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Prostate Cancer
The prostate gland is an organ that is located at the base or outlet
(neck) of the urinary bladder. (See the diagram that follows.) The
gland surrounds the first part of the urethra. The urethra is the
passage through which urine drains from the bladder to exit from the
penis. One function of the prostate gland is to help control urination
by pressing directly against the part of the urethra that it surrounds.
The main function of the prostate gland is to produce some of the
substances that are found in normal semen, such as minerals and
sugar. Semen is the fluid that transports the sperm to assist with
reproduction. A man can manage quite well, however, without his
prostate gland.
In a young man, the normal prostate gland is the size of a walnut
(<30g). During normal aging, however, the gland usually grows
larger. This hormone-related enlargement with aging is called benign
prostatic hyperplasia (BPH), but this condition is not associated with
prostate cancer. Both BPH and prostate cancer, however, can cause
similar problems in older men. For example, an enlarged prostate
gland can squeeze or impinge on the outlet of the bladder or the
urethra, leading to difficulty with urination. The resulting symptoms
commonly include slowing of the urinary stream and urinating more
frequently, particularly at night. Patients should seek medical advice
from their urologist or primary-care physician if these symptoms are
present.
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What is prostate cancer?
Prostate cancer is a malignant (cancerous) tumor (growth) that
consists of cells from the prostate gland. Generally, the tumor usually
grows slowly and remains confined to the gland for many years.
During this time, the tumor produces little or no symptoms or outward
signs (abnormalities on physical examination). However, all prostate
cancers do not behave similarly. Some aggressive types of prostate
cancer grow and spread more rapidly than others and can cause a
significant shortening of life expectancy in men affected by them. A
measure of prostate cancer aggressiveness is the Gleason score
(discussed in more detail later in this article), which is calculated by a
trained pathologist observing prostate biopsy specimens under the
microscope.
As the cancer advances, however, it can spread beyond the prostate
into the surrounding tissues (local spread). Moreover, the cancer also
can metastasize (spread even farther) throughout other areas of the
body, such as the bones, lungs, and liver. Symptoms and signs,
therefore, are more often associated with advanced prostate cancer.
Why is prostate cancer important?
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Prostate cancer is the most common malignancy in men and the
second leading cause of deaths from cancer, after lung cancer.
According to the American Cancer Society's most recent estimates,
192,280 new cases of prostate cancer would be diagnosed in 2009
and 27,360 would die from the disease.
The estimated lifetime risk of being diagnosed with the disease is
17.6% for Caucasians and 20.6% for African men. The lifetime risk of
death from prostate cancer similarly is 2.8% and 4.7% respectively.
As reflected in these numbers, prostate cancer is likely to impact the
lives of a significant proportion of men that are alive today.
Over the years, however, the death rate from this disease has shown
a steady decline, and currently, more than 2 million men in the U.S.
are still alive after being diagnosed with prostate cancer at some
point in their lives.
Although it is subject to some controversy, many experts in this field,
therefore, recommend that beginning at age 40, all men should
undergo screening for prostate cancer.
What are prostate cancer causes?
The cause of prostate cancer is unknown, but the cancer is not
thought to be related to benign prostatic hyperplasia (BPH). The risk
(predisposing) factors for prostate cancer include advancing age,
genetics (heredity), hormonal influences, and such environmental
factors as toxins, chemicals, and industrial products. The chances of
developing prostate cancer increase with age. Thus, prostate cancer
under age 40 is extremely rare, while it is common in men older than
80 years of age. As a matter of fact, some studies have suggested
that among men over 80 years of age, 50%-80% of them may have
prostate cancer! More than 80% of prostate cancers are diagnosed in
men older than 65 years of age.
As mentioned previously, African-American men are 1.6 times more
likely than white men to develop prostate cancer. They are also 2.4
times more likely to die from their disease as compared to white men
of a similar age. These differences in diagnosis and death rates are,
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however, more likely to reflect a difference in factors such as
environmental exposure, diet, lifestyle, and health-seeking behaviour
rather than any racial susceptibility to prostate cancer. Recent studies
indicate that this disparity is progressively decreasing with chances of
complete cure in men undergoing treatment for organ-confined
prostate cancer (cancer that is limited to within the prostate without
spread outside the confines of the prostate gland), irrespective of
race.
Genetics (heredity), as just mentioned, plays a role in the risk of
developing a prostate cancer. Prostate cancer is more common
among family members of individuals with prostate cancer. This risk
may be two to three times greater than the risk for men without a
family history of the disease. Earlier age at diagnosis (<60 years) in a
first-degree relative (father or brother) and disease affecting more
than one relative also increases the risk for developing prostate
cancer.
Testosterone, the male hormone produced by the testicles, directly
stimulates the growth of both normal prostate tissue and prostate
cancer cells. Not surprisingly, therefore, this hormone is thought to be
involved in the development and growth of prostate cancer. The
important implication of the role of this hormone is that decreasing the
level of testosterone should be (and usually is) effective in inhibiting
the growth of prostate cancer.
Recent evidence has suggested that sexually transmitted infections
are risk factors for developing prostate cancer. Men with a history of
sexually transmitted infections have a 1.4 times greater chance of
developing prostate cancer as compared men without this history.
Although still unproven, environmental factors, such as cigarette
smoking and diets that are high in saturated fat, seem to increase the
risk of prostate cancer. There is also a suggestion that obesity leads
to an increased risk of having more aggressive, larger prostate
cancer, which results in a poorer outcome after treatment. Additional
substances or toxins in the environment or from industrial sources
might also promote the development of prostate cancer, but these
have not yet been clearly identified. Geographical influences also
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seem to play a role in the development of prostate cancer with men
living in the Scandinavian and North American countries being at a
higher risk for the disease as compared to those residing in Asian
countries.
Of note, there is no proven relationship between the frequency of
sexual activity and the chances of developing prostate cancer.
What are prostate cancer symptoms and signs?
In the early stages, prostate cancer often causes no symptoms for
many years. As a matter of fact, these cancers frequently are first
detected by an abnormality on a blood test (the PSA, discussed
below) or as a hard nodule (lump) in the prostate gland. Occasionally,
the doctor may first feel a hard nodule during a routine digital (done
with the finger) rectal examination. The prostate gland is located
immediately in front of the rectum.
Rarely, in more advanced cases, the cancer may enlarge and press
on the urethra. As a result, the flow of urine diminishes and urination
becomes more difficult. Patients may also experience burning with
urination or blood in the urine. As the tumor continues to grow, it can
completely block the flow of urine, resulting in a painfully obstructed
and enlarged urinary bladder. These symptoms by themselves,
however, do not confirm the presence of prostate cancer. Most of
these symptoms can occur in men with non-cancerous (benign)
enlargement of the prostate (the most common form of prostate
enlargement). However, the occurrence of these symptoms should
prompt an evaluation by the doctor to rule out cancer and provide
appropriate treatment.
Furthermore, in the later stages, prostate cancer can spread locally
into the surrounding tissue or the nearby lymph nodes, called the
pelvic nodes. The cancer then can spread even farther (metastasize)
to other areas of the body. Symptoms of metastatic disease include
fatigue, malaise, and weight loss. The doctor during a rectal
examination can sometimes detect local spread into the surrounding
tissues. That is, the physician can feel a hard, fixed (not moveable)
tumor extending from and beyond the gland. Prostate cancer usually
metastasizes first to the lower spine or the pelvic bones (the bones
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connecting the lower spine to the hips), thereby causing back or
pelvic pain. The cancer can then spread to the liver and lungs.
Metastases (areas to which the cancer has spread) to the liver can
cause pain in the abdomen and jaundice (yellow color of the skin) in
rare instances. Metastases to the lungs can cause chest pain and
coughing.
What is active surveillance for prostate cancer?
Active surveillance is observing a patient while no immediate
treatment is given. Such a patient usually has a less aggressive,
small-sized, organ-confined tumor and no symptoms. This
management strategy is based on the premise that most early
prostate cancers are slow-growing tumors and will remain confined to
the prostate gland for a significant length of time. This implies that in
selected patients it may be possible to defer definitive treatment for
many years or avoid it altogether thereby preventing the side effects
associated with treatments like surgery or radiation. Understand,
however, that although active surveillance involves no actual
treatment, the patient still needs close follow-up and monitoring. The
follow-up involves frequent visits to the doctor, perhaps every three to
six months. The visits include questions about new or worsening
symptoms and digital rectal examinations for any change in the
prostate gland. In addition, blood tests are done to watch for a rising
PSA, and imaging studies can be conducted to detect the spread of
the cancer. Most experts also recommend performing a confirmatory
set of prostate biopsies to ensure that there is low-volume disease.
Additional prostate biopsy is required every year to detect any
increase in the volume and Gleason grade of the cancer. As
mentioned before, Gleason grade is a measure of aggressiveness of
the tumor and increase in this value may point toward a need to treat
the cancer with other means. If the history, examinations, or any of
the tests signal the possibility of an advancing cancer, the active
surveillance usually is discontinued and active treatment is
recommended, often with radiotherapy or surgery.
Active surveillance is different from watchful waiting. Watchful waiting
means following up patients without any tests or biopsies and treating
them only when symptoms arise. This is reserved for men who have
a life expectancy of less than 10 years. Therefore, watchful waiting
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seems to make sense for organ-confined (localized) prostate cancers
in men who are elderly. Additionally, watchful waiting often is the
most appropriate choice in men who are ill with other serious medical
diseases, such as heart or lung disease, poorly controlled high blood
pressure, diabetes, AIDS, or other cancers.
Active surveillance and watchful waiting in prostate cancer, however,
remains controversial. Some medical authors have stated outright
that it is not a good choice. They point out that few doctors would just
watch other cancers to see whether they would spread without
treatment. Furthermore, the treatment for an individual could become
less effective in the future if and when the cancer does progress.
Moreover, there is no standardized protocol for selecting appropriate
patients for active surveillance with different institutions having their
own different guidelines. Studies are under way to compare these
protocols with more established methods of treatment, and more
information is likely to emerge in the future.
What are the treatment options for prostate cancer?
Deciding on treatment can be difficult, partly because the options for
treatment today are far better than they were 10 years ago but also
because not enough reliable data are available on which to base the
decisions. Accordingly, scientifically controlled, long-term studies are
still needed to compare the benefits and risks of the various
treatments.
To decide on treatment for an individual patient, doctors categorize
prostate cancers as organ-confined (localized to the gland), locally
advanced (a large prostate tumor or one that has spread only locally),
or metastatic (spread distantly or widely). The treatment options for
organ-confined prostate cancer or locally advanced prostate cancer
usually include surgery, radiation therapy, hormonal therapy,
cryotherapy, combinations of some of these treatments, and watchful
waiting. A cure for metastatic prostate cancer is, unfortunately,
unattainable at the present time. The treatments for metastatic
prostate cancer, which include hormonal therapy and chemotherapy,
therefore, are considered palliative. By definition, the aims of
palliative treatments are, at best, to slow the growth of the tumor and
relieve the symptoms of the patient.
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What about prostate cancer surgery?
The surgical treatment for prostate cancer is commonly referred to as
a radical prostatectomy, which is the removal of the entire prostate
gland. The entire prostate, seminal vesicles, and ampulla of the vas
deferens are removed, and the bladder is connected to the
membranous urethra to allow free urination.
The radical prostatectomy is the most common treatment for organ
confined or localized prostate cancer in the United States. This
operation is currently performed in about 36% of patients with organconfined (localized) prostate cancer. The American Cancer Society
estimates a 90% cure rate nationwide when the disease is confined
to the prostate and the entire gland is removed. The potential
complications of a radical prostatectomy include the risks of
anesthesia, local bleeding, impotence (loss of sexual function) in
30%-70% of patients, and incontinence (loss of control of urination) in
3%-10% of patients.
Great strides have been made in lowering the frequency of the
complications of radical prostatectomy. These advances have been
accomplished largely through improved anesthesia and surgical
techniques. The improved surgical techniques, in turn, stem from a
better understanding of the key anatomy and physiology of sexual
potency and urinary continence. Specifically, the recent introduction
of nerve-sparing techniques for the prostatectomy has helped to
reduce the frequency of impotence and incontinence. Of men who
undergo these newer techniques, 98% are continent, and 60% are
able to have an erection.
Radical prostatectomy can be performed by open surgery,
laparoscopic surgery, or by robotic surgery (robotic assisted radical
prostatectomy). Currently, almost 70% of radical prostatectomy
surgeries in the U.S. are performed using the of the Da Vinci robotic
system. For robot-assisted surgery, five small incisions are made in
the abdomen through which the surgeon inserts tube-like
instruments, including a small camera. This creates a magnified
three-dimensional view of the surgical area. The instruments are
attached to a mechanical device, and the surgeon sits at a console
and guides the instruments through a viewing device to perform the
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surgery. The instrument tips can be moved in a variety of ways under
the control of the surgeon to achieve greater precision in surgery. So
far, studies show that traditional open prostatectomy and robotic
prostatectomy have had similar outcomes related to cancer-free
survival rates, urinary continence, and sexual function. However, in
terms of blood loss during surgery and pain and recovery after the
procedure, robotic surgery has been shown to have a significant
advantage.
If post-treatment impotence does occur, it can be treated by sildenafil
(Viagra) tablets, injections of such medications as alprostadil
(Caverject) into the penis, various devices to pump up or stiffen the
penis, or a penile prosthesis (an artificial penis). Incontinence after
treatment often improves with time, special exercises, and
medications to improve the control of urination. Occasionally,
however, incontinence requires implanting an artificial sphincter
around the urethra. The artificial sphincter is made up of muscle or
other material and is designed to control the flow of urine through the
urethra.
Transurethral resection of the prostate (TURP) involves the removal
of a part of the prostate by an instrument inserted through the
urethra. It is used as an alternative to prostatectomy in patients with
extensive disease or those who are not fit enough to undergo radical
prostatectomy to remove tissue that is blocking urine flow. This is
often referred to as a channel TURP.
What about radiation therapy for prostate cancer?
The goal of radiotherapy is to damage the cancer cells and stop their
growth or kill them. This works because the rapidly dividing
(reproducing) cancer cells are more vulnerable to destruction by the
radiation than are the neighbouring normal cells. Clinical trials have
been conducted using radiation therapy for patients with organconfined (localized) prostate cancer. These trials have shown that
radiation therapy resulted in a rate of survival (being alive) at 10
years after treatment that is comparable to that for radical
prostatectomy. Incontinence and impotence can occur as
complications of radiation therapy, as with surgery, although perhaps
less often than with surgery. More data are needed, however, on the
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risks and benefits of radiation therapy beyond 10 years, especially
because late recurrences (reappearances) of the cancer can
sometimes occur after radiation.
Choosing between radiation and surgery to treat organ-confined
prostate cancer involves considerations of the patient's preference,
age, and coexisting medical conditions (fitness for surgery), as well
as of the extent of the cancer. Approximately 30% of patients with
organ-confined prostate cancer are treated with radiation.
Sometimes, oncologists combine radiation therapy with surgery or
hormonal therapy in an effort to improve the long-term results of
treatment in the early or later stages of prostate cancer.
Radiation therapy can be given either as external beam radiation over
perhaps six or seven weeks or as an implant of radioactive seeds
(brachytherapy) directly into the prostate. In external beam radiation,
high energy X-rays are aimed at the tumor and the area immediately
surrounding it. In brachytherapy, radioactive seeds are inserted
through needles into the prostate gland under the guidance of
transrectally taken ultrasound pictures. Brachy, from the Greek
language, means short. The term brachytherapy thus refers to
placing the treatment (radiation therapy) directly into or a short
distance away from the cancerous target tissue. The theoretical
advantage of brachytherapy over external beam radiation is that
delivering the radiation energy directly into the prostate tissue should
minimize damage to the surrounding tissues and organs.
Potential disadvantages of radiation therapy include a transient
swelling of the prostate that may cause obstruction to the flow of
urine and increase symptoms that may already be present because
of an enlarged prostate. Side effects of external beam radiation
include skin burning or irritation and hair loss at the area where the
radiation beam goes through the skin. Both can cause severe fatigue,
diarrhea, and discomfort on urination. These effects are almost
always temporary. However, there are concerns about the long-term
effects of radiation, and although still not proven, some studies have
reported a higher chance of developing bladder or rectal cancer many
years after undergoing radiation for prostate cancer. Although surgery
can be done in case radiation therapy fails to cure prostate cancer
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(salvage radical prostatectomy), it is fraught with greater surgical
difficulty and involves a significantly higher chances of complications
like impotence and urinary incontinence.
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