- Overview of prostate cancer
- After lung cancer, cancer of the prostate is the second most
common cause of cancer deaths in men in the United States. It is estimated that up to
350,000 men are diagnosed with prostate cancer annually.
Adenocarcinoma of the prostate is the clinical term for
cancer that begins as a tumor on the outside of the prostate gland. As it grows, it may
spread to the inner part of the prostate. If identified early enough in its development
and treated before the malignancy spreads too far into the gland or out into surrounding
tissues, lymph nodes or bones, it can be treated successfully with a variety of medical
procedures. If not, the cancer cells will spread through the bloodstream, infecting other
parts of the body, and the disease will claim the person as one of its estimated 40,000
annual victims.
 Incidence and Prevalence
Prostate cancer is often described as a disease of men over age 50. A man's chances of
being diagnosed with prostate cancer during his lifetime are about 1 in 10 - roughly the
same as a woman's chances of having breast cancer. The number of reported new cases has
risen dramatically in recent years - 350,000 in 1996, compared to about 100,000 in 1990 -
as a result of improved tests which can detect the disease early in its development, often
long before symptoms appear.
The likelihood of developing prostate cancer in any given
year increases with age, but rises significantly after age 50. A recent study estimated
one in nearly 59,000 men age 40 to 44 are likely to be diagnosed with prostate cancer,
rising to one in about 2,600 from age 50 to 59, and one in 80 beyond age 80.
Apart from age, studies have identified several other
discrete groups with statistically higher rates of prostate cancer.
Of all racial groups, African Americans have the highest
incidence of prostate cancer in America; Caucasians have the lowest. No biological reason
has been found to explain this. Interestingly, Japanese men and black males living in
Africa have a low incidence of prostate cancer; rates for these groups increase sharply
when they emigrate to the United States. Experts have postulated that this suggests an
environmental connection, possibly related to American dietary habits, low exposure to
ultraviolet light, exposure to heavy metals such as cadmium, infectious agents, or
smoking.
Men whose families have a history of prostate cancer are
considered to be at high risk. Studies suggest a hereditary factor, but to date no
specific responsible gene or genes have been identified.
Diet-research suggests high dietary fat as a prominent risk
factor.
- What are the signs and symptoms of
the condition?
- In its earliest stages, prostate cancer often causes no
symptoms. It usually is detected when a person undergoes a routine rectal examination. For
this reason, it is important for men over 40 to have an annual prostate examination.
Caught early in its development, the disease has a high cure rate.
Detectable symptoms of prostate cancer may begin to emerge as
the disease progresses. When they do, they often resemble those of benign prostatic
hyperplasia (BPH). This can be dangerous, because noncancerous enlargement of the prostate
is common in men over 40, and a man experiencing difficulty with urination at this stage
in his life may ignore it as a natural sign of aging.
The longer prostate cancer is ignored, the greater chance it
will metastasize (spread), first locally in the tissues around the prostate or seminal
vesicles (sac-like structures attached to the prostate), then to other parts of the body,
like the lymph nodes or bones.
Chances of survival decrease as the disease spreads. If
confined to the prostate gland itself, the disease is usually curable. If it is locally
advanced, the prognosis is not good; a substantial proportion of such patients will die
within 5 years of the disease. Once cancer has spread to distant organs, life expectancy
is usually less than three years.
For these reasons, men experiencing any of the symptoms of
BPH should see their urologist or family physician immediately for a thorough examination.
These symptoms include:
- Frequent urination, especially at night
- Weak or interrupted urinary flow
- Inability to urinate
- Pain or burning during urination
- Blood in the urine or semen
- Pain during ejaculation
- Nagging pain or stiffness in the back, hips, upper thighs or
pelvis
How is this condition diagnosed?
- The following diagnostic tests for prostate cancer determine
how far along the disease is, as well as what treatment is appropriate.
Digital Rectal Exam (DRE)
In a DRE, the physician inserts a lubricated, gloved finger into the patient's
rectum to feel the surface of the prostate gland. Healthy prostate tissue is soft, like
the fleshy tissue of the hand where the thumb joins the palm. Malignant tissue is firm,
hard, often asymmetrical or stony, like the bridge of the nose. The test is subjective,
however, and relies on the physician's ability to interpret what he or she feels. Only
larger tumors can be felt; as many as one-third of patients subsequently diagnosed with
prostate cancer actually will still have a normal DRE.
Prostate Specific
Antigen (PSA) Test
If the physician suspects the presence of a tumor on the prostate, he or she will
likely perform an additional blood screening test called the prostate specific antigen, or
PSA test. This procedure can provide information about how much cancer is present and
whether it has spread.
Prostate specific antigen is a substance produced only by the
cells of the prostate capsule (membrane covering the prostate) and periurethral glands.
The test measures the amount of PSA present in the blood. An elevated or rising PSA level
can indicate the existence of prostate cancer.
PSA is measured in nanograms per milliliter (ng/ml) of blood.
A PSA of 4 ng/ml or lower is normal and a PSA above 10 ng/ml suggests the presence of
cancer; the range 4-10 ng/ml is a gray area, and readings in this range are considered
inconclusive.
Additionally, PSA levels are also related in part to the size
of the prostate, and patients with benign prostatic hyperplasia (BPH) or a prostate
inflamed by prostatitis also produce elevated levels of PSA. For these reasons, scientists
have modified the PSA testing process by developing several new PSA-based refinements:
Free/Total PSA (also known as PSA II) -- PSA in the blood may
be bound molecularly to a variety of serum proteins, or it may exist in a free or unbound
state. Total PSA is the sum of all existing forms; Free PSA constitutes the unbound PSA
only. Studies suggest that malignant prostate cells produce less Free PSA. Therefore, a
low proportion of Free PSA in relation to Total PSA might indicate a cancerous prostate,
and a high proportion of Free PSA might suggest a normal prostate or a condition
reflecting BPH or prostatitis.
Age-specific PSA -- Evidence suggests PSA levels increase
with age. Researchers have defined typical age-associated values for PSA norms. A PSA of
up to 2.5 ng/ml for men age 40-49 would be considered normal, as would those up to 3.5
ng/ml for men 50-59, 4.5 ng/ml for men 60-60, and 6.5 for men 70 and older. Lower PSA
levels in older men might indicate the presence of cancer that does not need to be treated
aggressively, whereas higher levels in younger men might warrant aggressive treatment.
PSA Velocity (PSAV) -- Researchers have studied the rate of
change in PSA over time in men whose medical outcomes were known. This rate of change in
PSA is known as PSA velocity (PSAV). A rate of change in PSA velocity of 0.75 ng/ml/yr or
higher has been conclusively linked to clinically significant prostate cancer. Therefore,
a man with a PSA in the gray area of 4-10 ng/ml, and who is found to have a PSAV of 0.75
ng/ml/yr, may have a cancerous prostate condition.
Prostatic Acid
Phosphatase (PAP) Test
Prostatic acid phosphatase is an enzyme produced by several types of tissue,
including normal prostate tissue. Its production increases as prostate disease progresses.
In conjunction with other testing procedures, PAP testing has been used to detect and
monitor advanced prostate cancer. It is not, however, used by itself in diagnosing
prostate cancer.
Prostate Biopsy
Once the physician has diagnosed a likely cancerous prostate condition by means
of a digital rectal exam or a PSA test, he or she may want to perform other tests to
determine the type of cancer, its location, and stage of development.
Prostate biopsies is done with a needle similar in size to
those used to draw blood or administer injections. A sample of tissue from the suspected
cancer site is extracted and analyzed by a pathologist (a physician who is a specialist in
diseases) to confirm the presence of cancer and to determine its type.
A patient undergoing a prostate biopsy is advised to abstain
from alcohol, aspirin, or non-steroid anti-inflammatory drugs for one week before the
procedure. He also is required to have a Fleet enema and to take an oral antibiotic
(usually ciprofloxacin) for 1 day before and 2 days after the biopsy.
The biopsy is performed with the patient lying on his side. A
biopsy needle may be inserted through the perineum into the tumor, or a probe, guided by a
transrectal ultrasound (TRUS) device, may be inserted into the rectum, and a needle
projected into the tumor through a port in the tip of the probe. A cell sample is then
extracted into a syringe and taken for analysis by the pathologist. Samples may be taken
from several parts of the tumor.
While the biopsy is a valuable conventional procedure, it
also carries risks. It may produce bleeding that is difficult to control, or it may cause
infection from rectal bacteria.
Additionally, doctors and researchers have noted that biopsy
of a cancerous tumor can cause spreading or "seeding" of cancer cells along the
path or track made by the biopsy needle. This could cause cancer that had been confined
solely to the prostate capsule to spread into surrounding tissues, making a serious health
concern even more problematical.
While cancer seeding from biopsy is uncommon, patients and
physicians should be aware of these potential risks, have a clear understanding of what
information they want to obtain from a biopsy, and what action will be taken based upon
that information.
Prostate Biopsy
Transrectal ultrasound (TRUS) imaging is commonly used to measure the size of the
prostate, and to detect and analyze cancerous tumors. This procedure uses a special probe
inserted through the rectum to project ultrasonic impulses against the prostate. The
results are viewed on a monitor, enabling the physician and operator to obtain a visual
image of the gland, surrounding tissue, and tumors that may be present.
Not all cancers can be seen ultrasonically, however, so as a
screening measure TRUS is most useful when performed in conjunction with a digital rectal
exam (DRE). Studies have shown that the combination of TRUS and DRE together is more
effective at detecting prostate cancers than either procedure performed alone.
Gleason Score
Once the presence of a cancerous tumor has been confirmed by biopsy, the pathologist will
evaluate its relative malignancy and potential for metastasizing (spreading). He or she
will examine the biopsy sample(s) under a microscope while looking for cells or groups of
cells that are markedly different from healthy tissue. The greater the disparity between
the healthy cells and those that are malignant, the more likely the tumor is aggressive
and will spread. The usual method for expressing the results of this analysis is the
Gleason Grading System.
Under the Gleason System, the pathologist examines biopsy
samples from two different parts of the tumor and assigns them a grade of 1 to 5 based on
their degree of differentiation (the amount by which they differ from healthy tissue). The
more abnormal the tissue, the higher the score. The results of these two samples are added
together to produce a Gleason Score of from 2 to 10. Gleason Scores of 2 to 4 are
considered well-differentiated, meaning the tissue is not too different from normal; 5 to
7 are moderately differentiated; 8 to 10 are poorly differentiated. Higher scores indicate
aggressive tumors that are likely to require aggressive treatment.
Lymph
Nodes and Lymphadenectomy
Lymph nodes are round or oval bodies that supply white blood cells to the circulatory
system. These cells, called lymphocytes, typically remove bacteria and foreign particles
from the blood. But when cancer cells invade the bloodstream, they can be spread to other
parts of the body, including the lymph nodes.
When prostatic cancer spreads, it usually migrates first to
the lymph nodes in the pelvis. The doctor can estimate the likelihood of this spread on
the basis of the biopsy results, PSA tests, and the size of the tumor. He or she also may
recommend removing these nodes for microscopic examination.
If it appears likely that the cancer has spread, the doctor
may recommend having them surgically removed through an incision in the lower abdomen.
This procedure, called surgical lymphadenectomy, can be done at the same time that the
cancerous prostate is removed (radical prostatectomy). Because the body has many lymph
nodes, the loss of a few in the pelvic region does not cause a problem.
The doctor also may examine and remove the nodes with a
laparoscope, a miniature telescopic device connected to a monitor. This device is inserted
through four small incisions in the lower abdomen. Laparoscopic lymphadenectomy requires
less recovery time in hospital for the patient than an open lymphadenectomy. But because
it constitutes a second surgical procedure, the desirability of performing this process
must be assessed relative to the need to remove the prostate as well. If it appears that a
radical prostatectomy will be necessary, the doctor and patient may elect to remove both
in a single operation.
Computed
Tomographic (CT) Scan
Also known as a computer-assisted tomography or "CAT" scan, the CT scan is a
type of X-ray procedure that gives three-dimensional images of internal organs or glands.
It can be used to detect pelvic lymph nodes enlarged by cancer, although some authorities
suggest its results are insufficient for a clear diagnosis. CT scans typically are used
only when tumors are large or associated with high PSA levels.
Bone Scan
A bone scan is a nuclear imaging procedure that can detect the spread of cancer to bones.
It usually is prescribed in cases where aggressive tumors and metastasis are suspected.
Normally, it is not used in patients with small cancers and low PSA levels.
- Staging this disease
- Before the physician can recommend a course of treatment for
prostate cancer, he or she needs to assess how far it has spread to surrounding tissues
and other parts of the body. This is called "staging." There are two systems
commonly used for staging prostate cancer: the Jewett-Whitmore System and the TNM (Tumor,
Node, Metastases) System.
Jewett-Whitmore System
Established in 1975, the basic Jewett System classifies all prostatic cancers into one of
four stages. These may be numbered 1-4 or distinguished by the letters A-D.
| Stage 1 (or A) |
Very early and without symptoms. Such cancers
typically are discovered accidentally, such as when a patient has surgery for relief of
benign prostatic hyperplasia (BPH). Cancer cells at this stage are confined to the
prostate. |
| Stage 2 (or B) |
Confined to the prostate, but palpable (detectable by
digital rectal exam) and/or detectable by elevated PSA reading. |
| Stage 3 (or C) |
Cancer cells have spread outside the prostate capsule
(membrane covering the prostate). The spread is localized (confined to the surrounding
tissues and/or seminal vesicles). |
| Stage 4 (or D) |
Regionally metastasized (spread) to lymph nodes, or to more
distant bones, organs (liver, lungs, etc.) and/or other tissues. |
Stage 1 and 2 (A and B) cancers are considered curable. Stage
3 and 4 (C and D) are treatable, but their prognoses are progressively discouraging.
Later refinements in the basic Jewett System added
subdivisions to reflect specific conditions within each category. This expanded
Jewett-Whitmore system uses an alphanumeric staging system.
| A1 - |
(Clinically undetectable) Found to be
well-differentiated. Such cancers usually are left untreated. |
| A2 - |
Moderately or poorly differentiated. Cancer cells are
present in several locations within the prostate. |
| B0 - |
(Confined to the prostate) Nonpalpable; PSA-detected. |
| B1 - |
Single cancerous nodule in one lobe of the prostate. |
| B2 - |
More extensive, involving one or both prostate lobes. |
| C1 - |
(Localized) Extending outside the prostate capsule. |
| C2 - |
Tumor causes bladder or urethral obstruction. |
| D0 - |
(Metastatic) Clinically localized, but showing elevated
blood PAP levels. |
| D1 - |
Regional lymph nodes involved. |
| D2 - |
Distant lymph nodes, bones or organs involved. |
| D3 - |
Metastatic patients who relapse after therapy. |
TNM System
The TNM (Tumor, Node, Metastases) System, adopted by the American Joint Committee on
Cancer and the International Union Against Cancer in 1992, uses stages generally similar
to those of the Jewett-Whitmore System, but with expanded alphanumeric subcategories to
reflect specific areas and degrees of infection.
Primary tumor (T)
| TX - |
Tumor cannot be assessed. |
| T0 - |
No evidence of primary tumor. |
| T1 - |
Clinically not palpable or visible by imaging, but: |
| T1a |
Found incidental to other surgery, present in 5% or less of
tissue. |
| T1b |
Found incidental to other surgery, present in 5% or more of
tissue. |
| T1c |
Identified by needle biopsy (performed owing to elevated
PSA). |
| T2 - |
Tumor confined within prostate, involving: |
| T2a |
Half a lobe or less of prostate. |
| T2b |
Half a lobe, but not both lobes. |
| T2c |
Both lobes. |
| T3 - |
Tumor extending through prostate capsule. |
| T3a |
Extension through one lobe. |
| T3b |
Extension through both lobes. |
| T3c |
Extension into seminal vesicles. |
| T4 - |
Tumor fixed, invading structures other than seminal
vesicles. |
| T4a |
Invasion of bladder neck, external sphincter or rectum. |
| T4b |
Invasion of muscles and/or pelvic wall. |
Regional Lymph Nodes (N)
| NX - |
Nodes cannot be assessed. |
| N0 - |
No regional node metastasis. |
| N1 - |
Single node metastasis, 2 centimeters (cm) or less at
largest point. |
| N2 - |
Single node metastasis, 2 cm to 5 cm at largest point, or
multiple nodes, no larger than 5 cm at largest point. |
| N3 - |
Metastasis larger than 5 cm in any node. |
Distant Metastasis (M)
| MX - |
Presence of metastasis cannot be
assessed. |
| M0 - |
No distant metastasis. |
| M1 - |
Distant metastasis. |
| M1a |
Non-regional lymph node(s) involved. |
| M1b |
Bone(s) involved. |
| M1c |
Other site(s) involved. |
- What are the treatments?
- How prostate cancer is treated depends upon the extent of the
disease's progression, the patient's age and overall health. Elderly patients, those whose
symptoms are slight, who have only early-stage cancers or who suffer from additional, more
serious, diseases may be treated conservatively, whereas those whose cancers are advanced
may require more aggressive treatment.
Below is a list of the more common treatments for prostate
cancer.
Watchful Waiting
As with BPH, some men with prostate cancer may be best served by a program watchful
waiting. While untreated prostate cancer will certainly continue to grow, it may take
years to reach a stage where its symptoms are problematic. Patients of advanced years,
poor general health, or whose cancers are in an early stage may choose watchful waiting as
a reasonable alternative to surgery. During this time, the doctor will continue to monitor
and evaluate the patient's condition. Any marked or unexpectedly sudden progression of the
disease may signal the need for more aggressive or radical treatment.
Surgical Options
Surgery for prostate cancer usually is recommended for patients whose overall health is
otherwise good, have a negative bone scan, tumors confined to the prostate gland (Stage 1
and 2), are under age 70 or who could reasonably expect to live another 10 years or more.
There are a variety of surgical options, ranging from the conservative to the
experimental. None guarantees an absolute cure, and some have considerable side effects,
but each offers a reasonable expectation of success for the prostate cancer patient,
depending upon the extent of the disease's progression.
Radical Prostatectomy
- The most common treatment for localized cancer of the prostate in men under age 70
without other health complications, radical prostatectomy involves surgically removing the
cancerous gland and some of the surrounding tissue, including the seminal vesicles. This
is done either through a surgical incision in the lower abdomen (retropubic prostatectomy)
or the space between the scrotum and the rectum (perineal prostatectomy). The latter
technique requires a separate incision to remove pelvic lymph nodes to see if they, too,
are cancerous; this procedure is done concomitantly during retropubic prostatectomy.
Survival rates are similar to those of patients who undergo
external radiation treatment. Results are not as good in men whose cancers extend beyond
the margin of tissues removed at surgery. Radiation therapy may be additionally prescribed
in radical prostatectomy patients whose cancers later return. Patients typically require
hospitalization for 3 to 5 days after surgery and usually wear a catheter for 2 weeks.
Side effects of radical prostatectomy include a risk of blood clots related to the
operation, which can cause heart failure. Urinary leakage (incontinence) is common after
surgery, but most healthy men eventually regain urinary control. Erectile Dysfunction is a
common complication. Surgeons try where possible to avoid removing or cutting the nerves
that control a man's ability to achieve an erection. Depending upon the patient's age and
the stage of tumor advancement, these so-called "nerve-sparing" techniques can
enable about 40% to 65% of men who were sexually potent before surgery to remain so
afterward.
Cryosurgery - This
treatment alternative uses a TRUS-guided probe to deliver freezing temperatures to the
cancerous tumor. Intermittent freezing and thawing kills the cancer cells. Long-term
results of cryosurgery are still unknown. Reported side effects include urinary
incontinence, rectal injury and impotence.
Radiation Therapy
Brachytherapy -
Technically, brachytherapy is more a form of therapy than a surgical procedure, but it
does involves a surgical element - the implantation of tiny, radioactive implants into a
cancerous prostate gland. Radiation emitted by the implants kills the malignant tumor. Men
whose cancers are small and confined to the prostate (Stage 1 or 2) are candidates for
brachytherapy.
The physician first uses an ultrasound device (TRUS) to
create a three-dimensional grid map of the prostate. A computer then is used to calculate
the volume of the gland, the number of radioactive implants (called "seeds")
that will be needed and where they should be placed.
The procedure, performed on an outpatient basis, takes 45 to
60 minutes and is done under local (spinal) anesthesia. From 50 to 100 rice-sized seeds
are then inserted by a special needle through the perineum and into the prostate in a
preplanned pattern, guided by the TRUS and grid map. The seeds contain a radioactive
isotope, usually Palladium 103 or Iodine 125, which emit radiation for about three months
before decaying to an inert state.
Brachytherapy patients can be discharged the same day and
usually resume normal activity within a day or two. A small proportion, generally those
over 70, experience incontinence or impotence problems. But brachytherapy has been found
to deliver a higher and better focused dose of radiation with fewer side effects and at
substantially lower cost than external beam therapy. In a recent study of 111
brachytherapy patients, 100% were prostate cancer free after five years.
External Radiation Treatment (XRT)
- This, too, is more a form of therapy than surgery. It usually is prescribed for patients
with localized cancer, that is, those whose tumors have spread outside the prostate
capsule, but are still likely confined to the immediate surrounding tissues. Treatment
involves projecting a high-energy beam of X-rays onto the prostate tissues from a machine
outside the body. The radiation kills cancer cells and shrinks tumors. Radiation treatment
usually is done on an outpatient basis over a period of 7 to 8 weeks. Common side effects
include impotence, particularly in older men, discomfort with urination, urinary urgency
and diarrhea, especially during the later stages of treatment.
Survival rates for external radiation therapy patients are
comparable to those experienced by patients who under surgical removal of the prostate
(radical prostatectomy). One study of 999 patients found 79% of Stage 1, 66% of Stage 2,
55% of Stage 3 and 22% of Stage 4 prostate cancer patients were still living 10 years
after treatment.
Hormonal therapy
Hormonal therapy: involves the use of anti-androgens, an androgen is a male
Hormone needed for the production of testosterone, to deprive the cancer cells of the
testosterone they need for growth. Side effects include gynecomastia, the development of
breast tissue. Examples of drugs that are used for hormonal control include Lupron
Depot®, Zoladex®, Casodex® and Eulexin®. The former two are semimonthly injections and
the latter are oral pills.
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