If the metastasis is extensive, several
surgical sessions may be required. Distant metastasis may require the involvement of
other surgical teams who specialize in organs such as the liver, lungs, brain or bone for
example.
Prostate Cancer is addressed by resectioning (removing) the prostate. This is
called a Prostatectomy. There are two types of prostatectomy. One is called the Radical
Perineal Prostatectomy (RPP); and, the other is called the Radical Retropubic
Prostatectomy (RRP).
The RPP was first described in 1905 and does not involve resection of the pelvic
lymph nodes. The RRP was first described in 1947 and involves PLND (Pelvic Lymph
Node Dissection). This procedure addressed local disease that had made its way to the
regional lymph nodes. These days if Prostate Cancer is diagnosed at early stage while it
is still localized, the PLND is not mandatory. Instead, there is a better understanding of
the risk of lymph node involvement based on a “probability” of Prostate Cancer spread
given specific prognostic indicators.63 Such probability is formatted into tables for easy
reference and interpretation by the surgeon. These are called Partin tables and depending
on the type of treatment (surgical or radiographic) the probable risk from these tables is
used to determine whether or not to proceed with the PLND. For example, for an open
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(large incision) RRP any Partin probability above 3% and the surgeon will typically
proceed with a PNLD. For the RPP any Partin probability above 10% and the surgeon
typically schedules another operation to perform the PNLD instead of proceeding with
that procedure at the same time as the RPP.64
It should be understood that now a days imaging has arrived to the point where
we have good understanding of what lymph nodes are first in line to receive the drainage
from the prostate (called sentinel lymph nodes) and can sample those to determine the
stage of cancer involvement instead of relying on probability tables and procedurally
removing pelvic lymphatic tissue based on probability charts. Unfortunately, although
sentinel node sample is common surgical practice for breast cancer, colorectal cancer and
lung cancer, sentinel node sampling for Prostate Cancer is still in the investigative stage
with mainstream medicine withholding approval until more conclusive evidence of its
effectiveness is reported. 65
The idea of a surgeon having to still rely on probability charts to make a decision
as to whether or not to proceed with a PNLD is, in my view, something less than optimal
and follows the same blind approach as does the ongoing use of TRUS guided manually
executed multiple core needle biopsy and the prognostic staging that relies on that.
Hopefully, known imaging techniques involving 11C-Choline enhancement able to
exactly pinpoint Prostate Cancer activity will be considered along with available robotics
and non-invasive means to arrive at a more reasonable and effective clinical solution to
determine and address lymphatic involvement in the pelvic area using sentinel node
sampling.
In 1982 better understanding of the neural and venous anatomy in the prostate and
pelvic area gave rise to the nerve-sparing technique that yielded better post-operative
results for urinary continence (ability to control bladder) and erectile function while
limiting the possibility of positive margin. 66 This nerve-sparing technique greatly
improves the quality of life aspects for the patient following prostatectomy.
Surgical cure only occurs if all of the tumor can be removed. It is reported that
approximately 20-30% of men with one or more positive margins following treatment
experience relapse of their Prostate Cancer. To improve on the long term disease-free
survival for those men considered high risk (i.e. men with very large prostates due to
tumor; high Gleason grade; or, high PSA) Neoadjuvant Androgen Deprivation (NAD)
therapy is an available option. NAD shrinks hormone dependent tumor which increases
confinement of the cancer to the prostate. It also decreases the incidence of positive
margins and is theorized to address occult (stealthy/hidden) regional and systemic
micrometastasis. It does; however, remain debatable as to the long term success of NAD
in being able to improve on overall survivability of those treated for PC. 67
It used to be that the only hormonal treatment for PC was for the patient to
undergo orchiectomy (surgical castration or removal of the testicles) as part of a strategy
to slow PC progression by reducing androgen output. This surgical solution is not
reversible. As stated, even with the testicles removed the body will still produce
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testosterone but at a much lower level via the adrenal glands. With that, the PC will
eventually continue to grow. These days other options are available for hormone
treatment such as chemical castration. These other types of “castration” involve the
prolonged prescription of drugs or agents. For chemical castration, testicular production
of testosterone restarts when the medication is halted. Also consider that these treatments
are expensive. When unavailable or when the failure of alternative hormonal treatment
has occurred with advanced hormone sensitive PC, surgical castration is still used.
Sometimes surgical castration is as well combined with the other types of hormonal
treatment.
In any case, beyond the immediate impact to hormone production and the
associated effect on slowing Prostate Cancer the result of surgical castration has an
enormous impact on the male post-orchiectomy physiology, physical attributes and
psyche.
Testosterone is the main androgen affected by surgical castration. The largest
contribution of it is made by a man’s testes and the loss of normal testosterone levels
associated with surgical castration in an adult male affects a number of physiological
aspects including but not limited to:
- Cognitive (which includes male aggressiveness and libido);
- Physical energy;
- Characteristic male increased muscle mass and strength;
- Bone density; as well as,
- Body hair. 68
Note to clarify – cognitive means relating to thought process; physical energy levels can diminish;
muscle mass and strength will be reduced and the possibility of gynecomastia (male development
of breasts) becomes higher; bone density will diminish and can become problematic with a much
higher risk of fractures and osteoporosis; and, body hair will reduce.
It is recognized that cosmetic procedures to restore the testicular area following
surgical castration improves a patient’s post-orchiectomy psychosocial adjustment and
long term quality of life. In 2004 a five year clinical study released its results regarding
the trial of a saline filled testicular implant. The principle investigator P. Turek, M.D.
stated that, “The implant can provide improved sense of well-being for patients who
receive this prosthesis that is beyond cosmetic surgery.” Testicular implants have been
available and performed since 1973; however, complications related to the use of silicone
implants resulted in the development and trial of saline filled testicular implants. 69
Testicular prosthetics or implants can sometimes be done immediately and as part
of the same session as the orchiectomy or it can be delayed. Delaying will allow more
time for the cancer diagnosis and treatment to be carried out before the area has to
accommodate cosmetic procedure. From my own experience undergoing chemotherapy
following CRC surgery I found that my ability to heal incisions became difficult during
that part of treatment. Good ability to heal is necessary to have a successful result from
cosmetic procedures. Although the desire to get all of the surgery “over with” as soon as
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possible is understandable, that will not happen if you are not healing well; or, if ongoing
aspects of cancer treatment compromise the cosmetic procedures by requiring more
surgery, for example. This is certainly something to consider.
Overall, the pros and cons of such reconstructive surgery, its timing and its
applicability to your particular case have to be discussed with your surgeon(s).
Surgeon and Surgical Teams
Genito-urinary surgeons contending with Prostate Cancer have the particularly
difficult task of operating in an area that is buried deep in the pelvis and in close
association with bladder, bowel and sexual structure and function. The prostate’s small
size; location; architecture; and, how it is knitted to the surrounding lymphatic, urinary,
circulatory, reproductive and nervous tissues makes for a complex and easily
compromised surgical environment. Even exploratory procedure such as core biopsy can
carry real risk in terms of inflicting collateral damage to the area’s structure that can
result in substantial and lasting impact on a patient’s quality of life. Clinical experience,
precision, thoroughness and finesse can make an enormous difference to the success of
your diagnosis, recovery and fight. If they proceed with the wrong surgical option, if
their technique is flawed, if they act hastily or without the necessary considerations it can
have disastrous effects on your constitution and physical abilities. Do remember;
however, that operating on the prostate and pelvic areas does have unavoidable risks,
despite the best of present day clinical technique and consideration. All to say make sure
your genito-urinary surgeon is very experienced in the techniques being used; make sure
they have an excellent record and reputation; and, make sure you are properly assessed
and prepared going into the surgery. This will minimize any associated surgical risk.
Again, remember that when you are seeking out a surgeon it has to be someone
that you are comfortable with. The more experienced the surgeon, the better able they
are to perform the procedure properly, and, foresee and address any complications. You
can ask them when you have your initial appointment just how many of the procedures
being proposed have they done. Ideally, the answer should be hundreds or more. From
the first appointment onwards you should expect that your surgeon has a completely
professional and calm approach to patient care. Their manner should be methodical and
to the point. They should be experienced, organized, and considerate. They should not
discourage your questions. Their explanations should be well presented, patiently
delivered and understood. They should brief you on the options for your condition, the
proposed procedure, the risks, and how the surgery will be modified in the event that
complication occurs.
If you have been admitted, the morning after surgery you should expect to be
visited by one of the surgical team members as they pass by “on rounds”. Doing the
rounds is something doctors do to check on their patients’ status. Sometimes the rounds
will be done by another member of the surgical team instead of the lead surgeon. This
will probably be a junior member of the surgical team such as the chief resident surgeon.
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The chief resident surgeon is a qualified medical doctor who is finishing off their
residency (apprenticeship) as a surgeon. The chances are that you will not have met this
doctor before your surgery. Apart from checking on how you are doing you can expect
that they will give you a thorough brief on what to expect in the period of surgical
recovery. It is not unusual for the team anaesthesiologist to stop by to ensure that any
pain is being adequately managed as well after the surgery.
Barring any complications such as infection, release from the hospital after
surgery usually depends on few things. Firstly, the patient has to be able to “get around
by their self”. In addition, adequate physiological function that may be disrupted by the
surgery has to be regained. As well, the patient has to be able to manage any post-surgical
pain. If the patient has not arrived at this minimum state of self-sufficiency, then chances
are pretty good they will not be released from the medical facility until they have. Exact
length of stay in the hospital after surgery can be clarified when you speak to your
surgeon(s) before you have your procedure.
Depending on the surgical procedure undergone, patients can be encouraged to
start moving around within a day after surgery. The idea is to keep as much strength and
mobility as possible by making your muscles and joints move through their range. Expect
some pain and discomfort doing this. Generally, the more regularly you exercise the
quicker you will recover, and the stronger you will be to commence any additional
treatment if required. You will be given instructions on what activity and exercise you
can do by the medical staff. Be mindful of these instructions.
Preparation for Surgery
A week or two before surgery the patient usually undergoes a standard series of
pre-operative work up tests. For outpatient surgery the patient usually arrives two or
three hours before the scheduled procedure. If being admitted, then the patient is usually
expected to arrive 12 to 24 hours before surgery depending on the medical facility.
During this time they will settle into their room, are briefed on the surgery, and then, be
physically prepared. If you are only admitted on the morning of your surgery, you will
probably be instructed to limit the type of food you take in within 12 hours prior to
surgery to juices and broths. General anaesthetic often causes nausea as a short term side
effect so having a stomach full of food going into surgery is probably not a good idea.
Deep vein thrombosis (DVT) is the formation of blood clots in veins when one
remains inactive (usually sitting) for extended periods of time. It is something that can
happen even to passengers on long range airline flights if they sit still for too long. Such
clots can cause all sorts of complications and even death if they wander through the
circulatory system and make their way to the brain or heart. If the proposed procedure is
forecasted to last several hours, to minimize the risk of DVT you may be required to put a
pair of compression stockings on hours before your surgery. These are basically a pair of
really tight nylons without toes called Thromboembolitic Deterrent Sockings (TEDS).
The idea is to squeeze your lower limbs to help prevent blood clots from forming in the
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veins of your legs during and after surgery. These “support hose on steroids” may seem
like one more thing to make you feel really silly. Never mind, it is better to feel a bit silly
than to contend with clots.
Prostate Surgical Procedure
So now it is time for the procedure that will address the abnormal growth in your
prostate. This round of surgery is the first and it will determine the stage of your Prostate
Cancer and attempt, as much as possible, to remove the bulk of the malignant growth
from you. It is normal to be apprehensive as to how all of this will go. The only thing
that I can suggest is think positive. The more positive you are, the easier this and
anything else to follow will be. Let us discuss with a bit more depth the more common
procedures associated with surgery for PC.
Prostatectomy
A common treatment option available to low risk and high risk PC patients
remains to completely resection the prostate.70 As stated, there are two types of
traditional open type prostatectomy. Open procedure means that the surgeon has “hands
on” direct access to the prostate through an incision.
The Radical Perineal
Prostatectomy (RPP) is the first one that we will discuss. The RPP involves removal of
the prostate through an incision between the scrotum and the anus. This area is known as
the perineum. As much as the patient’s condition will allow, nerve sparing technique is
used. If merited by Partin probability above 10%, for example, the surgeon will also
access and remove regional lymph nodes via an incision in the lower abdomen (see
Figure 29 at left). As you can see the abdominal incision is large resulting in major
disruption to abdominal musculature and long recuperation times.
If lymphatic dissection is not required the only incision will be that in the
perineum for the RPP. The operation takes on average between 2 - 3 1/2 hours and the
patient is typically discharged in 2 days with no more complication than any other type of
prostatectomy.71 Figure 29 illustrates the traditional abdominal incision and the perineal
incision. Length of the abdominal incision may not always be as diagramed.
The Radical Retropubic Prostatectomy (RRP) is the same as the RPP in that it
removes the prostate in its entirety; however, there is the additional performance of a
PLND (Pelvic Lymph Node Dissection) if merited by Partin probability above 3%, for
example. As such; it is the more “radical” of the two prostatectomies. Instead of
removing the prostate through a perineal incision, the prostate is removed through the
abdominal incision that is detailed at the left in Figure 29. The perineal incision is not
required.
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Figure 29. Incisions for the Radical Perineal Prostatectomy. Left - Abdominal retropubic incision;
Right - perineal incision.
source: http://www.cancer.gov/dictionary?cdrid=373938
Illustration: ©2005 Terese Winslow, U.S. Govt. has certain rights
The Transurethral Resection of the Prostate (TURP) is used to remove all or part
of the tissue from the prostate using a resectoscope. The resectoscope is a surgical
instrument that has a viewing scope and a cutting tool. It is inserted via the urethra of the
penis to access the prostate. This procedure is sometimes used to address tumor blockage
of the urethra before other treatment is done. The prostate is not removed en bloc (in
whole) with this procedure.
The TURP can be done under either general anesthetic or spinal anesthesia. With
the spinal anesthesia the patient remains awake during the procedure and typically feels
paralyzed in the lower half of the body when the anesthesia is in effect. The patient stays
in the hospital 1-3 days after the procedure and typically is asked to get up and move
around after the first day. A catheter will be installed following surgery to allow urine to
drain from the bladder. This device will also allow the medical team to prevent clogging
by residual bleeding with flushing liquid. The catheter is usually removed 1-3 days after
the surgery. 72
One of the post-operative effects of prostatectomy is that about one in five
patients experience shortening of the penis by as much as 15%. The reason for this is
theorized to involve two factors. Firstly, there is the element of permanent nerve damage
that may have occurred during surgery; secondly, it is known that temporary erectile
dysfunction can occur for several months after the surgery reported to affect anywhere
between 26% – 100% of those who have undergone prostatectomy. This temporary
condition basically prevents the penis going through its full range of muscular activity
and just like any other muscle not being exercised it will get smaller. Meticulous nerve
sparring procedures coupled with penile rehabilitation regimen are the best ways to
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minimize this effect. In terms of penile rehabilitation options, the Vacuum Erectile
Device (VED) seems to be one of the most effective of the solutions according to the
literature.73
Figure 30 is an illustration of the transurethral resection of the prostate.
Figure 30. Transurethral Resection of the Prostate (TURP).
source: http://www.cancer.gov/dictionary?CdrID=45932
Illustration: ©2006 Terese Winslow, U.S. Govt. has certain rights
Orchiectomy
There are two types of orchiectomy. One is performed via a 4” incision made in
the lower abdominal inguinal (just above the groin) area. This takes approximately 45
minutes to perform, usually involves a general anesthetic and an overnight stay at the
hospital.74 The other procedure is via an incision in the scrotum. The orchiectomy via
scrotal incision can be performed under either local or general anesthesia.
Orchiectomy can be unilateral (involving one testes) or bilateral (both testes).
Whether done by inguinal or scrotal incision the testes are removed en bloc (in whole)
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through the access incision. The remaining ducts that were connected to the testes are
clamped and sutured. Then the incision is closed.
As stated, reconstructive surgery to a restore cosmetic appearance of testes is an
option that can be discussed with your surgeon.
Prostate Conserving Surgery (PCS)
The details of the anatomical aspects of the prostate including its circulatory,
nervous and lymphatic systems are well documented. As well, recent advances in
imaging have rendered the ability to specifically view malignant prostate cells.75 In
addition, the ability to use real time MRI guidance of precision surgical systems is
available and used in prostate surgery. Nerve conserving technique for prostatectomy is
also a well-practiced technique; so it can be said that there is an awareness and
acceptance of the value of aspects of prostate conserving technique. As such; it would
seem that all of the technical ingredients necessary to conduct Prostate Conserving
Surgery have arrived.
The idea of conserving surgery is to address early stage disease with negative
margin so as not to compromise the patient’s survivability while preserving as much as
possible the organ and its function. Conservation procedures are commonplace for
cancer involving the colorectal complex; the lungs; and, the breast, for example. In the
literature, I see techniques that use radiation, cryoablation and High Frequency Ultra
Sound in what appears to be prostate conserving approaches; however, it is not clear from
the literature if present methods involve the surgical removal of only the tumor portion
(with sufficient margin) of organ contained disease and so leaving the better part of the
prostate intact. These approaches have varied side effects and some techniques have
better outcomes than others which will be discussed.
Laparoscopic Procedure
Advancements in manipulable endoscopic optics; miniaturization of surgical
tools; computer assisted imaging; radiographic positioning; and, surgical training have all
contributed to the use of techniques that provide sound and proven non-invasive surgical
procedure in a number of fields addressing cancer.
These days, endoscopic technique is at the point where radical prostatectomy is
safe and feasible through small, hidden incisions in the area of the lower abdomen. This
procedure is known as Laparoscopic Prostatectomy (LP). Just as was the case when
endoscopic technique was applied to the treatment of other cancer, the mainstream
medical community remains embroiled in debate as to the value of laparoscopic over
open procedures. Those in favor of open procedure argue that laparoscopic procedure is
costly with prolonged operation times; offers no significant clinical benefit to the patient
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despite much smaller incisions; has similar profiles for post-operative quality of life
result; and, seems to result in more complication and positive margins.76
On the side of laparoscopic technique consider that in the lower abdomen the
musculature is multilayered and multidirectional. Figure 31 is a side view illustration of
what the abdominal muscles looks like.
Figure 31. Abdominal musculature side view with body on its back.
source: http://en.wikipedia.org/wiki/File:Grays_Anatomy_image392.png
originator: Henry Gray (1825–1861). Anatomy of the Human Body. 1918
The abdominal muscles contribute substantially to counterbalance exertions on
the back; and, they are the focal point for lower and upper body strength and mobility.
When the abdomen is breached by large incisions it is severely compromised until it
heals; and, it never heals the same as it was before the surgery. As a colorectal cancer
patient I underwent laparoscopic surgery instead of the open abdominal procedure. My
colon resection involved four fingertip sized incisions with a fifth slightly longer
extraction incision all in the lower abdomen. This is a similar laparoscopic strategy to
that used to address prostate resection. I can say that these types of incisions not only
result in substantially less pain, less discomfort, less blood loss and faster incisional
recovery; but also, minimizes the possibility of later abdominal hernias because the 1015 cm (4 - 6”) incision associated with open procedures has been avoided.
Figure 32 illustrates the size and positioning of the incisions used for a
laparoscopic prostatectomy.
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Figure 32. Schematic of port placements during prostatectomy (circles at position 1, 2, 3, and 8).
source - http://openi.nlm.nih.gov/detailedresult.php?img=3250319_ymj-53-236-g003&query=pelvic
laparoscopy &fields=all&favor=none&it=none&sub=none&uniq=0&sp=none&req=4&npos=691&prt=
originator: J.H. Jung et al.
Laparoscopic Pelvic Lymph Node Dissection (LPLND) has been performed
extensively particularly in the field of gynecology so it is, in fact, quite a common and
standardized laparoscopic procedure.77 In terms of Prostate Cancer it is used to exclude
high risk patients from non-curative therapy, as well as, to stage high risk patients at the
time of laparoscopic prostatectomy.78 LPLND avoids the lengthy incision associated with
open PLND by port access incisions that are illustrated in Figure 33.
Figure 33. Laparoscopic Pelvic Lymph Node Dissection port placements.
source http://openi.nlm.nih.gov/detailedresult.php?img=2917550_11701_2010_189_Fig1_HTML&query=pelvic
laparoscopy &fields=all&favor=none&it=none&sub=none&uniq=0&sp=none&req=4&npos=207&prt=
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Figure 34 shows a laparoscopic surgical team at work on a patient.
Figure 34. Surgical team viewing image monitors during laparoscope procedure.
source: http://upload.wikimedia.org/wikipedia/commons/c/c3/Laparoscopic_stomach_surgery.jpg
originator : http://www.defenselink.mil; VIRIN: 050131-F-1936B-008
Notice that the laparoscopic operation is being done manually with the surgical
instrumentation brought through placement port incisions. The lower abdomen is inflated
during surgery using carbon dioxide to assist in creating a positive space allowing the
surgical team to better view and work on the area of interest. Several large screens
display the magnified image being transmitted from the endoscope which is positioned
via a navel access. This gives the surgical team an enhanced ability to see minute detail
which is critical to nerve preserving procedures and the minimization of post-operative
urinary incontinence, bowel incontinence, and erectile dysfunction.
As is the case with any kind of surgical procedure, you must ensure your surgeon
is familiar with and “well exercised” in any procedure that is going to be done with
laparoscopic technique. This way you can ensure the best result and minimize risk of
complication. If that means going to a different facility or changing surgeons then do
that. I did this when the first surgeon handling my colorectal cancer proposed open
procedures. I ended up getting a second opinion and having a laparoscopic procedure
done instead by a specialist at another facility. I was in and walked out of that hospital in
less than two days having received a colon resection. I had almost no pain; several small
incisions in my lower abdomen; and, I healed very fast. Compared to open procedures, it
was marvelous!
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Robotic Surgery
Surgery is hard work and not only requires expertise but also focus, finesse,
precision, physical strength and a set of steady hands. With the successes and regular use
of laparoscopic techniques the medical industry has taken the next step in endoscopic
surgery by introducing robotic systems to assist the surgical team. The use of robots
with hydraulic arms, enhanced optics and integrated computerized control allows the
operating surgeons to perform minimally invasive procedure from remote locations
(away from the patient) with precision and tirelessness that would otherwise not be
attainable. If needed, the surgeons that commence the operation can now be replaced by
other surgeons mid-operation with seamless results. This is particularly useful when
dealing with lengthy procedures or advanced cancers in other parts of the body perhaps
requiring different surgical teams.
Figure 35 shows one of these robotic systems. During an operation attending
staff stay with the patient to assist the surgeon(s) who perform the procedure(s) at control
stations away from the robot.
Figure 35. da Vinci® Robotic surgical system with patient in position under the hydraulic arms
equipped with surgical instruments.
source : http://openi.nlm.nih.gov/detailedresult.php?img=2628019_ymj-49-891-g002&query=pelvic
laparoscopy &fields=all&favor=none&it=none&sub=none&uniq=0&sp=none&req=4&npos=559&prt=
originator : S.H. Baik
The surgeon’s control station has a comfortable seat; a viewing port to allow the
surgeon see the area being operated on; and, controls to manipulate the assorted surgical
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tools that the robot is configured with. The operating surgeon may be at a control station
located near the operating room with the patient or on the other side of the world.
Figure 36 shows such a station with the surgeon at work.
Figure 36. da Vinci® robotic surgeon’s console with surgeon at work.
source : http://openi.nlm.nih.gov/detailedresult.php?img=2628037_ymj-49-886-g001&query=da
vinci&fields=all&favor=none&it=none&sub=none&uniq=0&sp=none&req=4&npos=8&prt=
originator : Y.T. Kim et al.
Telesurgical technology now allows for experts to conduct or assist in surgery
from remote locations. The same applies for the traditional non-robotic laparoscopic
surgery. In short, having benefit of high levels of surgical expertise from other facilities
to oversee or assist in procedures is now a reality.
Techniques to more accurately biopsy the prostate are now being evaluated. So
far it would seem that manual manipulation of surgical instrumentation is more efficient
in addressing the issues of accurate prostate biopsy than are robotic sampling solutions.
The results of MRI guided biopsy were comparable in time and accuracy between manual
and robotic biopsy; however, manual set up is considerably less “technically involved”
than that of the robotic solution. 79
Figure 37 shows a patient positioned for MRI guided biopsy and the robotic
surgical extension that has been designed for biopsy. Restraining straps are used to
ensure that the patient’s position remains stable. The time and complexity of the set up
imposes obvious discomfort to the patient.
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Figure 37. Robotic prostate biopsy with patient and robotic extension in position for MRI guidance.
source http://openi.nlm.nih.gov/detailedresult.php?img=2628037_ymj-49-886-g001&query=da
vinci&fields=all&favor=none&it=none&sub=none&uniq=0&sp=none&req=4&npos=8&prt=
originator : M.G. Schouten et al.
Surgical Options for Advanced Metastasis
In 1889 Stephen Piaget conducted autopsies on 700 women who had died from
metastatic breast cancer and formulated the “seed and the soil” hypothesis of cancer
metastasis. Essentially this hypothesis states that the seed (cancer cells) has an affinity
for specific soil (organs). This theory still stands to the present. Generally, cancer cells
migrate to areas where blood and energy supplies are abundant (such as the bones, lungs
and liver) OR to places where they are separated from the immune system by physical
barrier (such as in the brain). 80
When Prostate Cancer cells migrate or metastasize to other parts of the body they
maintain their particular type of microscopic character. So, in the case of PC, no matter
where the cancer infects next it still can be identified as Prostate Cancer. As such; it is
still referred to as Prostate Cancer even though it may be occupying another organ. This
is the same with other cancers as well.
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Depending on the type of primary treatment, Prostate Cancer recurrency can
occur locally, regionally or distantly. Advanced prostate almost always develops bone
metastasis. Metastasis in the bones is usually accompanied with severe bone pain and in
many patients the skeleton carries the most significant tumor burden.81
Strategy to address metastasis in the bones or other organs such as the liver
depends on a number of factors including patient condition, treatment history to date,
tumor size and location, and state of the metastasis in other parts of the body to name a
few. The variables, options and risks will be discussed with you by your oncology and
surgical team leads.
If PC metastasis is found on the liver the cancer may be such that the liver can be
surgically resectioned or not, depending on the location and number of lesions or tumors
on the liver. The more advanced the cancer in the liver the more painful it becomes.
Surgical removal of a part of the liver is called a hepatic resection.
RFA or radiofrequency thermal ablation is a non-invasive image guided therapy
used to address liver cancer that would otherwise not be amenable to conventional
resection. The idea is to guide a RFA probe into the affected tumor using imaging
technology to the suspect areas of the cancer. The probe is then energized with
alternating current and manipulated in and around the area being treated. This causes
necrosis (death of tissue) and thermal desiccation (drying out) of the treated area. The
RFA energy effectively “cooks” the tumor.82
Figure 38 below shows the working end of an RFA probe. Notice the ablation
“tines” that spread out at the end of the probe. These are retractable to facilitate
positioning into the tumor. There is also a center electrode that extends (not shown)
when the probe is in use through which an electrical current travels.
Figure 38. Example of an RFA probe.
source: http://openi.nlm.nih.gov/detailedresult.php?img=2840607_TOBEJ-4-3_F1&query=Radio
Frequency thermal
ablation&fields=all&favor=none&it=none&sub=none&uniq=0&sp=none&req=4&npos=112&prt=
originator: I.A. Chang
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Another treatment that is presently under review is Isolated Liver Perfusion (ILP).
This is also referred to as Isolated Hepatic Perfusion and is a highly invasive surgery
involving the complete isolation of the liver’s vascular system so as to enable point
specific delivery of high drug doses (typically melphalan) to the tumor(s), without a
subsequent toxic impact on the rest of the liver. It is reported that this type of treatment is
responsible for high response and survival rates.83
Figure 39 shows a simplified diagram of the liver divided into segments based on
its circulatory system.
Figure 39. Anterior view of the liver. Hepatic segments (I- VII) with portal venous (PV) branches
separated by the hepatic veins (HV). HA is the hepatic artery.
source: http://openi.nlm.nih.gov/detailedresult.php?img=2627163_kjr-8-302-g001&query=liver
segments&fields=all&favor=none&it=none&sub=none&uniq=0&sp=none&req=4&npos=5&prt=0
originator : H.Y. Lee et al.
As you can see the extent and complexity of the liver’s circulatory network is
formidable and this organ continues to challenge the best efforts of surgeons and
oncologists who treat metastasized cancers.
Surgical Risk
By professional code of ethics your surgeon has to brief you on the risks and
possible side effects of the procedure before the surgery and the patient has to sign a
document of consent which states the patient understands the risks and the procedure that
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they are giving consent to. The list of risks, possible side effects complications vary with
the specific procedures being done. Depending on the type of prostate surgery the list
may include abscess; sepsis; severe infection; seroma; lymphedema; injury to nearby
nerves and muscle structure resulting in erectile dysfunction; bowl or urinary
incontinence; bleeding; heart attack; blood clots; and, death. Your surgeon will make it
clear that most of these have a very small chance of happening; but, because they can
occur, they have to be discussed.
General anaesthetic as well has its risks. The longer a patient remains under the
influence of a general anaesthetic the greater the risks. This is one of the reasons why
surgeons concern themselves with the amount of time a particular operation takes. The
risks associated with anaesthetics related to specific prostate procedures can be answered
by your anaesthesiologist. You will have an opportunity to speak to this specialist before
your surgery. The exact type of anaesthetic you are given depends on the procedure you
are having. For operations requiring general anaesthesia, the sedation may be initiated
with a drug injected through the cannula. A cannula is a small device that can accept
needles that is usually installed on the vein in your wrist, or fore arm or bend of your
elbow.
Before going into the operating room you will know how long the procedure
should take. Typically you will be retrieved in your room by an orderly and wheeled on a
gurney up to the operating wing. There you will meet the assisting nurse and
anesthesiologist. They will help transfer you to the operating table. Shortly thereafter the
anesthesiologist will access the cannula on your wrist and within about ten seconds (or
less) you will be “asleep”.
I found an overview on the following website that basically answered most of my
questions about general anesthesia:
http://www.surgeryencyclopedia.com/A-Ce/Anesthesia-General.html
The following is my understanding of the practical aspects of general anesthesia
in a nutshell. Starting the anaesthetic is known as the "induction". When I was operated
on for colorectal cancer I was “induced” through a cannula but it is also possible to
induce sleep with anaesthetic gases breathed through a mask.
After you are asleep you will be given a mixture of oxygen and anaesthetic gases
through a flexible tube put into your windpipe. This part of anaesthetic is known as
"maintenance".
To control pain during and the first 24 hours after surgery, your anesthetist will
inject you with strong painkiller. This is usually done through the cannula while you are
still in surgery.
During the operation, you will be connected to monitoring systems that give
ongoing information to the anesthesiologist. Most countries have the same or similar
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standards and guidelines for this monitoring. These standards typically address patient
oxygenation, ventilation, circulation and body temperature.84 As such; the monitors that
are commonly in place during surgery and what they do are:
An ECG (electrocardiogram) monitor - Three sticky pads on your chest
connect to a monitor which shows the electrical activity of your heart on a TV
screen. This shows how fast your heart is beating, and allows the anesthetist to
pick up problems such as an irregular heartbeat or signs that the heart is not
getting enough oxygen;
A BP (Blood Pressure) cuff - This cuff goes round your upper arm. From time to
time it will squeeze your arm tight, to find out the pressure of the blood in your
arteries. It is important that this is neither too high nor too low. An automatic
blood pressure machine usually shows four numbers, the high, average, and low
pressures with each heartbeat, and the heart rate;
A pulse oximeter - This is a device which goes on a fingertip or earlobe, and
measures the amount of oxygen in your blood. It works by detecting a slight
change in the blood color from the usual bright pink to blue as the blood oxygen
level decreases, long before this change is visible to the naked eye;
A temperature monitor - This is an electrical thermometer which checks that
you are neither too hot nor too cold; and
A carbon dioxide monitor - This measures the amount of carbon dioxide in your
breath, which shows that you are breathing adequately. It is connected to the
breathing tubes coming from the anaesthetic machine.
These days the monitoring machines have integrated alarm systems to signal the
anesthesiologist in the event of a patient distress. As well, the anesthesiologist remains
with the patient from the time the patient goes to sleep until they are stable in the
recovery room.
After the Surgery
When the procedure is complete the anaesthetic gases are stopped and the patient
begins to wake up. A drug to reverse the effects of any muscle relaxant is administered
and the patient is moved to the recovery room where a nurse will provide one-to-one
care. The nurse is there to monitor the patient’s heart rate, blood pressure and other vital
body functions and make sure the recovery from the anaesthetic goes well. It is possible
that you will not recall anything of this time.
The anaesthetic “maintenance” tube that was in your throat will usually be
removed shortly after you wake up before you are returned to your room. You may not
even recall it being removed. I didn’t remember this being removed after my CRC
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resection. Your throat may feel a bit dry and perhaps a bit sore from having experienced
this tube.
It is routine to be given oxygen to breathe through a face mask. Instead of a mask
you may be given oxygen by a non-invasive assisted pressure (NIV) oxygen line fitted in
your nostrils. This looks a bit like a clear tube with a couple of small prongs. The prongs
are positioned one in each nostril.
Some patients feel nausea after the general anaesthetic but medication is usually
given to control the nausea. Once the anesthesiologist is satisfied with the patient
progress, the patient is disconnected from the monitors and taken back to their room.
After the surgery if you have not had “day surgery”, you will have a time to rest
in your room. You will likely not feel too much pain at this point because of the ongoing
sedation. It is now that you will see the dressings of your operation, and a number of
“lines” leading from an IV (intravenous) rig to you. As well, you can expect to have a
catheter for the next week, so as not to disrupt healing and allow for unhindered bladder
relief. For those of you who do not know, a catheter is a tube that is inserted via the
urethra (plumbing where the urine usually comes out) into the bladder for drainage. It is
usually inserted while under the general anaesthetic in preparation for the operation.
Don’t even think of pulling it out by yourself because there is a special technique that has
to be performed by a trained staff to remove it. Trying to remove it without this medical
technique will cause substantial damage to your “parts”, to say nothing of the pain that
would ensue.
While sedated and in surgery usually not a lot of emphasis is given to the
exchange of patient status and progress of the operation to those “in waiting”. This lack
of update can make the operation a long and worrisome period, especially if the patient is
overdue. It is understandable how the surgical team has its hands full with the operation.
Nevertheless, spouses and “significant others” waiting should know that they can ask to
be brought up to the recovery room as soon as you are stable. As well, if you ask the
nursing staff on the operating floor for an update you are more likely to get one.
The very next thing that will happen will probably be a visit by a senior surgical
resident, who participated as part of your surgical team. They will be able to tell you
how the surgery went and what was discovered.
Shortly thereafter the anaesthologist will likely arrive and reconfirm what has
already been told to you by the other surgical team member. The anaesthologist is an
experienced doctor who has seen many surgeries. They will explain what to expect in
terms of function and recovery in the next week or two. You may find that you are
attached to a PCA or Patient Controlled Analgesia pump. The anaesthologist will
explained was how this pump is configured to administer morphine at your command.
If you know anything about opiates, the bag of morphine hanging above your head in the
confusion of bags of saline, electrolytes, anti-biotics and vitamins, is probably enough
morphine to put the entire ward and staff down for 12 hours or maybe even kill an
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elephant. Morphine is a) highly addictive, and, b) lethal if too much is taken all at once.
The anaesthologist will explain that the PCA Patient Controlled Analgesia pump has a
safety mechanism that restricts the delivery of any dosage of morphine that is
commanded during a predefined time period. This is called a “lock out” period. In
effect, it is not possible to over medicate or overdose. Of course, the lock out period has
to be correctly programmed according to the anaesthetic and dosage prescribed, AND,
the pump has to actually behave as expected. Despite any concern about having such a
thing tapped directly into your circulatory system; and, even you are not experiencing
much pain, the chances of you convincing the anaesthologist to disconnect the PCA so
soon after surgery are probably very remote. Anaesthologists have a way of being very
“pro” sedation when it comes to managing pain.
The United States Pharmacopeia (USP) is a body in that country that oversees
patient safety. They have a mandate to review anything that has to do with patient care
and safety and make recommendations through Quality Reviews to alert patients and
practitioners. Quality review #81 details the high rate of medication errors associated
with the PCAs. The USP has found that there are some advantages to self-delivery of
pain killer for non-critically ill patients. Generally, these pumps have been shown to
improve pain management with less sedation and fewer adverse effects. Despite these
advantages however, the USP has reported the chance of patient harm increased more
than 3½ times over the normal staff assisted delivery of painkiller. According to
MEDMARXsm, the United States national database for medication error, the error rate
affects approximately 2% of all patients, that’s 1 out of every 50. The most common
types of error reported are improper dosage (38.9%) and the incorrect drug being
delivered by the PCA (18.4%).85
One of the things about surgery and treatment is that you are going to be exposed
to drugs and agents for the first time. One of the standard things for the medical staff to
do is to ask you and keep track of those known allergies that have already been
discovered. Be aware, morphine does not always produce a “euphoric high” to all
patients. There are those who will instead present an immediate allergic reaction. Such a
reaction could involve a strong sensation of “tingling” all over the body. Extremities
may go numb. Hands and feet may turn blue (cyanic). Vomiting may occur within a
minute or two after being administered a dose.86 If you have never experienced a certain
agent or drug and you are self-administering via something like a PCA, it is probably not
a bad idea to wait until medical staff is nearby before you initiate your first dose. This
way, if you have an allergic reaction there is someone there who knows exactly what has
happened and so will be able to promptly respond to your reaction. Again, for those
patients who have known allergies, it is important that the medical staff is reminded of
the allergy anytime new medication is being administered.
Before discharge, patients are given the details of their next appointments with the
surgeon and laboratory for follow up. The patient’s incision(s) will have been closed
with either stitches (which are often dissolvable and do not need to be removed) or
staples (metal clips) that are normally removed after 10-14 days. The nurses on the ward
can do this, or district nurses if you have already returned home.
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When a patient undergoes an operation it is normal for some blood and fluid to
exude from the surgical incision(s), therefore, a drain or tubes may be installed to remove
this fluid. This flow will be monitored and the tube will be removed when the flow
decreases. The nurse will remove the drain on the ward. These procedures are not painful
but can be a little uncomfortable.
Patients are made to get up and walk remarkably soon these days. Often, you can
expect the day after surgery to be encouraged to do this. Generally, discharge from the
hospital occurs after they manage to tolerate an oral diet, when their postoperative
discomfort can be controlled with oral pain medication, and when they can get up and
move around “reasonably well” on their own.
Infection and Antibiotics
The prevention, treatment and control of infection for any surgery are of the
utmost importance. Bacteria can infect the patient through sources either internal to the
body or externally. Steps to minimize the risk of any infection are a consideration of any
surgical option. The following is some information so that you can better understand
familiar terms associated with infection.
A septic abscess is a pocket or capsule of pus formed by the body’s immune
system in response to invading foreign organism or material. Pus occurs when white
blood cells called neutrophils attack foreign organisms or material. The neutrophils are
phagocytic, meaning that they “eat” or ingest foreign cells. Unfortunately, when
neutrophils ingest foreign cells or material they do not survive the meal. The main
component of pus is dead neutrophils, but it also consists of live white blood cells, as
well as, the invading foreign material or organism(s) and enzymes.
As the neutrophils respond in defense, the invading organism or material
continues to kill the local cells. As this occurs there is a release of toxins. These toxins
trigger an inflammatory response in the tissue giving rise to a swollen, red, sore area that
feels unusually warm. Healthy cells near the site of infection eventually form a wall
around concentrated areas of pus. This separates the pus and infected area from the
healthy tissue, but such encapsulation tends to trick the incoming immune cells and
prevents them from attacking any foreign organisms or objects still in the pus. The
lancing of an abscess is a procedure used to drain the concentrated area of pus and any
remaining foreign organism or material therein.
Surgical Site Infections (SSI) for those undergoing open versus laparoscopic
robotic surgery is significantly lower for robotic procedures. According to a study in
2011 SSI rates following retropubic radical prostatectomy (RRP) was 4.5% compared to
a robotic prostatectomy SSI occurrence of only 0.6%. In addition it was reported that
those SSIs associated with robotic prostatectomy involved much less severe infection. 87
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The use of prophylactic antibiotics in Prostate Cancer surgery has yet to be
standardized even though this is a common approach for many other types of surgery.
Prophylactic means a measure that is done before something has happened. In a report
analysing the effectiveness of prophylactic antibiotics in urological surgeries it was found
that shorter durations of prophylactic antibiotics yield lower incidences of SSIs. It is
theorized that is due to bacteria developing resistant strains with longer exposure to the
same antibiotic.88 Nevertheless, the incidence of urinary post-surgery SSIs is reduced by
prophylactic anti-biotics. Since most infections occur well after the Prostate Cancer
patient has been discharged from the hospital a discussion regarding the use of
prophylactic antibiotics has merit and should be had with your surgeon.
Septicaemia is a rare but potentially life-threatening infection in which large
amounts of bacteria are present in the blood. It is the result of bacteria spilling over from
a known primary infection site, such as an abscess, into the blood and is commonly
referred to as “blood poisoning”. The infecting bacteria are carried throughout the body
via the circulatory system and Systemic Inflammatory Response Syndrome (SIRS) can
result. SIRS is a condition whereby the entire body becomes inflamed. The bacteria
strains most commonly responsible for septicaemia include Escherichia coli (E. coli),
Pneumococcus, Klebsiella, Pseudomonas, Staphylococcus and Streptococcus. 89
For the patient, the onset of septicemia usually begins with fever and chills.
Profuse sweating may occur. As the fever becomes more intense the patient’s heart rate
and respiratory rate may increase. At this point, the patient will likely feel very ill and
weak. The skin can become very pale and the person may exhibit petechiae. Petechiae
are tiny (1-2 mm in size) red or purple spots on the skin. These are the result of minor
hemorrhaging. As the condition worsens the patient’s blood pressure starts to fall and
they may lapse into unconsciousness. If the blood pressure is allowed to fall sufficiently
it could cause organ failure. This is called “septic shock” and can be fatal.
Septicaemia is treated with intravenous (IV) antibiotics. Quick treatment is
essential if the patient is to survive. Typically the attending physician will start antibiotic
treatment before the test results that identify the bacteria strain come back from the
laboratory. In this case, topical (broad spectrum) anti-biotics are normally used until the
lab has identified the particular bacteria causing the septicaemia. Then the antibiotic
treatment is altered to eradicate those particular bacteria. Additional infection
management options depend on the cause of the infection and the presence of
complications. These may include the introduction of IV fluids and drugs to maintain or
boost blood pressure; surgical removal or drainage of the primary infection site; and/or
removal of the foreign material or objects such as a catheter.90
Infection following surgery can be related to a number of factors. These can be
specific to the patient, the surgical environment, an institution’s standard operating
procedures (SOPs) pertaining to prophylactic infection management, or, the
administering of drugs and radiotherapy for continued cancer treatment. In the patient
list of factors, old age, malignancy, malnutrition, obesity and the harbouring of other
disease such as diabetes have all been implicated in higher susceptibility to infection. In
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terms of the surgical environment, contamination, the management of the wound after
contamination, prolonged surgery in excess of 2 hours, blood loss requiring transfusion,
and the use of “open” drains to remove fluids have, as well, been linked to higher
infection rates. Researchers have also found that if a patient has surgery towards the end
of the day’s surgical list, as opposed to early on in the day, it makes them substantially
more susceptible to infection.91 In this regard it seems better to be scheduled in the
operating room in an early morning slot.
One of the side effects of chemotherapy, in a conventional sense, is that it impacts
on the production of blood components. This reduction in the white and red cells and
platelet production compromises the body’s immuno-response, ability to transport
oxygen, and ability to heal. The result is that the patient is substantially more susceptible
to infection from any invading bacteria, fungus or virus.
The more extended the regimen of chemotherapy, the greater its impact on the
blood components. Normal white cell count in humans is between 4300 to 10,800 cells
per mm3.92 It is not unusual to see a white cell count below 4000 cells per mm3 half way
through a 12 session regimen of chemotherapy. As stated, neutrophils are white blood
cells that defend against foreign organism and material invasion. Normally they
comprise approximately 60 to 70% of all your white blood cells. With this substantial
reduction in white blood cell count, there is a corresponding reduction in the body’s
immuno-response.
The range of Absolute Neutrophil Count (ANC) is roughly between 1,500 and
7,500 cells per mm3. If the patient’s neutrophil count drops below 1500 cells per mm3
they are considered neutropenic.93 Your hospital will have “protocols” or guidelines of
policy stating when treatments can proceed or not. In the case of low neutrophil count,
for example, chemotherapy may be delayed until the count recovers to above 1500
cells/mm3. This is what happened to me when I was undergoing chemotherapy for CRC.
The scientific name for red blood cells is erythrocytes. The bone marrow
produces about 4 -5 billion red cells every hour in an adult human. Red blood cells are
involved in the transportation of oxygen from the lungs to the muscles, tissues and
organs. They do this with the help of a protein called haemoglobin. The haemoglobin
can bind with a number of gases including oxygen and carbon dioxide. After the red
blood cells have delivered oxygen they transport carbon dioxide waste from that same
area and deliver it back to the lungs through the veins. The carbon dioxide is then
released or expelled through the lungs. A red cell only lasts about 120 days and then it is
removed from service by the spleen.94
During chemotherapy the production of red blood cells usually diminishes too.
The result is that the patient may experience general fatigue. I found that the further into
my chemotherapy regimen I was, the more tired I became. If the patient is tired and
feeling without energy it makes them susceptible to invasion from foreign organisms. I
know that when I am tired it affects morale as well. Morale is critical to the patient’s
“will to fight”. The solution is to rest and intake more foods rich in iron such as red meat
and dark green vegetables. This will provide additional material to build red blood cells
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during the time between chemotherapy sessions. I found that, in my case, maintaining an
exercise regimen helped a lot in alleviating the feeling of fatigue.
Platelets play a major role in the body’s ability to stop bleeding and heal. They
are capable of “filling in” small gaps that develop in the circulatory system. Platelets can
also form “plugs” in response to vessel injury. In addition, they secrete growth factors to
stimulate healing after injury.95
Normal platelet count in adult humans generally range between 150 000 to
450 000 platelets per mm3. Thrombocytopenia is a condition where the patient has a
reduced platelet count. 96
Determining the exact count of platelets is not so straight forward. Platelets in a
blood sample have a tendency of decreasing rapidly with time. In effect, delays in
analysis of the blood sample can result in a report of low platelet count when, in fact, the
platelet count is much higher. What I noticed was that during my chemotherapy
treatment my usual ability to heal from cuts and abrasions in a couple of days turned into
weeks as my platelet count fell below the lower bounds of normal limit. Open sores and
prolonged periods without healing make the body vulnerable to infection from any
source.
Radiotherapy (RT) will impact any cell in its delivery path. A week long course
of RT may not produce any obvious side effects in terms of infection; however, if the RT
course is sustained over a four week period for example, or, coupled with chemotherapy,
it can have an impact on the patient’s ability to fight off infection for the same reasons as
does sustained chemotherapy.
As stated, one of the problems with infection is that it often strikes a patient after
they have left the hospital. Normally patients who have had surgery feel a bit better
every day. If suddenly you start feeling worse it could mean that you are harboring
infection. As such; it is important for the patient to recognize the signs of infection. Be
aware that you may only have one of the symptoms listed below. If you suspect infection
take immediate action by calling your contact nurse or overseeing physician. Be
prepared to be able to tell them a description of your symptoms, your temperature and
pulse rate. Do this before you have taken any aspirin or “over the counter” medication
that would reduce the fever.
The signs of infection include but are not restricted to:





Feeling of being tired and without energy (Malaise);
Fever in excess of 38 degrees Celsius (101 Fahrenheit);
Increased pain around the incision;
Redness around an incision;
Swelling/hardening on or near the incision or post-surgical port or drainage
tube(s);
 Foul smelling pus or discharge from the incision.97
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Treatment of infection varies depending on the area of the body and the degree of
infection. The more common medications to treat infection include penicillin,
cephalosporin, tetracycline, aminoglycosides, macrolides, chloramphenicol, ivermectin,
rifamycins, polymyxin, and bacitracin, for example.98 Antibiotics have varied delivery
strategies and depending on the medical protocol may be given by mouth, injection or IV.
In more severe cases the patient may have to be admitted to the hospital. If the patient is
undergoing chemotherapy or RT the oncologist may order that the regimen be delayed
until white blood levels have returned to normal and the infection is gone.
Prevention is “key” and there are a number of things that a post-surgery patient
can do to minimize the risk of infection. Common sense and good personal hygiene must
prevail. The number one behavior that must occur is that the patient must wash their
hands more frequently and keep them away from the face and mouth or the incision(s).
This is especially important after having been out in public areas or using the bathroom,
and before eating. Keeping the assorted incisions clean until healed with regular changes
to dressing is a must. This can be arranged with the patient’s nurse or physician. Be
aware, washing if not done correctly, can actually “stir up” bacteria under surface skin
plates and increase the number of bacteria on the washed surface. This is one of the
reasons why surgeons wear gloves during surgery.
Additionally, stay away from crowds or individuals where colds and flu are an
issue. Clinics and hospitals are full of runny noses and coughing, so it is best to arrange a
set time to see the doctor rather than just showing up and sitting for hours in a waiting
room. Do not receive any vaccination (including flu shot) unless it has been approved by
your physician or oncologist. 99
Finally, if you are neutropenic you have to be especially vigilant and consider not
eating things that are uncooked or unpasteurized until the count recovers into the normal
range.100
On the topic of spillage, healthy tissue can become contaminated with cancer
cells if the malignant tissue is not properly handled and contained during surgical
removal. Telltale signs of spillage can be a line or grouping of small “wart–like”
recurrent tumors on the skin surface around the extraction incision scar or in the
underlying tissue depending where the contamination occurred. In the case of recurrent
tumors on the skin, they may be visible within several weeks after the initial surgery. A
vigilant eye should be kept on the healing process and incisions for the first several
months and any irregularities reported to your doctor immediately. I had a couple of
small bumps appear near my extraction incision after about a month. It turns out they
were the result of a buried suture that had somehow not been removed. After it was
removed everything was fine. So don’t jump to conclusions if you see a couple of small
bumps.
One of the effects of surgery is the fact that the tissues surrounding the incision
will be swollen for days or several weeks after. This is in part a result of fluids and blood
leaking from capillaries and damaged tissues in the area. Swelling can restrict
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movement, slow recovery and aggravate or cause pain. One solution is the use of ice to
reduce swelling. Sports physiotherapy often makes use of icing as a way to treat
inflammation and pain associated with acute and chronic injury. Typically very large
bags of ice cubes are applied on the affected area, held loosely into position by wrapped
elastic bandage or towel, and left for approximately 20 minutes or until the area feels
somewhat numb. Then the ice is removed. Repeating this procedure four times a day
during the healing period can help with recovery. Care must be taken not to wet or
contaminate the incision or the dressing during icing. Ice “double wrapped” in plastic
bags should keep any leakage contained. Ice cubes are used because they afford a degree
of flexibility between the cooling agent (ice) and the injured surface that may be tender.
Hard plastic “ice packs” designed for cooling food and beverage usually fail to make
adequate contact with the affected surface, and they hurt so they are really not that useful.
Icing may be started shortly after surgery with your physician’s permission. Just ask
your floor nurse to prepare a bag of ice for you and to bring a couple of towels along with
it.
Be aware that icing can reduce blood flow by temporarily “shrinking” vessels in
the iced area. As such; it is especially important that you consult your physician and/or
physiotherapist to ensure the appropriateness of icing for your post-surgical condition and
use correct technique.
Post-Operative Condition and Rehabilitation
Exercise can be a valuable assistance in recuperating lost range of motion,
regaining strength and reducing pain after the trauma of any surgery. Apart from the
patient having to regain abdominal and/or perineal integrity from open procedures, the
prostatectomy is associated with a number of other upsets that can last for years the likes
of which may respond to a well-directed and followed exercise regimen. Erectile
dysfunction; urinary incontinence; and, bowel incontinence are some of the afflictions
that exercise regimen have been tailored to address following prostatectomy. Initially
exercise should be done under supervision. One of the members of your treatment team
will be a physiotherapist. They are typically assigned to you before your surgery and
will brief you on post-surgical breathing exercises to assist in your recovery. After the
surgery they will be involved in the regimen to assist you in regaining strength; range of
motion and functionality.
It has been reported that those who undergo prostatectomy seem unaware of its
repercussions and so have false expectations of how much of their former functionality
will be regained. The known shortcomings from prostatectomy will be the inability to
ejaculate or produce sperm. Orgasm dysfunction is possible. For those capable of
orgasm, a number of men may experience pain and urinary incontinence with orgasm.
As well, Peyronie’s disease may develop within 3 years of the operation.101 In addition;
it may take upwards of two years to regain ability to experience a normal erection. 102
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Note to clarify - Peryonie’s disease is a connective tissue disorder where scar tissue forms in the
thick sheath of tissue surrounding the corpora cavernosus (see Figure 5) causing pain, erectile
dysfunction, indentation, loss of penile girth and shortening.
In any event, the key is patience, consistency in doing the regimen, and
persistence. Sometimes pain and embarrassment will have to be “worked” thorough in
order to have improvement. So you can expect to be guided into routine that is not
always comfortable.
According to an overview presented in the 2012 Annual Meeting of the
Urological Association of Physicians Assistants, the largest complaint from those who
have undergone radical prostatectomy is “sexual bother” which includes urinary
incontinence (especially during orgasm); erectile dysfunction; and bowel incontinence.
The data indicates that the overall rates of these afflictions are not affected by
rehabilitation regimens; however, the timeframe for those who will be restored to postoperative maximum functionality is much shorter if rehabilitation is followed.
Additionally, it has been reported that penile rehabilitation minimizes long term penile
shrinkage. The secondary benefits are that sexual relations are improved; which in turn,
eases the burden of sexual related upset and stress on significant relationships. 103
The following are some considerations and examples of what you can expect to
encounter in post-operative Prostate Cancer rehabilitation program:
There are several types of Pelvic Floor Muscle Training (PFMT) programs. The idea is
to consciously contract the pelvic muscles, and, in so doing develop awareness, strength
and control over traumatized or unexercised pelvic, rectal and urinary muscles. Such
training includes:
- Exercises to strengthen pelvic floor muscles [Kegels];
- Physiotherapy with biofeedback; and,
- Physiotherapy with rectal electrical stimulation.104
Notes to clarifyKegels are an exercise that is used to promote urinary sphincter control similar to how someone
would arrest urinary stream mid-flow. There are two sphincters associated with the urinary tract.
One is at the base of the bladder; the other is at the apex of the prostate (i.e. just after the prostate
on the way to the penis);
Biofeedback involves the uses of small devices (sometimes handheld) to cue on and signal subtle
body changes (like skin conductivity, for example) allowing a person to become aware of their
ability to control what are normally automatic body mechanisms and response;
Rectal electrical stimulation is used to train and develop the rectal muscles using a low energy
electrical current. The device emits an adjustable electro-pulse which is sustained for several
seconds and causes the rectal muscles to contract and release.
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Regarding Penal rehabilitation the goals are to promote early return of erection;
improve cavernous muscle oxygenation (muscles have to have oxygen to function); help
reduce fibrosis (formation of excessive connective tissue) and apoptosis (cell death); and,
minimize loss of penile size (length and girth). 105
Regimens and rehabilitation strategy vary greatly between medical facilities since
there is really no standard as to the content or timings. In addition, individual patients
have different profiles and conditions so regimens have to be flexible enough to get
results.
The following is an example of a proposed rehabilitation strategy:
2 - 4 weeks prior to surgery
- Assessment questionnaires;
- ED risk Assessment;
- Patient/Partner counselling;
- Commencement of prophylactic therapy with PDE5s.
Note to clarify – PDE5s stands for phosphodiesterase-5 inhibitor therapy. PDE5 therapy involves taking
oral agents such as sildenafil citrate (Viagra®) which is one of a number of sildenafil citrate agents used to
treat post-prostatectomy nerve sparing ED.
10 - 14 days after surgery
-Foley catheter is removed;
- Medical therapy involving oral medication of 2g/day L-Arginine; nightly
PDE5; IUA; and, vacuum erection device (VED) therapy 20 minutes/day.
Notes to clarify –
L-Arginine is one of the most common amino acids. It is a precursor to the formation of nitric
monoxide, which is a chemical made in our body that, among other things, is involved in erection
response;
IUA stands for Intra-Urethral Alprostadil. Medicated Urethral System for Erection (Muse®) is a
term sometimes used as well. This is an “erection on demand” drug that involves the insertion of
a suppository into the urethral opening of the penis. When the drug is absorbed it promotes the
production of a chemical called cAMP which can affect better blood flow for an erection. It is
reported that this prescription increases risk of penile or urethral burning for those who have had
radical prostatectomy.
One month after surgery
- Continued medical therapy as directed;
- Start using PDE5s prior to intercourse;
- IUA titration;
- Combination therapy prior to intercourse (PDE + IUA, PDE +VED).
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Note to clarify – IUA titration means increasing the dose.
Three months after surgery
- possible penile injection therapy 2-3 tmes per week if previous meds not
effective
- re-challenge with PDE5s.106
Notes to clarify –
Penile injection therapy involves the direct injection via a needle of either a single or
combination of erectile enhancement drugs into the side of the penis.
Re-challenge with PDE5s means to try the oral medication again.
Post-Operative Pathology Report
After surgery your pathology report will be delivered to your surgeon. When this
happens you can expect to be contacted by that surgeon and they will tell you the results.
It is probably a good idea to take a tape recorder because this can be a time of upset and it
may be difficult to maintain focus and really understand or remember what is being said.
Make it clear to your surgeon that you want to have detailed explanation of everything on
the report. They, as well, will usually give an overview with the bottom line options for
any further treatment and prognosis.
Most often a copy of the report will not be given to the patient unless it is
specifically requested. It is a good idea for you to keep a copy of this report with your
personal records. You many not completely understand the report at the time of
receiving it, but a little research will usually make things more clear as to exactly what
your condition is.
The report will detail exactly what was removed, where the tissues were located,
and, the state of those tissues. It will also describe in plain language the abnormal tissue
and in which part of the abnormal tissue the cancer was. Also in plain language will be a
comment as to whether or not the cancer had developed or metastasized beyond the
prostate and the location of invasiveness if discovered during the surgery.
If you have cancer the stage of the disease can be extrapolated with your specialist
from the pathological details in the report. Don’t expect your surgeon to “sugar coat” the
findings. They are usually straight forward as to what the next step is and that may be a
referral to the oncologist depending on the stage of your condition. The pace of this
referral and initial appointment is usually fast. You can expect to be set up for an
appointment within 7 to 10 days or sooner, if not then find out why.
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Lymphedema
Secondary lymphedema is a condition that causes tissue to swell because the fluid
balancing aspect of the lymphatic system has been disrupted, in the case of PC treatment
due to PLND (Pelvic Lymph Node Dissection) OR damage to the lymphatic tissues as a
result of radiotherapy. Swelling occurs because the drainage of lymph cannot keep up
with the demand. There is no cure for lymphedema; however, it can be managed. Figure
40 shows a picture of a man who has developed lymphedema in the lower extremities. It
is an example of what can occur if the condition is not properly managed.
Figure 40 – Lymphedema in lower extremities.
source:
http://openi.nlm.nih.gov/detailedresult.php?img=2962263_ijmsv07p0353g02&query=Lymphedema&fields
=all&favor=none&it=none&sub=none&uniq=0&sp=none&req=4&npos=33&prt=
originator - E.K. Symvoulakis et al
Treatment for lymphedema seeks ways to help the drainage of the accumulated
lymphatic fluids. Keeping one’s weight more to the ideal, compression devices,
bandaging, special drainage techniques using massage therapy, exercise, elevated resting
positions, and, physical therapy are all strategies used to help move the excess lymphatic
fluid into the circulatory system where they can be naturally excreted from the body.
When the pelvic lymphatics undergo dissection or damage the risk is that
lymphedema will occur in the trunk, pelvic area or lower extremities over time. This
condition can be quite painful and involve substantial swelling and complication. As
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107
such; it is important to keep a close eye on swelling and report this immediately to your
physician.
Long-term Surgical Outcome
Data was analyzed on 844 Prostate Cancer patients diagnosed with early Prostate
Cancer from 1989 through 1998 in Geneva, Switzerland. Majority treatments included
prostatectomy; radiotherapy; watchful waiting; and, hormone therapy. It was reported
that, for the period in question, surgery offered the best chance of long term survival (10
year relative survival) in particular for patients younger than 70 years old and patients
with poorly differentiated tumors. It was found that men who opted for Prostate Cancer
treatment with EBRT (External Beam Radio Therapy) instead of surgery were 2.3 times
more likely to die of Prostate Cancer in the ten year period following treatment. Men
who opted for “watchful waiting” were 2.0 times more likely to die of Prostate Cancer in
the period up to ten years after diagnosis than those who had surgery. 107
According to interviews with the overseeing researchers of a follow up 2007
study, it is proposed that this increased survivability for those who had surgery is related
to more thoroughly addressing the bulk of the localized disease; and/or, the fact that
patients who had undergone surgery had more treatment options to address recurrency
than the others who did not have surgery.108
Spousal and family reaction to Hard Times
So by now you have gone through what feels like a gauntlet of diagnostic test and
procedure for Prostate Cancer. By the time I was ready for chemotherapy with my cancer
I felt like I had been pricked, probed, squeezed, stabbed, scanned, cut, snipped, sutured,
stapled, magnetized and irradiated all over a part of my body that I really preferred not to
have “poised to the breeze and attentions” of a plethora of medical staff and stranger. I
felt like my dignity was considered completely irrelevant. Then I started considering the
facts of my advanced condition along with the eerie realization that I was headed for even
more vast “uncharted waters”. At that point I started looking back and thinking about
wrong turns and all the “if onlys” that contributed to my condition. I thought, if only the
detection technology could have been better; if only I was a little better informed; if only
I had exercised more or ate better or knew about the relative whose same condition
predated mine. But all of that did not matter. Of course, you don’t want to repeat the
known mistakes that put you where you are, but what matters is to look forward to
what can be done to help fight.
At this point one of the things you should consider is making sure you have the
support of those that matter around you. Cancer, in any form, is a battle that you must
win. To win a battle you have to first know your enemy. Then you must fight with
focus, resolve and what resource you have. I will tell you that it is a lot easier if you have
someone to talk to “now and then” that matters. Making sense out of what you are going
through and coming to terms with it may not be so easy initially, but you will.
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If you have a spouse or a mate, bring them close. Hold them and let them know
that you intend on bouncing through the battle. They may want to drift, because it is a
natural thing to do in order to cope, but don’t let them. Tell them you need their energy
when yours is waning. Tell them you need them to hold your hand. Tell them you need
something to look forward to every day; but understand, watching someone you love and
care for go through such a fight is not easy. Neither is coming to terms with it. So stand
your ground and make the effort to address the issues instead of withdrawing.
We all fight in different ways. How, when and who in your circle you inform will
be yours to decide. At least consider informing the ones that make you feel good and
laugh a little. If you speak to any floor nurse in oncology they will tell you that attitude
and will are major factors in how successfully a patient fights. It is important to keep the
most positive of attitudes. It is important to want to make your way back to good health.
One more thing, if you still smoke, STOP NOW! Other than the common sense
aspect of improving the overall climate for your recuperation, it has long since been
reported from a study involving 47,781 men that smoking seems unrelated to the
incidence of Prostate Cancer; however, actively smoking does have a significant impact
on the occurrence of fatal Prostate Cancer. 109
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Chapter 4
Non-Surgical Treatment and Therapy
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At any point following diagnosis of Prostate Cancer a patient has options. Initial
treatments do not always involve surgery. The same can be said for treatment of
advanced disease. Let us examine some of the non-surgical options for PC treatment. As
stated, surgical option is used for low, medium, high risk and advanced disease given the
appropriate patient profile and condition. Clinically approved alternative management
options include Active Surveillance; External Beam Radiotherapy (EBRT);
Branchytherapy; Cryosurgery; High Intensity Focused Ultrasound (HIFU); and,
Chemotherapy.
Active Surveillance is used for those patients who have low risk disease that is
considered to be indolent (lazy) PC. This is basically a “wait and see” approach that
favors Quality of Life without treatment over immediate intervention. Repeat biopsies
(every one or two years); annual DREs; and, PSA testing (every 3-6 months) make up the
bulk of the surveillance protocol. The understanding is that if surveillance shows
unacceptable progression then intervention options are available such as prostatectomy,
radiation therapy or hormonal therapy, for example. 110 One of the problems of this
approach is mistakenly categorizing PC that actually poses higher risk or is more
aggressive than expected.
External Beam Radiotherapy (EBRT) is used for low, intermediate and high risk
disease, as well as, advanced condition.111 The idea is to use directed beams of radiation
to kill the cancer cells. The problem with this therapy involves collateral damage to all
cells through which the radiation beams pass; long term side effects of radiation
treatment; and, not being able to confirm what degree of margin was actually attained
following the therapy.
Branchytherapy can be used to address low, intermediate and high risk patients.
This strategy involves the delivery of radiation either near or in the PC tumor using a
segment of radioactive wire (typically Iridium) inserted through a guidance needle that is
positioned in the desired area. Such delivery “seeds” are usually permanently implanted
with low dose radiation emission. Alternatively they can be temporarily implanted then
removed after several minutes having delivered a high dosage of radiation to the area.
Guidance of the needle/wire complex is usually done using IMRT. Protocols can call for
either stand-alone or combination therapies used in conjunction with branchytherapy. 112
Cryosurgery is the solution that involves killing cancer cells using extreme cold.
This is not a common treatment and its relative non-use in the urological field makes it
difficult to know exactly how effective it is or not. The technique is to position one or
more probes in the suspect area via perineal access using radio-guidance such as TRUS.
These days argon gas delivery is possible so the probe is sharp enough for direct
insertion to the area. The argon gas delivers temperatures of -187 degrees Celsius (- 304
degrees Fahrenheit) to the tumor. This cryo-albilation is then followed by warming
helium to neutralize the freezing. 113
Focused Ultrasound (HIFU) is a trans-rectal procedure used to treat localized
disease on patients that are not suitable candidates for radical surgery.
This is a
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treatment option that is repeatable. It delivers a brief (less than one second) high energy
heat charge to the suspect area causing rapid coagulation necrosis (death by thickening of
the liquid components) of the targeted tissues without causing damage to surrounding
tissue.114 According to one of the formative researchers of HIFU, H. Ahmed, this is a
treatment that occupies the middle ground between active surveillance and radical
surgery offering non-invasive day case treatment while substantially reducing the side
effects associated with traditional PC treatment options.115 In a study involving 172
patients with local PC treated by HIFU, no evidence of disease was reported for 159 of
the 172 patients after one treatment.116
The following is an example of the management options for the assorted
categories of PC. The specifics of your facility’s management options may vary from
this as there is no common set of PC management options.
Low risk disease management options
Active surveillance;
External beam radiotherapy (EBRT);
Low does rate (LDR) brachytherapy;
Cryosurgery;
High Intensity Focused Ultrasound (HIFU).
Intermediate Risk disease management options
EBRT;
Brachytherapy
- LDR (low dose radiation)
- HDR (high dose radiation);
Cryosurgery.
High Risk disease management options
EBRT + Androgen Deprivation Therapy (ADT);
Androgen Deprivation Therapy (ADT).
Advanced disease management options
Radiation therapy.
Stage T1-4, N1-3, M+ Hormone Sensitive Disease management options
Castration is the preferred treatment. Non-surgical castration strategies include:
Medical castration with
LHRH analogue; or
Single agent anti-androgens.
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Stage M+ Castrate Resistant disease management options
Palliative radiotherapy;
Strontium 89;
Palliative chemotherapy
1st line Docetaxel ;
2nd line Mitoxantrone; and,
Bisphosphonate therapy.117
To oversee and implement your PC treatment you will be assigned members from
the Department of Oncology. Here is where your cancer will be reviewed and addressed
by the specialists in the field of cancer. Their intent will be to either cure, if possible, or
manage the cancer so that it progresses more slowly and you live longer with a
reasonable quality of life. In any case, to do this your team will be a concert of specialists
in oncology, pharmacology, surgery, radiology, nutrition, physiology and psychology.
They will tailor a treatment regimen depending on your age, size, stage, affected organs,
the success of your initial surgery or previous treatment(s), your overall mental and
physical condition, and, their institution’s resource and programs. If you reside in a
country where there is no social health system, your ability to pay will also impact on the
measure and availability of treatment options. PC treatment can be very expensive.
What most impressed me as a patient when I entered my hospital’s Oncology
ward was the overwhelming sense of calmness and respect that prevailed over the entire
area. The waiting room was not crowded with patients who had to wait for hours before
being seen. There were no loud speaker announcements calling patients into examination
rooms. The staff dealt with me “one to one” in a kind and informative way. My mate
came with me, and we looked around during our brief wait and saw patients afflicted with
cancer. Some were alone, most were not. There were those who looked frail and ill and,
there were others like myself, who seemed oddly out of place and in apparent good
health. Everything was very ordered. The patients, old, young and in between, came and
went “with minimal delay”, without event.
Oncologists and Oncology Staff
An oncologist is a physician who studies and treats cancer. Their field is a
bombardment of information, research, practical application, and, an endless line of
patients hosting disease that can reach into and confound every conceivable aspect and
functionality of the human body. Oncologists witness the “known and unknowns” of
cancer every day and are there to address these in the best and most effective way
possible.
In your first appointment with the oncologist you can expect to be briefed on your
condition. This doctor will discuss your pathology report and the options of treatment for
your Prostate Cancer. They will also answer any questions you have. If you are unsure as
to how best to proceed after this, you can ask them for another appointment before you
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make a commitment to further treatment. In the interim, you will have time to absorb the
information that you have just been given, research further if necessary, and, decide what
you would like to do. As well, a second or third opinion on the options of treatment can
be sought from oncologists in other institutions.
After my first appointment I was really not at all sure of the options. I had
already gone through surgery and was told I required adjuvant (post-surgical)
chemotherapy. I was not in any way familiar with the proposed drugs to be used in
chemotherapy, methods of delivery and side effects. I was not even so sure as to whether
or not a different approach to treatment was in order. So I asked for a second
appointment and a brief delay so I could research the options of treatment that were given
to me by my oncologist. I came back for next appointment about a week later better
informed and with more precise concerns. After that I went ahead with chemotherapy.
Although your surgical team may be optimistic that they had managed to remove
all the infected tissues, there remains the nagging fact that, at a cellular level, it is
impossible with present technology to say exactly if any cancer cells escaped into the
body, or where or how many of those cancer cells remain. Adjuvant chemotherapy or
radiation is a way to address any cancer that is either known or has a high probability of
having exceeded the bounds of the prostate. This way the chances of “recurrency” are
minimized. Adjuvant therapy is usually started within 6 weeks after surgery. This is
because the effectiveness of treatment to prevent recurrency has been founded on clinical
trials where treatment was started it during that period. Any later and no one is really
sure of how effective it will be.
The timeframe for adjuvant treatments varies with the patient profile and the
treatment type and regimen. For example, in metastic, hormone sensitive PC patients
will undergo Androgen Deprivation Therapy (ADT) as part of standard management. In
some cases continuous and intermittent ADT are both considered viable options.118 This
means that ADT can go on for years.
For those Prostate Cancer patients that are considering Prostate Cancer at a
microscopic level [and everyone should] you should be aware that the general trend for
mainstream medicine in the treatment of Prostate Cancer thus far does not seem to
recognize or apply measures that address Prostate Cancer on a microscopic level until
there is clear indication of primary treatment failure. This indication is usually in the
form of rising PSA following surgery or radiation therapy. Further, it has been pointed
out that cueing on rising PSA after primary treatment inevitably allows metastic PC
recurrence at a very high rate (as high as 70% at the 10 year mark) with certain mortality
from that recurrence if the patient does not expire from other unrelated cause first.119
These facts are some of the most compelling reasons to screen for early stage disease and
intervene in a timely way so that the patient has the best possible chance of cure given the
shortcomings that present treatment protocols have in addressing the obvious aspects of
microscopic invasion and spread of PC.
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So that you know, there are basically two types of cancer therapy. These are
neoadjuvant and adjuvant. Neoadjuvant therapy is given before surgery to make the
cancer tumor or diffuse spread more amenable to surgery by reducing its size. Radiation
therapy or combinations of radiation therapy and chemotherapy can be used to do this.
Adjuvant therapy is given after surgery and is used to increase survivability and reduce
the risk or recurrency. Primary treatment refers to what was first used to address known
cancer. Cancer treatment is either curative or palliative. Curative means that the
treatment intention is to cure. Palliative means the treatment is being given to slow the
progression of the cancer or improve the patient’s quality of life as the cancer proceeds.
There are a number of different strategies of how to treat Prostate Cancer. The
treatment regimens are always evolving, as are the drugs and techniques themselves. As a
result, patients with Prostate Cancer have better support in their fight today than was the
case ten years ago. Still, cancer represents complex dynamic and self–organizing
biosystems.120 It is considered adaptable and often develops resistance to assorted
treatment regimens.121 Your oncologist has the difficult task of finding the recipe that is
effective treatment. Sometimes this may involve combinations of drugs and schedule
that are different from what is prescribed for others undergoing treatment for the same
type of cancer.
Be advised, due to the pace of research and the scope of treatment for Prostate
Cancer, it is a full time job to keep up with what is has been developed, its state of
regulatory approval, its clinical status, and, availability for treatment. Your oncology
specialists are the best ones to consult in this regard. If they do not know of something
you have heard of, then they will likely research it or refer you to someone who does. As
well, because incidence and survivability statistics take years and large samples of
patients to yield meaningful results, the newer treatments simply will not have this kind
of statistics available to support their effectiveness. In short, the “cutting edge” of new
drugs and treatment development, for the most part, proceeds with relatively little
statistical support as to exactly how effective they truly are. So don’t expect any
questions regarding chances of survival or effectiveness to be answered with clear
percentages for these types of treatment.
Some hospitals have the additional aspect of Naturopathic medicine. Naturopathic
strategy can as well be incorporated into cancer treatment regimens and be beneficial to
the fight and recovery. To do this; however, the Naturopathic staff must be working in
communication and concert with your oncologist. In terms of self-administered
naturopathic treatment, consult your oncologist before you supplement the treatment
course they have prescribed with anything else such as vitamins or holistic remedy
or agent. This is especially important because even the most seemingly innocuous and
common of supplements, for example, vitamin C, may have an adverse impact on the
effectiveness of drugs used in your treatment, for example.122
Patients who have undergone primary treatment and are experiencing recurrency
may be candidates for either salvage chemotherapy or salvage radiotherapy. Salvage
means it is not preventative, but, instead is addressing certain recurrency. If one has
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castrate resistant disease that has metastasized, palliative chemotherapy or palliative
radiotherapy are both included in the PC management protocols.123
To assist and deliver the chemotherapy agents are the Floor Nurses in the
Department of Oncology. These are the staff with the greatest empirical exposure to the
patients and treatments of cancer. They administer the chemotherapy treatment for all
types of cancer. As such; they have a broad understanding of the drugs, current trends of
research and development, treatment regimens, delivery strategy, problems with clinical
applications and technique, side effects, and each patient’s response to treatment.
Normally, you will be introduced to the floor staff when you arrive for your initial
consultation with the oncologist. These nurses are a select few that specialize in
oncology. Their focus is to care for and assist cancer patients with dedication and
compassion. Usually the number of oncology floor staff is such that every time you
come back for treatment you will see a familiar face.
Further to the floor staff, you will usually be assigned a Case Nurse. This nurse
will review the details of the proposed treatment with you, ensure that your questions and
concerns are properly addressed, and will likely be your “point of contact and resource”
for anything that pertains to your condition, treatment, recovery and follow up.
Another specialist associated with the Department of Oncology is the
Pharmacologist. This specialist is the expert in preparing and managing the
chemotherapy drugs that are being administered for treatment, as well as the drugs used
to mitigate (soften) the side effects, and any required painkiller. If you have any
questions about your treatment drugs this is the person to ask. Usually, on your first
treatment, you will meet the pharmacologist and they will give you an overview of the
drugs that are going to be administered to you, as well as, answer any of your questions.
For those of you who are prescribed radiation therapy, you will meet the radiation
oncologist and their technical staff to discuss your treatment. These are the experts on
cancer treatment using radiation.
Clinical Testing
Before any agent or technique can be approved for human use in anything more
widespread than research treatment or trials, studies on humans must be conducted that
support the reactive process associated with the introduction of the agent or technique in
treatment. As well, statistical proof has to be made to confirm that the treatment is
effective, and, has benefits that outweigh the side effects. To do this various regulatory
bodies, for example the FDA (Federal Drug Administration) in the United States, oversee
phases of trial or studies whereby agents and regimens are tested. These are called
clinical trials.
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Leading up to any clinical trial is laboratory research and testing on the proposed
agent or treatment. This usually means that some testing has been done using animal
models to ensure that the effects are reasonably predicted, understood and in all
likelihood “safe” prior to exposing humans to it. Common animal models involve mice,
for example. Studies using mice as subjects are called murine studies.
Clinical trials are conducted on humans when the exact effects of the agent or
treatment in trial, as observed on a large number of individuals, has not been proven. As a
result, there can be grave and serious risks involved with participating in such studies.
The agent or regimen or treatment may have no effect at all; or, may have unforcasted
side effects or results. One of the things you should be aware of is that in some clinical
studies comparisons are done on subjects that have had benefit of the treatment, as well
as, subjects that have not. The researchers try to keep “all things equal” between subjects
except the reception of the active agent or experimental treatment. The bottom line is
that you may participate in such clinical studies thinking you are receiving the agent,
when you are in fact not. In the case where you are not given the trial agent, you are
unknowingly participating in the study as part of a “control group” and instead are given
what is known as a placebo. A placebo is something that gives the impression of the real
aspect but is not. The classic placebo for example is a sugar pill that has the same
appearance as the active drug.
The idea of giving the placebo is to account for the
psychosomatic aspect of patient response. In short, control groups rule out the notion that
any benefit is “all in the head”.
Generally, the research is conducted by medical institutions or pharmacological
establishments that have an interest in seeing the agent come to market for wide scale
use. The people that participate are called subjects. The subjects for such studies are
“solicited” by these institutions or establishments. Sometimes the study may call for
healthy subjects or subjects that are already afflicted with disease at a certain stage. An
example of how this solicitation is done can be found on the web page for the Mayo
Clinic, whereby interested persons are provided with a contact name and number of the
individual overseeing recruitment of subjects. Subjects are as well usually
“compensated”. Compensation may be in the form of some small amount of participation
bursary or, hopefully by benefiting from treatment with the new agent or regimen.
Clinical trials in North America are conducted in four phases. The timeframe
involved can be years. The essence of what occurs in each phase of clinical trial is as
follows:
Phase I tests a new drug or treatment in a small group. This involves the initial
studies to determine the metabolism and pharmacologic actions of drugs in
humans, the side effects associated with increasing doses, and to gain early
evidence of effectiveness. The subjects of such studies may include healthy
participants in addition to patients;
Phase II expands the study to a larger group or sample of people. Controlled
clinical studies are conducted to evaluate the effectiveness of the drug for a
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particular indication or indications in patients with the disease or condition under
study and to determine the common short-term side effects and risks;
Phase III expands the study to an even larger sample size. Expanded controlled
and uncontrolled trials are allowed after preliminary evidence suggesting
effectiveness of the drug has been obtained. The intention is to gather additional
information to evaluate the overall benefit-risk relationship of the drug and
provide an
adequate basis
for the
physician
labeling;
and,
Phase IV takes place after the drug or treatment has been licensed and marketed.
Post-marketing studies are used to detail additional information including the
drug's risks, benefits, and optimal use.124
For information regarding clinical trials in Australia/New Zealand consult the site
at: http://www.anzctr.org.au/default.aspx
For information regarding clinical trials in China consult the site at:
http://www.chictr.org/en/
For information regarding clinical trials in the European Community consult the
site at: https://www.clinicaltrialsregister.eu/
For information regarding clinical trials in India consult the site at:
http://ctri.nic.in/Clinicaltrials/login.php
`
For information regarding clinical trials in Russia, former Soviet Republics and
Eastern Europe consult the site at: http://gctrials.com/
In the course of reviewing the literature on the effectiveness of various agents and
treatment regimens one may encounter the expression of a hazard ratio (HR). A hazard
ratio compares the death rate for patients receiving a given treatment, to the death rate for
those receiving no treatment. A hazard ratio of 1.0 means the treatment is ineffective and
gives no apparent boost to assist in fighting the cancer. A hazard ratio of greater than 1.0
means that the treatment is actually making matters worse. Ratios of less than 1.0 mean
the patient’s survival is extended due to the regimen. In short, the lower the HR value is
below 1.0 the greater the regimen’s effectiveness.
Since the 1990’s the treatment of breast cancer with adjuvant chemotherapy has
resulted in substantial improvement of breast cancer survivability. 125 Encouraged by
these results and others, researchers continue to investigate agents and regimen that can
be applied to the adjuvant treatment of Prostate Cancer.
In a review of adjuvant treatment in clinical trial registered in the United States it
is obvious that the greatest research interest is focused on combination adjuvant solution
for those at high risk of recurrency and those with advanced PC disease. 126 Combination
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adjuvant solution is the use of an agent in combination with another or several other
agents or other therapy or procedure; such as, radiotherapy or stem cell transplantation.
Chemotherapy
There are a number of books written that deal exclusively with chemotherapy. For
the purpose of this section, chemotherapy will be considered in more general terms to
lend an overview of the drugs in clinical use for treating PC as well as the more common
treatment regimens. I found the website http://www.chemocare.com, whose content is
provided by the Cleveland Cancer Care Center as part of the Scott Hamilton CARES
initiative, particularly helpful in addressing my questions regarding the details of specific
chemotherapy drugs. My intention here is to provide you with enough information so
you can to have a solid discussion regarding these type treatments with your Oncologist.
Typically, chemotherapy is not prescribed in PC therapy unless someone is at
high risk of recurrency and demonstrating rising PSA; or, is already in a state of
advanced disease.127
It has been suggested that the definition of advanced PC be modified to a more
contemporary definition which would include patients with lower-grade disease and with
an increased risk of progression and/or death from Prostate Cancer; along with those with
widely disseminated metastatic disease.128 Presently, the definition of advanced PC
basically dictates the type and timing of its associated therapy.
Sometimes advanced disease can progress quickly; or, be resistant to hormone
therapy; or, develop resistance to ongoing treatment. These factors along with the overall
benefit in prescribing a chemotherapy regimen to support curative or palliative intent are
all considered by your oncologist.
Chemotherapy can involve one or several drugs depending on each patient’s
disease and profile, as well as, any previous treatment. Sometimes these drugs are
combined with other agents (like Hormonal Therapy) or strategies (like Radiation
Therapy) to enhance effectiveness. Hormonal therapy is designed to target PC that is
known as non-castrate resistant. In other words if one had that type of PC and were to
be castrated, the disease would slow from the immediate reduction in available androgen
hormone.
Generally, conventional chemotherapy drugs are designed to target cells that
exhibit quick growth and development throughout the body. In effect, they not only
target cancer cells but also every other kind of cell that grows rapidly. Amongst these are
normal, healthy, rapidly growing cells such as bone marrow (the producer of blood cells),
mouth and gastro-intestinal membrane linings, hair follicles, and, skin. Side effects are
directly related to healthy cells and systems being impacted by the chemotherapy. The
good news is that the damage to healthy tissue usually begins to repair itself as soon as
the chemotherapy is stopped. Unfortunately, damage to Peripheral Nervous Tissue due to
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platinum based chemo regimens (such as Cisplatin which is now under trial) may take a
couple of years to regain normal functionality. In the interim, you can find yourself
dealing with loss of dexterity, “prickly” sensations or numbness in the hands and feet,
and, subsequent difficulties with balance and foot placement as did I, for example.
Chemo delivery method is varied. These include for example, intravenous
injection (IV), intra-arterial injection, pump or pressurized dispenser, intraperitoneal
catheter or oral methods. Each drug has a preferred method of delivery, so it really is not
so much about what delivery mode you would prefer. Instead it is more about if a
specific drug is used for a particular strategy or regimen, then the necessary mode of
delivery is going to be whatever is most effective.
A session of chemotherapy with a rest period is called the cycle. In order to
ensure sufficient functionality and recovery of the impacted bodily systems, a period of
time between treatment sessions is set. In my case, treatment was initially scheduled to
occur every 14 days over a period of 6 months. A course of treatment is made up of a
series of cycles. Time frame between sessions and the dosage can be adjusted to
accommodate patient response and mitigate the severity of side effects. Length of the
course is variable, and dependant on the extent and location of the metastasis. Sometimes
treatment can last for many months or years in an effort to slow the progress of cancer or
shrink invasive tumor.
Chemotherapy drugs usually have a generic name and one or more registered
trademark names. The generic name is the one that cannot be registered as a trademark.
The trademark name is followed by an ® if officially registered or ™ if not. This name is
specific to a particular pharmaceutical manufacturer. Sometimes the trademark was the
first version of the drug so it is more widely used and recognized. Otherwise the generic
name is used. For Prostate Cancer, some common chemotherapy agents and combined
chemotherapy agents and applications include:
High Risk disease management options
Androgen Deprivation Therapy (ADT) either with or without EBRT
Stage T1-4, N1-3, M+ Hormone Sensitive Disease management options
Medical castration with:
- LHRH analogue (luteinizing hormone-releasing hormone agonist used to
disrupt the release of testosterone); or
- Single agent anti-androgens
Stage M+ Castrate Resistant disease management options
Palliative chemotherapy
- 1st line docetaxel (Taxotere®)
- 2nd line Mitoxantrone; and,
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- Bisphosphonate therapy.129
In terms of vaccine therapy used to boost the immune system there is only one
FDA approved drug called Sipuleucel-T (Provenge®) that is a custom made drug for each
specific patient.130 It is costly and reported to extend survival in advanced PC by
approximately 4 months over a two year period.
There is a number of chemotherapy drugs registered in the United States Trial
database undergoing evaluation as to their benefit in treating PC either as stand alone or
in combination regimen. The list covers a wide spectrum PC type and stage. The
following are some examples:
High risk Local disease
docetaxel (Taxotere®) for neoadjuvant and adjuvant treatment;
docetaxel (Taxotere®), Estramustine Phosphate combination;
docetaxel (Taxotere®) , Zoledronic Acid combination ;
Prednisone;
Mitoxantrone hydrochloride;
docetaxel (Taxotere®), goserelin acetate, leuprolide acetate combination;
docetaxel (Taxotere®), Casodex, and Zoladex or Lupron combination with RT;
Advanced disease
Ixabepilone;
docetaxel (Taxotere®) with 3DCRT;
stem cell transplantation with filgastrim; camustine; cisplatin; melphalan; vinorelbine
tartrate combination;
monoclonal antibody therapy plus chemotherapy then stem cell transplantation;
bryostatin 1, paclitaxel (Taxol®) combination;
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Castrate resistant
interferon alfa; docetaxel and Estramustine; and,
filgrastim, carboplatin docetaxel, Estramustine phosphate sodium.131
Regimens for chemotherapy vary and are not the same from one country or region
or facility to another. For this reason the agents and combinations listed are not in any
way to be considered a complete list.
In terms of delivery method, measures to reduce the trauma of multiple injections
are used when patients are involved in lengthy chemotherapy treatment regimens.
Instead of having to endure the unsavoury aspect of being pricked in the arm repeatedly,
patients are typically given the option of having a “port” or catheter installed. The
advantage of these types of devices is that they stay with the patient throughout treatment
and usually for several months afterward. Any intravenous needles can then be plugged
into mechanical leads serving the port or catheter, which substantially minimizes effect of
the patient feeling like a big pin cushion. Arm catheters are typically installed in the
veins either in the fold of the arm or under the arm below the armpit. I have seen these
installations on other patients and quite frankly I cringe at the idea of having a catheter
planted “long term” in a place that is constantly moving, such as an arm. As well, I am
informed that care must be constantly given to ensure that the arm installation, if not
buried beneath the skin, is not made wet during bath or shower. The dressings for these
kinds of installations are also quite obvious, not so easy to conceal and require constant
maintenance. This may be a consideration for those patients who are still carrying on
with their day to day routine while undergoing treatment. Figure 41 shows examples of
port-a-cath installation on the right side of the chest.
Figure 41. Example of subcutaneous installation of a port-a cath.
source: http://commons.wikimedia.org/wiki/File:Port-catheter.jpg
originator: RecurrentbreastCA.gif
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In my case I elected to have a chest port-a-cath. It was installed underneath the
skin (subcutaneously) by surgical procedure. The port-a-cath typically accesses the subclavian artery feeding the heart, and, once installed and healed into position, it is
relatively easy to forget about. This device is easy to conceal; has no associated
dressings or considerations that preclude the patient from taking baths or showers when it
is not in use; minimizes the possibility of IV infection and thrombosis, and it is relatively
painless. For chest installations, even when being plugging into and out of the port-acath is a relative “non-event” because it is so well anchored that it really does not move.
The only thing a patient feels is a pin prick when being plugged in. As I understand, such
installations can as well be done on the left side of the chest, as well as, the underarm.
The “bulky round thing” that protrudes under the skin is the port disc where the delivery
needle can be poked into to administer drugs. The line or tube leading upwards from the
port ties into an artery near the base of the neck in this installation and remains attached
for as long as the device is in the patient.
It has been my experience that when the patient is scheduled for their first session
of chemotherapy they undergo the installation of a port or catheter. Installing the port-acath is a surgical procedure done in the Department of Radiology with local anaesthetic.
This is because the surgeons use radiographic imagery to connect the port-a-cath to the
artery. Imaging minimizes the size of the incision necessary for the procedure. As soon
as the surgical procedure for installation was complete, I walked down the hallway to
start my chemotherapy. One thing though, the first “plug in” is not really felt because it
is done while the anaesthetic for the surgical procedure is still very much effective. This
is not the case for the first “unplug”. Expect that the first unplug will be a bit “tender”
because it will be only days after the installation of the port-a-cath and the area still has
stitches or staples and has yet to heal and the needle for the portable bottle of chemo
drugs is really well anchored in the port-a cath disc and so requires it a bit of a tug to
unplug. Other devices that are commonly used in chemotherapy are PICCs (Peripherally
Inserted Central Catheters) or central venous catheters. These are also known by
manufacturer names like the Groshong® or Hickman® catheters. Figure 42 shows an arm
installation of a central venous catheter.
Figure 42. Example of a central venous catheter installed in the arm.
source: http://visuals.nci.nih.gov/retrieve.cfm?imageid=4489&dpi=300&fileformat=jpg
originator : National Cancer Institute, Rhoda Baer (photographer)
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The main disadvantage with this type of access device is that it is not buried under
the skin. This makes the opening into the body around the catheter much more
susceptible to infection. This type of catheter is typically used as a shorter term access
installation to support treatment such as a 5 week RT/Chemo course. It can be installed
in the arm as well. Shorter term regimens lasting approximately a month typically do not
require any port installations.
Chemotherapy is not given in dosages that “kill” all the rapidly growing cells at
once. Instead, dosage is balanced in such a way as to ensure the cancer cells are
destroyed over a period of time, while minimizing the “nasty” side effects associated with
chemotherapy impact on normal, healthy cells.
As I found out, the patient can expect that the side effects become progressively
worse the further along the course of treatment is. The reason for this is two-fold. First,
it takes a while for the body to process some of the drugs. If processing time is longer
than the time between treatment sessions then there can be a cumulative effect that
results in more severe side effects. Second, depending on the drugs used, the extent of
healthy cells being impacted can be substantial if the course of treatment is prolonged. In
simple terms, there is not enough time between cycles to regain 100% functionality for
the healthy cells that have been impacted.
The side effects for Prostate Cancer chemotherapy regimens are varied. Each
drug has its own set of side effects. Side effects can be further compounded when
combination strategies are used. The nursing staff is constantly being challenged to keep
ahead of the onslaught of new drugs and each drug’s specific “alert signs” for patient
distress during treatment. One of the things you will be asked at each treatment is what
side effects did you experience from the previous session. It is therefore important for
you to keep a record of this. Write down the date, what you experienced in terms of the
side effect, and how long it lasted. Bring this with you every session. This will assist the
medical staff in making suggestions to minimize the side effect(s). At the beginning of
my course, one floor nurse who happened to be on her last day before retirement smiled
at me and said, “We have a recipe for every side effect.”
Side effects for the common PC chemotherapeutic regimens depend upon the
agent(s) involved, their combinations with other types of treatment, patient profile, as
well as, patient response that can change throughout the course of treatment. Some
patients may only experience one or a few of the listed side effects associated with a
particular agent. Other patients may experience more. For those who have gone through
conventional prostate chemotherapy, fluid retention with weight gain; swelling of the
ankles or abdominal area; peripheral neuropathy (diminished dexterity from numbness or
prickling in finger and toes); nausea; vomiting; diarrhea; loss of appetite; mouth and lip
ulcers; anemia related fatigue and weakness; infection; hair loss; muscle/bone joint pain;
increased risk of bruising and bleeding (from low platelet count); finger and toenail
aberrations (purple coloration, ridges and weakness);132 and, heart rhythm
abnormalities133 are all reported occurrences. Your oncology pharmacologist can give
you a more precise and comprehensive list of the side effects associated with each agent
involved in your proposed treatment regimen.
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My adjuvant chemotherapy for CRC was platinum based and I had a number of
these side effects. I see that Cisplatin is being investigated in trial for possible benefit in
treating PC. Cisplatin is one of the platinum based drugs. In my case, some of the
effects, like diminished dexterity; purple digits; and, prickling in the extremities, lasted
more than a year after my treatment had ended.
Nausea is something that occurs naturally when the body “believes” it has been
poisoned. Some say this is one of our “preservation” behaviours. The idea being that a
quick response rejecting the contents of the stomach should remove the source of poison
if it was something “bad” that was swallowed. As some of us have no doubt experienced,
this usually accompanies excessive alcohol intake when “throwing up” makes most
people begin to feel better. Nausea, however, is not very effective solution to poisonous
stings, snake bites and chemotherapy. When certain agents of chemotherapy are
introduced, the body responds by producing higher levels of a neurotransmitter called
serotonin. Serotonin is responsible for stimulating vomiting. In any event, the thing
about most side effects is that they don’t last. So you can expect improvement and
gradual return to normal as soon as the chemotherapy is arrested and you have had a little
time to recuperate. Besides, the oncology pharmacist knows about this nausea and
usually has effective anti-nausea countermeasures.
When you proceed to chemotherapy with an IV delivery you will usually arrive
on the day of each new cycle at the oncology department where you will receive the
cycle. Delivery usually involves sitting down in a room in a comfortable chair alongside
of others who are being treated that day. The nurse assigned to you will verify your
prescription and then properly “Plug you in” for delivery. Beside you will be an IV rig
with several liquid filled bags dripping into their respective line “feeds”. Some of these
will be the chemo agents, and others will be the “carrier” solutions for the chemo agents.
I suggest that you bring something to do because the time there passes slowly.
Carrier solutions, for example 5% Dextrose (a solution of distilled water and
dextrose sugar) or 0.9% NaCl saline (a solution of distilled water and the salt called
sodium chloride), are fed by IV at the same time as the chemo agents. Each chemo agent
has its preferred carrier solution. The carrier solution is designed to assist in the
circulation and absorption of the chemotherapy. To control nausea and vomiting usually
an antiemetic (anti-nausea) such as Granisetron (Kytril®) and a corticosteroid will be
administered to you before the chemo drip is started. Granisetron is in a group of
medications called 5-HT3 receptor antagonists. It works by reducing the levels of
serotonin.134
When chemo agents are delivered by IV, sometimes it may involve, for example a
two hour “drip” in the hospital. After this, more chemo agent may be delivered via a
small pressure dispenser over the next 46 hours. The agent, in the small pressure
dispenser, is generally taken home and worn in a pouch until empty. At that time, a nurse
at a local clinic with a prearranged appointment can remove and dispose of the bottle
with the appropriate medical considerations. It is important that trained medical staff is
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involved in the unplugging and removal of such a chemo pressure dispenser. The reasons
for this are as follows:
1) Depending on the drug used there may be a potential to cause irritant
reactions at the injection site or vesicant reactions if leaked onto either the
patient or the caregiver’s skin. An irritant reaction is usually short lived and
involves patient symptoms such as redness along a vein or at the injection site,
warmth, and, soreness. Vesicant reaction is the more severe and can be
delayed for 6 to 12 hours after the leakage onto the skin. Symptoms include
redness, blistering, itching, pain and severe skin damage if the appropriate
immediate action is not taken;
2) The agents introduced to your body during chemotherapy make your bodily
fluids “cytotoxic”. What this means is that they are toxic to normal cells so
anyone that is not being treated must not be exposed to them; and,
3) In unplugging the port- a-cath the nurse has to properly irrigate the port-a-cath
site and line with the anticoagulant heparin, as per the directions of your
attending oncologist. It is important to ensure that they see visible blood
backflow in the irrigation syringe to minimize risk of embolism (a wandering
mass) or the introduction of air bubbles via the port-a-cath into your
bloodstream. An embolism, depending where it migrates to, can cause all
sorts of complications including death.
The effectiveness of the chemotherapy and its impact on the blood components,
electrolytes, and tumor markers are monitored with blood work (usually performed the
day before each chemotherapy session). You will likely find that your oncologist is not
too concerned with the ups and downs of tumor markers. The fact is that such markers
can have erratic counts throughout the course of treatment. What is important is the end
result. So do not get overly fixated or concerned about such things. Do, however,
consider what you can do to keep your white (neutrophil) and red blood cell counts up.
During the course of treatment, expect that platelets are going to be “hit hard” and
decrease in count. In the blood, platelets last 7-10 days when they are effective in their
blood clotting role before they are removed by the liver or spleen. Normal platelet count
is 150,000 – 450,000 per microliter.135 If the platelet count goes below 20,000 per
microliter there is a potential risk of spontaneous bleeding. This condition is called severe
thrombocytopenia.136 The options, in this case, are either a platelet transfusion or
stopping treatment for a period to allow the bone marrow to recover and replenish the
platelet count.
The platelet transfusion is delivered by IV either through a vein in the patient’s
arm or, if a catheter or port-a-cath is installed, via these. A unit or bag of platelet serum
takes 15-30 minutes to receive. One bag may be enough depending on the patient’s
initial platelet count.137
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The conventional drugs of cancer chemotherapy can basically be categorized into
five groups based on how they work and their chemical structure. These groups are
alkylating agents, anti-metabolites, anthracyclines, topoisomerase inhibitors, and mitotic
inhibitors. These are not all of the groups of chemotherapy agents but they do comprise
what is known better as the conventional groups. Some of the agents actually fall into
two or more categories. In any case, the following is a summary of each group of
conventional chemotherapy agents:
Alkylating agents are a group of drugs that work by damaging DNA, and, so they
inhibit cell reproduction. These drugs are called non-specific in that they affect the cell
no matter what phase the cell is in its cycle. This group of agents or drugs are used to
treat many types of cancer including breast, lung, leukemia and colorectal. One of the
facts of alkylating agents is that their action on DNA can cause long term damage to the
bone marrow. With this there is a risk of inducing a secondary cancer called leukemia
that increases with the strength of dosage received. The appearance of leukemia is
highest 5 to 10 years after having received chemotherapy involving alkylating agents.
Grouped in with alkylating agents (because they kill cells in a similar way) are the
platinum based drugs such as Cisplatin (Platinol®). These drugs are less likely than the
alkylating agents to cause leukemia.138 Estramustine (Emcyt®) in combination with
estradiol is an example of an alkylating agent used in treating advanced Prostate
Cancer.139
Among its side effects of Cisplatin is the short term impact on the peripheral
nervous system. This is known as peripheral neuropathy. When I went through
chemotherapy for CRC I experienced this peripheral neuropathy as a result of the drug
Oxaliplatin (Eloxatin®). What this meant for me is that I experienced symptoms like
tingling in the fingers and toes that was further aggravated by a greatly increased
sensitivity to cold. As well, the ends of my fingers and toes where the tingling was most
severe turned a purple hew and remained that way for a good long while after the course
of treatment had ended. It has taken the better part of three years to regain my normal
coloration. I also had a “metallic” taste in the mouth and prickly feeling in the throat
which was made worse by drinking any cold liquid especially if it was sweet. The
surface of my tongue would feel like it had been burnt by hot liquid. My hands would
become unsteady and I experienced reduced manual dexterity. Also, my calves would
ache as though it was the day after I had done a hard work out on that muscle group in the
gym. When first started chemo all of these symptoms would begin during session and
initially last a week or so after. As the treatment went on such side effects intensified and
never left between sessions. During that time I would lose complete interest in drinking
anything cold or remotely sweet (such as orange or sugared cranberry juice). This was a
problem because one of the things about the recovery period in between sessions is that
you have to keep your fluids up. The solution was to drink warm soups and green tea
instead.
Anti-metabolites are a group of drugs that interfere with the production of cell
DNA and RNA by occupying sites on the unzipped replicating template reserved for the
nucleotide building blocks. The agents act during the synthesis or S phase of the cell
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cycle (see Figure 16).140 They are commonly used to treat breast cancer, as well as,
leukemias, colorectal and ovarian cancers. Examples of such gents used in Prostate
Cancer treatment include Capecitabine (Xeloda®) and, 5-Fluorouracil (5-FU).141
Capecitabine (Xeloda®) is a pill form of 5-fluorouracil which is usually administered
intravenously. One of the side effects of capecitabine involves a hand and foot syndrome
which causes pain, redness, dryness and swelling to the point where the patient has
difficulty with everyday normal activity.
Anthracyclines are another group of chemotherapy drugs that are used on a wide
variety of cancers. These are effective during all phases of the cell cycle except G0 (the
sub-phase where the cell does not replicate). They work by interfering with enzyme
production that is essential for DNA replication. One consideration in the use of drugs
from this group is that they can cause permanent damage to the heart if given in high
dosage. Consequently, lifetime dose limits are placed on these drugs. 142 Mitoxantrone
(Novantrone®), also known as DHAD, is an example of an anti-tumor antibiotic
anthracycline. Its delivery is by IV.143
The next group of drugs is called Topoisomerase inhibitors.144 In order to
replicate the DNA strands have to “unzip” and separate into two daughter cells.
Topoisomerase I and II are enzymes that assist in this unzipping. In simple terms,
Topoisomerase inhibitors work by interfering with the topoisomerase enzymes so that the
DNA strands cannot unzip and make copies. 145 This group of drugs is commonly used to
treat some leukemias, lung, ovarian, and gastrointestinal cancers. 146 There is a suggested
benefit reported by a study investigating use of the Topoisomerase I inhibitor Irinotecan
(CPT-11 or Camptosar®) in combination therapy with cisplatin for small cell carcinoma
of the prostate. 147
A common and major concern with the use of Irinotecan is the side effect of
severe diarrhea that can occur a few hours or days after drug reception. If left unchecked
the subsequent severity of the diarrhea can cause serious chemical imbalance and/or
dehydration to the point of being life threatening. 148
To let you know how quickly dehydration becomes fatal I had a colleague who
went into remission for stage III CRC at the same time as me. Three years later he had a
relapse and so left work the first week of December to be treated for a stage IV condition.
Within a couple of weeks after starting chemotherapy he experience severe diarrhea that
for some reason was left unchecked. I corresponded with him two days before Christmas
and he said everything was going well. This was before the diarrhea. Sadly, he passed
five days later from dehydration. In short, dehydration is to be taken very seriously.
Mitotic inhibitors are a group of drugs derived from natural products such as
plant alkaloids. These drugs typically are most effective in the Mitotic (M) phase of the
cell cycle (see Figure 16); however, they can damage cells in all phases. They work by
inhibiting the production of a protein called tubulin which is involved in a number of the
cell’s structural components and in mitosis. As such; these drugs can stop mitosis from
occurring. This group of drugs is used to treat a number of cancers including breast,
myelomas, lymphomas, leukemia and lung cancer.149 Included in this group of drugs are
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the taxanes for example docetaxel (Taxotere®) which is a common PC chemotherapeutic
agent used in advanced disease treatment.
Something you should be aware of is that Mitotic inhibitors are known for their
potential peripheral nerve damage as a side effect. Such side effect has to be managed by
limiting the dosage of this type of drugs. 150
When I was undergoing chemotherapy my oncologist prescribed
Prochlorperazine to reduce any short term effects of nausea. When I researched it I
found that prochlorperazine is as well prescribed as an anti-psychotic drug in much
higher dosages than those used for the treatment of chemotherapy related nausea. Among
the list of serious side effects for this drug I found that it could cause irregular heartbeat
and seizures.151 I decided not to take any of this anti-nausea/anti-psychotic medication as
I reckoned “the fewer drugs I had floating around in me the better”. Neither did I like the
idea that I could be launched into a seizure at times when I was for the most part alone.
Instead, I found that the nausea would typically diminish if I ate something. In the event
that the nausea became “more than a nuisance”, I would take a couple of over the counter
Philips Milk of Magnesia tablets and everything settled right down. It is likely that what I
did will not work for everyone, but it may be worth a try.
As far as the other side effects go, the mouth sores I addressed with a drop of
over the counter methlyn blue touched to the ulcer at night, and, salt water rising 3 to 6
times during the day. The gritty feeling of the eyes improved with the more liquids I took
in. Cold water splashed in the eyes provided relief if I woke with this gritty feeling. The
other side effects just ran their course.
Non-Conventional Chemotherapy
Hormone therapy, also called Hormonal Therapy or Androgen Deprivation
Therapy or Androgen Suppression Therapy. This therapy uses several strategies to slow
or stop the growth of hormone sensitive PC cancer by either blocking the body’s ability
to produce the androgen hormones (more specifically testosterone; and/or.
dihydrotestosterone) OR by interfering with the hormone’s action that is necessary for
prostate tissue (healthy or cancerous) to grow. It only works on PC that is hormone
sensitive. This means that the PC is not castrate resistant (also known as refractory).
Such treatment is used for androgen sensitive high risk; metastic; recurrent; or,
progressive PC. Some doctors recommend intermittent ADT. Intermittent therapy means
the treatment is periodically stopped then restarted. This practice presumably improves
patient quality of life in terms of sexual function.
Prostate Cancer response to a testosterone suppressing serum was first reported in
1941 by two researchers Huggins and Hodges. Beginning in 1971 and over the next three
decades a number of LHRH agonists were developed and put into clinical use. These
drugs work by blocking the pituitary gland from producing the precursor hormone that
cues the production of testosterone. Leuprolide; Goserelin; Triptorelin; and, Histerlin are
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all commercially available LHRH agonists in clinical use today and are typically used to
treat metastic and advanced PC.152
When LHRH agonists are first used the immediate result is called a “flare”
response where testosterone levels in the patient actually balloon. This not only
aggravates the symptoms in advanced disease but can also be fatal if somehow prescribed
for voluminous metastic PC. Voluminous metastic PC just means the disease is quite
advanced and affects a lot of the body. After the flare the testosterone levels diminish to
near zero which is the intent of the therapy. These days the flare response is preempted
by prescribing an anti-androgen agent before starting LHRH therapy. Other concerns in
the use of LHRH agonists in therapy are side effects which include hot flashes; erectile
dysfunction; lack of libido; musculoskeletal impact (reduced strength and osteoporosis),
hematologic impact (anemia) and cardiovascular impact leading to assorted related event
and affliction. Men who are being treated with LHRH therapy are advised to make
lifestyle changes to compensate and minimize these side effects. This means stop
smoking; decrease alcohol intake; and, perform resistance exercise while taking calcium
supplement to keep bone density levels up.153 Caffeine intake should as well be decreased
because it too has been reported to cause bone loss.154
Consider having a close look at the contents list on the bottle of any calcium
supplement. Calcium is an element which is marketed in several forms in supplements.
Calcium carbonate and calcium citrate are the most common forms. Other forms found
in supplements are calcium gluconate, calcium lactate, bone meal and hydroxyapatite.
Coral calcium is simply calcium carbonate. Hydroxyapatite is a second generation bovine
(cow) “bone meal” supplement that presumably has managed to exclude contaminants
that were associated with plain bone meal supplements. Vitamin D level is an important
player in calcium absorption. Vitamin D deficiency substantially impacts the ability to
absorb calcium. Calcium carbonate requires an acidic environment to be absorbed and
optimal absorption occurs if taken at mealtime. Calcium citrate does not require this
acidic environment; so, it is the best supplement option for those who are
supplementing outside of mealtime or those who have suspected achlorhdydria,
inflammatory bowel disease or absorption disorders. Calcium citrate may also be a way
around gastro-intestinal supplementing effects of calcium carbonate such as gassiness and
constipation. Total daily intake of calcium for adult men and women (don’t forget that
calcium is derived from food intake as well) should be no less than 1000-1200 mg/day
and not exceed 2500 mg/day. 155
Inappropriate calcium supplementation with or without vitamin D is associated
with elevated incidence of irregular cardiovascular behavior such as myocardial
infarction and heart attack.156, 157 As well, calcium has the potential to interact with other
medications that are being taken.158 In short, your physician has to know what you are
supplementing with and follow up with the appropriate tests to ensure that your blood
calcium levels, heart and bone density are responding in an acceptable way.
Depending on the origin of the supplement, manufacturers of dietary supplements
may or may not be required to comply with any government standard. It is important to
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look for a seal which indicates an independent overseeing body has verified that the
supplement product is in fact what is labeled. Examples of such overseeing organizations
in the United States are the USP (U.S. Pharmacopeial) and ConsumerLab (CL); and, in
Europe it would be EP (European Pharmacopoeia).
Another type of hormone therapy involves the prescription of Anti-androgens.
There are two types of anti-androgen agents. One type inhibits androgen production in
the adrenal glands.
These include ketoconazole; assorted corticosteroids and
aminoglutethimide. Anti-androgens are typically administered at the time of biochemical
disease progression. 159 This means that biomarker levels, such as PSA, begin to increase
indicating a relapse of PC following primary treatment. Examples of anti-androgen drugs
are flutamide (Eulexin®, Drogenil®); nilutamide (Nalandron®); and, bicultamide
(Casodex®).
Common side effects of androgen suppression drugs include:
- Hot flashes;
- Loss of bone density
- decreased levels of HDL (good cholesterol);
- Loss of muscle mass;
- Weight gain;
- Decreased mental alertness;
- Fatigue and depression;
- Gynecomastia (breast development);
- Anemia;
- Sexual dysfunction and loss of libido. 160
Estrogen therapy used to be a mainstay of hormonal therapy; however, they have
been associated with inducing significant cardiovascular toxicity and so have fallen out of
favor. 161
Ultimately advanced disease PC finds its way around hormonal treatment in all
patients and progresses to end stage. In short, the benefit of hormonal therapy is in
prolonged survival not cure. 162
Castrate resistant PC (CRPC) is defined as progressive disease that persists with
less than 50 ng/dL testosterone detected. Post-castration levels of testosterone are usually
somewhere below 20 ng/dL. A number of targeted and immunotherapeutic options are
being assessed in clinical trial for survival benefit for CRPC patients in terms of
secondary therapy and perhaps even tertiary therapy scenarios.163
Targeted therapy uses a group of drugs that attack cancer cells more specifically
than conventional chemotherapy drugs can. Such research and the development of
effective PC specific drugs are footed in the better understanding the internal processes
and genome of the targeted cancer cells. “Target specific drugs” attack by recognizing
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mutant or modified versions of specific genes; or, cells that are expressing too many
copies of a particular gene.
Two examples of target therapy drugs in trial for CRPC are Abiraterone which is
delivered orally and is a targeted androgen inhibitor; and, MDV 3000 which is a drug that
targets androgen receptor function.164
Most recently is the reported effectiveness of a targeted drug conjugate (PSMA
ADC) involving a protein that binds to the surface of Prostate Cancer cells as a way to
deliver the drug monomethylauristatin E (MMAE) to the PC. This conjugate targeted
therapy has just completed its phase I clinical trial. Once the conjugate binds to the
surface of the cancer cell the MMAE is absorbed by the PC cell causing its death. Antitumor effects occurred in approximately 50% of the trials patients who had previously
undergone up to 2 prior failures in chemotherapy and hormone therapy. Phase II clinical
trial involving 75 patients is underway and being overseen by researcher, D. Petrylak
M.D. of Yale University Medical Center. 165
Anti-tumor antibiotics are another group of chemotherapy drugs that are derived
from a “strain” of microorganism called Streptomyces. These drugs act in a number of
ways. For example, such action includes causing breakages in a cell’s DNA; or, blocking
the synthesis of DNA and RNA. These drugs work in all phases of the cell cycle.
Unfortunately, they again also affect healthy cells and so have a range of side effects. As
stated, Mitoxantrone is an example of an anthracycline anti-tumor anti-biotic that has
clinical approval and is typically used as a second line palliative treatment in advanced
PC.166 Mitoxantrone plus prednisone is reported to reduce pain and improve the quality
of life in men with advanced CRPC; however, it does not improve survival. 167
Corticosteroids are a group of drugs that are used in chemotherapy, and, in the
treatment of nausea side effects as a result of chemotherapy, among other uses. These
compounds are produced naturally in the outer layers of the adrenal glands called the
adrenal cortex. Humans have two adrenal glands. They are attached to the top part of
each kidney. Cholesterol is a necessary component in the synthesis of corticosteroids.
The quantity of corticosteroids required for medical purpose requires that these drugs are
manufactured artificially outside of the human body by pharmaceutical companies.
Prednisone is a specific type of corticosteroid that is used in the treatment of
advanced PC.168 It has anti-inflammatory properties and can be used to decrease the
swelling around tumors in the spine, brain or bone. The way corticosteroids work in this
capacity is by inhibiting infection fighting white cells from making their way to infected
areas in the body. This decreases the pressure on tumor aggravated nerve endings and in
so doing gives relief from pain in advanced disease, for example; however, it also makes
someone more susceptible to infection. 169
Another group of chemotherapy drugs are those called differentiating agents.
Remember the higher grade the cancer cell the less “differentiated” it is. When there is a
lack of differentiation, the cell from a specific area or organ loses its mature, healthy
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distinctness and functionality. Differentiating agents cause cancer cells to mature into
normal cells.170 As an example of differentiating agents presently under investigation for
Prostate Cancer, researchers have reported that a combination of isoflavone and 3,3′diindolylmethane (DR-DIM) substantially inhibits the signaling that promotes cell
differentiation in PC bone metastasis. 171
In an effort to minimize the impact of non-specific chemotherapy drugs on
healthy tissues, two strategies for drug delivery have been developed. Intra-Arterial
Chemotherapy (IAC) is considered a regional chemotherapy technique that allows
chemotherapy drugs to be concentrated directly in the area of a tumor. If the Prostate
Cancer has metastasized to the liver, IAC delivers anti-cancer drugs directly to the liver
through the hepatic artery. Chemoembolization is a more enhanced form of intra-arterial
chemotherapy also uses microspheres to temporarily block the flow of blood to the
tumor. A microsphere is a very small (2 one millionths of a meter or 2 microns) globule
made up of long repeating chains of proteins or polypeptides and formed into a biological
membrane that contains no genetic material. The result traps chemotherapy drugs in the
area of the tumor and so helps to target the treatment area.172
An antigen is a substance or foreign substance that causes the body’s immune
system to produce antibodies. Antibodies are produced in the blood and made in
response to antigen invasion. When made by the body, antibodies are specifically
designed to attack the particular antigen that caused the antibody to be made.
Antibodies are capable of functional interference of the enemy’s essential
biological pathways; they can signal cellular toxic response; they can signal or activate
other systems in the body to assist in the battle; and, improve the uptake efficiency of
other cells (phagocytes) designed to “consume” the invading substance. The production
of antibodies is our immune system’s custom response to address specific invasion. They
are the “hands-on” Field Marshals of your body’s natural defense system.
Immunotherapy drugs are given to stimulate a patient’s natural immune systems
so as to more effectively recognize and attack cancer cells OR boost an immune system
with immune system components. These drugs focus on cancer vaccines, targeted
immunotherapy, and non-specific immunotherapy.173
One of the biggest challenges with immunotherapy drugs is to identify a common
or set of common antigens specific only to PC or PC tumor surface molecules that can
serve as targets. 174 Knowing this would allow researchers to develop antigens that
specifically attack PC cells.
To date, a number of antigens and “overexpressions” have been identified that are
related to PC; however, almost all of these are found either in healthy prostate tissue
and/or tissues from other parts of the body, as well as, PC cells. 175 As such; antibodies
cueing on these are not efficient and can impact healthy tissue.
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Even so, the development and approval of immunotherapy drugs that provide
some survival benefit is ongoing. For example, the immunotherapy drug Sipuleucel-T
gained FDA approval for treatment of asymptomatic or minimally symptomatic CRPC.176
Promising research is investigating the possibility of developing immunotherapy
that cues on a substance called Survivin. Survivin is an inhibitor of cell death (apoptosis)
and promotes proliferation (cell growth). Both of these qualities are essential to any
cancer. Survivin is widely expressed in a number of cancer’s including PC. As well, it
is something that is almost completely absent in well- differentiated adult tissues. 177
As stated, there are approximately 50,000 to 100,000 genes in the human genome.
Decoding the genome and understanding the effects and impact of changes to the content
and order of specific genes relating to a beneficial cancer therapeutic response is a
colossal task.
Recently advances in decoding the complex genomes associated with breast
cancer are becoming more successful in identifying changes in genes and the genetic
signatures of cancers. As well, technology is approaching methods that can safely deliver
genetic solution with specific results and no side effects. Still the results have yet to
make their way into the clinical applications of main stream medicine with widespread
impact on any cancer.
In the meantime, the suitability of targeting cancer with gene therapy remains a
challenge since the consensus is that cancer is a culmination of a multi-step process that
involves a variety of somatic gene alterations or mutations.178 In short, it is not just a
simple matter of finding “the cancer gene” and sorting it out. As such; gene therapy
strategy is investigating several approaches in research and clinical trial with varying
degrees of success.
These approaches generally fall into five groups. The following is a brief
summary on each approach:
Enzyme/ prodrug systems (Suicide Gene Therapy) – involves lacing a tumor with
an agent that can either inhibit or destroy the tumor when in the presence of
activation enzymes. This agent is called a prodrug. The activation enzymes are
supplied by non-human genes that are introduced to cause the short term
activation of the prodrug and subsequent tumor arrest;
Gene correction therapy – are those strategies aimed at correcting imbalances
between tumor suppressor genes and genes that give rise to tumors called protooncogenes. This is done by introducing a tumor suppressor gene OR by
deactivating the proto-oncogene;
Note to clarify: a proto-oncogene is a normal gene that when mutated contributes to
cancer.
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Immune-gene therapy - seeks ways to genetically promote a better immune
system response in the body either by making cancer cells more “visible” to the
normal mechanisms that typically act on and destroy them is a healthy human OR
by introducing non-human genes that result in boosting cancer specific immune
response;
Drug resistance gene therapy - the use of non-specific chemotherapy drugs is
highly toxic to the body. The impact of such treatments on healthy cells limits
dosage and effectiveness of the drugs used to combat cancer. The idea behind
drug resistance gene therapy is to introduce genes that will make the healthy cell
population more resilient to non-specific chemotherapy drugs; and,
Chemo-gene therapy - is the approach that attempts to enhance the effectiveness
of chemotherapy agents by introducing genes that modify specific cellular
expressions or productions.179
Gene therapy trials have been underway since the early 1990’s for PC. In spite of
encouraging results, an effective gene therapy strategy for PC has yet to be realized.
Recently, an immune gene therapy approach involving the use of a thyroid gland gene
NIS as a vehicle that can be transplanted in PC cancer cells is proceeding to Phase I
clinical trial. The NIS gene gives the thyroid the ability to uptake and concentrate iodine.
When the NIS gene is transplanted into PC cells and exposed to radiation laced iodine PC
cell death occurs resulting in prolonged survival benefit. 180This could have curative
implications for PC and other cancers as well.
Advances in understanding the genetic makeup of breast cancer are ongoing and
have yielded some interesting results that may eventually apply to PC research. Recently
a team, co-led by Dr. M. Ellis, genetically analyzed 348 tumors from women with breast
cancer. From this analysis, four distinct subtypes of breast cancer based on common
genetic disruptions were reported. These are luminal A; luminal B; HER2; and, basallike. In light of this discovery, Dr. Ellis suggests that tumors should be classified and
treated by the genes that are disrupted instead of by where they are located in the body.181
In other words, it doesn’t matter where in the body the cancer starts, what matters is what
genetic changes have occurred that makes the cancer occur, and allows it to defeat
immunoresponse and progress. This suggestion, if correct, could have enormous impact
in the study and treatment of all cancer.
A current theory suggests that most, if not all malignancies, are the result of a
sub-population of “stem cell like” tumor cells. To simplify, the theory is that cancer cells
are produced from their own set of stem cells. The development of therapies specifically
targeting cancer stem cells represents a strategy to completely eradicate tumors and
potentially lead to cure, even in advanced-stage disease. As well, the identification of
cancer stem cell markers have potential for use in early detection and in being able to
provide valuable predictive and prognostic information.182
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For those of you not acquainted with the notion of a stem cell, normal stem cells
can be found in embryos or in adult humans. In the human embryo these cells have the
ability to change into any kind of specialized embryonic tissue. Embryonic stem cells
can give rise to the full spectrum of organs and tissues found in a mature adult. Adult
stem cells are not as “capable” as the embryonic ones. Adult stem cells act as the body’s
repair system and allow for cell replenishment in tissues that have cell turnover such as
blood and skin.183
In May 2012 researchers at the University of Texas Anderson Cancer Center have
identified Prostate Cancer Stem Cells. These PC stem cells feature low PSA level
expression. As well, the PC stem cells thrive in an androgen low environment; divide
slowly and so have an ability to resist chemotherapy; and, when they divide they make a
copy of themselves, as well as, a PSA positive cell. The PSA positive PC cells divide
rapidly (making them vulnerable to chemotherapy); divide making only one copy of
themselves; and, require androgen to progress. This research outlines a need to develop
therapy that will target PC stem cells. 184
Radiation therapy
Radiation therapy or radiotherapy is used as a way to control malignant cells
using ionizing radiation. Radiation therapy can be tailored for therapeutic or palliative
treatment. Therapeutic treatment means that there is a survival benefit to the patient and
the treatment may well be curative. Palliative treatment means that cure is not possible
and the aim is to control or slow the disease or reduce symptoms.
The intent of the therapy, as well as the “how” and “when” it is delivered depends
on a number of variables including tumor location, type and stage of the cancer, patient
age and general health, the patient’s treatment history and whether or not additional or
other treatment will be required, for example. Radiation therapy has a number of different
strategies and can be delivered before (neoadjuvant), during (intraoperative) or after
surgery (adjuvant). 185
Radiation works by damaging the DNA of the cells that absorbs it. The idea is to
so damage the cancer cells that they either cannot reproduce or simply die. The problem,
however, is that radiation damages non-cancer cells too. Therefore, a number of different
delivery strategies and techniques are used to minimize this “collateral damage” to
healthy normal cells that are in the path of the radiation and surrounding area of the
targeted cancer.186 The actual irradiation is totally painless.
Tumor cells typically have an inability to maintain higher levels of oxygen. As a
tumor grows its vascular system typically becomes choked and unable to develop at a rate
to keep up with the rest of the rapid tumor growth. This poor vascular development
equates to low oxygen levels in the cancer cells. Low oxygen levels in tumor cells
actually give them a resistance to radiotherapy. This is because the DNA damage caused
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by the radiotherapy is most likely to become permanent only when cellular oxygen levels
are high.187
The radiation used in conventional radiation therapy involves photon particles and
is measured in and unit called a “gray” or Gy. Radiation is delivered either by external
beam or some kind of injected radioisotope. Medical radioisotopes are short term
radioactive materials can be introduced into the patient for treatment which then decay
rapidly (within a few weeks or months) to low emission levels.188
Figure 43 shows an example of an external beam radiation delivery system.
Figure 43. External Beam Radiation Delivery system with patient in position.
source: http://en.wikipedia.org/wiki/File:Radiation_therapy.jpg [modified]
originator : D. Wakulchik
Over the years, radiation therapy has branched into specialized modes of delivery
to minimize damage to healthy tissue. For external beam delivery, there is 3Dimensional Conformal Radiotherapy (3-DCRT). 3-DCRT involves photon radiotherapy
delivery in which several radiation beams are adjusted and shaped to fit the profile of the
targeted tumor. This reduces the relative toxicity of radiation to the surrounding normal
tissues, and also allows a higher dose of radiation to be delivered to the tumor than
conventional techniques could allow.189
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Intensity-Modulated Radiation Therapy (IMRT) is the next generation of photon
radiation delivery and features improved calculation of beam numbers, angles and dosage
compared to 3-DCRT. 190 The goal is to be able to address tumors with more accuracy
and minimize the exposure of healthy cells to the radiation.
Further to the new equipment and technique developed to minimize the amount of
collateral tissue damage associated with “poor aim” is the use of real-time imaging
combined with real-time adjustment of the therapeutic beams to enhance photon beam
accuracy and focal point. This new technology is called Image-guided radiation therapy
(IGRT). This is also referred to as “four-dimensional radiotherapy”.191
Proton Therapy (PT) involves a different kind of radiation that does not use
photon beams. Instead it uses proton beams. A proton is still ionizing radiation;
however, the beams used in proton therapy have different emission characteristics that
are presumed to allow for a more pin point delivery with lower exposure levels for the
collateral tissues enroute to the target; less spread at the target; and, less penetration
beyond the target than would be the case with conventional photon delivery.192
In a comparison of the effectiveness of IMRT, 3DCRT and PT in the treatment of
localized PC the researchers Sheet et al. have reported that those treated with IMRT
compared to 3DCRT have less associated gastro-intestinal problems; less post-therapy
incidence of hip fracture; and, less need for additional cancer therapy; however, IMRT
resulted in more erectile dysfunction. As well, Proton Therapy outcome was not
significantly improved over IMRT; and, proton therapy had a greater incidence of
associated gastro-intestinal problems compared to IMRT patients.193
Sometimes, instead of using external radiation an “internal” delivery is used. One
method uses unsealed radiation introduced in the body by IV to target tumor. An
example of this is the use of Selective Internal Radiation Therapy (SIRT) to address
inoperable liver tumor.
SIRT strategy involves the use of SIR-Spheres®. These small vehicles called
microspheres are laced with radioactive yttrium-90. A catheter is emplaced through the
groin into the hepatic artery of the patient and then millions of microspheres are injected
and delivered directly to the tumor site. The irradiated microspheres emit Beta radiation
and target the liver tumor with radiation that is approximately 40 times stronger than
conventional radiotherapy while sparing healthy liver tissue.194
Branchytherapy, as already has been discussed, is another form of internal
radiotherapy where a radiation source is placed inside or next to the area requiring
treatment either permanently or temporarily.195
During radiation therapy the total dose is usually fractionated, which means it is
spread out over time. This is done in order to minimize damage to normal cells OR to act
on cancer cells during the most vulnerable parts of their cell cycle.196 Fractionation
regimens are highly individualized between different countries, radiotherapy centers, and
even between individual doctors. Sessions continue until a total cumulative dosage has
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been received by the patient. If the radiation is delivered in smaller dosages several times
a day it is known as hyperfractionation. When the radiation is delivered in several large
dosages less than once a day it is called hypofractionation.197
Common short term radiation therapy side effects are expected and are usually
most prevalent in the area that has been irradiated. The skin through which the radiation
is aimed tends to change and may exhibit dryness, itching, peeling or blistering.
Depending on the area of your body being treated nausea, diarrhea, fatigue, swelling and
hair loss and trouble swallowing may also be experienced. For the most part, these are
short term side-effects and usually go away a couple of months after the radiotherapy is
halted.198
There are also long term side effects associated with radiotherapy that typically
present 6 months or more after treatment. Any tissue that has been irradiated generally
becomes less elastic over time due to diffuse scarring. This is called fibrosis. Sweat and
the mucosa linings in the irradiated area can become dry. Hair loss on skin in the
irradiated field can become permanent with single doses of generally 10 Gy or greater.
Lymphedema or localized tissue swelling due to damaged lymphatic tissues can occur. In
addition, there is a small risk of inducing secondary malignancies due to radiation therapy
anywhere between 5 and 30 years after treatment.199
Further to the different types and strategy using RT are the clinical and trial
combinations of RT with surgery, chemotherapy; non-conventional chemotherapy; and,
even other types of RT, for example branchytherapy with IMRT.
In 2010 a Phase III trial reported a substantial overall survival and disease specific
survival benefit for the combined approach of Androgen Deprivation Therapy +RT in the
management of patients with locally advanced Prostate Cancer with no significant
increase in late treatment toxicity. In view of this data, the researchers suggested that
combined ADT+RT should be the standard treatment approach for these patients. 200
In any case, the type of combination regimen and if and when they are applied is
constantly evolving, particularly when it comes to advanced disease that has failed
previous treatment. The intent is to improve on survival benefit. The appropriateness of
combination RT therapy to your case is a matter to discuss with your oncologist.
Recurrence following treatment
Cancer, when exceeding the bounds of the primary organ containment, invariably
presents more difficult challenges in terms of cure. Any remaindered tissue still infected
with disease following primary treatment is as well problematic. When I had my
resection for colorectal cancer my surgeon was confident that his team had managed to
remove all the infected areas. Nevertheless, he still referred me to the department of
oncology for chemotherapy treatment. When I looked at the literature involving the
clinical use of adjuvant chemotherapy I found something like a 16% better chance of 5
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year relative survival for those who elected to undergo that adjuvant treatment at my
stage disease. In a discussion with my oncologist it became clear that cancer was a
microscopic disease that migrated and that fact was better not ignored. I figured that I
could use the improved chances on survival so I proceeded with treatment. I had a
colleague that had nearly the same condition as me and underwent resection without
chemo. Less than three years later he was in relapse at stage IV with tumors in the lung
and liver. He did not make it. I am glad I did what I could at the time to improve my
chances. Anyone being treated for cancer should have a hard look at what the treatment
options are and what habit can be changed or modified to improve the chances of
remaining disease free.
Despite best clinical or trial efforts to address the disease, sometimes there is
failure of primary treatment. This means relapse from a “disease free” state and usually
more treatment to address recurrency. Recurrency rates vary and depend on a number of
factors including patient profile; previous treatment regimens; stage of disease; attitude;
lifestyle habits; diet; and, exercise to name a few.
For instance, in a study published in 2011, it was reported that current smokers
have a 61% higher risk of dying from PC and a 61% higher risk of relapse compared to
men who never smoked. Smoking was associated with more aggressive disease at
diagnosis; and, current smokers diagnosed with non-metastatic disease had an 80%
increased risk of dying from PC. Men who had quit smoking 10 years or more before
had risks similar to those who had never smoked. Also, men who were current smokers
had poorer outcomes in treatment with Emission Bream Radiation Therapy (EBRT);
Androgen Deprivation therapy (ADT); and, radical prostatectomy. 201
To assist in diagnosis of relapse, biomarkers such as PSA are monitored. Often
it is obvious from PSA values that the PC was not eradicated during primary treatment
well before any physical symptoms of recurrency are obvious to the patient. PSA
doubling is a concept used by clinicians to determine the rate of disease progression.
This along with imaging such as FDG PET/CT scans, for example, assists in providing
disease status upon which the need for further treatment is decided.
Sometimes PC relapse will involve local recurrence, other times the disease may
have migrated to other parts of the body and this as well can depend on the type of
primary treatment involved. For example, in terms of primary treatment with radiation
therapy it was recently reported that local recurrency usually occurs at the same site as
the dominant primary tumor at baseline. 202
Relapse can occur then be arrested then reoccur. In 2011 a study involving 122
men who had undergone RT primary treatment failure then underwent salvage
cryoablation to address local recurrency. As stated, salvage treatment just means the
next round of treatment to address the relapse or remaining disease. In any case, of these
patients 28% experienced a 5-year disease-free survival following salvage
cryoablation.203 This means the remainder experienced more relapse in the 5 year period
that resulted in death.
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Quality of Life (QOL)
In hand with considerations involving relative survival for those afflicted with PC
are the considerations for Quality of Life (QOL) and how it is impacted by PC treatment.
In a review of current research in PC treatment between the years of 1999 and 2005, it
was reported that those treated with prostatectomy; or, radiation including brachytherapy;
or, cryotherapy; or, androgen deprivation therapy all experienced significant impact on
QOL for men with local or advance disease whether in the short or long term.
Alterations in sexual functioning cause the most pronounced reduction in QOL. 204
A review of measures to improve on the sexual function of those who have
undergone nerve sparing radical retro-pubic prostatectomy (RRP) has reported that
sildenafil citrate (Viagra®) has demonstrated efficacy as a PDE-5 inhibitor able to
address post-RRP erectile dysfunction. 205
High Intensity Focused Ultrasound Therapy
Before we leave this chapter I would like to point out the recent trial efforts, and,
findings of high intensity focused ultrasound (HIFU) therapy which now seems able to
address localized Prostate Cancer tumor using what amounts to be a “prostate sparring
strategy”. According to the Prostate Cancer clinical guideline 58 released by Europe’s
National Institute for Health and Clinical Excellence in 2008, High Intensity Focused
Ultrasound (HIFU) therapy was then under trial for treatment of men with low,
intermediate, and, high risk Prostate Cancer.206
In a study involving 41 men (aged between 45-80 years old with low risk to high
risk localized PC and no previous treatment), it has been reported this year (2012) that 39
of 41 participants had no evidence of disease on multi-parametric MRI at 12 months
following focal therapy. As well, there is a low rate of genitourinary side effects. The
patients received focal therapy using high-intensity focused ultrasound (HIFU), delivered
to all known cancer lesions, with a margin of normal tissue, identified on multiparametric MRI, template prostate-mapping biopsies, or both. 207 One wonders if this
treatment may even be improved upon using imaging involving 11C-Choline PET/CT.
Although the report must be taken in context of benefit after only one year
following treatment, the success of this type of therapy would seem to me more than
encouraging especially when considering the clinical treatment options for localized
disease. Even more so that it reports a procedure that does not target and disable the
entire prostate. How civilized. Let’s keep our fingers crossed that the 5 year disease free
relative survival of these patients is even more encouraging.
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Chapter 5
Alternative Strategy & Prevention
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I sometimes run into anecdotes by those in denial of their marginal or poor health
who cite the longevity of a grandparent or a parent who apparently ate all the wrong
things, smoked, never exercised, never saw a doctor and still lived to a ripe old age. To
these comments I reply, we can only speculate how long they may have lived and how
their quality of life would have been had they practiced a few good habits. The question
is what is their example of habit doing for you?
Dominant theory is that everyone harbors the ability to produce cancer cells.
Fortunately, not everyone has cancer cells that progress and develop in a way that is
beyond their immune system’s capability to defend against. The medical community is
slowly coming to realize that each individual likely has a distinct immunological
response that is either capable of keeping the cancer “seed” under control or not. The
robustness and effectiveness of this immunological response is therefore becoming a
focal point in cancer research aimed at both prevention and treatment.
From all the clinical and trial treatments thus far used to address Prostate Cancer,
it is clear that there are many varied approaches to treating the disease. One treatment
may yield satisfactory results on one patient and on another be completely unsuccessful.
This fact is because Prostate Cancer, like any other cancer, is a multi-dimensional disease
and grows as a result of a wide range of influencing factors. These influencing factors
combine to eventually compromise or overwhelm the host’s immune system.
The trend these days in the mainstream medical community is to explore and use
combined methods of treatment in an attempt to defeat poorly understood and robust
cancer mechanisms that apparently have an ability to evolve resistance to some treatment
regimens. These treatments involve combining changes to certain aspects of a patient’s
diet, environment, and habit along with other more commonly practiced treatments such
as surgery, chemotherapy and radiotherapy. The advantage to such treatment is that there
is often a reported synergistic effect by doing this. A synergistic effect is one where the
total effect of the combined treatment is greater than the result of each part if applied
alone. Figuratively speaking, it is kind of like finding out that 1 +1 can equal 3.
There are numerous legitimate studies that have been published in reputable and
refereed scientific journals reporting results clearly in support of the benefits of these
alternative strategies in helping to deal with cancer. Nevertheless, they stand in the wings
and are not necessarily recommended or used. Generally, if you ask what else you can do
to improve on your survivability beyond the recommended surgery, chemotherapy or
radiation therapy, don’t be surprised if your physician responds by saying “nothing in
particular”. I have an opinion as to why such a response is given. That opinion is based
on what I have seen and heard in my own experience with our medical system and those
who work in it.
Firstly, the medical staff that handle you are at the “pointy end of the stick”. To be
aware of all of the research while handing an unending patient load is a difficult
combination of tasks.
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Secondly, cancer treatment has historically been shaped by the emphasis and rules
of the medical community and regulating agencies overseeing it. With the exception of
clinical trials, these rules and emphasis are such that only those regimens and drugs that
are “scientifically and clinically” proven to be effective on humans are used and
accepted. This means that “common sense” strategies, which should be a foregone
conclusion, receive little emphasis. Modern medicine traditionally involves intervention
with surgery, drugs and/or radiation. These methods are great for addressing trauma and
isolated affliction. Except, Prostate Cancer is not trauma, and, when it is invasive, it is not
isolated either.
Thirdly, the medical community and the pharmaceutical industry feed off of each
other. Both are big business. Funding availability and research direction align so that
huge profits can eventually be realized with the development of drugs and strategies that
can be “patented” and used for treatment. As such; directing effort to find a cure is not
always the same as directing effort to make profit.
In the meantime, patients are left to stumble onto these alternative strategies on
their own because the larger part of medical community adhere to convention and are
either not so versed or disposed to make the recommendations beyond that convention.
Any physician going against convention potentially exposes themselves to the
disapproval of their colleagues, funding bodies and their insurance underwriters. So they
take care not to step too far away from convention.
A prime example of this reluctance is demonstrated in the history involving direct
and second hand exposure to tobacco smoke. Despite the obvious “common sense”
association between tobacco smoke and lung cancer, it took the better part of twenty
years before the majority of government health agencies and medical institutions were
prepared to publish recommendations and warnings against the use of tobacco. Even
then, tobacco is still government sanctioned, it is a legal product and remains a constant
source of government funding through tobacco taxation. As well, you can go to any
hospital and see the continued tolerance of patients in poor health pushing their IV rigs
outside to have a smoke. The whole makes no sense when you consider the loss of life,
and the economic cost of treating and maintaining those afflicted by the host of tobacco
related disease. Such is the influence of big business on the delivery of healthcare.
Nevertheless, occasionally there are those researchers, medical staff and
institutions that boldly depart from conventional opinion and practice. In so doing, they
produce the “unglamorous” studies and strategies that support “common sense” solutions
that can be added to treatment and prevention regimens. Such strategies touch on the
benefits of diet, environment, exercise and attitude. In addition to the common sense of
said strategies, is the well-researched science that supports it.
It is an unfortunate fact that it seems these alternate strategies are often left on the
wayside until conventional treatment of cancer reaches the point of being ineffective or
unavailable. This usually means that the disease has progressed to the point of extensive
invasiveness or has fallen out of remission into a difficult relapse. It also means that
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likely the patient already has damaged or missing organs, tissue, and immune system
response due to the disease and its conventional treatment. In point of fact, alternate
strategy can be adopted by anyone at any time to help boost or repair compromised
immunological response.
There are basically three ways to defeat cancer cells. Introduce an agent or
procedure that can identify and kill or remove them outright; promote conditions of
cancer cell apoptosis (cell death) whereby the cancer cells self-destruct; or, promote
conditions that inhibit cancer cell angiogenesis so that they cannot grow a system of
blood vessels. Your body’s immune system, when given the proper conditions and the
right food, can do all of these things.
Now, let us assume that the foundation of a patient’s immunological system is
still relatively intact and responsive. Then apply a strategy designed to promote the
recovery of the patient’s immunological response with the intent to revive the patient’s
inherent immunological defenses. These defenses are what we have to address not only
cancer, but, virtually all manner and type of disease. Existing and widely practiced
conventional cancer treatment regimens are crude and inefficient replacement for the
precision and effectiveness of our internal immunological defenses when they are
working properly.
So what would such a strategy involve in terms of the tangible and how is this to
be applied? Well, the first thing to understand is that there is no silver bullet or
magic snake oil to completely avoid or rid us of Prostate Cancer or any other cancer
for that matter. The studies suggest; however, that there is a way to improve on our
immunological responses by following some common sense habit and diet.
Unfortunately, human nature being the way it is, change and following “common sense”
habit and diet is, for most of us, a very difficult thing to do.
Can you imagine the alarm and outcry of the general public if 40% to 45% of all
commercial flights ended with a crash? Passenger service would be halted over night
from public outrage and panic. Now consider that the probability of having cancer
during their lifetime for the average Canadian is 40% - 45%. On the basis of current
mortality rates one of every four Canadians will die from cancer.208 The World Health
Organization’s International Agency for Research on Cancer (IARC) has released its
2008 report on cancer. In this report the IARC expects that by the year 2030 there will be
approximately 27 million new cases of cancer annually; another 75 million people will be
within 5 years of having been diagnosed with cancer; and 17 million cancer deaths will
occur every year.209 Even with such blatant fact and projection everyone seems blissfully
content to pay no attention and continue with habits and diet that are totally inconsistent
with the high risk involved. IT MAKES NO SENSE!!!!
We all like the food that we grew up on, it gives comfort and a sense of home. To
abandon our accustomed dietary habit is, like abandoning our heritage and identity.
Further, we are all slaves to the stresses imposed by residing where we do at this point in
time. The practical rigors of making work and home function can be formidable and not
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at all conducive to good health or healing, especially if there are chronic problems with
work or home. In any case, if your immunological system is to be restored or boosted, a
more hospitable balance must be found and this will involve change.
Be advised, of those that do manage to accommodate such change, it may be a
long slow road to repairing and regaining the health of your immunological system. It
can take years and there are no guarantees. So patience, tenacity, resolve, and faith are
all required ingredients. My suggestion is to adopt the changes early on, ideally, well
before you are ever afflicted with a disease like PC. For those who are already with the
disease, the sooner one starts the sooner one will see results. Your motivation must be to
improve on your baseline health so you can enjoy a better quality of life and live longer.
For me this motivation is made easy because I have a mate that has gone through
the loss of her mother to terminal breast cancer; and, experienced her own treatment and
recovery from an auto-immune disease as a teenager. In response my mate tailored her
own “stay healthy” routine, which was a pretty good example of how I should proceed
with the issue in terms of diet and exercise.
In considering my mate’s informal guidelines, I find striking commonality with
the suggestions in Dr. David Servan-Schreiber’s recent book, Anti-Cancer A New Way
of Life. For those of you who do not know, Dr. Servan-Schreiber is a physician,
researcher, author, public speaker, and, a survivor of brain cancer. In his fight with
cancer he has been through surgery, chemotherapy, radiation therapy, remission, relapse
and more treatment. At some point in all of this fight, he made a comprehensive review
of the scientific literature on the subjects of diet, environment and habit to understand
their effect on the immune response. This review is reflected in his book. It is
encouraging to have a prominent member of the medical community open the curtain to
all the research that has been going on with alternative cancer strategy. I hope that it
promotes a more receptive attitude to the value of such strategies within the medical
community.
Predating Dr. Servan-Schreiber’s book are the efforts and work by Dr. Richard
Béliveau and Dr. Denis Gingras, who have done a phenomenal job researching the
content and chemistry of foods that fight cancer and relaying that research in accessible
books such as Foods that Fight Cancer: Preventing Cancer Through Diet.
When I speak of change I am a realist. I understand that the average person is
bound by circumstance and is not usually in a position economically or otherwise to
adopt and nurture grossly different routine. Living alone may make change even more
difficult. Nevertheless, the idea is to review your daily habits and see what small changes
can be made to help improve your immune response.
Small changes that can be maintained are better than sweeping changes that are
abandoned out of frustration from apparent lack of result or resource. Further, small
changes that occur 2 or 3 or 4 times a week regularly, are better than no changes at all.
These represent a beginning to more changes that can be accommodated after you
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become accustomed to and encouraged by the result of the changes that came before. I
say again, sustained small changes are better than no changes at all.
Diet
My intent with this section is to give an overview of what the considerations in
diet should be if one is concerned with enhancing the immunological response over the
long term. It is a “short list” of what is affordable and easy to implement. It is not
intended to be a replacement for consultation with qualified medical nutritionists in
combination with your treatment. It is intended to get you started on the right track and
explain a few basics.
Modern agriculture and food production introduces a host of pesticides,
preservatives, plastics, and other synthetic compounds into our food, both directly and
indirectly. “Processing methods” used on our food further alters and reduces the content
of the chemical molecules naturally found in different foods that can have a beneficial
effect on our immunological response. Guidelines are dictated by government bodies
regulating farmers and producers to adhere to “acceptable” levels of certain compounds.
As well, governments publish daily recommended dietary intakes of food types.
Unfortunately, there is little consideration paid to the notion that the average consumer
has no regard or understanding of what the daily requirements are for most aspects of
their diets. Nor do they have an understanding of even how to assess them. Nor do they
care, for the most part.
It has been my experience that the average person who is eating meals and snacks
every day, several times a day or more, does so simply because they are feeling “hungry”.
They have no regard for any possible health benefits or daily allowances. Policies that
publish daily recommended allowances are doomed to failure simply because they ignore
this fundamental lack of regard. Further, although the health benefits of factors such as
higher ratios of Omega-3 have been clearly identified and publicized, the majority of
food production still avoids methods that could enhance the compliment of such factors
in our food.
All to say, the food industry is an enormous industrial complex intertwined with
local, regional and federal government policy and consumer habit. It is not going to
change in the immediate future. For the moment, the only concern should be to identify
and find suitable produce and product so that we may satisfy our immediate need for
immunological repair or boost.
When it comes to diet a familiar saying resounds in my head “You are what you
eat”. Of course, this is nonsense in the literal sense because none of us is going to turn
into a piece of corn, a chunk of a beef or a head of lettuce. What is more the case is that
we humans are at the top of the food chain. When we eat anything we generally absorb
all of the elements that particular “tasty” has eaten or been exposed to. The same is true
for drink.
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In our ignorance or denial we typically plod along eating foods that undermine
our immunological system. Of course, due to the fantastic resilience of the human body,
we get away with it for a while. Later on though, it does catch up to us and compromises
both quality and length of life.
Much attention and publicity has been given to the beneficial results of antioxidants as a way to minimize or undo damage in our bodies that occurs because of “free
radical” reactions. It is widely theorized that this free radical interaction contributes to
cancers and that anti-oxidant intake in humans has clinical benefits. Research to that
regard is ongoing but has yet to provide conclusive evidence.210
For those who don’t know, anti-oxidant theory considers the following:
We humans are basically one big bundle of ongoing chemical reactions. Many of these
chemical reactions release molecules or atoms in an unstable (free radical) state as byproduct. This instability allows free radicals to easily react with other molecules that
they should not be reacting with. The result can cause chain reactions that confound all
kinds of cellular processes and structure to the point of even killing cells. Long term or
substantial free radical reactions either exhaust or overwhelm the body’s ability to repair
lost and damaged cells. This can lead to disease and is the essence of aging.
Anti-oxidants are molecules that have an ability of neutralizing free radical
molecules without becoming free radicals themselves. This idea is that intake of antioxidants through dietary sources, for example, protects cells from damage due to free
radicals.211
Dietary sources of anti-oxidants include vegetables, fruits, nuts, grains, some
meats, poultry, fish and green tea. The list below details some common antioxidants and
some of their dietary food sources.
Type of anti-oxidant nutrient and dietary sources are:
Beta-carotene- sweet potatoes, carrots, cantaloupe, and squash, apricots, pumpkin,
mangos, collard greens, spinach, and kale;
Lutein – egg yolk, corn, kiwi, grapes, spinach, zucchini, and orange peppers;
Lycopene - tomatoes, watermelon, guava, papaya, apricots, pink grapefruit, and
blood oranges;
Vitamin A – liver, kidney, carrots and carrot juice, sweet potatoes, pumpkin,
spinach, collards, and kale;
Vitamin C (ascorbic acid) – citrus fruits their juices, green peppers,
strawberries, tomatoes, broccoli, sweet potatoes, cantaloupe, papaya, mango,
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watermelon, brussel sprouts, cauliflower, cabbage, winter squash, red peppers,
raspberries, blueberries, cranberries, and pineapples;
Vitamin E – wheat germ oil, almonds, sunflower oil, safflower oil, hazelnuts,
peanut butter; and,
Selenium – is a mineral not an antioxidant nutrient; however, this mineral is a
component of anti-oxidant enzymes. Produce grown in soil rich in selenium, as
well as, stock reared in selenium rich regions will have higher levels of selenium
in their tissues that will be passed on to you when you consume them. 212
Now let us briefly examine the foods that we eat being mindful of what promotes
good health or not. It is not my intention to be exhaustive in this regard. There are
numerous books by reputable nutritionists that are far better in detailing a comprehensive
list. I simply want to point out some obvious and common food sources that should be
avoided or at least reduced and those that should be given priority in your diet.
General rule:
Food that is processed, or fried, or smoked should not be regarded as a suitable main
meal. As well, red meat and alcohol taken in excess is not a good thing to do. This does
not mean that these foods are totally taboo. What you have to do is change the way you
regard these types of food. If you want to eat food of this type then do so only
occasionally and in moderation. In short, they are to be regarded as a rare “treat” instead
of a regular staple.213
When I was a child the only time I could count on having a hamburger was in the
fall at a local county fair. That happened once a year. French fries were something that
occurred a couple of times in the summer when the seasonal “chip stand” opened up in
my home town. I didn’t even taste a pizza until I was 12 years old. You have probably
gathered by now that I did not grow up in a large urban center. Nevertheless, the point is
still valid. I used to thoroughly enjoy these small treats now and then, but, they were not
part of my regular diet.
Metabolic process is the way we take in fuel (food) and turn it into useable
energy. This “useable energy” is called ATP (adenosine triphosphate) in a human. It is
derived mostly from metabolic pathways in the body that convert food into simple sugars.
These days a Western diet is largely composed of starch, sugar and meat. The
proportions of these foods have evolved since the 1940’s to the point now where most of
us consume a staggering amount of refined sugar and starch originating from cane, sugar
beets, corn and wheat.
What this means, in terms of human biochemistry, is that in digesting this pile of
sugar and starch, our metabolic processes produce very large amounts of simple sugar in
the form of glucose and fructose. Glucose and fructose are then further processed or
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metabolized in our bodies to meet our cells’ energy needs. When there is too much for
our bodies to use, much of the excess is converted and stored in the body.
Excess sugar and starch consumption contributes to obesity, cancer and a
host of other sugar induced illness.214 This excess consumption is easily controlled if
you simply start eating more vegetables or fruits during the course of the day when you
feel hungry and use a bit of moderation as to the amount of food intake during a day.
Sugar, Starch and other things Sweet
In reviewing a bit of sugar information let us consider the following:
1) There are a number of sugars; however, our bodies can convert the simple sugars
glucose and fructose into energy. Glucose and fructose are both monosaccharides. A
monosaccharide means “single sugar” and refers to the chemical structure of these
sugars. Galactose is also a monosaccharide but does not contribute to our cells energy
needs to the extent that fructose and glucose does. Glucose, fructose and galactose have
chemical structures that are best referred to as simple sugar “units”;
2) A disaccharide means that two simple sugar units are married together. Sucrose,
maltose and lactose are examples of disaccharides. The composition of the two simple
sugar units determines which disaccharide is formed. For example, sucrose is made up of
a unit of glucose and a unit of fructose; and,
3) Starch is what is known as a polysaccharide. Poly means “many”, saccharide means
“sugar”. A polysaccharide is basically a very long chain of simple sugar units joined
together by either Alpha or Beta linkages. Starch is a polysaccharide that is formed with
Alpha linkages and it is broken down into simple sugar units that are further metabolized
into the fuel used by our cells. Humans have the necessary enzymes to easily break down
the Alpha linkages, but not so effectively the Beta linkages. An example of a
polysaccharide with Beta linkages is cellulose. Cellulose is “roughage”. We don’t
digest roughage so well. In short, roughage moves along our digestive tract and exits
without much contribution to our metabolic needs; starch and sugars, on the other hand,
are main dietary contributors to our metabolic needs.
Consumption of roughage is necessary. Roughage serves to normalize bowel
movements; helps maintain bowel integrity and health; lowers blood cholesterol levels;
helps control blood sugar levels; and, aids in weight loss. 215 As you have probably heard
a thousand times, eating more whole grains (like spelt, bran and flax) and a range of
vegetables will satisfy your requirement for roughage.
Other sources of the “sugar fuel” used by our cells can be derived from the
consumption of synthetic sugars like HFCS (High Fructose Corn Syrup). HFCS is a
sweetener used in a whole bunch of processed foods, drinks and candy. Although it is
often labeled as “natural” on the ingredient lists of many products it is not natural. It is
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the synthetic result of an enzymatic refining process whereby the amount of fructose is
controlled. This idea is to produce a sugar that approaches the sweetness levels of regular
white sugar (sucrose). There are three types of HFCS. These are HFCS -42, -55 and,-90.
HFCS is composed of the following ratios of fructose and glucose:
HFCS-42 is 42% Fructose and 53% Glucose;
HFCS-55 is 55% Fructose and 42% Glucose; and
HFCS-90 is 90% Fructose and 5% Glucose.216
There has been a lot of discussion over the years as to the benefits of natural
sugars versus refined sugars versus artificial sweeteners. To clarify the differences; all
natural sweeteners that find their way onto our tables as syrup, a tablet, a powder or
granules have been extracted and refined. In simple terms, there are basically six
naturally derived sugars. These are fructose, glucose, galactose, lactose, maltose, and
sucrose. Fructose is the sweetest of the natural sugars and occurs in fruit and plant
extractions such as maple syrup, honey, corn syrup, sugar cane, and sugar beets.217 Agave
nectar is composed of fructose and glucose. Depending on how it is processed, agave
nectar has been reported to have up to 92% fructose in it.218 Fructose and sucrose are the
two natural sugars commonly found on our tables. Lactose is the sugar that is naturally
in milk. Maltose is the sugar found in germinating cereals like barley. It is used
commercially in the brewing of beer.
I found that there can be substantial differences in the reported ratios or
percentage of natural sweeteners. In in rough approximation the sugar composition of
some natural sweeteners is as follows:
Agave nectar HoneyMaple sugarMolasses-
92% fructose, 8% glucose;
48% fructose, 39% glucose, 9% maltose, 2% sucrose; 2% other
95% sucrose, 4% glucose, 1% fructose; and,
54% sucrose, 24% fructose, 22% glucose.
Healthy cells generally rely on energy released from a chemical reaction that
combines glucose with oxygen in the body. This reaction is called aerobic respiration.
This is a very efficient chemical reaction, which means it does not require a lot of energy
to make it happen and it gives off a lot of energy in return.
According to the Nobel Prize recipient Otto Warburg, glucose is essential to the
metabolism of malignant tumors, as well as, normal tissue growth and maintenance.
From his work it was discovered that malignant tumors, unlike healthy cells, reside often
in an anaerobic state.219 An anaerobic state is one where oxygen is in relatively short
supply. This is probably because of the confused spaghetti-like strategy of angiogenesis
that cancer cells typically exhibit. In this anaerobic state, the cancer cells rely on the
fermentation of glucose to produce energy and grow. This fermentation process is called
glycolysis which is also known as anaerobic respiration.
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Unlike aerobic respiration, glycolysis is a very inefficient chemical reaction.
Aerobic respiration produces a net release of approximately sixteen times more energy
than glycolysis for the same amount of glucose processed.220 This means that cancer cells
need a lot more glucose fuel to support cellular activity compared to normal cells.
Glucose actually has two forms. The one that occurs naturally in higher living
organisms like us is called D-glucose. It is also known as Dextrose. This form of basic
sugar is what our internal processes can make out of the food we put into our bodies. It is
fundamental to the way we make energy. For the most part, this conversion of food into
energy is generally done through two common metabolic pathways. One is called
aerobic respiration, and the other is called glycolysis or anaerobic respiration.221 There
are other metabolic pathways that are in play as well; however, these other pathways are
generally not as significant as aerobic respiration and glycolysis.
Healthy cells relying on aerobic respiration can “make due” with substantially
less D-glucose compared to cancer cells relying mostly on the process of glycolysis.
Malignant tumor cells need an abundance of D-glucose to develop and spread. Anyone
taking in large amounts of refined sugar and starch is providing a convenient stockpile of
raw material that cancer cells use to satisfy their energy needs. So, as cancer fighting
strategy #1 take control of their fuel lines by cutting down on your intake of dietary
sugar and starch. The healthy cells will not suffer because they can do just fine with less
than the average Westerner eats in the course of a day. This means lay off the desserts,
sweets (especially soft drinks), and excessive amounts of wheat based food like breads,
pizzas and pastas.
To continue, many processed foods that are advertised as “sugar free” actually list
what is described as “sugar alcohols” as sweeteners. These are in fact not sugars or
alcohols. Instead they are carbohydrates that have chemical compositions that are similar
to either sugar or alcohol. Typically their sweetness is less than or equal to sucrose.
They as well have caloric value. Falling into this category of sweeteners are sorbitol,
mannitol, xylitol, erythritol, isomalt, lactitol, and maltitol.222 Although digestible, the
long term effects of consuming these sweeteners is not really understood. As such; I
personally avoid them since I don’t know what they can do to me.
The reason why I am so dubious of any unnatural sweetener over the long term is
founded in the history behind the sweetener called saccharin. Saccharin is a nonnutritive sweetener that has been around for about 100 years. A non-nutritive sweetener
is one that has little or no caloric value. This sweetener was discovered by researchers
working on coal tar derivatives. About thirty years ago it was reported to be causing
cancer in animal studies. The food and drug administration (FDA) “black listed” it but
since then some 30 human studies have reported it fit for human consumption and so
saccharin is back on the shelf again.223 As far as I am concerned, I would prefer not to
take the chance.
In this category of “non-nutritive” sweeteners are a number of compounds that
range between 160 and 13,000 times sweeter than white sugar. They have been
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popularized by those seeking to lose weight by reducing the number of calories in their
diet. The long term effects of all of these are poorly understood in a large scale human
population. All of these “non-nutritive” sweeteners carry recommended daily amounts
not to be exceeded. Some of them are either correlated in studies or associated by
anecdote with side effects such as nausea, hair loss, abdominal pain, dizziness, induction
of lupus, depression, dementia, confusion, and even cancer. Among these “non-nutritive”
sweeteners are saccharin, aspartame, sucralose (which is trichlorogalactosucrose, yes,
that means it has chlorine in it), acesulfame K (contains the carcinogen methylene
chloride), and neotame.224 Again, I would rather simply reduce the amount of sugar I eat
and get used to the lack of sweetness rather than take the chance.
Toxic Contamination and Organic Produce
Modern farming and food production methods can introduce a variety of toxins
into our food and water supply. In my view, some consideration should be given to
consume food and drink that will minimize your intake of toxins so as to reduce the
overall stress on your immune system. Later in this chapter there is a discussion on the
foods that are best to eat in terms of fighting cancer.
As an aside, be aware of “where” the produce comes from. Some countries have
vastly different ways of policing their producers in terms of contamination rules. If you
intend on eating cultured fish regularly ensure that your supply of fish is not being reared
on contaminated feed. There is an ongoing local study in Montreal right now reviewing
the frequency of consumers with high levels of mercury due to cultured fish
consumption. This most likely is the result of rearing cultured fish on feed containing
high levels of mercury. Mercury poisoning damages the central nervous system, can
result in all sorts of nasty side effects and can even cause death. It is something we can
certainly do without.
Organically farmed produce is a new trend making its way into most major
supermarkets. Although not strictly regulated, those who advertise organically farmed
produce generally are using techniques that stay away from heavy reliance on pesticides,
hormone augmentation to promote quick growth, genetically altered feeds, and forced
rearing strategies. In so doing, these farmers should be bringing stock and produce to
market that are comparatively much lower in contaminants and unaccustomed alteration.
As well, in using a strategy of “grass feeding” their stock and fowl, the ratios of
Omega-3 fatty acids to Omega-6 fatty acids in the meat, dairy and eggs of that livestock
and fowl is much higher. Higher Omega-3 to Omega-6 ratios reduces inflammation, fat
storage, and, growth of cancer cells.225
More specifically, Omega-3’s are needed for synthesis of anti-inflammatory
molecules and are linked to reduced risk of breast, prostate and colorectal cancer. Excess
Omega-6 fatty acid in the body is linked to chronic illness like cancer and cardiovascular
disease.226
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Do not misunderstand to think that we do not need either of these fats. They are
both essential. Omega-6 competes with Omega-3 for the same rate limiting enzymes;
and, higher ratios of Omega-6 to Omega-3 shifts the body’s tissues toward pathogenesis
(the generation of disease).227
The problem is that modern Western diets typically have high amounts of Omega6 polyunsaturated fatty acids. These diets have high Omega−6 to Omega−3 ratios
reported to fall at or slightly above 15:1. Optimal ratio of Omega-6 to Omega-3 fatty acid
is reported to be much lower. For example, in the case of CRC it was reported that a
ratio of 2 ½:1 reduced rectal cell proliferation. 228
On a practical note, one drawback to organic product that I have found is that it
typically costs more than non-organic. Unfortunately, this is probably a major reason
why people do not buy the food labelled “organic”. If you have been avoiding organic
food simply on the principle that it should not cost so much, you must understand that
organic methods have lower yields than conventional farming techniques. So if the
farmer is to exist they have to charge more. If you cannot afford organic food, then at
least make sure you properly wash your fruits and vegetables with soap and water.
Peeling off the skin can also help reduce intake of toxins. Eating wild game is an
effective alternative to non-organic meats and fowl. As well, replacing a large part of
your meat and fowl with more ocean caught fish will help.
Your Omega-6 to Omega-3 ratio can be lowered by boosting the intake of
Omega-3 fatty acids. Eating fish, whole grains, fresh fruit, vegetables, cold pressed olive
oil (virgin), garlic, and having a daily glass of wine (red) at mealtime will do this.229
For those who don’t know, “cold pressed” means the oil is extracted without the
use of heat. Oil extraction using high heat levels usually alters the oil’s chemical
structure. The result is that the oil is changed into a hydrogenated fat. Generally
speaking, hydrogenated fats are bad for you. Reducing the amount of hydrogenated
sunflower oil, corn oil, soybean oil, margarine and any other hydrogenated fats in your
diet will also lower your ratio of Omega-6 to Omega-3 fatty acids, and again, is exactly
what you want to do.
Be aware, Omega-3 fatty acids are not stable and break down into elements that
do not have the same anti- cancer and anti- inflammatory benefits when they are left on a
shelf for a period of time as is the case with store bought Omega-3 supplements. It is
therefore important to seek out dietary food sources of Omega-3s to ensure that your
Omega- 3 intake is beneficial.230
One last thing before we leave this bit of discussion on Omega fats; don’t get
lulled into paying more for food at the grocery store because it has a sticker on it saying
that it has a higher content of certain Omegas. In short, an egg is an egg is an egg.
Stickers and advertising does not make it have any more Omega content than the ones
without the advertising that cost less.
As far as drink goes, measures to reduce toxin can include running your tap water
with a good carbon filter at home. If you drink tap water from a treated municipal supply
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without any home filtration, pouring the water into a container that is openly exposed to
air for approximately 24 hours will reduce the chlorine levels in your water. Although
the levels in your municipal drinking water are considered safe, chlorine is a known
mutagen or agent that causes mutations. As well, it was used quite effectively in WWI as
a weapon. The less intake of chlorine you have the better.
Metronomics
A metronomic regimen is a treatment that calls for relatively low grade amounts
of drugs or compounds to be administered under a continuous schedule to combat
disease. Unlike conventional regimens of chemotherapy, for example, metronomic
regimens are better suited to long term strategy to prevent, suppress or keep disease from
recurring. It is with this strategy in mind that doctors Béliveau and Gingras, both
prominent researchers in the effects of foods on cancer at the Université de Montréal,
have investigated the use of food as a natural way to continually deliver anti-cancer
compounds to the body. This is known as nutratherapy.231
Foremost in their research is the notion of depriving the cancer cells of food and
oxygen. This can be done most effectively by limiting or preventing the formation of
blood vessels specifically made to supply cancerous growth.
Compared to Western society, there are those cultures that typically have lower
incident of certain cancers. Research into the diets of these cultures reveals the intake of
foods and spices whose chemistry has been found to have anti-cancer properties when
consumed in quantities that are similar to those of their related cultural diet. These foods
feature a wide range of natural chemicals that can act either independently or in
combination to substantially reduce the ability of cancer to develop. Such chemicals are
known as phytochemicals and include polyphenols, terpenes, sulfides, and saponins.
Phytochemicals are also what is used by plants to defend themselves against
microorganisms, insects and animals.232
According to Béliveau and Gingras, there are a few foods and drink that are
reported to have a specific inhibiting effect on the growth of Prostate Cancer. These are
green tea, garlic, soy, tomatoes, onions, leeks, shallots, cabbage, cauliflower, broccoli,
brussel sprouts, turnip, kale, watercress, and collard greens. In addition to these there
are a number of other foods (some of which are from related food family to what has
already been mentioned), spice and drink that have known cancer inhibiting properties.
For example, citrus fruit, grapes, raspberries, cranberries, turmeric combined with pepper,
and red wine.233
As you can see these foods, spice and drink are easily found at most grocery
stores. What is important is that you alter your diet to incorporate some of these foods in
your meals every day. Eventually, when you and your family become more used to
eating these types of vegetables, you can gradually evolve your meal content so that the
bulk of the meal is made up of vegetables and fruit instead of the meat, fowl or fish. You
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can also evolve your diet so that over time it is mostly made up of the foods mentioned
above.
When I refer to you and your family I do so intentionally. The following are my
reasons for including family in this effort. First, it is much easier to make changes to diet
or lifestyle if you have the support of those around you. Being constantly faced with
temptation and opposition by members of an entire household, who are neither interested
nor participating, makes the task of change really difficult. Second, if you or someone in
your family has been diagnosed with cancer, this is the proof that your present conditions
can conspire to cause illness. It is time to do something for those already afflicted, and
those who could become afflicted if allowed to proceed on the same path without change.
Do keep in mind that the recommendations of this type of diet are outlined to lend
a stronger hand to those who are either fighting PC or in remission. For these persons, it
is important that larger changes are made sooner than later. It is important that such
change becomes a way of life. For those who do not have the disease of cancer but are
concerned, adopting these changes in your diet and habit gradually will help to make you
that much more the resistant to any disease and is certainly a healthy way for you and
your family to proceed.
To continue, the research suggests that additional cancer slowing benefits are
found by using spices from the Terpene family in your meals. Terpene family spices
include mint, thyme, marjoram, oregano, basil and rosemary.234 Ideally, the fresher
these spices are the better they are for you. This means have a look in the vegetable
section of the grocery store for small bundles of fresh herb. These can be used in meals
and, in the case of mint, can be decanted as herbal tea. Rosemary has also been found to
have a synergistic effect when combined with chemotherapy. The spice that has been
found to be a powerful anti-inflammatory and cancer inhibitor is turmeric. Commonly
found in Far and Middle Eastern food, its active ingredient is curcumin. Anyone who has
eaten chicken noodle soup out of a can is familiar with the yellow color and taste of
turmeric. These days you can find this in the spice section of any grocery store and it is
inexpensive.
Turmeric is one of the main spices in curries. Research has also found that
combining turmeric with pepper increases absorption of turmeric by two thousand
times.235 So don’t forget the turmeric and pepper next time you make a curry or Cajun
shrimp!
So far we have discussed food that basically addresses the main course of a meal.
Now let’s look at what can be used in terms of snacks, desserts and drink. Reducing
sugar and starch intake effectively rules out most of the “goodies” that we typically
indulge in between and after meals. Unfortunately, this is something that must be done.
So what is a suitable substitute for these goodies? Thankfully there is the berry.
According to research, strawberries, raspberries, blackberries, cranberries and
blueberries are strong detoxifiers and inhibitors of cancer cell angiogenesis. Their
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active ingredients include polyphenols and ellagic acid. Berries can be fresh or frozen
without diminishing the effectiveness of the active ingredients.236
In addition, 70% (or higher) dark chocolate contains polyphenols to the extent
that a very small amount (a couple of small squares a day) has an effect in slowing the
development and spread of cancer cells. Of course, 70% dark chocolate has some sugar
in it, so eat it sparingly! As well, you should know that mixing milk with dark chocolate
cancels is cancer slowing effects.237 The logical extension of this is to stay away from
milk chocolate. So between the fruit, a bit of dark chocolate and your imagination, you
should be covered for dessert and snacks. Next is drink.
The most obvious of drinks that will assist in your fight against cancer are those
blended from the list of berries above. They can be mixed with ice, water, or other
juices. If you are going to use commercial juice be mindful of the amount of sugar in the
juice. Remember, you are trying to keep the sugar content down.
Pomegranate juice is a detoxifier, anti-inflammatory and slows the spread of
cancer.238 It has been one of the staple drinks in the Middle East for centuries.
Unfortunately, it has been my experience that in most grocery stores, the available
pomegranate juice is filled with sugar, to the point where the juice is almost undrinkable.
The alternative to this is to go to a health food store and pick up pomegranate juice that is
usually not sweetened at all. I like to mix it with sparkling water at the dinner table.
One of the side effects of my platinum based chemotherapy was that the throat
became really uncomfortable with exposure to anything even remotely cold. The effect
felt like you were drinking jagged ¼ inch particles of slush ice (without the brain freeze).
Beverages and food had to be room temperature or warmer to avoid the effect. I also
found that anything sweet, in terms of a beverage, made me feel even more nauseous than
I already was. Still I had to keep my liquids up and so I struggled to find something I
could drink. It was then that my mate introduced me to green tea.
After I did a bit of reading I found that apparently most of the world knew about
green tea except me. Even more surprising was the reported property of green tea to
inhibit cancer cell angiogenesis in the literature. The active cancer inhibiting ingredient
in green tea is a chemical called epigallocatechin gallate (EGCG). 239 The green tea has
to be allowed to steep for about 10 minutes before drinking and must be drank within a
couple of hours of steeping or it begins to lose its cancer inhibiting properties.240
I also found that green tea comes in an assortment of flavours, which makes it
easy to substitute if you are already accustomed to drinking Tisane. Further, no sugar is
required. Also, you can just buy plain green tea then flavor it yourself by adding herbs
like mint leaves or citrus peel or berries to the steep in with the tea.
If you are considering drinking black teas instead, be aware that black tea is green
tea that has undergone a fermentation process. The unfortunate result of this
fermentation is that the tea loses its cancer inhibiting property. So black tea is not
beneficial to drink in terms of a cancer inhibitor. Another drink that is full of cancer
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inhibiting chemicals is citrus juice. The zest (peel) and juice of orange, lemon,
grapefruit, and lime are all good for you in this regard.241
The last drink I will discuss it one which has enjoyed a considerable amount of
recent publicity as to its health benefits. This drink is red wine. Red wine typically has
about 12% alcohol content. Alcohol is something that is very easily converted into fat in
humans. Alcohol is also a poison, so it does impose stresses on the body in order to
process it through the liver.
Red wine contains substantial levels of polyphenols that slow the development
and spread of cancer.242 All to say, if taken in moderation with a meal, red wine can be a
pleasant and effective addition to your anti-cancer diet.
The next big question is HOW MUCH of this stuff should one be eating and
drinking every day? The answer is that it amounts to about a total of 2 – 2½ cups of
“core” fruit and vegetable matter per adult every day. When you think of this in terms of
3 meals, it really is not that much. There is nothing to prevent you from adding other
vegetables, fruits and nuts to this list to round things out. As well, small portions of
protein in the form of red meat, fowl, and fish can be included. Just keep the portions
small. May I suggest around 200 grams (3-4 oz.) per serving, so forget about the 28 oz.
steaks even if it is barbeque season!!! I know you think that you are going to starve; but
you won’t.
The following is what I try to take in (along with a daily serving of a protein like
fish or a small portion of foul or meat) during an average day:
Garlic
2 cloves
Onions, shallots
½ cup
Cauliflower, broccoli, cabbage
½ cup
Spinach, watercress
½ cup
Flax seeds (finely ground)
1 tablespoon
Turmeric
1 teaspoon
Black pepper
½ teaspoon
Raspberries, black berries or blueberries
½ cup
Citrus fruit Juice
½ cup
Green Tea (steep for 8-10 minutes)
3 cups
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Red Wine
1 glass
Dark Chocolate (70%)
40 grams
In addition, tomatoes, asparagus, fiddleheads, red chicory (radicchio), turnips,
beets, and eggplant are all vegetables with anti-cancer properties that can be substituted
now than then to lend some variability to the core of your diet.243
This list is for the most part derived from the pocket guide detailed in Béliveau
and Gingras’ book Foods That Fight Cancer. It is not exactly the same but I think it is a
good start. The differences are because there are foods in their list that:
a) I simply do not like (so call me fussy); or,
b) I don’t want regularly in my diet (for instance soya).
In any case, be sure to take your time and chew your food well. This allows a
better release of the chemicals you seek to introduce to your diet. If you don’t already do
it, it is time to get used to not overcooking these core foods. Overcooking alters their
chemical effectiveness. This should be easy since the above vegetables are typically
served up in salads as well as braised, boiled, broiled, pureed into soup or stir fried to
name a few ways.
There are two controversies that seem to persist in terms of what to omit or add to
this anti-cancer core diet. The first involves Soya. Although soya has known polyphenol
content, it has been reported that Soya is linked to the increased frequency of breast
cancer in animal models. On the other hand, there are studies that point out the benefit of
Soya intake to inhibit both prostate and colorectal cancer (CRC).244 Again, I prefer to be
more conservative and not take the chance of introducing something that can actually
promote another cancer.
The second controversy is in the use of dietary supplements. During one of my
chemotherapy sessions I sat in the oncology ward while hooked up to my port-a-cath and
listened to a very ill old man undergoing treatment himself. In his impatience he asked
the floor nurse why they did not have a bottle of liquid or a pill that could be taken and be
done with all this fuss of treatment. His comment made everyone in the room smile, as
we all thought “what a great idea”. Unfortunately, as I have already stated, there is no
magic pill.
When it comes to phytochemicals the facts and research do not support the use of
phytochemical supplements as a substitute for dietary sources of phytochemicals. The
reason for this is that phytochemicals are notoriously unstable and they deteriorate
quickly and lose effectiveness when outside of the protective cell walls of the plants from
which they come. As a result, by the time the supplement has been shipped and sat on a
shelf then consumed the remaining content of an active phytochemical in the supplement
tablet can be absurdly low.245
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Secondly, the research has only identified a small part of all the phytochemicals in
each plant. It is entirely likely that there are complex chemical mechanisms that act in
the dietary intake of phytochemicals that are either fundamental or contributory to the
overall anti-cancer effect. It cannot be assumed that any one phytochemical, taken in the
form of a supplement, will have beneficial results.246
Thirdly, in the case where the supplement is very fresh, higher doses of chemicals
do not necessarily give greater benefits. In fact, over supplementing can confound your
absorption system, making it less effective in recognizing and taking in natural molecules
that actually have a beneficial result.247
In summary the dietary recommendations are to:
1) Relegate processed, smoked and fried food to the category of “rare treat”
instead of regular staple;
2) Drastically cut back on your consumption of starch and sugar;
3) Cut down on your intake of red meat and alcohol. Drink one glass of red
wine with your evening meal as a normal habit;
4) Evolve your meals and snacks around more fruits and vegetables, and whole
grain items as well, don’t forget to keep the roughage levels up;
5) Introduce foods that are less contaminated by modern farming and lower
your Omega-6 to Omega-3 intake ratio. This includes substituting ocean
caught fish for non-organically raised meat and fowl. Be aware, the larger the
fish caught in the ocean, the higher it is on the food chain and the more
contaminants it carries. So eat the smaller ones; and,
6) Rely on natural intake of phytochemical through your diet (instead of
supplements).
Attitude and Environment
In my first two sessions of chemotherapy I spoke to several of the floor nurses in
the oncology ward about treatment and survivability. They were all quick to volunteer
their anecdotes and opinion on the value of maintaining a positive attitude and having the
support of someone who cares.
As I tried to piece together the causes of my cancer in the literature it became
obvious as to just how effective the body’s immune response is in fighting disease. It
also became clear to me that the effectiveness of those defenses can be impacted both
negatively and positively by external influences. Then I started thinking about all the
negative influences that may have played a part in the development of my disease. One
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of the undeniable factors that had been consistently there throughout the last ten years
prior to my diagnosis was the element of psychological stress.
Stress can be divided into two types and are either short-term (acute) or longterm (chronic). The reactions to acute or chronic stressors cue behavioral and biological
responses in humans which can manifest themselves physically, psychologically and
physiologically.248
Acute stress is the reaction to a perceived immediate threat. The presence of an
actual threat is not necessarily required to cause the response. Instead, it is the perception
of a threat that is important. Such acute stressors typically elicit what is known as a
“fight or flight” response. This response is typically deactivated when the perception of
the immediate threat is gone and this is called the relaxation response. Examples of acute
stressors are noise (which can illicit response even during sleep), competitive endeavor,
trauma, exposure to dangerous event, or the recollection of exposure to dangerous
events.249
Chronic Stress is the reaction to stressful situations that are persistent and not
short-lived. “Fight or flight” response is generally not appropriate to chronic stressors
because the chronic stressor carries an element of omnipresence (being everywhere).
This means that they are part of the fiber and weave of the individual’s environment.
With this omnipresence is the perception or reality that the stressor cannot be defeated or
escaped from, and, therefore, such stressors continually act on the individual with little
solution or resolution.250
Chronic stressors include ongoing high pressure work, problems with significant
domestic relationships, loneliness, persistent financial worries and disease like cancer
(even if it is in remission). The common sense inference from this is that any set of life
circumstance that seats an individual in the path of such stressors for a prolonged period
makes that individual potentially vulnerable to the effects of chronic stress.
With this, I made my way through the definitive review of the scientific literature
regarding psychological stress and its effect on the human immune system. In a study
reviewing thirty years of scientific inquiry, Segerstrom and Miller, define chronic stress
to be consistently and reliably associated with decreases in almost all functionally
measured immune system response. They summarized chronic stressors with the most
detrimental effects to the individual’s immune response as those that:
1) Act on the individual over an extended period;
2) Are persistent rather than intermittent;
3) Act in such a way as to alter the individual’s identity or social role; and,
4) Are less controllable and afford less hope that they will be controllable in the
future. 251
The same researchers also noted that men are more biologically vulnerable to
stressors impacting on the immune system than women. Acute stressors, on the other
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hand, seem not to have a detrimental impact on the immune response at all. In fact, it has
been noted that acute stressors of short duration may actually boost the immune
response.252
There are a number of books on stress management and how to best cope with
stress. The techniques vary and include solutions involving biofeedback, meditation,
philosophy, religion, psychological therapy, and, prescription of drugs to name but a few.
Their detail, appropriateness and effectiveness are beyond the scope of my discussion. I
will say that, in my view, solutions to chronic stress should rely on a bit of common sense
and change.
The first thing is to do is to recognize and admit your chronic stressors. This
seems like a very straight forward and obvious point, but, it has been my experience that
those confronted with problems with no apparent solution tend to cope by “burying their
head in the sand” or trying to forget about them. No matter how good your ability to
compartmentalize problems, the unattended significant problems will eat away at you,
fester and resurface.
I have come to realize that most problems have a dynamic aspect about them, so
the problem or the initial conditions around it change with time. This means if you have
chronic stressors, perhaps you should review them every once in a while to see if there is
something that can be done to mitigate (soften) them. Of course, every individual’s
specific problems have their own particulars and unique solutions. All problems have
solutions and it usually just boils down to a question of cost, timing and ability to apply
the appropriate measure.
I understand that to find acceptable solution is “easier said than done”, especially
when I consider my own case. For years I had worked in a demanding field. This was
coupled with a miserable marriage, and an absolute nightmare of a divorce that I had to
defend against while still raising a family. The ensuing litigation and subsequent orders
put me in a place of financial turmoil carrying a large burden of a prolonged spousal
support. When reviewing my chronic stressors against the list noted by Segerstrom and
Miller, it would seem that all four qualities had been realized, time and time again.
At this juncture, I am still in the process of addressing my chronic stressors. This
became even more problematic when I had to contend with cancer as a patient. To
explain, consider that there is no such thing as a “bout” of cancer. Cancer is not like a
cold or flu that runs its course and never revisits. Instead, it is a disease that, even with
“cure”, always looms overhead and is to be constantly monitored and guarded against for
the rest of your life. To think that softening a handful of chronic stressors for a few
months then reverting back to your “old ways” will satisfy all of your immediate and
future immune requirements is absurd. In this case, you must resign yourself to the fact
that the changes necessary to repair are the same ones that will probably keep you alive.
If you cannot soften a chronic stressor, consider trying to simply “off load” it
instead. The easiest chronic stressor to deal with is loneliness. Humans are a gregarious
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species. Gregarious means that we need the company of others. For some, only a small
amount of company is enough. If family and friends are not an option, social clubs,
hobbies, taking a course, volunteer work, and support groups are all places to meet and
speak with others. Now is the time to start becoming involved so that you have someone
to “look forward to” or be around that can lend a sense of companionship. In this day
and age it is obvious how often people seek out company and connection. Just look at the
popularity of cell phones, as well as, on line chat rooms, dating and social networking
sites.
Studies have also reported that even a pet can satisfy a large portion of this basic
human need to have company.253
On the work front, we usually stay with an occupation for any one of a number of
reasons. Convenience; limited career choice; a sense of owed loyalty; fulfilling the needs
of a desired lifestyle; harsh economic times; or, just plain “target fixation” all come to
mind. If your occupation carries unrelenting levels of pressure to perform or succeed,
then changes must be made. There is seldom an occupation that is so binding and
inflexible that redefinition or replacement is not an option. Changing occupation may
mean that your financial situation will be impacted, but creating a more positive
environment for yourself has to take priority.
When I speak of a “positive environment” I am referring to surroundings that
make you feel good. These are aspects that can be counted on to promote laughter, light
heartedness, affection, a sense of comfort, accomplishment and calmness. In my case,
one of the facts about my work is that it took me away from home a lot. Except for the
occasional phone contact, my “away from home environment” was almost completely
devoid of those things that reliably make me feel good. So this is an example of
something that I had to change.
In terms of your domestic situation, it is time to deal with the negative aspects that
continually frustrate and over burden you. Marriages or long term relationships that are
“bad” have to be improved. Although anger, frustration or apathy may stand in the way,
try to address the source of the problem together with your mate. If this does not work
then get help with counseling. Religious institutions, clinics, and the courts all have
counseling services, some of which are free. The idea is to get to the source of the
problem and find solutions. If this does not work then consider separating. As a
defendant in a divorce process, I experienced one of the most nasty and unrelenting of
separations and divorces. The resulting acts of bad faith, committed by my ex-spouse,
were only compounded by the subsequent nonsensical orders that came from the Court.
The result imposed a totally unnecessary burden of stress that, in all likelihood, was one
of the major contributors to my cancer. Knowing what I do now I would have changed a
few things, but, in retrospect, it is easy to see the flaws in a situation. Nevertheless, the
end result of divorce was an enormous improvement in lending and promoting positive
aspects in my day to day life.
It has been my experience with any fight that it is important to maintain a calm
and positive attitude. If you go into a fight “scrambled” and with the notion that you are
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going to lose, you probably will. Scrambled causes you to lose focus. Without focus it is
difficult to determine or apply what is important. A positive attitude will allow you to
continue the fight the cancer with what you have. Do not underestimate the impact of
your resource and effort, no matter how meager or inconsequential it may seem.
All said I will leave this section on environment and attitude with some words of
mine to ponder regarding the effect of even the smallest of things on the overall outcome
of enemy and fight:
A few grains of sand acting on a soldiers foot is enough to ruin his will and ability to march.
Sand, if allowed to infiltrate a column of soldiers, can bring an advance to a standstill. Sand can
confound even the most well trained and technically advanced army. So never let it be said that
“It is only sand”.
Next, I would like to consider the element of exercise as a way to make you
stronger and more able to fight and endure the regimens that will be imposed on you by
cancer and its treatment.
Exercise
The benefit of exercise in helping fight cancer is an issue that has passed well
beyond any doubt. There are reports on how it lowers the risk of assorted cancer and that
it is able to benefit those diagnosed with cancer. Exercise can be a valuable assistance in
cancer prevention, recuperating lost range of motion following treatment, regaining
strength and reducing pain after the trauma of surgery.
In a study involving 2,705 men diagnosed with non-metastatic PC observed
between the years 1990 to 2008, it has been reported that physical activity was associated
with lower overall mortality and PC related mortality in these men. Vigorous activity
such as biking, tennis, jogging, or swimming for 3 hours or more a week may
substantially improve PC specific survival. 254
In my view, the stronger you are, the easier it is to maintain and endure mental
and physical hardship. No one can say how much exercise is “enough” to improve on the
effects of Prostate Cancer treatment or to harden you against cancer in general. No one
can say what type of exercise is the best. This is because we are all different and all
respond in different ways. As has already been said, the medical community is
accustomed to basing its recommendations and treatment on research with reproducible
results and causative link. The best combination of frequency and type of exercise to
address any cancer can only be speculated because there are simply too many
uncontrolled variables in the lives, disease and response of those willing to participate in
such a study. In any case, fighting cancer requires you to deal with mental and physical
hardship. So I suggest you proceed with the idea that any natural thing to make you
stronger is going to help. Of course, it is strongly advised that any exercise routine is
discussed and approved by your overseeing medical staff before you begin.
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Again, it is not my intent to exhaustively discuss the “universe” of exercise. This
is a topic that has and will continue to spawn an unending array of books and comment. I
will say that generally any exercise, even the smallest amount, is better than doing no
exercise at all. Like dietary change, exercise is likely going to require a change in your
habit and does not call for drastic change all at once!
A few years ago, I heard an interview of Robert Greene who is an author of
several exercise and nutrition books, the first of which was co-authored with one of his
clients Oprah Winfrey. In this interview, he drew attention to the fact that his books
related to diet sell much better than those related to exercise. I found this odd, since he is
renowned as THE “Trainer to the Stars”. Mr. Greene’s contention is that people, in
general, seem to prefer to address elements of their health and physique with diet instead
of exercise. When I listened to this interview I remembered, as a teenager, how difficult
it was to get my Dad to do a bit of exercise. It was as though there was absolutely no
place or provision for this in his day. My Dad went on to endure several heart attacks,
bypass surgery, diabetes and several strokes before he passed. I believe that the greater
part of his poor health was directly related to smoking for nearly four decades, coupled
with an unfaltering pact to avoid even a small amount of dedicated exercise. Sadly, I
never understood the mentality or the lack of motivation contributing to such
deterioration.
I suppose the argument can be made that exercise didn’t help me avoid cancer.
To this I reply, I am still alive and it may be so only because I luckily kept myself strong
with exercise and activity.
I look at today’s busy world where everything is processed and compressed from
the time we wake to the time we “drop” in the evening with exhaustion. I see parents
frantically ferrying their children from one tightly scheduled activity to the next, as
though on a mission to completely extinguish both child’s and parents’ will to do any
activity by sheer overexposure. I see people clearly out of shape and overweight
waddling to yet another “line up” for buffet or fast food. I see unreleased frustration in
the flexing mandibles and fidgeting eyelids of women and men who have nothing to look
forward to except to eat, sleep, work or watch television. In all of this I ask myself:
Where is the common sense? Where is the connection with self? Where is the
understanding that you must take care of yourself?
One needs only to look at a group of small children playing to realize the benefit
of activity. Cheeks become rosy, lungs expand, laughter prevails, calories are burnt,
sleep is sound, illness is deflected, and friendships are made when we exercise. All of
these things are an essential part of living a healthy life and having a good immune
response. Why then is there so much resistance to exercise as we grow older? The
following are the lines I have heard over the years from friends, family, and associates
regarding the reasons not to exercise. Do any of them sound familiar to you?
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I’m too tired.
I’m too lazy.
I’m too sick.
I don’t want to get injured or sore.
I’m too sore.
I’m injured.
I don’t want to look like a body builder.
I look like “@hit” and don’t want to be “seen” like this.
I don’t like to sweat.
It’ll ruin my hair.
I’m not comfortable.
It’s too nasty outside.
I don’t have time.
I just need to rest.
I already did some a few days ago.
I don’t know how to exercise.
I don’t like to exercise.
Exercise really doesn’t do anything for me.
I’m embarrassed.
I’ll go next time.
I don’t need to.
It seems that there is always a way to defer exercise activity in the face of
diversion, affliction or lack of motivation. All of this has to be overcome. For those of
you already diagnosed with cancer your motivation is simple. Do what you can to stay
alive and have a good quality of life.
Starting any exercise regimen from scratch is not an easy thing to do, even if you
are healthy and not afflicted by cancer. I believe that what stands mostly in the way of
exercise is your frame of mind. Almost anyone can exercise regardless of their physical
state. You do not need a gym membership. You do not need elaborate equipment. You
don’t need a lot of free time. You do not need to be concerned about being injured or
getting sore. You do not need to make a fashion statement. What you do need is the will
to start exercising for a few minutes every day and stick with it.
Time and time again I hear the media report that walking is a good place to start if
you do not exercise. Guess what? Walking is good exercise! You can walk on a
treadmill, but, exercise indoors and in isolation does not have the same effect as being
outside where you can come in contact with the change in scenery, fresh air, your
community and others. Of course, there are those who may reside in places where there
is just nowhere to go for a neighborhood jaunt. I expect that you will use your judgment
in this regard and stay safe.
Swimming, spinning (riding a static cycle), and bicycling are all excellent for the
cardio-vascular system and easy on the bones, back, and joints. I compare these to
running or jogging which can wreak havoc on the body of even the most seasoned
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athlete. Most Decembers I spend a week in South Beach Miami where each morning I
witness the arrival of those trying desperately to get back in shape. I can only describe
what I see as misguided effort involving running or jogging in the sand for really long
distances in the heat of the day. Too much, too soon! At any given time I expected to
see any one of these out of shape individuals collapse in “sunbathed” cardiac arrest.
Meanwhile, the water has practically no one in it, and I only see a handful of cyclists the
whole time I’m there. I know that there is an entire generation out there who harbor
irrational fears of going in the water; thank you very much Mr. Peter Benchley. I believe
it is time we got over the sensationalism of shark tales and start taking advantage of the
recreational and exercise value associated with water activity. I suggest for those who
want to do more, to just get in the water and walk against its resistance. If you find this
too easy then make an effort to move through the water column quicker by walking faster
or walk in a little deeper water. Rest assured that you will soon feel the effects of the
water’s resistance. That resistance will produce result in the way you look and feel.
Again, use common sense, don’t overdo it, be consistent and be patient. Results take
time. If you don’t relish the idea of going into ocean, lake or river find a pool and
exercise there.
For those who have no way to exercise in water and have no gym, consider your
surrounding work or domestic area as a place to conduct calisthenics, isometrics and
stretching. The routine does not have to be done all at one time. It can be adapted to fit
into small segments that are available throughout your entire day. Isometrics is a type of
strength training that involves exerting a force on something that is immovable, like a
wall or heavy object. The force (pushing, squeezing or pulling) is exerted for ten to thirty
seconds against the immovable surface in the same way as you normally do the full range
exercise, but without the movement through the range when exerting the force. The
advantage of such exercise is that it may be better suited to the needs of someone who
has been substantially weakened by surgery.
Exertion, either isometric or the full motion calisthenics such as dips, pull ups,
push-ups, squats, calf raises, sit ups, back arches and lunges are exercises that can be
done without a gym and only a couple of minutes “here and there” with relatively
painless and effective result. To do these exercises all you need for “equipment” is a
couple of sturdy chairs, a bit of floor, and a doorway. If you have never been taught
the proper technique for these exercises then I suggest you ask your physiotherapist
or go to your local gym and consult a certified trainer. Say that you need to adapt a
routine, with the above exercises, to the space, equipment, time and physical constraints
of your condition. The same can be done for stretching. Ten minutes of stretching
should be lots. Be careful not to over extend or bounce when stretching. The idea is to
increase your range of motion and elongate your muscles, not tear them. Make sure you
are warmed up first. A hot soak in the bath or a bit of exercise helps to do this. If you
are relying on a warm up from exercise, plan to do your stretching at the end of your
routine. A twenty to forty minute routine of exercise and stretching every day is plenty.
As I said, it does not take much to have result but you have to be consistent about doing it
regularly.
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For those who are already diagnosed and athletically inclined, or otherwise quite
active, consider the rigors of surgery and treatment will require you to “ease off” for a
few weeks. Let the incisions heal. Don’t become overtired from too rigorous an exercise
routine either. Use common sense, keep your physician informed, and keep active. I
started my chemotherapy and continued exercising. By the end of a six month regimen
of chemotherapy I had lost at least half of my strength. It took the better part of two
years thereafter to regain the lost levels, but I persevered and I am pretty much back to
my accustomed self.
It is known fact that the act of sex is a great exercise with many physical,
physiological and psychological benefits. Sexuality in the face of illness is a topic that
has a broad scope of considerations as discussed by the authors Schover and Jensen in the
book Sexuality and Chronic Illness, a Comprehensive Approach. Men who undergo most
currently prescribed clinical treatment for Prostate Cancer will likely have to contend
with substantially impacted sexual function. In addition, to prostate trauma or removal
from initial treatment there is the possibility of continued therapy regimen that may
further impact on recovery of sexual function, self-esteem, physical ability and sexual
appetite. Whether you do or do not participate in regular sexual activity during and after
Prostate Cancer treatment is a matter of personal choice.
You should be aware that the acts of intimacy (not just intercourse) and the
chemistry involved has a number of reported benefits including positive effect on
longevity; reducing risk of heart disease and cancer; increasing immune response;
improving ability to fall asleep; promoting youthfulness; improving fitness; improving
sexual and reproductive health; increasing ability to manage pain; reducing stress; and,
improving self-esteem, among other things.255
Sounds like a magic pill to me. Of course, all of this is contingent on you and
your lover’s success in coming to terms with your actual or perceived condition. The
only thing I can suggest is to keep talking and touching. Don’t assume anything is
understood unless it is said and say it well in advance if you can. This way both of you
have time to find a way. Love, like life, will find a way.
Acupuncture
Cancer is an old disease and the medical techniques that are conventionally used
to treat it are comparatively new. Traditional medicines such as those developed by the
Chinese have been practiced for roughly two thousand years of recorded history.256
Acupuncture is one of the branches of Traditional Chinese Medicine (TCM). In
the ongoing quest for solution, conventional consideration is now being directed at
dissecting traditional medicine and using portions of it to assist mainstream cancer
treatment and care. Although one is hopeful that this is opening the door to the greater
use and understanding of such “alternative” medicine, I question the value of any study
that passes judgment on the effectiveness of traditional techniques when those elements
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of medicine have been far removed from the forum or expert practice in which they are
normally found.
The largest barrier for those of us that are not from culture that relies on
traditional medicine is our lack of familiarity and understanding of it. Nevertheless, its
effectiveness in providing relief for aspects of human affliction and disease is known and
accepted by a staggering large part of the world’s present population.
Since the 1970’s in the United States, acupuncture began to be brought under the
umbrella of recognized government standards for training curriculum content and
practice.
The United States presently has some 41 states with either Acupuncture Practice
Acts or Statues; or, laws governing education and qualification to practice acupuncture.257
In 1996 the FDA approved acupuncture needles as a medical device.258 In the UK, there
are some 7,000 nurses, physiotherapists and doctors who have training in acupuncture.259
In Canada the regulation of traditional acupuncture is established in four provinces
namely, Alberta, British Columbia, Quebec, and Ontario.260 In Australia the Chinese
medicine profession (which includes acupuncture and Chinese herbal medicine
practitioners) has been approved for inclusion in that country’s National Registration and
Accreditation Scheme for Health Professions as of July 1, 2012. 261
In the eyes of the western medical community there are two types of
acupuncturists, those that are trained and practicing according to a set of accredited
governmental standards, and those that are not. What goes along with those practicing in
accordance with the government standards are baseline protocols in procedure; minimum
conversancy with the material; and, safety. Arguably, it would seem to me that
mainstream physicians from western medical communities who have studied acupuncture
in some brief way are bound by their medical training to apply it in a way that denies the
other elements of TCM that in all likelihood makes acupuncture effective.
Not to belittle the need for regulation and standards in the practice of
acupuncture; however, to me it makes sense that those who have had an extended period
of study under a master; have practiced TCM for decades; and, are in good standing with
the medical community in their country offer treatment that is effective because they are
using acupuncture in a way that it was trained and intended over thousands of years.
In terms of how acupuncture works the scientific explanation is that the needles
used for treatment are positioned in specific locations on the body to stimulate the body’s
neurophysiological chemical process.262 In reality; however, acupuncture technique and
process is not well understood by the medical community as a whole. This understanding
can be likened to the field of anaesthology in conventional medicine. In short, real
understanding of its application is reserved for those who are experienced and wellpracticed in the techniques.
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Traditional explanation of how acupuncture works is rooted in Chinese
philosophy and science and the concept of Qi (pronounced as Chee) and Xue. Qi is the
body’s vital energy. Xue is the body’s blood. It is said that the flow Qi is affected by the
balance of Yin and the Yang. Yin is the female side of universal energy and is dark.
Yang is the male side and is light. All energy is a combination of the Yin and the Yang.
They do not exist separately. Good health involves a balance between the Yin and Yang.
If the balance is good, Qi “flows” freely along the energy lines or meridians of the body.
Specific imbalances lead to specific health problems. Poor health is treated by
manipulation and revitalization of the body’s meridians with a combination therapy of
needles, herbs, massage, counseling and exercise. This combination therapy is the how
TCM (Traditional Chinese Medicine) is practiced.263, 264
Figure 44 shows a simplified diagram of the body’s acupuncture meridians.
There are approximately 2000 acupressure points on the body. The head, hands, feet and
sides all have meridians and points. Most of these are not depicted in this diagram.
Figure 44. Simplified illustration of acupuncture meridians and points on the body.
source: http://en.wikipedia.org/wiki/File:Chinese_meridians.JPG
originator : Phil Perez
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The needles that are used in acupuncture are very fine and when inserted are not
really “felt” by the patient as would be a needle used for taking blood, for example. The
depth of insertion is shallow and penetrates to just below the patient’s skin. Once
positioned these needles are left in for as much as a half an hour. Sometimes
practitioners use the needles as conductors for laser, microwave, tactile, and mild electro
pulse stimulation OR not. Acupressure is another variation and uses the same meridian
pressure points without the needles.
In Acupuncture, the number of needles and their placement varies with the
affliction and a host of other considerations. The number of sessions required to have
results also varies. Reports of effectiveness focus mainly on the sedative aspects of
acupuncture.265 For example; there are numerous reports where acupuncture is being used
quite successfully instead of anaesthetic during surgical procedures in China.
Unfortunately much of this ongoing treatment seems not to be published in what is
considered recognized scientific journals. As such; the scientific proof needs to be made
available so that questions on acupuncture effectiveness can be properly weighed.
In 1997 the United States National Institute of Health began studies on the
effectiveness of acupuncture. So far, the results reported are that acupuncture can be
effective in: boosting the body’s immune response in cancer patients; and, relieving
symptoms of pain and nausea associated with cancer and the side effects of
conventional treatment. Ongoing Clinical trials studying the effects of acupuncture on
side effects caused by conventional cancer treatments including weight loss, cough, chest
pain, fever, anxiety, depression, night sweats, hot flashes, dry mouth, speech problems,
and fluid pooling in the arms or legs. The results are indicating that for many patients
treatment with acupuncture either relieves symptoms or prevents them from getting
worse.266
One unexpected aspect of the “piecemeal” application of acupuncture with
regards to tumor treatment is the thought that treating a tumor with acupuncture would
“unbind” the energy that caused the formation of the tumor in the first place.
Consequently, there are non-TCM acupuncture practitioners who refuse to treat tumors
because of concern that the tumor will be dispersed throughout the body leading to more
complication. It is questionable whether or not this is sound logic or whether this is in
fact the way that the body would respond to acupuncture tumor treatment.267
One of the certainties of acupuncture is that it has application and effectiveness
for a number of afflictions. As well, given the spectrum of those practicing this science,
it makes sense to seek out practitioners who are experienced and specialize in cancer
treatment or prevention if that is what they are going to be required to do. Some hospitals
have practicing acupuncture MDs that work in concert with the oncology department and
treatment regimens. Alternatively, almost every country has acupuncture associations
that can be contacted to find a reputable acupuncture specialist that best fits your needs.
In reviewing the literature regarding the applicability and effectiveness of
acupuncture, I find that this field of medicine is prominent in the United States Clinical
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Trials (see http://clinicaltrials.gov/ct2/results?term=acupuncture) and there are now some
trials regarding acupuncture that are registered in the recently available on line European
Community Clinical Trial site (see https://www.clinicaltrialsregister.eu/ctrsearch/search?query=acupuncture). In addition, similar activity is registered on the
Australian Clinical Trial Registry (see http://www.anzctr.org.au/trialSearch.aspx). As
such, it is clear that acupuncture has been received and is becoming an integral part of the
mainstream medical community’s theatre of available service.
Early Recognition and Screening
The mainstream medical community is torn between those who recommend
Prostate Cancer screening for early detection; and, those who unconvinced of the value of
such procedure given the current clinical treatment options in the event early stage PC is
discovered.268
On one side of the debate are organizations such as the American Urological
Association and the Urology Care Foundation who believe that early detection and risk
assessment for PC should be offered to asymptomatic men 40 years of age or older who
have a life expectancy of at least 10 more years. They also state that men being screened
should have PSA testing and a DRE.269
So let us examine some of the more prominent studies on Prostate Cancer
screening. In a study initiated in the early 1990’s involving 182,000 men between the
ages of 50 and 74 years of age from seven European countries the results of this “colossal
undertaking” found that PSA based screening reduced the rate of death from Prostate
Cancer by 20%; but, was associated with a high risk of over-diagnosis. 270 In another
study began in 1994 involving 20,000 men that started out between the ages of 50 and 64
it was reported that over a period that extended to the year 2008 (14 years) Prostate
Cancer screening (involving mostly PSA testing) reduced mortality by almost half.
Similarly, this study states that the risk of over-diagnosis was substantial. 271 So here we
have two large studies involving 200,000 men over a couple of decades where there is
clear and significant mortality benefit for those who participated in PC screening.
On the other side of the fence, for example, is the U.S. Preventative Services Task
Force whose current recommendation for Prostate Cancer screening before diagnosis
concludes “that many men are harmed as a result of Prostate Cancer screening and few, if
any, benefit. A better test and better treatment options are needed. Until these are
available, the USPSTF has recommended against screening for Prostate Cancer.” 272
USPSTF co-Chair M. LeFevre, M.D, MS.P.H. goes on to say that, “The members
of the USPSTF face the same concerns and fears about health challenges as other people.
This decision was reached only after extensive consideration and thoughtful debate. It is
based on science and rooted in the knowledge that, while everyone wants to help prevent
deaths from Prostate Cancer, current methods of PSA screening and treatment of screendetected cancer are not the answer.” 273
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To justify their position the USPSTF have published what they call a review of
the evidence. In this document they state their screening recommendations were based
on the results from four questions they answered, those being:
- Does PSA based screening decrease Prostate Cancer–specific or all-cause mortality?
- What are the harms of PSA-based screening for Prostate Cancer?
- What are the benefits of treatment of early-stage or screening-detected Prostate Cancer?
- What are the harms of treatment of early-stage or screening-detected Prostate
Cancer?274
Having looked at the USPSTF review myself, I have concerns with the USPSTF
conclusions and any medical entity that embraces them. To clarify:
Firstly, there is no doubt that PSA based screening (that usually involves a DRE)
has benefit both in early detection of PC, as well as, impact on PC related mortality as
reported by the European studies involving 200,000 men;
Secondly, PSA-based screening is not harmful. The harm lies in the current
protocols that are in place to address elevated PSA levels discovered from the testing.
Percentage based core needle biopsy and biomarker probability charts are the
predominant methods used to press on with diagnosis. In my view, reliance on such
method to arrive at a diagnosis is what has been resulting in the false positive results and
damaging diagnostic procedure; and,
Thirdly, the questions of harms and benefits; and more specifically, what to do
when one is diagnosed with early stage PC remains a heated debate within the
mainstream medical community. I think the question of “what to do?’ is not for the
mainstream medical community to address. This question should be addressed by the
patient who should be better informed.
The mainstream medical community should be more concerned and focused on
better ways to diagnose and treat early stage PC so as not to be so blatantly rooted in
radical procedures or procedures that are so ineffective and damaging to quality of life
that a “WAIT, WATCH AND SEE” option is actually condoned and offered as a
legitimate way to address poorly understood disease that can progress to the point of
being terminal in timeframe that no one, to date, can be certain of.
One example of screening advancement that could result in a reliable, noninvasive, and, affordable clinical screening application as soon as 2014, involves
diagnostic nanotechnology featuring a computer chip able to detect prostate specific
biomarkers.275
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In any case, awareness, informed screening and taking advantage of more
advanced clinically approved methods are all helpful in catching this disease early on and
more precisely identifying the extent of the PC. As has already been discussed, such
clinically approved methods involve for example,
FDG PET/ CT imaging;
PET/CT combined with the contrast agent
precisely;
11
C-Choline to image PC more
SPET/CT to determine an individual’s specific prostate lymphatic drainage
patterns; and,
MRI guided biopsy.
Catching the disease early on means that you know where you stand. Early
diagnosis means you can take advantage of much less radical options, like HIFU, that
may be arranged and actioned early enough to prevent not only advanced stage disease
along with its confounding ability to cure; but, also the enormous quality of life impact
associated with more invasive treatment regimens. This is just common sense.
Overall and in my view, there is no disadvantage with seeing your physician as a
young adult to have a Lifetime Risk Assessment of Prostate Cancer done. Know and
advise your physician of your family history relating to Prostate Cancer so they can factor
that into their assessment. At the same time ask for baseline PSA testing and DRE. The
results from this can provide useful data that later screening results may be compared
with. Finally, consider asking for a practical demonstration on the correct way to
perform self-DRE.
If it turns out you have a moderate to high lifetime risk I suggest you make a
reasonable plan for screening that involves a specialist and some good imaging like a
FDG PET/ CT scan.
Prevention
So apart from quitting smoking, adopting a “cancer unfriendly” diet, exercising
and having a lifestyle with less chronic stress what else can be done to prevent you from
being one of the six men in a room diagnosed with Prostate Cancer?
According to a study involving 47,843 men from the United States between the
years 1986 and 1998, alcohol does not appear to be a strong contributor to Prostate
Cancer risk, except possibly in men who consume large amounts infrequently and in men
with type II diabetes mellitus.276 Similarly, in a European study involving 142,607 male
participants between the years 1992 and 2000, it was concluded that the use of alcohol
has little or no association with the risk for Prostate Cancer. 277
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In a study involving 69,991 men from the United States it was concluded that
obesity increases the risk of more aggressive Prostate Cancer and may decrease either the
occurrence or the likelihood of diagnosis of less-aggressive tumors. Men who lose
weight may reduce their risk of Prostate Cancer. 278
Along the lines of specifically exercising the prostate and it sexual functions,
research has reported that that a reduced ejaculatory output in otherwise normal males is
associated with an increased risk of Prostate Cancer, especially if this commences early
in adulthood.279 Another study involving predominately white males suggests that
ejaculation frequency is not related to increased risk of Prostate Cancer; although high
ejaculation frequency may possibly be associated with a lower risk of total and organconfined Prostate Cancer.280 In perusing the literature on this topic, it seems to me that
more data with larger numbers of participants and more accurate reporting on sexual
frequency has to be analyzed before any accurate conclusions on the relation of sexual
activity and risk of Prostate Cancer can be made.
Follow Up
One thing you must keep in mind after you have been diagnosed with Prostate
Cancer with or without treatment is the Follow up. Follow-up is not standardized and is
in fact quite variable. Your clinician will discuss the exact details as they pertain to your
case so that you are aware of what protocol your facility uses and what to expect. As
stated, you are your own best manager of your health file. If you have not received
appointments when expected then make the appropriate calls to ensure the follow up
process is scheduled and done. Follow up has to be done to monitor your condition. It
determines if the measures that are in place are adequate; and, affords clinicians the
information necessary to make decisions on whether or not additional treatment is
recommended.
The following are some commonly used types and timings of follow-up:
•
For those diagnosed with PC opting for Watchful Waiting - PSA testing (with
DRE) every 3-12 months. For those with asymptomatic metastic PC, bone scans
once a year OR alternatively, when the total PSA level arrives at 40 ng/ml as an
indicator as to whether or not ADT is merited;
•
For those who have undergone Radical Prostatectomy – PSA testing every 3 to 4
months for the first 2 years; PSA testing every 6 months thereafter up to year
five; at year five once a year every year;
•
For those treated with EBRT – PSA testing (with DRE) every 3-6 months for 5
years. Annual PSA testing (with DRE) thereafter. Some practitioners recommend
biopsy 18-24 months following treatment;
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•
For those treated with Brachytherapy- PSA testing (with DRE) every 3-6 months
for a year. Thereafter, annual PSA testing (with DRE) should be done. Some
practitioners recommend biopsy 18-24 months following treatment; and,
•
For those exhibiting signs of biochemical recurrence (PSA levels rising) - Closer
follow up than what is detailed above with consideration of alternative therapy. If
PSA levels double every 10-12 months OR if PSA level reaches 20 ng/ml then
imaging is recommended.281
In terms of follow up that I do on my colorectal cancer, I supplement my follow
up with an annual “neck to toe” FDG PET/CT scan. I do this because I know the
imaging is thorough, comfortable, fast, safe, does not involve a lot of unpleasant
preparations, and it covers parts of my body that are beyond the initial area of the cancer.
It is the way I address the chronic stressors associated with being in CRC remission. It is
also the way I can look at those around me and honestly say that everything is fine. Take
note that the cost of a PET scan is not cheap in the area of $2,500.00. So it really helps if
you have health insurance coverage.
Miscellaneous and Promising Research
There was a news release in 2010 reporting on the meta-analysis led by P.
Rothwell from the University of Oxford finding that participants who took one regular
pill of Acetacylic acid (Aspirin®) for an average of 4 years had a 44% reduced risk of
dying from cancer compared to those in the study who did not take aspirin. From this
analysis it was further pointed out that in follow up it was found that 20 years later a
subset of those participants who took the aspirin still experienced a 20% reduction in the
risk of dying from cancer.282 The whole seemed too good to be true, one cheap little pill
that has been around for over a hundred years substantially reducing the risk of dying
from cancer; but those are the reported results. On the down side of this reported miracle
pill is the predominant concern in the medical community that low dose acetacylic acid
use can cause severe gastrointestinal bleeding. As such; the benefits and risk of low dose
acetacylic acid use over a period 4 years or more must be weighed against lifetime risk of
cancer.283 Certainly such preventative strategy merits discussion with your physician.
On another note, there has been substantial interest on the use and effect of
Vitamin D both in the mainstream medical community and the naturopathic health
community. To clarify,
1) Vitamin D is really not a vitamin at all, instead it is a fat-soluble prohormone involved
in the production of hormones;
2) There are two majority sources of this prohormone. One is from plants called D2. The
other is called D3 and is made by the body when exposed to sunlight. Both are turned into
the active form in the body called 1,25-dihydroxyvitamin D also known as calcitriol.
Calcitriol is involved in the body’s uptake of calcium among other things;
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3) There are recommended daily minimums on Vitamin D intake that are age dependent
and range from 5 μg (=200 IU) up to 50 years of age to as much as 15 μg (=600 IU) when
one is 71 years or older. This daily minimum can be arrived at by dietary intake, by
absorption of the sun or by taking supplements. Excessive intake of vitamin D can cause
some very undesirable effects including:
- calcinosis (the deposit of calcium salts in soft tissues such as the kidneys, heart,
and lungs) and/or
- hypercalcemia (high blood levels of calcium); and,
4) Associated symptoms of excessive vitamin D intake may include heart rhythm
abnormalities; confusion; pain; conjunctivitis; anorexia; fever; chills; thirst; vomiting;
and weight loss. 284
There are some 481 clinical trials registered in the USA involving vitamin D and
its role in aspects of a number of cancers. The benefits of vitamin D intake for breast,
colorectal, Prostate Cancers and leukemia, as well as, chemotherapy treatment side
effects such as peripheral neuropathy (common to platinum based regimens) and
reduction of bone loss during ADT is certainly a strong interest of the trials.285 Overall;
however, there is nothing that I see in the literature indicating that the minimum daily
intake level of vitamin D is consistently correlated to lowering the topical risk of cancer.
In any case, vitamin D minimum daily intake should be adhered to for all of the
normal bodily functions it supports.
On the side of promising new developments we find researcher M.Q. Wei of the
University of Queensland who’s research is focused on using clostridial spores found in
grey kangaroos to arrive at a ‘Trojan horse” vector for cancer gene therapy. Apparently
the genetically modified clostridial spores have intrinsic properties allowing them to
colonize and destroy tumors, as well as, having a seemingly unlimited capacity to carry
exogenous genes when acting in the role of a genetic vector. The curative potential, in
my view, is mind boggling. Thus far; however, this promising discovery has not made its
way through clinical development.286 So with hope and patience we wait.
Patient Support
When I was diagnosed with cancer there was a string of repercussions that went
along with diagnosis and treatment that touched virtually every facet of my life. How I
was received by friends and family; how I was perceived by colleagues; ability to work;
ability to travel; ability to be insured; financial situation; diet; and, considerations for the
future were all impacted. “When it rains it pours.” The whole thing can be more than
overwhelming at a time when you should be focusing on your fight instead of all these
other challenges.
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One of the things that will happen when you first arrive at your oncology unit for
consultation and treatment is that you will be briefed on what support and help is
available. This information details local discussion groups, possible financial assistance,
psychological counselling, local clinics, an overview of Prostate Cancer as a disease and
its treatment, as well as, a point of contact at the oncology department. Take this
information as a start point and don’t be afraid to ask for more help if you need it.
Prostate Cancer surgery and treatment can be harsh and the effects more than
“bothersome” to self-esteem and significant relationships. There are a number of
programs associated with treatment facilities that serve to help patients adjust and come
to terms with these effects and changes. Your medical facility will be able to direct you
to your local initiative in this regard.
In terms of finances, there are a few things you can to do to make sure any
transition away from a regular pay check during a period of disability is uneventful. My
suggestion is to take out insurance for critical illness or being unemployed before you
are diagnosed. Insurance companies always ask for the date of diagnosis when you
make a claim. Once you are diagnosed it is too late to apply for such coverage. All major
credit cards have this available, and it can usually be made active with a simple call to
customer service. Make sure you do this for every active credit card you have. If it
becomes necessary to have the insurance cover your credit card debt then you will
probably have to fill out a couple of insurance forms supplied by each credit card
company’s insurer to describe and verify the details of your condition. This is no
problem if you have been keeping a file of you case history.
Critical illness and unemployment coverage is also available for mortgages and
loans. Unfortunately you typically only have one opportunity to apply for this coverage,
and it is when you initially apply for the loan or mortgage. In any case, sometimes policy
is different between lending institutions, so if you are not covered at least ask.
If you are faced with a monthly payment of income on a short or long term
disability scheme, call your creditors and let them know what is going on. This way they
can adjust your bill payment time to a date when your disability money arrives.
If your employer makes your payments on your life and disability insurance when
you are on short term disability, make sure your payments for both will still be made
when you are moved over to long term disability. Sometimes this is not the case, and
suddenly you find yourself without any life insurance coverage, for example. Also make
sure these things are in writing.
When I was diagnosed I thought I was pretty well insured. After 6 months into
treatment I transitioned from short term to long term disability income which only gave
me 45% of what I was accustomed to in terms of gross income. Suddenly, I found
myself unable to make ends meet financially. In short, make sure that you are adequately
insured and do this well before you ever have to face diagnosis. When you are young and
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healthy insurance of this nature is easy to get and does not cost much to maintain from
one year to the next.
Sometimes despite the best efforts of fight and medical technology there will be
those patients whose Prostate Cancer condition evolves in such a way that it is not
curable. In hand with palliative treatment is palliative care. Family members or close
friends may often be the only recourse to seeing such patients through. Full time,
“around the clock” attendance to the needs of a terminally ill patient is daunting task even
for someone who has background in chronic or palliative care. This is further
compounded by emotional attachment of watching a loved one deteriorate; and, possible
poor health of the caregiver themselves. To assist patient and caregiver there is an
assortment of network, information, programs and support that can be called upon.
Details of such support are usually available at your local health care centers and
hospitals.
Praying and Belief
Man’s world is a complicated weave of differences in belief and faith that has
historically been at the root of both war and peace, and, will probably always continue to
be. Medical intervention is a developing part of man’s ability to “help oneself”. For the
most part, it is consistent with the majority of religious and atheistic (non- religious)
beliefs. Still, when the best efforts of man-made solutions fall short, critical illness has a
way of moving people towards any means that can help them or those they care for.
How belief and faith works for any one individual is a personal matter that defies
words. It has to be respected that belief and faith can have a profound effect in terms of
fight, recovery, or coming to terms with loss.
Cancer Foundations
If you go to the internet and type in Prostate Cancer Foundation on a search page
like Google it results in approximately 4,150,000 possible results to review. If you type
in Cancer Foundation this number expands to a whopping 112,000,000!! This is clear
indication of the attention and energy being allocated to disease like Prostate Cancer
disease through foundations. Most of these foundations are small and tailored to a scope
emphasising support and assistance at regional and local levels. There are, however,
foundations that function at national and international levels. Regardless of whether they
are local, regional, national or international, the emphasis of these foundations vary and
provide support through fundraising dedicated to assorted cancer awareness, acquisition
of needed equipment, prevention through screening initiatives, research, specialized
training, and, medical facility upgrade.
In spite of this, cancer prevails and confounds lives every day, everywhere. Still
there is progress towards awareness, prevention, better treatment and cure. The rate of
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progress is directly proportional to the amount of funding available. Every little bit helps.
Together we can find a way to drastically reduce the number of lives affected by this
silent killer.
In the meantime, take care of yourself and don’t give up the fight.
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Glossary of terms
abscess - a pocket or capsule of pus formed by the body’s immune system in response to invading foreign
organism or material.
acupuncture - one facet of traditional Chinese medicine using pressure or needles to restore body energy.
adenoma - a benign abnormal growth of glandular origin.
adenocarcinoma - a cancer that originates in glandular tissue.
adjuvant therapy – post surgical treatment used to extend survivability or prevent recurrency.
ADT – androgen deprivation therapy.
aerobic respiration – efficient chemical reaction occurring in healthy cells that releases energy when
glucose is combined with oxygen in the body.
AJCC – American Joint Committee on Cancer.
anaerobic respiration - (glycolysis) inefficient chemical reaction that occurs in cells in the absence of
oxygen resulting in the fermentation of glucose to produce energy.
anaesthetic – a drug or combination of drugs used to control pain or discomfort.
anaesthesiologist – a physician that specializes in the study and administration of drugs to allow surgery or
control pain and discomfort.
ANC – absolute neutrophil count.
anemia – a condition where there is inadequate transfer of oxygen to the tissues and organs of the body.
This can be the result of excessive blood loss, excessive blood cell destruction or deficient red blood cell
production.
angiogenesis - the formation of blood vessels in cells and tissues.
antibodies- immune system component produced in response to invasion by a foreign substance. Designed
to combat infection.
antigen - a substance or foreign substance that causes the body’s immune system to produce antibodies.
anus - the opening at the end of the digestive system from which feces (waste) exits the body.
apoptosis - cells self-destructing.
arterial – related to the arteries.
ATP - adenosine triphosphate is a useable energy source that drives human metabolic processes.
axillary - pertaining to the armpit.
benign - being without cancer.
biopsy – the sampling of a small portion of tissue.
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branchytherapy – radiotherapy involving the implantation of a radioactive material either temporarily or
permanently.
CAD – computer aided detection.
cannula - a small device that can accept needles usually installed on a vein in the wrist, fore arm or bend
of an elbow.
carcinoma – a malignant growth that arises from the epithelium (the covering of internal and external
surfaces of the body, including the lining of vessels and other small cavities). This includes the skin and
lining of the organs such as breast, prostate, lung, stomach or bowel.
catheter – a device inserted into the bladder via the urethra to assist drainage of urine.
cellulose – (roughage) a polysaccharide formed of simple sugar units joined by beta linkages and virtually
indigestible by humans.
chemotherapy – treatment involving chemicals to target and eradicate, reduce or slow cancer cell growth .
chromosome – a “package” of genetic material. In humans there are 46 distinct chromosomes, which
together contain all the information required for making a living person.
CIS – (Carcinoma in situ), the cancer is restricted to the mucosa or surface on which it resides. This is the
earliest stage of cancer.
coelomic – pertaining to the body cavity also known as the coelome.
Corpora cavernosus – muscles involved in penile erection
CRC- colorectal cancer.
cryoabilation – removal by freezing.
CRPC – castrate resistant Prostate Cancer.
CT - (computed tomography) scan that uses radiation to make an image of body structure.
curative - designed to cure.
cyanic – blue tinge of tissue associated with deprivation of oxygen or excessive levels of carbon dioxide in
the body.
cytokine - is a group of small proteins that stimulate and regulate the immune response.
cytology – the study of cells.
cytotoxic – poisonous or toxic to cells.
desiccation – to dry out or remove liquid from an area or structure.
dextrose- a sugar in the form of D-glucose often used as a carrier solution during chemotherapy.
diagnosis - medical determination of disease or syndrome performed by a physician.
differentiate – a cell’s ability to develop into recognizable shape, structure and function specific to normal
cell types associated with organs or systems of the body.
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disaccharide – sugar made up of two simple sugar units together. Sucrose, lactose and maltose are each
examples of disaccharides.
DNA – deoxyribonucleic acid. One of two types of complex chemicals that make genes.
DRE – Digital Rectal Exam
DVT – (deep vein thrombosis) the formation of blood clots in veins when one remain inactive (usually
sitting) for extended periods of time.
dysplasia - the earliest form of pre-cancerous lesion that a pathologist can recognize.
EBRT – external beam radio therapy.
ECG - (electro-cardiograph) an assessment of heart performance and condition using externally attached
probes that receives and records the electric transmissions of the heart as it beats.
ED – erectile dysfunction.
edema – swelling due to fluid accumulation under the skin.
EGCG - (epigallocatechin gallate) active cancer inhibiting ingredient found, for example, in green tea.
embolism – blocked blood flow as a result of migrating foreign object or air bubble.
En Bloc - surgical method of removing a growth as one entire intact piece.
erythrocytes – red blood cells
FDG - 18F-floro-2-deoxy-D-glucose. Compound used in PET scans to detail possible cancer activity.
fibrosis – formation of excessive connective tissue.
fractionated – specifically used to describe radiotherapy that is spread out over time to give normal cells a
chance to recover.
fructose – monosaccharide or simple single sugar unit used to fuel energy to cells found in fruit for
example.
ganglia - minute tentacles that can radiate from an area such as a tumor or lesion.
genome - the full genetic material of an organism.
glucose – monosaccharide or simple single sugar unit used to fuel energy to cells.
glycolosis – anaerobic respiration.
G.P - general practitioner. One who practices general medicine.
grade – how closely cancer cells resemble normal tissue when looked at under a microscope.
gynecomastia - male condition of developing breasts.
hazard ratio - compares the death rate for patients receiving a given chemotherapy, to the death rate for
those receiving no chemotherapy.
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HIFU – high intensity focused ultrasound.
Kegel - exercise that is used to promote urinary sphincter control similar to how someone would arrest
urinary stream mid-flow.
hematopoiesis – the development of blood cells.
hemolysis - blood cell destruction.
hemorrhage – excessive blood loss.
helix - a twisting structure that resembles a long, partially stretched strand curly hair.
hepatic resection - the surgical resection of liver.
HFCS - (High Fructose Corn Syrup) a synthetic sweetener used in processed foods.
immunogens – foreign bodies that have invaded.
immunological response - the body’s defence response to inflammation and infection.
immunotherapy – treatment that involves drugs that stimulate a patient’s natural immune system response.
IMRT – intensity modulated radiation therapy.
induction – the commencement of the delivery of the anaesthetic during surgery.
interferon - (IFN) is a cytokine that is used in immunotherapy.
Interphase – a stage of cell replication.
interstitial fluid – fluid between the cells of the body.
intra-arterial – within an artery.
intravenous - (IV) within a vein.
IUA - Intra-Urethral Alprostadil . Erection on demand drug.
laparoscopy – surgical procedure using optic scopes, monitor screens and minimally invasive surgical
tools and technique.
leukopenic – condition where white cell count drops below 4000 cells per mm3.
LHRH - luteinizing hormone-releasing hormone agonist used to disrupt the release of testosterone.
liver - a large organ located above and in front of the stomach. It filters toxins from the blood, and makes
bile (which breaks down fats) and some blood proteins.
lymph – fluid that is picked up from the body and eventually moved into the blood .
lymphandenectomy - removal of a part of the lymphatic system.
lymphatic system – bodily system responsible for the movement of lymph and supporting a defence
response to inflammation and infection.
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lymphedema - swelling that occurs due to insufficient lymph drainage.
MRI – (magnetic resonance imaging) examination of body structure using a machine that induces mini
magnetic emissions in the body’s hydrogen nuclei which can be captured and stored by a scanner.
malignancy – being with cancer.
margin – a surgical term used to describe the distance between identified cancer cells and healthy tissue.
metabolism – the processes related to the exchange, conversion, storage and use of energy in cells.
metastasis - the invasion of cancer beyond its initial site of development into the circulatory system and
other organs of the body.
metronomic - treatment that calls for relatively low grade amounts of drugs or compounds to be
administered under a continuous schedule to combat disease.
mitosis – process of cell replication.
monoclonal – meaning all the same or “cloned”.
monosaccharide – a simple sugar such as galactose, glucose or fructose.
NCI – United States National Cancer Institute.
necrosis – death of living tissue
neoadjuvant - treatment given before surgery in order to shrink tumor(s) that are too extensive or
complicated to be removed by surgery alone.
neo-plastic – a benign abnormal tissue mass that has developed as a result of uncontrolled cell growth
occurring usually after a genetic mutation and if allowed to persist could eventually become malignant.
neurons - responsive cell in the nervous system that process and transmit information by electrochemical
signaling.
neurotransmitter - chemicals that are involved in the relay, amplification and modulation of signals
between a neuron and another cell.
neutropenic – condition where neutrophil count drops below 1000 cells per mm3.
NIV feed - (non-invasive assisted pressure) oxygen line fitted in a patient’s nostrils.
non-nutritive sweetener - synthetic compounds that can range from 160 to 13,000 times sweeter than
sucrose (white sugar). Saccharin, aspartame, neotame, acesulfame K, sucralase, trichlorogalactosucrose
are examples of these compounds.
nutratherapy – use of food as a natural way to deliver dietary origin anti-cancer compounds, on a
continual basis, to the body.
Omega-3 – unsaturated essential fatty acid that can be derived only from intake of food or supplements in
humans.
Omega-6 - unsaturated essential fatty acid that can be derived only from intake of food or supplements in
humans. Reported to be linked to ailments such as heart attack, thrombotic stroke, arrhythmia, arthritis,
osteoporosis, inflammation, mood disorders and cancer if its ratio to Omega-3 fatty acids is excessive.
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oncologist - a physician who specializes in the study and treatment of cancer.
oncology – the study of cancer.
occult - hidden or otherwise not obvious.
orchiectomy – surgical castration or removal of the testes.
palpation – using the hands or fingers to feel something in an examination.
palliative – care or treatment that focuses on reducing the severity of disease when cure is not possible.
pathology - the laboratory based study of disease.
PC – Prostate Cancer
PCA pump – (Patient Controlled Analgesia) pump that delivers attached drug on command of the patient.
PCD – programmed cell death.
perineal – the space in the pelvic floor between the anus and the base of the scrotal sac in males. In
females, the space between the anus that the vaginal opening.
peritonitis - abscess or inflammation of the abdominal wall.
PET – Positron Emission Tomography.
peryonie’s disease – connective tissue disorder where scar tissue forms a thick sheath of tissue surrounding
the corpora cavernosus.
phagocytic – cells that have the ability to “eat” or ingest foreign cells such as neutrophils.
piecemeal – surgical method of removing an abnormal growth in small sections.
placebo – substitute agent that is given in place of the active agent or drug. For example, sugar pills.
platelet – a group of blood cells responsible for blood clotting and stimulation of healing after injury.
PLND – pelvic lymph node dissection.
polysaccharide - a long string of simple sugars joined by Alpha or Beta linkages.
Port-a-cath – a small receptacle installed surgically under the skin and accessing the circulatory system
used to minimize the trauma of successive intra venous injections associated with treatment such as
chemotherapy.
prophylactic – a measure that is done to prevent something from happening.
progesterone – C-21 steroid hormone involved in menstrual cycle, pregnancy and embryogenesis.
progestin – synthetic steroid that has similar effect to progesterone.
prognosis - outlook or “best guess” as to what a patient will do given their profile, the state of the disease
and the proposed treatment regimen.
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prostatomegaly – benign prostate enlargement.
prosthetics – implant or artificial aspect designed to replace or augment parts of the anatomy.
PSA – Prostate Specific Antigen
QOL – quality of life.
replication – the making of cells.
resection – the surgical removal of a part of an organ.
red blood cell – a group of cells responsible for the delivery of oxygen to tissues and the transport of
waste, such as carbon dioxide, for removal.
RFA – (radiofrequency thermal ablation) procedure using electrodes surgically inserted in the affected
liver tissue and inducing an alternating current that causes necrosis (death of tissue) and thermal desiccation
(drying out) of the treated area.
relative survival – survivability quotient that excludes unrelated mortality.
RNA – ribonucleic acid. One of two types of complex chemicals that make genes.
RPP – radical perineal prostatectomy.
RRP – radical retropubic prostatectomy.
RT – (radiotherapy) treatment using x –ray waves to target, reduce or slow cancer cell growth.
saline – a salt water solution.
salivary glands - glands located in the mouth that produce saliva. Saliva contains enzymes that break down
carbohydrates (starch) into smaller molecules.
SEER – Surveillance Epidemiology and End Result.
sentinel lymph nodes – lymph nodes first in line to receive lymph drained from the prostate.
septic – the state of being infected.
septicaemia - (“blood poisoning”) is a potentially life-threatening infection in which large amounts of
bacteria are present in the blood
seroma – yellowish pocket of fluid that occurs under the skin as a result of surgery.
serotonin – a neurotransmitter responsible for stimulating vomiting.
SIRS - (systemic inflammatory response syndrome) syndrome where bacteria in the bloodstream cause the
entire body to become inflamed.
SIRT – selective internal radiation therapy.
SPECT/CT - Single Photon Emission Computed Tomography/ CT
Skene’s gland – female prostate gland.
starch – a digestible polysaccharide that is formed by simple sugar units joined by alpha linkages.
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subcutaneous – underneath the skin.
sugar alcohol - carbohydrate sweetener that is neither sugar or alcohol and has caloric value. Examples
are sorbitol, mannitol, xylitol, erythritol, isomalt, lactitol, and maltitol.
target therapy – treatment involving the use of a group of drugs that attack cancer cells more specifically
than conventional chemotherapy drugs can.
telesurgery – surgery conducted at a distance from the patient using closed circuit television (CCTV).
Terpene- a family of spices including mint, thyme, marjoram, oregano, basil and rosemary.
thrombocytopenia – condition where platelet count is reduced and falls below 150 000 per mm3.
topoisomerase – a group of enzymes involved in the unzipping of a DNA strand.
transcoelomically - within the coelome (body cavity).
TNM convention – method to stage or arrive at a prognostic group for cancer.
TRUP – transurethral resection of the prostate.
TRUS – trans rectal ultra sound.
tumor – a neo-plastic swelling or lesion that can be benign, pre-malignant or malignant,
tumor spillage – the unintentional contamination of an organ or area by cancerous cells during the surgical
removal of malignant growth. Also known as implantation.
UICC - Union Internationale Contre Cancer.
USP – United States Pharmacopeia.
ultrasound – imaging of internal bodily organ and structure using sound waves.
Urethra – duct leading from bladder through which urine travels when exiting body.
USG – ultrasound.
USPSTF - U.S. Preventative Services Task Force.
ultrasound – imaging of internal bodily organ and structure using sound waves.
VED - vacuum
erection device
venous – related to the veins
vesicant - a substance that causes tissue blistering.
white blood cell – A group of blood cells that include neutrophils, B, T and NK cells and are involved in
the body’s immunological response.
WHO – World Health Organization.
3DCRT – 3D conformal radio therapy
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INDEX
abscess – 38, 94, 98
acupuncture – 168
acinar adenocarcinoma – 41, 42
adenoid cystic carcinomas - 42
adenocarcinoma – 41, 42, 43
adjuvant therapy – 114, 115
alcohol – 125, 130, 149, 158, 174
alkylating agents – 127
alternative strategy - 142
anaerobic respiration (glycolysis)- 54, 151, 152
anaesthetic – 77, 81, 94, 95, 96, 97, 123 171
anaesthesiologist – 73, 81
anemia – 45, 124
aerobic respiration- 54, 151, 152
androgen – 13, 14, 17, 40, 78, 79, 112, 114, 119, 120, 129, 130, 131, 132, 136, 139, 140, 141
androgen deprivation therapy – 112, 114, 120, 129, 139, 140, 141
androgen receptors - 40
angiogenesis – 145, 151, 156, 157
anti-metabolites – 127
anti-tumor antibiotics - 132
anthracyclines – 128
anti-tumor antibiotics – 132
apoptosis – 37, 105, 134, 145
archives – 75
arterial – 24, 120, 133
attitude – 160
basal cell carcinomas - 42
benign – 37, 38, 40, 45, 56, 61, 63, 77
Béliveau & Gingras – 146, 155, 159
biopsy – 11, 50, 51, 52, 61, 62, 63, 64, 65, 69, 72, 77, 78, 80, 90, 91, 173, 175, 176
CAD (computer aided detection)- 50, 51, 52
cannula - 94
carcinoma – 38, 39, 40, 41, 42, 43, 55, 67, 128
carcinosarcomas – 42
castration – 40, 57, 78, 79, 112, 120, 131
catheter – 13, 83, 96, 105, 118, 120, 122, 123, 124, 126, 138
CPE (clinical prostate examination) – 10, 50
cell cycle – 32, 34, 35, 127, 128
cellulose (roughage) – 150
central venous catheter - 123
chemotherapy – 119, 129
chromosome – 29, 30
CIS (Carcinoma in situ) – 39, 67
Clinical testing – 116
CT (computed tomography) – 26, 53, 54
cyst – 38
cytology – 27
desiccation – 92
dextrose (D-glucose) – 125
diagnosis - 8, 9, 11, 12, 14, 45, 50, 51, 56, 62, 63, 71, 79, 80, 108, 111, 140, 161, 172, 173, 174, 175,
175, 177, 178
diet – 147
differentiate – 39, 55
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differentiating agents - 133
disaccharide – 150
DNA (deoxyribonucleic acid) – 28, 29, 30, 32, 33, 34, 35, 36, 127, 128, 132, 136
DVT (deep vein thrombosis) – 81
dysplasia – 39
ECG (electro-cardiograph) – 73, 95
EGCG (epigallocatechin gallate) - 157
embolism – 126
En Bloc – 83, 84
erectile dysfunction - 83
erythrocytes – 100
estrogen receptors- 40
exercise – 164
EBRT (external beam radiotherapy) – 111, 112
FDG (18F-floro-2-deoxy-D-glucose )- 54, 140, 174, 176
follow up – 13, 45, 50, 63, 108, 130, 177, 178
foundations - 179
fractionated – 139
fructose – 149, 150, 151
gene therapy – 134, 135
genome – 28
glucose – 54, 149, 150
glycolysis – 149, 150, 151, 152
gynecomastia – 79
hazard ratio - 118
helix – 28, 32
HFCS – 150, 151
HIFU (High Intensity Focused Ultrasound) – 111, 112, 141, 174
Hormone therapy – 131
hyperplasia – 38
hypertrophy - 38
immunological response – 143, 145, 147
immunotherapy – 133, 134
IMRT (intensity modulated radiation therapy) – 111, 138, 139
induction – 94, 153
infection – 98
initiation – 35, 37, 39, 40, 58
interphase – 32, 33, 34, 35
interstitial fluid – 27
intra-arterial – 120, 133
intravenous (IV) – 54, 57, 96, 99, 120, 122, 128
invasiveness – 64
laparoscopy – 87, 89
lesion –39, 41, 51, 52, 64, 92, 141
liver – 92, 93, 126,133, 138
lymph node – 13, 24, 26, 66, 77, 82, 87, 107
lymphatic system – 23, 24, 27, 107
lymphedema – 107
MRI (magnetic resonance imaging) – 50, 56, 57, 58, 59, 60, 62, 73, 85, 90, 91, 141, 174
malignancy – 13, 30, 51, 63, 99
metabolism – 54, 117, 151
metaplasia - 38
metastasis – 7, 25, 26, 27, 55, 57, 59, 60, 66, 67, 77, 92
metronomics - 155
mitosis – 35, 128
mitotic inhibitors -128, 129
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mitotic phase – 32, 34
molecular imaging - 54
monoclonal anti-bodies– 121
monosaccharide – 150
musculature – 20, 21, 82, 86
mutagens – 36, 155
nausea – 81, 96, 125, 129, 132, 171
NCI (National Cancer Institute) – 49, 70, 123
necrosis – 92, 111
neoadjuvant – 67, 78, 115
neo-plastic – 40
nerves – 9, 17, 20, 22, 37, 94
neurotransmitter - 125
neutropenic – 100, 102
NIV feed (non- invasive assisted pressure) – 96
nutratherapy - 155
non-nutritive sweetener – 152
Omega-3 – 147, 153, 154, 160
Omega-6 – 147, 153, 154, 160
oncologist - 113
oncology – 8, 54, 92, 109, 113, 115, 116, 122, 124, 125, 139, 159, 160, 171, 178
orchiectomy – 78, 79, 84
Otto Warburg – 151
palliative treatment – 132, 136, 179
pathology - 62
PCA pump (Patient Controlled Analgesia Pump) – 96, 97
PCD (programmed cell death) – 31
PCS (prostate conserving surgery) – 40, 85
Pelvic floor – 13, 20, 21, 104
PET (positron emission tomography) – 54, 176, 183
PLND (pelvic lymph node dissection)- 77, 82, 87, 107
phagocytic – 98
platelet – 100, 101, 124, 126
polysaccharide - 150
port-a-cath – 122, 123, 126, 159
praying - 179
prevention – 174
primary treatment – 114, 115, 139, 140
progesterone – 40
prognosis – 43, 51, 69, 71, 77, 106
progression – 9, 24, 30, 39, 72, 78, 111, 119, 131, 140
promotion – 39
prostate- 17
prostate self-examination - 46
prostate zones – 19
prostatitis – 9, 37, 38
prostatodynia – 36, 37
prostatomegaly – 38
PSA (prostate specific antigen) – 9, 11, 12, 13, 14, 46, 50, 63, 64, 67, 68, 78, 111, 114, 119, 131, 136, 140,
172, 173, 174, 175, 176
PSA doubling – 140
QOL (quality of life) - 141
Radical Perineal Prostatectomy (RPP) – 77, 82
radical prostatectomy- 13, 85, 98, 104, 105, 140, 175
Radical Retropubic Prostatectomy (RRP)- 77, 82
reconstruction – 80, 85
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recurrence – 54, 114, 139, 140, 176
red blood cell – 45, 126
rehabilitation – 83, 84, 103, 104, 105
relative survival – 71, 72, 140, 141
resection – 77, 82, 83, 84, 86, 139, 140
RFA (radiofrequency thermal ablation) – 92
RNA (ribonucleic acid) – 28
robotic surgery - 98
RT (radiotherapy) – 31, 77, 99, 101, 107, 108, 111, 115, 116, 119, 136, 137, 138, 139, 143
saline – 77, 94, 123
screening – 9, 11, 12, 46, 47, 50, 55, 56, 172
second opinion – 74, 75, 88
SEER – 7, 19, 22, 70, 72
septic – 98, 99
septicaemia (blood poisoning) - 99
Servan- Schreiber - 146
serotonin – 125
skene’s gland -9, 17, 18
SIRS (systemic inflammatory response syndrome) – 99
SIRT (selective internal radiation therapy) - 138
SPECT/CT – 26, 27
spillage – 27, 102
staging – 39, 55, 64, 65, 78
starch – 149, 150, 152, 156, 160
stress – 145, 153, 158, 161, 162, 163, 168, 174, 176
subcutaneous – 122
support –160, 163, 178, 179
surgical treatment and therapy – 76
survivability – 70
symptoms of PC – 45
symptoms of infection – 101
target therapy – 132
Terpene- 155, 156
thrombocytopenia – 101
topoisomerase – 127, 128
TNM convention – 65
TRUS (trans-rectal ultrasound)- 50, 51, 52, 61, 62, 73, 74, 78, 111
tumor – 7, 27, 41, 51, 52, 54, 55, 63, 64, 65, 66, 77, 78, 83, 85, 92, 111, 115, 126, 128, 132, 133, 134,
135, 136, 137, 138, 140, 141, 152, 171
ultrasound – 50, 51, 52, 111, 112, 141
vesicant -126
vitamin D – 130, 176, 177
watchful waiting- 13, 108, 175
white blood cell – 100
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ACKNOWLEDGEMENTS
I would like to thank my friend Tony, who is a long term Prostate Cancer survivor and
fighter, for sharing his insight and perspective.
As well, I would like to thank those who contributed their time and knowledge as
reviewers.
Finally, I would like to thank those who have graciously contributed to the clarity of this
this discussion by lending their permission to display their illustrations and images as
examples.
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DISCLAIMER
This publication is intended for educational and informational purpose only. The
content of this discussion relays the author’s overview of the disease of Prostate Cancer.
It is a way to consolidate the subject matter of Prostate Cancer that is largely, but not
exclusively, available on internet sites. The figures herein are used as examples only and
are not necessarily the most definitive or current associated with their associated aspect in
discussion. The comments and discussion herein are the author’s layperson understanding
and interpretation of aspects of fact and consideration of that disease as it pertains to a
patient perspective and emphasis up to the date of publication release. The author is not
offering a medical opinion either in whole or in part in this book, nor is this book and the
discussion herein designed to substitute or in any way replace expert medical advice
provided by a professional practicing in the associated fields of medicine. Those who use
this book should make their own determinations with expert medical advice regarding
specific prevention, diagnosis, prognosis, treatment and follow up options. Neither the
author, nor the publisher KnowingHelps Corp nor any third party contributor can be held
responsible for any damage or liability incurred as a consequence from the use or
application of any of the contents of this book.
The figures herein are used as examples only to support the discussion. Image
and illustrations from the third party contributors are reused under the provision of
permissions and their copyrights are to be respected accordingly. If anyone is aware of
any violation of copyright in this publication please send notice to
[email protected] so that the appropriate adjustments can be made.
THE SILENT BATTLE WITHIN, A PATIENT’S VIEW OF PROSTATE CANCER
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SYNOPSIS
In the new year of 2008 the author was diagnosed with a tumor. At the time no
emphasis was given to the fact that it could have been an invasive adenocarcinoma even
though the initial pathology report clearly stated this.
By springtime, when appointments were finally solidified for a surgeon’s review,
he became increasing aware that there was something substantial about his condition and
that the medical solution could have life altering repercussions.
Nothing was making any sense, so he dove into the literature on his cancer in an
attempt to understand. What he found was a mountain of information featuring the entire
spectrum of medical effort and anecdotal discussion on the topic. As a patient, he wanted
to know what to expect. Finding the answers was a real struggle. Often the answers
were not available until he actually went through the phase of diagnosis and treatment.
After surgery advanced stage cancer was confirmed and a course of chemotherapy
followed. During this time he wrote a book in an effort to record and understand what he
found to be important facts and considerations on his cancer, from a patient’s
perspective, in one easy to access place.
When he finished that book it occurred to him that understanding and accessing
the information for patients of other cancers was a problem as well. So he decided to
research and write a series of books dealing with the most frequently diagnosed cancers.
The intention is to point out reputable sources and examples that are readily available to
the average layperson; then make sense of them in the context of the disease as a whole
so that the condition and options can be better understood when in discussion with the
one’s medical specialists.
This book is part of the Silent Battle Within, A Patient’s View ™ series and
discusses Prostate Cancer. Hopefully it helps in imparting some good, easy to access
information.
The Silent Battle Within, A Patient’s View of Prostate Cancer by Dale Hollenbeck,
last revised in December 2012.
A publication of KnowingHelps Corp.
COPYRIGHT © 2012
ALL RIGHTS RESERVED
knowinghelps.com
HEALTH / ISBN: 978-1-927768-03-7
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