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JUST
DIAGNOSED
A GUIDE FOR MEN
AND LOVED ONES
June/09
For additional copies and information please visit:
prostatecancer.ca or call 1-888-255-0333
prostatecancer.ca
Prostate
Cancer
JUST DIAGNOSED:
A GUIDE FOR MEN
AND LOVED ONES
Table of Contents
What’s the prostate?................................................2
Is it cancer?.............................................................3
What is the prognosis or “How bad is it, doc”?........5
Digital rectal exam..............................................5
Prostate-specific antigen (PSA) test......................5
Biopsy & transrectal ultasound (TRUS).................7
Grading prostate cancer.......................................7
The Gleason Grading System......................8
Staging prostate cancer.....................................10
TNM staging............................................11
Whitmore-Jewett staging..........................13
Other test................................................14
Putting it all together: prediction tools & risk.....15
What are the treatment options?...........................18
Active surveillance............................................18
Surgery............................................................19
Radiotherapy.....................................................22
Brachytherapy...........................................24
Hormonal therapy..............................................27
Antiandrogen therapy..............................29
Chemotherapy..................................................31
Complementary therapies.................................33
What next?...........................................................34
Questions to ask about follow up.......................34
Living well after treatment.................................35
Where can I turn for more information or help?.......39
Prediction tools and nomograms..............................40
What’s the prostate?
The prostate is a gland located deep inside a man’s
pelvis below his bladder and in front of his rectum.
The prostate surrounds the upper part of the
urethra, the channel that lets urine and semen pass
through the penis. The prostate’s function is to
produce a part of the semen that nourishes and
protects sperm. It also helps regulate the flow of
urine, and, during a man’s orgasm, its muscle cells
contract to help propel the semen out the penis.
A healthy prostate is the size of a golf ball, but it is
actually more like a small, ripe plum. Its outer
covering is soft, and it is spongy to the touch. If,
while doing a digital rectal exam (DRE), your doctor
discovers an enlarged, irregularly shaped, or hard,
lumpy, or tender prostate, you may have a prostate
problem.
The prostate also produces an enzyme that helps
the semen remain in liquid form after ejaculation.
This enzyme, prostate-specific antigen (PSA), is
usually produced only in the prostate gland itself
and can be found in semen or blood.
Prostate
Cancer
Is it cancer?
Prostate cancer is only one of a number of
problems that can occur within the prostate.
Prostatitis, an infection or inflammation of the
prostate, is not cancer. And there is no evidence
that prostatitis leads to prostate cancer.
Prostatitis is usually categorized as acute or
chronic and as either bacterial (being caused by
bacteria) or nonbacterial. The most severe and
least common form is acute bacterial prostatitis.
The most common form is chronic nonbacterial
prostatitis. Prostatitis treatment can include
antibiotics, anti-inflammatory drugs, alpha
blockers (tamsulosin), 5-alpha- reductase
inhibitors (Proscar® or Avodart®), bed rest, and
drinking plenty of fluids.
Benign prostatic hyperplasia (BPH) is also
not prostate cancer. BPH is a non-cancerous
(benign) overgrowth of cells (hyperplasia) in the
prostate gland (prostatic). Basically, BPH is an
enlarged prostate, and the condition is common
in older men. Luckily, many men with enlarged
prostates experience no symptoms. But, for some
men, the growing prostate can progressively
squeeze the urethra, which lets urine travel from
the bladder, through the prostate, and out the
penis. This narrowing of the urethra can reduce or
obstruct the flow of urine and lead to a gradual
loss of bladder function. BPH is treated through
changes in diet and lifestyle; through medications
such as alpha blockers and 5-alpha-reductase
inhibitors; and through surgery.
Prostatic intraepithelial neoplasia (PIN) is
not cancer either, but it is an abnormal and
uncontrolled growth of prostate cells, specifically,
of the cells that line the external and internal
surfaces of the prostate gland. PIN cells do not
have the ability to invade surrounding tissue, so
they are not malignant (not cancerous), but they
are atypical. The most abnormal cells are
2
3
classified as high grade PIN, and cells that appear
almost normal are classified as low grade PIN. Low
grade PIN (sometimes called mild dysplasia) does
not appear to increase a man’s risk of prostate
cancer. But high grade PIN, in which cells can be
very irregular and share some of the genetic
abnormalities of prostate cancer cells, is sometimes
called a pre-cancerous condition (defined as a
condition that leads to cancer). Still, having high
grade PIN does not mean that you will develop
prostate cancer inevitably. But, because evidence
tells us that most prostate cancers start out as high
grade PIN, men with this condition are monitored
carefully for prostate cancer, usually through
biopsies. Other than the vigilant monitoring of men
with high grade PIN, no other follow-up or therapy
is usually required.
Prostate cancer is a disease in which some of the
cells of the prostate, the cancerous ones, have lost
normal control of cell growth and division. The
natural processes of cell growth and death no
longer apply to them. They lose their normal
structure, so they cannot function properly. Also
they can escape the prostate and invade other parts
of the body, growing there and crowding out the
normal cells necessary for the body’s health.
To be cancerous, a prostate cell has to have all of
these characteristics: uncontrolled growth,
abnormal structure, and invasiveness (ability to
invade and escape the prostate, where it originally
grew).
Tumours (clusters of cells growing into a mass in an
uncontrolled way) are not necessarily cancer. They
can be benign. A benign tumour does not spread to
other parts of the body; it is not invasive.
A prostate cell can be abnormal in structure and
not cancerous. PIN or prostatic intraepithelial
neoplasia is a condition in which prostate cells are
abnormal but not malignant or invasive.
4
Prostate
Cancer
What’s the prognosis or
“How bad is it, doc”?
A prognosis is an educated assessment of the
severity and nature of your cancer, as well as a
medical forecast about the probable course of
your illness and the best way to treat it. Your
medical team will use many tools to evaluate
your condition:
Digital rectal exam (DRE)
A digital rectal exam (DRE) is most frequently
used in diagnosing prostate cancer, but it can
help indicate how serious prostate cancer is or
how it might be treated. During a DRE, the
physician inserts a gloved and lubricated finger
into the rectum to feel the rear of the prostate for
hard, lumpy areas. If an abnormality is felt, the
examiner can note whether it seems contained
within the prostate, is distorting the gland, or
appears to be pushing through and growing
outside the prostate. The larger a tumour is and
the closer it is to escaping the prostate the more
potentially dangerous it is if a biopsy shows that
it is cancerous. As biopsies can cause swelling
and discomfort, which can make subsequent
DREs difficult to conduct or inconclusive, the
physical exam you had before the biopsy may be
very important in assessing your cancer.
Prostate-specific antigen (PSA) test
This test detects the amount of prostate-specific
antigen (PSA) in the blood. Each man’s normal
level depends on individual factors such as his
age or the size of his prostate. Although, in the
past, most doctors considered PSA levels below 4
nanograms per millilitre of blood (4.0 ng/mL) to
be normal, recent research has found prostate
cancer in men with PSA levels below this.
Currently, in men 49 and younger, PSA levels
above 2.5 ng/mL might be considered elevated,
and for men aged 50 to 59, the cut-off level
might be 3.5 ng/mL. If you have an elevated PSA
level, it does not mean that you have prostate
5
Prostate
Cancer
cancer, but your doctor may counsel you to have
further tests done to investigate the possibility. In
general, the higher the cancer-related PSA level, the
poorer the prognosis.
PSA density (PSAD) compares a man’s PSA level
to the size of his prostate, which is measured when
he undergoes a transrectal ultrasound (TRUS).
Higher PSA densities (i.e., above 0.15) indicate
increased risk.
The percentage of free to total PSA may be
measured too, because, as a general rule, cancer
cells make less free PSA than healthy prostate cells.
What is free PSA? It is prostate-specific antigen
that is not bound to other proteins in the blood. So
the lower the percentage of free PSA the worse the
prognosis. (Readings between 10 per cent and 25
per cent are difficult to assess, but readings under
10 per cent are worrisome.)
PSA velocity (PSAV), which is a measurement of
how quickly levels of prostate-specific antigen
increase over time, is another tool. A rise in PSA
level of more than 0.75 ng/mL per year will often
trigger a biopsy.
PSA doubling time (PSA-DT) measures the time
it takes for the amount of PSA detected in your
blood to double. The shorter the doubling time the
more aggressive the cancer and the worse the
prognosis, in most cases.
PSA levels, PSA velocity, and PSA doubling time can
be used in assessing prostate cancer that recurs
after treatment. If the cancer recurs at least 2 years
after treatment, the PSA doubling time is greater
than 12 months, and the PSA velocity is less than
0.75 ng/mL per year, the likelihood is that the
cancer is recurring in the prostate or in the area
where the prostate was before its removal and
further local treatment (e.g., radiotherapy) may be
helpful. A time of recurrence that is less than 2
years, a PSA doubling time of less than 6 months,
and a PSA velocity of greater than 0.75 ng/mL per
year suggest a more distant site for the cancer and
the need for systemic therapy.
6
Biopsy & transrectal ultrasound (TRUS)
In a biopsy of the prostate, the physician inserts
into the rectum a device that incorporates an
ultrasound probe and can also hold biopsy
needles. The transrectal ultrasound allows the
physician to position the biopsy needles close to
suspicious areas of the prostate, and then these
needles are deployed to remove samples of the
prostate tissue. The microscopic analysis of these
tissue samples is a powerful diagnostic and
prognostic tool. It can give information on
• The areas from which tissue samples were
taken and the dimensions of these samples
• Whether prostatic intraepithelial neoplasia
(PIN) is present
• Whether the tissue samples are positive or
negative for cancer and, if they do show cancer
(if they are positive), how much cancer was
found in each sample
• What type of cancer is present
• How abnormal the cancer cells look under the
microscope (the grade or Gleason score of the
cancer)
• Whether there is evidence that the cancer has
spread along the nerves within the prostate
(perineural invasion)
Grading prostate cancer
Grading prostate cancer means describing how
closely its cells resemble the normal cells of the
prostate. The lower the grade, the better the
news. Low grade prostate cancer has highly
differentiated cells, which means these cells still
retain many of the qualities that make prostate
cells unique. In intermediate grade prostate
cancer, cells look more abnormal. These cells are
moderately differentiated, which means that they
can still be recognized as prostate cells but look
odd and disorganized. High grade prostate
cancer cells are poorly differentiated and barely
resemble prostate cells. The Gleason grading
system is commonly used.
7
Prostate
Cancer
The Gleason Grading System
Grade 1
• Well-differentiated; cells resemble normal
prostate cells
• Tiny glands of the prostate are round, have
defined edges, and are tightly packed; Tumour not
expected to grow quickly.
Grade 2
• Less well-differentiated; cells not as normal
looking
• The glands are still round but are loosely packed
with less distinct edges
Grade 3
• Moderately differentiated
• The glands are larger with irregular shapes and
spacing. Their edges are badly defined and show
infiltration.
Grade 4
• Poorly differentiated
• Glands are of different sizes and shapes; they are
fused together in masses or chains
Grade 5
• Poorly differentiated; Cells are very strange
looking
• Glands are not really visible; Tissue appears
composed of solid cellular sheets, single cells, or
nests of tumour
8
Gleason score: A man will often have a number
of different grades of cancer present within his
biopsy sample, so Gleason developed a scoring
system to take this into account. The Gleason
score is equal to the sum of the two most
common grades of cancer evident in a patient’s
biopsied tissue. For example, if cells with a
Gleason grade of 4 are the most common, but
about 10 percent of the cells have a Gleason
grade of 3, the Gleason score would be 7. (If the
secondary grade makes up less than 5 per cent of
the cancer cells, it is considered insignificant, so
the grade of the dominant and only significant
pattern would be added to itself.)
• a Gleason score of 2 to 6 is usually considered
low
• a Gleason score of 7 is considered intermediate
• a Gleason score of 8 to 10 is considered high
Note, however, that even scores considered low
may be composed of poorly differentiated cells
with a Gleason grade of 4 or 5. The presence of
these cells is worrisome, and a Gleason score of
6 that has grade 4 cells as its dominant pattern
(Grade 4 + Grade 2 = Gleason 6) is riskier than
the same score based on grades that indicate the
presence of only moderately differentiated cells
(Grade 3 + Grade 3 = Gleason 6).
9
Prostate
Cancer
Staging prostate cancer
The stage of prostate cancer is determined by the
tumour size, whether the cancer has spread to the
pelvic lymph nodes that drain the prostate, or
whether cancer has spread to an area of the body
remote from the prostate. In other words, important
factors are how big the tumour is and how much the
cancer has spread: whether there are any distant
metastases. Two main methods of staging are
TNM and the Whitmore-Jewett system, which uses
letter designations A through D.
TNM staging: In this method, the T represents
the primary tumour, the N represents the nodes
of the lymphatic system (lymph nodes), and the
M represents metastasis (or whether there is
evidence of the cancer’s spread to distant areas).
T STAGE
TX & T0 T1
Tumour is not
palpable nor visible
by imaging
TX
Tumour
cannot
be
assessed.
T1a
T1a Tumour found
incidentally in less
than 5% of prostate
tissue sample
T1b
Tumour found
TO
incidentally in more
No
than 5% of prostate
evidence tissue sample
of
tumour T1c
Tumour found during
needle biopsy (e.g.,
because of elevated
PSA)
10
T2
Tumour is confined
to the prostate
T3
Tumour extends
beyond the prostate
T4
Tumour has invaded
neighbouring tissues
T2a
Tumour involves
50% or less of one
lobe
T3a
Tumour extends
beyond the prostate
capsule on one side
(unilateral
extracapsular
extension) or on both
sides (bilateral
extension)
The tumour is fixed or
invades areas
adjacent to the
prostate other than
the seminal vesicles,
e.g., the bladder neck,
the external sphincter,
the rectum, and the
pelvic wall
T2b
Tumour involves
more than 50% of
one lobe but not
both lobes
T2c
Tumour involves
both lobes
T3b
Tumour has invaded
the seminal vesicles
11
Prostate
Cancer
Whitmore-Jewett staging: In the WhitmoreJewett staging system, prostate cancer is specified
first by letter (A through D) and then by number.
N STAGE
NX & N0
NX
Lymph nodes near the
prostate were not or
cannot be assessed.
N1/N+
Metastasis in regional
lymph nodes
WHITMORE-JEWETT STAGING
NO
No regional lymph
node metastasis
A
Early stage cancer
confined to the
prostate, not
detectable by DRE
and producing no
symptoms
A1 Cancer cells look very
much like normal cells (well
differentiated) and are
focused in one area of the
prostate
A2 Cancer cells are more
abnormal (moderately or
poorly differentiated), and
cancer is in several locations
in the prostate
B
Cancer is confined
to prostate but is
detectable by either
DRE or because of
elevated PSA
B0 Cancer cells are confined
to the prostate, are not
detected by DRE, but cause
elevated PSA
B1 There is one area (nodule)
of cancer in one lobe
B2 There is extensive cancer
in one lobe or some cancer in
both lobes
C
Cancer has extended
out of the prostate
capsule but has not
spread to regional
lymph nodes or
more distant areas.
C1 The cancer extends
beyond the prostate
C2 The cancer extends
beyond the prostate and
obstructs the bladder or
urethra
D
Metastatic prostate
cancer; the cancers
has spread to
regional lymph
nodes or to more
distant areas
D1 The cancer has spread
only to regional lymph nodes
D2 The cancer has spread
to distant lymph nodes,
bones, organs, or tissues
D3 Designation for D2
patients who have
relapsed after treatment
M STAGE
MX & M0
MX
Distant metastasis of
cancer cannot be
determined or
assessed.
MO
No metastasis of the
cancer beyond the
regional lymph nodes
M1
There are distant
metastases; the cancer
has spread beyond the
regional lymph nodes
M1a The cancer has
spread to non-regional
lymph nodes
M1b The cancer has
spread to the bone
M1c The cancer has
spread to other distant
sites, with or without
metastasis to the bone
12
Testis
Penis
13
Prostate
Cancer
Other tests
Your medical team may use other tools to assess
your cancer and determine the best treatments.
Many of these diagnostic or staging procedures
investigate whether prostate cancer has spread
beyond the prostate:
Bone scans provide images of the skeleton to
investigate whether prostate cancer has spread to
the bone. During a bone scan, injected low-level
radioactive material is taken up in the bone more
rapidly by fast growing cells, producing “hot spots”
on the scan and indicating the possibility of cancer
in the bone.
Chest x-rays are often ordered to see whether
cancer has spread to the lungs or the ribs.
Computerized axial tomography (CT or CAT)
scans use computers to combine pictures gathered
by rotating x-ray beams, creating cross-sectional
and three-dimensional images of organs. These
scans are useful for finding enlarged lymph nodes
or other abnormalities.
Magnetic resonance imaging (MRI) uses a large,
powerful magnet, radio waves, and a computer to
create images of the prostate and pelvic area or
other body regions; these images are sometimes
used to provide information about cancer spread
outside the limits of the prostate gland or into the
lymph nodes, bone, or elsewhere.
Pelvic lymph node dissection, or the surgical
removal of the lymph nodes in the pelvis and their
microscopic analysis, is the most accurate way of
determining whether prostate cancer has spread to
the lymph nodes. This procedure is typically
performed during surgery to remove the prostate.
ProstaScint scans use radioactive monoclonal
antibodies to investigate prostate cancer spread.
These antibodies attach to suspect cells and expose
“hot spots”– where cancer may be present. The
test is not always reliable, and results can be
difficult to analyse. It is not widely used nor
available in Canada.
14
Putting it all together:
Prediction tools and risk
Most important in gauging the risk posed by
prostate cancer is whether it has spread beyond the
prostate. If all indications are that it has not, you
have clinically localised prostate cancer, and
statistics indicate that between 75 % and 93 % of
men in this situation survive their disease for 10 to
15 years. This stage of prostate cancer development
is called “clinically localised” because there is still a
risk that microscopic cancer cells have escaped the
prostate—and escaped detection by clinical tests.
Because the clinical stage of a man’s prostate
cancer is often difficult to gauge, especially before
surgery, physicians have developed mathematical
models that put together all known information
about a man’s cancer and make predictions about
his risk based on statistical data gathered from
other men’s experiences with the disease. These are
called nomograms. Partin tables use your PSA
level, Gleason score, and estimated clinical stage
(e.g., T1c) to calculate probability percentages that
your cancer has spread. Han tables use similar
information to estimate the probability that your
cancer will recur after a radical prostatectomy.
Modern computer technology has made possible
the development of new tables and nomograms
(representations of numerical relations). See the
section “Where do I go for more information?” to
find online versions of some of the prediction tools
useful for men with prostate cancer.
Remember, however, that these tools base
predictions on only a few factors. They do not know,
for example, much about your general health, your
life, or your medical history. Your own medical team
is your best resource in assessing your prognosis
and in recommending appropriate treatment.
Still, most predictions of prostate cancer risk are
based on three clinical factors. The larger the
tumour, the higher the Gleason score, and the more
detectable prostate-specific antigen (PSA) in the
blood, the greater this risk.
15
Prostate
Cancer
What are the treatment options?
As is evident from the chart connecting risk
category and standard treatments, the usually
recommended treatments for prostate cancer that
seems to be confined to the prostate are either
surgery to remove the prostate (radical
prostatectomy) or radiation to kill prostate cells. The
greater the chance that your cancer has spread
outside of the prostate, the more significant
becomes a systemic (system-wide) treatment such
as hormone therapy.
Active surveillance
This strategy, which is sometimes called watchful
waiting, involves monitoring a man’s prostate
cancer carefully and only treating the cancer if it
becomes aggressive. This monitoring is done
through regular digital rectal exams, PSA tests, and
biopsies of the prostate.
Is it for me? If your cancer is unlikely to threaten
your health during your lifetime, it might be.
Perhaps your life expectancy is less than ten years
and your cancer is non-aggressive. Perhaps all tests
indicate that the cancer is slow growing and will
not escape the prostate or cause symptoms.
Perhaps you have other health problems that make
aggressive treatment an inferior option. Or you may
decide that, given the anticipated low risk currently,
you are not ready to undergo other treatments and
can cope with the knowledge that cancer remains
in your body.
Disadvantages: Monitoring cancer is far from an
exact science, as all bodies are unique. Your cancer
might grow more rapidly than expected, escape the
prostate, and reach an incurable stage before your
medical team has a chance to react. Although this
theoretical situation does not occur very often, you
may be unwilling to live with the possibility that it
might occur at all.
18
Surgery
A radical prostatectomy is one of the most common
and effective treatments of localised prostate
cancer—prostate cancer that has not left the
prostate gland. In this procedure, a surgeon
removes the prostate gland, the seminal vesicles,
and, sometimes, the lymph nodes in the pelvis.
There are various methods of performing a radical
prostatectomy:
• In a radical retropubic prostatectomy, the
surgeon makes an incision that begins just under
the navel and runs to just above the public bone.
• In a radical perineal prostatectomy, the surgeon
makes the incision in the area between the
scrotum and the anus. Although less used
because it gives a poorer view of the bladder and
other significant anatomical features, this
approach makes sense in some cases, for
example, when a man has extensive scar tissue
from previous abdominal surgeries.
• Nerve-sparing techniques are now commonly
used with radical retropubic prostatectomy, as
long as the cancer is not too close to the
cavernous nerves. These nerves and
accompanying veins run in two bundles from
behind the bladder, along the sides of the
prostate, and into the penis. Surgeons try to leave
these nerves and veins intact because both are
involved in achieving and maintaining erections.
• In a laparoscopic radical prostatectomy, a scope
inserted through a small incision in the abdomen
lights and magnifies the area surrounding the
prostate, sending an enlarged view of the
surgical field to a monitor in the operating room.
Then, microsurgical instruments are inserted
through four or five other small incisions made
on each side of the abdomen, and the prostate
gland and seminal vesicles are removed. Pelvic
lymph nodes may also be removed.
• Robotic-assisted radical prostatectomy also
uses a laparoscope and microsurgical instruments
inserted through multiple, small incisions in the
19
Prostate
Cancer
abdomen. In this case, though, the instruments
are connected to robotic arms that perform the
operation, guided by the surgeon’s movements,
which the robot converts into micro-movements.
The patient and the surgeon need not be in the
same room.
Surgery without laparoscopes or robotic systems is
often called “open surgery.” And, in the hands of
an experienced surgeon, an open nerve-sparing
radical prostatectomy can have excellent results in
terms of cure, continence, and potency. Less blood
loss, faster postoperative recovery, and shorter
hospital stays are advantages of laparoscopic or
robotic-assisted prostatectomy. But the verdict is
out concerning which surgical approach offers the
best treatment of prostate cancer and the least
likelihood of long-term side effects.
incision location for a radical retropubic
prostatectomy
location of small incisions for a
laparoscopic radical prostatectomy
Is it for me? Surgery may be for you if your cancer
is confined to the prostate or the tissues immediately
surrounding it, and there is no evidence of distant
spread (metastasis). The clinical stages T1, T2, or a
small T3 tumour would fit this description. For men
20
with localised prostate cancer, a radical
prostatectomy offers one of the best chances for a
cure. If your cancer has spread to the lymph nodes or
if there are distant metastases, then hormone
therapy or another system-wide treatment will
usually be recommended, either on its own or with a
radical prostatectomy. If, after the surgery, there is
evidence that cancer cells have been left behind
(e.g., positive surgical margins), post-operative
radiotherapy may be useful.
Disadvantages: Radical prostatectomy is a fairly
serious surgical operation, no matter how it is
performed. It will require two to five days of
hospitalization and three to six weeks of recovery
time at home. You will need a catheter and urine
collection bag, which can usually be disposed of
after one to three weeks. You will most likely
experience some short-term lack of control over
urination. But, in most cases, things return to normal
in one month to a year. A more serious consideration
for some men is that, after a prostatectomy, they will
no longer be able to father children without the use
of a sperm bank. Men can reach orgasm but no
longer ejaculate after this surgery. Other long-term
consequences of the operation can include erectile
dysfunction (impotence), chronic incontinence, and
narrowing of the urethra. A common long-term side
effect is erectile dysfunction. Estimates are that, by
two years after surgery, approximately half of the
men who were fully functional before surgery have
recovered erections. Penile rehabilitation and nervesparing surgical techniques are improving these
odds. A smaller percentage of men will suffer
permanent stress incontinence (the leakage of urine
when sneezing or engaging in strenuous activity). An
even smaller percentage will experience total and
permanent incontinence and may require an
implanted artificial sphincter. Another complication,
the narrowing of the urethra because of scar tissue,
can make urination difficult. Minor surgery can
usually correct this problem.
21
Prostate
Cancer
Radiotherapy
Radiation therapy directs radioactive energy to a
particular area to kill cells by causing breaks in their
DNA. Because cancer cells generally replicate
quickly, they are more susceptible to radiation than
healthy cells, which divide and multiply more slowly.
Still, radiation usually causes some damage to
healthy tissue and, in some patients, may produce
radiotherapy-induced side effects.
Radiation therapy is given in one of two main ways:
by focussing an external beam of radioactive energy
at the cancer (external beam radiation) or by
implanting radioactive material near the cancer.
External beam radiation: In external beam
radiation, a computer-guided machine delivers high
energy x-rays to the prostate gland containing
cancer cells in brief sessions (called “fractions”)
that are usually scheduled five days a week over
about seven to eight weeks. As much as possible,
the rays are focussed toward the location and
depth of the prostate cancer, but some healthy cells
will be affected as well. Both the benefits and the
possible side effects of radiation therapy are
gradual and cumulative because cell death or
inflammation from radiation continues for several
months after treatment stops. Many techniques are
commonly practiced today in order to enable
precision in external beam radiation therapy,
thereby increasing treatment efficacy and reducing
damage to healthy cells:
22
• 3-dimensional conformal radiation therapy (3DCRT) This form of external beam radiation therapy
is now a standard treatment for prostate cancer.
It uses a CT scan or MRI to measure the prostate
in three dimensions and computers to calculate
how the radiation should be delivered. An
individualized plan emerges from this
information, one that directs radioactive beams
so they conform or shape to the area targeted to
receive radiation. Before the plan is followed, a
radiation oncologist will check its safety by using
all data to estimate the radiation dose required
to kill cancerous cells and the amount of
radiation this would deliver to neighbouring
healthy cells.
• Intensity modulated radiation therapy (IMRT)
Like 3D-CRT, this form of external beam radiation
therapy uses a CT scan or and MRI to create a
three dimensional picture of the prostate and a
computer to calculate how to irradiate cancerous
areas while sparing healthy ones. Unlike 3D-CRT,
intensity modulated radiation therapy can deliver
radiation at varying intensities or doses
throughout the targeted area being irradiated.
IMRT fine-tunes 3D-CRT by enabling the
radiation’s intensity (dose) to be modulated
(varied), so cancerous areas can receive high
intensity radiation while radiation to other areas
is minimized.
• Image-guided radiation therapy (IGRT) Over the
years, doctors have used steadily improving
technology to view the prostate and to mark the
location of a prostate cancer tumour. X-rays,
ultrasounds, CT scans, and MRI technology all
provide images that can help guide radiation
therapy. Typically, during radiation therapy
planning, radiation oncologists will consult these
images and use drops of permanent ink on a
patient’s skin or small metallic markers inserted
into a patient’s prostate gland to indicate the
area that should receive radiation. To compensate
for movement of the prostate during treatment or
23
Prostate
Cancer
possible changes to the tumour’s shape or size
between treatments, doctors expand the
treatment area slightly—to be as sure as they
can that all the cancer cells are irradiated. In
some cancer centres today, a technology known
as image-guided radiation therapy (IGRT) allows
doctors to see the tumour’s location just before
the delivery of radiotherapy or even during a
treatment, enabling them to adjust the radiation
beams to hit a tumour more precisely and reduce
the amount of healthy tissue exposed to
radiation.
Brachytherapy: This form of radiation therapy
involves introducing radioactive material directly
into the prostate so as to deliver radiation at close
range.
• Seed brachytherapy, the most common method,
uses surgery to implant tiny radioactive pellets or
“seeds” into the prostate through the perineum
(the region between the scrotum and the anus). A
transrectal ultrasound (TRUS) helps surgeons view
the prostate so the seeds can be placed
appropriately. The procedure is usually done while a
man is under a general or an epidural (waist down)
anaesthetic and does not normally require
hospitalization. The seeds, each one smaller than a
grain of rice, stay in the prostate permanently,
emitting radiation steadily for about 6 months or
more until they lose their radioactivity.
• High dose rate (HDR) brachytherapy involves
similar surgical procedures but it delivers
significantly higher doses of radiation over a much
shorter period. Thin tubes or catheters (12 to 18 or
more) are inserted into the patient’s prostate using
a transrectal ultrasound probe for guidance. Doctors
verify the position of these catheters using a CT
scan and then connect them to the treatment
machine, which releases radioactive material into
the catheters. A computer helps doctors assess how
long the prostate cells adjacent to each part of each
catheter should be exposed to radioactivity to give
24
the tumour cells the desired dose of radiation and
to avoid, as much as possible, damage to healthy
cells. After treatment, the radioactive material and
catheters are removed.
Is radiation therapy for me? If you have
localised prostate cancer and a life expectancy of
between 7 and 10 years, external beam radiation
therapy may be for you. It may also be the
recommended treatment for younger men with low
or intermediate risk cancers who have health
problems that make them poor candidates for
prostate surgery. An advantage of external beam
radiation is that no hospitalization is necessary, and
daily treatments are fast, causing minimal
disruption in a man’s day if the radiation facility is
nearby.
Seed brachytherapy as a treatment on its own is
usually recommended only to men diagnosed with
early prostate cancer who are in the low risk
category. Also, if you have a large prostate or a
history of urinary problems, or if you have had a
transurethral resection of the prostate to remove a
urinary blockage, this treatment is not the best
option for you.
HDR brachytherapy is a relatively new treatment
that may not be available locally. It is sometimes
offered in combination with external beam
radiation (as a boost). Research into its
effectiveness as a therapy for men with stages T1 to
T3b prostate cancer is ongoing.
Convenience is a major benefit of brachytherapy; it
allows men to avoid both the lengthy recovery time
necessary after major surgery and the long-term
treatment schedule needed for external beam
radiation.
Disadvantages: The major disadvantage of all
forms of radiation therapy is that, because the
prostate is not removed, cancer cells that are not
killed by treatment can re-grow and new prostate
cancer cells may grow. Short-term side effects of
external beam radiation can include fatigue, skin
25
Prostate
Cancer
reactions, and hair loss in the area receiving
radiation. Brachytherapy, which involves piercing
the prostate in several places, can cause the gland
to swell temporarily. Radiation treatment can also
affect the bladder and rectum, and a man may have
difficulty with urination, diarrhoea, or rectal
bleeding.
A common long-term complication of radiation
therapy is erectile dysfunction. Erectile difficulties
caused by radiation develop gradually in the
months following treatment, unlike those caused by
surgery. Also, radiation therapy “dries out” the
prostate, which, in many cases, stops making the
substances that constitute semen and nourish
sperm. Most men become infertile, although still
able to achieve an orgasm. Incontinence and bowel
problems are rare long-term complications.
Hormonal therapy
Hormonal therapy works by depriving prostate
cancer cells of the male hormones (androgens,
including testosterone) that they need to grow and
flourish. This androgen deprivation can be
accomplished through undergoing an orchiectomy
that removes the testicles or by taking medication
that either prevents the production of androgens
(LHRH analogue therapy) or blocks their effects on
prostate cells (antiandrogen therapy). By itself,
hormonal therapy cannot cure prostate cancer, but
it can slow or stop cancer growth for many years. It
is also a systemic rather than a local therapy,
meaning that it can arrest prostate cancer cells no
matter where they are in the body.
Orchiectomy: This procedure, also known as
surgical castration, involves removing the testicles,
which produce most of a man’s testosterone, the
principle male hormone. Although an orchiectomy is
a relatively quick and simple operation that causes
less long-term inconvenience and expense than
drug-based hormonal therapy, few men choose this
option today, possibly because its effects are not
reversible.
LHRH analogue therapy (medical castration):
Paradoxically, luteinizing hormone-releasing
hormone (LHRH) analogues interfere with the
production of androgens by over-stimulating the
pituitary gland to produce luteinizing hormone (LH).
The gland exhausts itself and shuts down LH
production altogether, thus depriving the testicles
of what they need to manufacture testosterone. The
therapy is usually administered by injection every 2
to 6 months or monthly. In Canada, the most used
LHRH analogues are Eligard® (leuprolide acetate),
Lupron Depot® (leuprolide acetate), Suprefact®
(buserelin), and Zoladex® (goserelin). Because
LHRH analogues initially stimulate the production
of LH and, consequently, of testosterone, a man
may experience a testosterone surge that heightens
cancer symptoms in the first weeks of treatment.
26
27
Prostate
Cancer
After about two weeks, the level of testosterone
falls dramatically and remains at extremely low
levels as long as the drug is continued.
Common
LHRH
Analogues
Injection Route
Buserelin Subcutaneous
(Suprefact®)
Usual time between
injections
2 or 3 months
Goserelin
(Zoladex®)
Subcutaneous
1, 3 months
Leuprolide
(Lupron®)
Intramuscular
1, 3, or 4 months
Leuprolide
(Eligard®)
Subcutaneous
1, 3, 4, or 6 months
Antiandrogen therapy: Antiandrogens are drugs
that block or otherwise interfere with the normal
effects of male hormones on prostate cells. There
are two types: steroidal and non-steroidal. Steroidal
antiandrogens, which act like female sex hormones,
are usually taken orally each day. They include
megestrol acetate (Megace®) and cyproterone
acetate (Androcur®). Non-steroidal antiandrogens
include fultamide (Euflex®), bicalutamide
(Casodex®), and nilutamide (Anandron®). Nonsteroidal antiandrogens are sometimes used in
combination with LHRH analogue therapy or
orchiectomy to block the effects of androgens
produced outside of the testicles (in the adrenal
glands, for example).
Hormonal therapy is used at various times for a
variety of purposes. It may be given before a local
treatment, such as radiation or a radical
prostatectomy, to reduce the size of a tumour, for
example. This is called neoadjuvant hormonal
therapy. More commonly, it is used directly after
surgery or radiation to treat any microscopic
cancerous cells that may remain in the body.
Doctors often use the term minimal residual disease
(MRD) to refer to these isolated or disseminated
cancer cells. Hormonal therapy after prostatectomy
or radiation is called adjuvant hormonal therapy,
and studies confirm that it can prolong survival for
men with locally advanced prostate cancer.
Besides the different timing of hormonal therapy,
there are various treatment regimes, and new ones,
as well as new drugs, are being tested all the time.
• Combined androgen blockade (CAB) combines
the use of antiandrogens with either chemical or
surgical castration. The idea is to block the action
of even the small amount of androgens present
in the body during LHRH analogue therapy or
after an orchiectomy. Research suggests that men
treated with CAB, which is sometimes called
maximal androgen blockade (MAB) or total
androgen blockade (TAB), may live longer, on
average, than men treated by LHRH analogue
therapy alone.
28
29
• Intermittent androgen blockade (IAB), often
referred to as intermittent hormonal therapy or
intermittent androgen suppression (IAS), is still
being investigated as a treatment option. It
involves administering hormone therapy drugs
until a man’s prostate cancer seems in check,
e.g., his PSA levels drop and stabilize. Then, the
man stops hormonal therapy until his PSA rises to
a predetermined level or at a certain speed. The
hope is that stopping hormone therapy
periodically and then restarting it will enable men
to enjoy a better quality of life during offtreatment times and may postpone the day when
hormone therapy no longer works well to control
their cancer (i.e., they develop hormone resistant
or hormone refractory prostate cancer).
Is it for me? Hormone therapy is the treatment of
choice for men whose prostate cancer has spread
to the lymph nodes, bones, or elsewhere in the
body (N1 or M1). It is also recommended for those
whose cancer returns after radical prostatectomy or
radiation therapy, or for those who are at a high
risk of experiencing such a recurrence.
Disadvantages: The main disadvantages are that
hormone therapy does not cure prostate cancer and
that treatments only work for a certain amount of
time, until prostate cancer cells become hormone
resistant or hormone refractory. (Hormone resistant
prostate cancer may respond to a change in
hormonal therapy while hormone refractory
prostate cancer progresses in spite of any hormone
therapy treatment regimen.) Men on hormonal
therapy may experience hot flashes, swelling or
tenderness of their breasts, lack of energy, anaemia,
mood swings, or depression. Over the long term,
hormone therapy can cause a loss of muscle
strength and bone density, which can lead to
osteoporosis. Many patients are placed on Vitamin
D and calcium to prevent bone loss. The most
common side effects are a decreased sex drive
(libido) and the eventual loss of erections (erectile
dysfunction).
30
Prostate
Cancer
Chemotherapy
Before 2004, no chemotherapy agent had been
proven to extend the lives of men with prostate
cancer. In that year, two international studies
confirmed that docetaxel (Taxotere®), a
chemotherapy drug made from the needles of the
European yew tree, improves the survival time and
quality of life for men with advanced stage prostate
cancer that is resistant to hormone therapy.
Generally, chemotherapy uses drugs that circulate
throughout the body to destroy cancer cells.
Taxotere®, which has been used since 1995 in the
treatment of breast and lung cancer, kills cancer
cells by disrupting the formation of their internal
structures, thereby stopping cells from dividing and
multiplying. Still, in the treatment of prostate
cancer, chemotherapy drugs are used mainly at the
hormone refractory stage, when a man’s cancer no
longer responds to hormone therapy. Some
chemotherapy agents, such as mitoxantrone
(Novantrone® and Onkotrone®), are used primarily
to relieve the pain associated with the late stages
of this disease. This palliative chemotherapy greatly
improves the quality of life of men with advanced
disease, but it does not prolong their lives. The
discovery that docetaxel (Taxotere®) does prolong
patients' lives (usually by about 25 % compared to
similar patients not taking the drug) and also
reduces the pain associated with advanced disease
has led to research that provides better options for
men with hormone refractory prostate cancer.
What about clinical trials
or new therapies?
Promising new prostate cancer therapies are being
tested right now. And some treatments once
considered promising just a few years ago have
faded from view. One way to discover relevant
innovations in prostate cancer treatment is to
research what clinical trials are being offered to
patients like you. (A clinical trial is a carefully
designed investigation into the effects and
effectiveness of a drug, treatment, or medical
31
Prostate
Cancer
device on a particular group of people, e.g., men
with clinically localised prostate cancer.) The Clinical
Trials Group of the National Cancer Institute of
Canada provides an online listing of all current
cancer trials in the country. You might even consider
participating in such a trial.
Some of the more unusual or experimental prostate
cancer treatments that you might hear about
include the following:
• Angiogenesis inhibitors are drugs that may be
useful in stopping prostate cancer growth by
keeping new blood vessels from forming;
prostate cancer tumours depend on the growth
of blood vessels (angiogenesis) to feed cancer
cells.
• Cryotherapy or cryosurgery uses liquid nitrogen
or Argon gas, delivered to the prostate through
probes positioned using transrectal ultrasound, to
freeze and kill prostate tissue, including cancer
cells. It may be used to treat early prostate cancer
or when radiation therapy is not successful.
Cryotherapy is offered in very few Canadian
centres.
• Gene therapy attempts to alter the genetic
structure of cancer cells, so they can be killed
more easily, either by other cancer treatments or
by the body’s own defence mechanisms.
• High-intensity focused ultrasound (HIFU)
destroys prostate tissue and prostate cancer cells
using focused, high-energy ultrasound waves to
generate intense heat. Men treated with HIFU
generally have low to intermediate risk prostate
cancer. Treatments are not covered by provincial
medical plans.
• Immunotherapy or biotherapy is designed to
repair, stimulate, or enhance the body’s immune
system so it can fight prostate cancer. Vaccines
such as the experimental Provenge are often
used in immunotherapy.
32
• PRX302 uses prostate-specific antigen (PSA) to
activate a series of steps leading to cell death. It
may prove effective in treating either prostate
cancer or benign prostatic hyperplasia.
• Trans perineal microwave ablation of the
prostate uses microwave energy to heat the
prostate and destroy cells; the microwaves are
delivered through needles positioned in the
prostate with the help of an ultrasound probe. It
has been used to treat men who still have
localised prostate cancer after radiation therapy.
Remember, you should always consult impartial
medical experts when making treatment decisions.
Also be aware that the efficacy and long-term
consequences of many of these emerging therapies
have yet to be tested against those of more
standard prostate cancer treatments.
What about
complementary therapies?
A complementary therapy is one that is used in
addition to standard treatment. Complementary
therapies for men with prostate cancer can include
anything from unconventional approaches such as
acupuncture, massage, and meditation to strategies
that are recommended by physicians, such as
lifestyle and dietary changes or other therapies that
help relieve certain symptoms of the disease or side
effects of its treatment.
Men on hormonal therapy may need
complementary therapies to minimize the risk of
other health problems e.g., cardiovascular disease,
diabetes, and osteoporosis. Men treated with
chemotherapy may need to address pain or nausea.
And some who have undergone surgery or
radiation may require complementary therapies to
improve their quality of life, for example, to treat
incontinence or erectile dysfunction. (See “Living
well after treatment” and “Life as a couple.”)
33
Prostate
Cancer
Always consult your medical team before adding a
complementary therapy to your treatment plan.
Some can interfere with both the effectiveness and
side effects of standard treatments and increase
your risk.
What next?
Questions to ask about follow up
How will we judge whether the treatment has
worked or is working?
What follow-up medical appointments and tests
should we arrange to monitor my health, and how
often should these take place?
What signs or symptoms of prostate cancer
recurrence should I watch for?
What are my options if the cancer comes back?
When can I expect to recover from some of the
short-term side effects of treatment?
Can I do anything to encourage my recovery?
Are there lifestyle changes, strategies, or therapies
that will help me maintain or regain urinary control
and erectile function or combat fatigue, anaemia,
and bone and muscle mass loss?
What are my options if I experience long-term
complications or secondary health issues because
of essential prostate cancer treatment?
34
Living well after treatment
Most treatments for prostate cancer can cause both
short-term and long-term side effects. Surgery and
radiation can result in incontinence or, more rarely,
damage to the bowels. Men on hormone therapy
may experience hot flashes, fatigue, mood swings,
and, over time, a decrease in muscle mass and an
increased risk of osteoporosis. Although it is
important for you to be aware of these risks, keep
in mind that treatment saves lives and that the
possible side effects of treatment can also be
treated.
Incontinence, or the loss of the ability to control
urination, can be a side effect of prostate cancer
surgery because the prostate is close to the bladder
and surrounds the tube that allows urine to flow
outside the body (the urethra). Urinary
incontinence is rare following radiotherapy. Still,
any treatment that removes the prostate or
destroys its tissue carries the risk of interfering with
the process of urination, although more precise
techniques minimize this risk. Treatments for urinary
incontinence include
• Kegel exercises, which strengthen the muscles
you squeeze to stop urinating
• Lifestyle changes, such as drinking fewer liquids,
avoiding caffeine and alcohol, not drinking
before bed, and losing weight
• Medication, such as decongestants to tighten the
muscles of the urethra or anticholinergic drugs
(e.g., oxybutynin) to block messages to the
bladder nerves and prevent bladder spasms
• Bulking agents, e.g., collagen, injected into the
bladder neck to reduce urinary leakage
• Opening up any stricture (narrowing) of the
urethra caused by scar tissue, which can be done
by cutting into the scar tissue or by stretching the
urethra
• Surgically introducing a sling that compresses
the urethra below the sphincter
• Surgically implanting an artificial urinary
sphincter
35
Prostate
Cancer
Bowel side effects that last are rare with surgery
but may occur following radiotherapy. You may
experience some temporary decrease in rectal tone
after a prostatectomy, so it is important to avoid
constipation. Radiation therapy that exposes a
significant area of the rectal wall can cause bowel
inflammation, urgency, and faecal incontinence.
However, new imaging techniques, more precise
methods of delivering radiation, and using
neoadjuvant hormonal therapy to shrink tumours
reduce the risk of these complications even further.
Hormonal therapy side effects can also be
addressed. Hot flashes can be controlled with
medication or by making lifestyle changes. Exercise
(both aerobic and weight-bearing) and proper
nutrition are good ways to reduce fatigue, weight
gain, and the risk of bone or muscle mass loss.
Bisphosphonates such as pamidronate (Aredia®) or
zoledronic acid (Zometa®), as well as calcium and
vitamin D are possible treatments to reduce the risk
of osteoporosis or to treat it.
Life as a couple
Many men feel that the challenges posed by
prostate cancer and its treatment eventually
strengthen their loving relationships, even though
changes in self-perception, in family role, and in
patterns of sexual intimacy often result.
Maintaining open and honest communication with
partners and getting timely medical and counselling
help are essential when it comes to weathering
these changes, which can include infertility,
decreased sex drive, and erectile dysfunction.
Infertility: Most men will be infertile after surgery
or radiation therapy. Ejaculation (but not orgasm) is
impossible after radical prostatectomy, and the
radiated prostate and seminal vesicles could
produce semen that cannot transport sperm well.
Hormonal therapy, which can reduce sexual desire,
poses its own difficulties. Men who want to start a
family after prostate cancer treatment should
consider having their sperm frozen.
36
Decreased libido: For a man diagnosed with
prostate cancer, a lowered interest in sex should
not be treated with testosterone, which feeds the
growth of cancerous cells. Talking things over with
your partner or visiting a counsellor or sex therapist
together is very useful. A couple may find that the
need to discuss desire and not take it for granted
enables a more honest and giving sexual intimacy.
Erectile dysfunction (ED): Erectile dysfunction is
defined as the inability to achieve or maintain an
erection adequate for sexual intercourse. Varying
degrees of ED are common following radical
prostatectomy, even when the surgeon spares the
nerve bundles upon which a man’s erections
depend. After all, prostate surgery is quite
traumatic. Most men treated with nerve-sparing
surgery experience an improvement in their
erections over time. Some, however, never recover
the ability to get a spontaneous erection. Men who
have radiation therapy also develop erectile
difficulties, but these occur slowly and over time, as
the benefits and negative side effects of radiation
accrue. Erectile dysfunction can be treated in the
following ways:
• Oral medications such as sildenafil (Viagra®),
vardenafil (Levitra®), and tadalafil (Cialis®) can
help prevent the natural breakdown of chemical
substances emitted by erectile nerves. These
substances (neurotransmitters) are produced
when a man is sexually stimulated, and they
bring about a dilation of the blood vessels in the
penis, which causes engorgement of penile tissue
and an erection.
• Injecting drugs such as alprostadil, papaverine,
or phentolamine into the side of the penis
(intracavernous injections) can cause blood
vessels to relax and the penis to fill with blood,
creating an erection even in the absence of
sexual stimulation.
• The medicated urethral system of erection
(MUSE) involves inserting a small suppository of
alprostadil into the urethra through the opening
37
in the tip of the penis. Once the penis is
massaged lightly to speed absorption, blood
vessels expand and an erection occurs.
• Constricting rings are adjustable or elastic bands
that a man can place around the base of his
penis before it is aroused. The ring assists by
retaining blood in the penis once an erection is
achieved.
• A vacuum erection device (VED) works by
drawing blood into the penis and keeping it there
by means of a constricting ring, but VEDs do not
produce a physiological erection. Consequently,
erections neither look nor feel normal, and they
do not promote the healing circulation of fresh,
oxygenated blood to the organ.
• A penile implant is a prosthetic device
introduced into the penis during surgery. It can
be semi-rigid or inflatable.
Prostate
Cancer
Where can I turn for more
information or help?
Prostate Cancer Canada
Tel: 416-441-2131
Toll Free: 1-888-255-0333
Fax: 416-441-2325
E-mail: [email protected]
http://www.prostatecancer.ca
Canadian Prostate Cancer Network
Tel: 705-652-9200
Toll Free: 1-866-810-CPCN (2726)
Français: 1-888-322-5735
(service fourni par La fondation québécoise
du cancer)
Fax: 705-652-0663
E-mail: [email protected]
http://www.cpcn.org
Procure Alliance
Tel; 514-985-1320
Toll Free: 1-866-899-CURE (2873)
Fax: 514-985-1363
http://www.procure.ca
La fondation québécoise du cancer (French only)
Téléphone: 418-657-5334
Sans frais: 1-800-363-0063
Service en français pour CPCN: 1-888-322-5735
Télécopieur: 418-657-5921
Courriel: [email protected]
http://www.fqc.qc.ca
38
39
Prediction tools and nomograms
Partin tables (Johns Hopkins)
http://urology.jhu.edu/prostate/partintables.php
Han tables (Johns Hopkins)
http://urology.jhu.edu/prostate/hanTables.php
Prostate cancer nomograms
(Memorial Sloan-Kettering)
http://www.mskcc.org/mskcc/html/10088.cfm
Prostate Cancer Risk Calculator
(Sunnybrook Health Sciences Centre)
http://www.sunnybrook.ca/content/?page=3144
Prostate Cancer Assessment Tools
(Prostate Cancer Canada)
http://www.prostatecancer.ca/english/calculator/calculator
Risk Assessment Quiz
(Prostate Cancer Canada)
http://www.prostatecancer.ca/Prostate-Cancer
Prostate Cancer Canada thanks
Dr. Robert G. Bristow for his contributions
to the production of this booklet.
This publication has been made possible through an
unrestricted educational grant from sanofi aventis.
40