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Prostate Cancer |
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Adenocarcinoma of the prostate is the clinical term for a
cancerous tumor on the prostate gland. As prostate cancer
grows, it may spread to the interior of the gland, to tissues
near the prostate, to sac-like structures attached to the
prostate (seminal vesicles), and to distant parts of the body
(e.g., bones, liver, lungs). Prostate cancer confined to the
gland often is treated successfully.
Anatomy
The prostate gland is located in the pelvis, below the
bladder, above the urethral sphincter and the penis, and in
front of the rectum in men. It is made up of glandular tissue
and muscle fibers that surround a portion of the urethra. The
gland is covered by a membrane (called the prostate capsule)
that produces prostate-specific antigen.
Incidence and Prevalence
According to the American Cancer Society (ACS), prostate
cancer is the most common type of cancer in men in the United
States, other than skin cancer. The ACS estimates that about
230,900 new cases will be diagnosed in 2004 and about 29,900
men will die of the disease. Prostate cancer is the second
leading cause of cancer death in men, exceeded only by lung
cancer.
Prostate cancer occurs in 1 out of 6 men. Reports of diagnosed
cases have risen rapidly in recent years and mortality rates
are declining, which may be due to increased screening.
African American men have the highest incidence of prostate
cancer, and Asian and Native American men have the lowest
incidence. Rates for Asian and African men increase sharply
when they emigrate to the United States, suggesting an
environmental connection (e.g., high-fat diet, smoking).
The risk for developing prostate cancer rises significantly
with age, and 60% of newly diagnosed cases occur in men over
the age of 70.
Risk Factors
A family history of prostate cancer increases the risk. Other
possible risk factors include the following:
55 years old and older
Diet high in saturated fat
Exposure to heavy metals (e.g., cadmium)
Race (African American)
Sedentary lifestyle
Smoking
Signs and Symptoms
Early prostate cancer usually is discovered during a routine
digital rectal examination (DRE).
Symptoms are often similar to those of benign prostatic
hyperplasia. Men observing the following signs and/or symptoms
should see their physician for a thorough examination.
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Blood in the
urine or semen
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Frequent
urination, especially at night
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Inability to
urinate
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Nagging pain
or stiffness in the back, hips, upper thighs, or pelvis
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Painful
ejaculation
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Pain or
burning during urination (dysuria)
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Weak or
interrupted urinary flow
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Diagnosis
Several tests are used to diagnose prostate cancer.
Digital rectal examination (DRE)
In a DRE, the physician inserts a lubricated, gloved finger
into the 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, and often asymmetrical or stony, like the bridge of the
nose. However, as many as one-third of patients diagnosed with
prostate cancer have a normal DRE.
Transrectal ultrasound (TRUS)
TRUS is used to measure the size of the prostate and visually
identify tumors. A probe inserted into the rectum emits
ultrasonic impulses against the prostate. The images are
projected on a monitor, so the physician can examine the gland
and surrounding tissue for tumors.
TRUS and the digital rectal examination are effective
prostate-cancer screening tools.
PSA and PAP Tests
Blood tests taken to check the levels of prostate specific
antigen (PSA) and prostatic acid phosphatase (PAP) in a
patient who may have benign prostatic hyperplasia help the
physician eliminate or confirm a diagnosis of prostate cancer.
Prostate-specific antigen (PSA) is produced by the cells of
the prostate capsule (membrane covering the prostate) and
periurethral glands. Patients with benign prostatic
hyperplasia (BPH) or prostatitis produce greater amounts of
PSA. The PSA level also is determined in part by the size and
weight of the prostate.
The test measures the amount of PSA in the blood in nanograms
per milliliter (ng/mL). A PSA of 4 ng/mL or lower is
considered normal; 4 – 10 ng/mL, slightly elevated; 10 – 20,
moderately elevated; and 20 – 35, highly elevated. Most men
with slightly elevated PSA levels do not have prostate cancer,
and many men with prostate cancer have normal PSA levels. A
highly elevated level may indicate the presence of cancer.
The PSA test can produce false results. A false positive
result occurs when the PSA level is elevated and there is no
cancer. A false negative result occurs when the PSA level is
normal and there is cancer. Because of this, a biopsy is
usually performed to confirm or rule out cancer when the PSA
level is high.
Free and total PSA (also known as PSA II) PSA in the blood may
be bound molecularly to one of several proteins or may exist
in a free, or unbound, state. Total PSA is the sum of the
levels of both forms; free PSA measures the level of unbound
PSA only. Studies suggest that malignant prostate cells
produce more bound PSA; therefore, a low level of free PSA in
relation to total PSA might indicate a cancerous prostate, and
a high level of free PSA compared to total PSA might indicate
a normal prostate, BPH, or prostatitis.
Age-specific PSA Evidence suggests that the PSA level
increases with age. A PSA of up to 2.5 ng/mL for men age 40–49
is considered normal, as is 3.5 ng/mL for men age 50–59, 4.5
ng/mL for men age 60–69, and 6.5 ng/mL for men 70 and older.
The use of age-specific PSA levels is not endorsed by all
medical professionals.
Use the PSA Age/Race Quiz or the PSA Velocity Quiz to
determine your risk of prostate cancer.
Prostatic acid phosphatase (PAP) test Prostatic acid
phosphatase is an enzyme produced by prostate tissue. The
level of PAP increases as prostate disease progresses.
Tumor Biopsy
If a tumor is found, a biopsy is performed to determine the
type of cancer, its location, and stage of development.
Before undergoing the biopsy, patients should abstain from
alcohol, aspirin, and nonsteroidal anti-inflammatory drugs
(e.g., ibuprofen) for 1 week. They are required to take one
Fleet enema the night before the procedure and one 2 hours
before the biopsy. An oral antibiotic (usually ciprofloxacin)
is prescribed to be taken the day before, the day of, and 2
days after the biopsy.
The biopsy is performed with the patient lying on his side
with his knees brought up to his chest. A biopsy needle,
similar to one used to draw blood or administer injections, is
inserted through the perineum into the tumor. A probe, guided
by transrectal ultrasound (TRUS), is inserted into the rectum
to help the physician properly place the needle, which is
projected through the tip of the probe. A cell sample is
extracted from one or several areas of the tumor into the
syringe. The sample(s) is analyzed by a pathologist to confirm
the diagnosis of a cancerous tumor and determine its type. The
results are obtained within 5–10 working days.
Gleason score The biopsy sample(s) is examined under a
microscope 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
(metastasize).
The pathologist examines two tissue samples taken from
different areas of the tumor and assigns a score of 1 to 5 to
each sample. The more abnormal the tissue, the higher the
score. The sum of the two produces the Gleason score. Gleason
scores of 2 to 4 indicate that the cells are well
differentiated, meaning the tissue is not too abnormal; 5 to 7
moderately differentiated; 8 to 10 poorly differentiated.
Higher scores suggest aggressive tumors that likely require
aggressive treatment.
Complications
After a biopsy, blood in the urine (hematuria) and stool is
common and usually diminishes within 1–2 weeks. Patients also
experience a dull ache in the perineum for several days. Men
are advised to refrain from sexual intercourse for 3–5 days.
Blood may appear in the semen.
If the patient develops a large number of blood clots or
cannot urinate, the physician should be contacted or the
patient should go to the emergency room.
Rarely, biopsy of a cancerous tumor also may cause spreading,
or "seeding," of cancer cells along the path of the biopsy
needle.
Computed tomography (CT scan)
Computer-assisted tomography (CAT scan or CT scan) is an x-ray
procedure that produces three-dimensional images of internal
organs and glands. It can be used to detect pelvic lymph nodes
enlarged by cancer, but results may be insufficient for
diagnosis. CT scans are used only when tumors are large or PSA
levels are high.
Bone scan
A bone scan is a nuclear imaging procedure that is used to
detect metastasis to bones. It is not used in patients with
small cancers and low PSA levels.
Staging
The physician "stages" the tumor based on its size, the
character of its cells, and the extent of metastisis. Two
systems commonly are used for staging prostate cancer: the
Jewett-Whitmore system and the TNM (tumor, node, metastases)
system.
Jewett-Whitmore system
In the Jewett-Whitmore system, prostate cancer is classified
first as stage A, B, C, or D. Stages A and B cancers are
considered curable. Stages C and D are treatable, but their
prognoses are discouaging. A number is then assigned to
describe specific conditions within each stage. For example, a
tumor classified as stage B1 is a single cancerous nodule
confined to one lobe of the prostate.
Click to enlarge the image. Stage A
Very early and without symptoms; cancer cells confined to the
prostate
A1 Well differentiated and slightly abnormal cancer cells
A2Moderately or poorly differentiated and abnormal cancer
cells in several locations within the prostate
Click to enlarge the image. Stage B
Confined to the prostate, but palpable (detectable by digital
rectal exam) and/or detectable by elevated PSA
B0Confined to the prostate, nonpalpable; PSA elevated
B1Single cancerous nodule in one lobe of the prostate
B2Extensive, involvment in one or both prostate lobes
Click to enlarge image. Stage C
Cancer cells found outside the prostate capsule (membrane
covering the prostate); spread confined to surrounding tissues
and/or seminal vesicles
C1Extends outside the prostate capsule
C2Bladder or urethral obstruction
Click to enlarge image. Stage D
Metastasis (spread) to regional lymph nodes, or to distant
bones, organs (e.g., liver, lungs), and/or other tissues
D0 Metastatic, clinically localized, and showing elevated
blood PAP levels
D1 Regional lymph nodes involved
D2 Distant lymph nodes, bones, or organs involve
D3 Metastatic disease after treatment
TNM System
The TNM (tumor, node, metastases) system stages are similar to
those of the Jewett-Whitmore system, but with more specific
alphanumeric subcategories.
Primary tumor (T) TX Tumor cannot be assessed
T0 No evidence of primary tumor
T1 Clinically not palpable or visible by imaging
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
T2 Tumor confined within prostate
T2a Involving half a lobe or less of prostate
T2b Involving half a lobe
T2c Involving both lobes
T3 Tumor extends through prostate capsule
T3a Extends through one lobe
T3b Extends through both lobes
T3c Extends into seminal vesicles
T4 Involves structures other than seminal vesicles
T4a Invades bladder neck, external sphincter, or rectum
T4b Invades 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 Metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
M1a Distant lymph node(s) involved
M1b Bone(s) involved
M1c Other site(s) involved
Medical Treatment
Treatment for prostate cancer depends on the stage of the
disease and the patient's age and overall health. Elderly
patients with minor symptoms, early stage cancer, or
coexisting illness may be treated conservatively.
Watchful waiting is a reasonable course of action for patients
who are elderly, in poor health, or with early stage cancer.
Untreated prostate cancer may take years to become
problematic. During this time, the physician monitors the
patient's condition for any marked or sudden progression of
the disease, which may signal the need for more aggressive
treatment.
Hormone Therapy
Hormone therapy for prostate cancer involves the use of
antiandrogens to block production of testosterone, which
prostate cancer cells use to grow. Drugs used for hormone
therapy include leuprolid acetate (Viadur®), goserelin acetate
implant (Zoladex®), bicalutamide (Casodex®), and flutamide (Eulexin®).
Viadur® is a matchstick-sized titanium pump inserted under the
skin on the upper arm that delivers a constant rate of
leuprolide acetate for 1 year. This prostate cancer treatment
suppresses androgen (e.g., testosterone, estrogen) production,
causing the tumor to shrink or stop growing and reducing
symptoms (e.g., pain, urinary retention, urinary frequency).
A tablet located in one end of the implant draws moisture from
surrounding tissue in the arm. The moisture exerts pressure
within the device that steadily pushes medication from the
other end.
The device is inserted under local anesthesia through a small
incision. The incision must be kept dry for 24 hours and must
remain bandaged for a few days. Strenuous physical activity
should be avoided for 48 hours. The implant is removed after
12 months and a new device may be inserted.
Side effects associated with hormone therapy include the
following:
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Blood in the
urine (hematuria)
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Depression
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Enlargement
of breast tissue (gynecomastia)
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Headache
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Hot flashes
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Lack of
energy
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Local
reaction to insertion (e.g., bruising, burning, itching)
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Uretheral or
bladder outlet obstruction
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Patients may also experience an increase in
prostate cancer symptoms for approximately 2 weeks, due to a
temporary increase in testosterone levels. Patients with
advanced disease (e.g., large bone, bladder, or spinal cord
tumors) may be unable to tolerate this increase in
testosterone. Studies have shown that abarelix injection (Plenaxis™),
which does not cause a surge in testosterone, can be used in
some of these patients to relieve symptoms (e.g., bone pain,
inability to urinate).
Plenaxis may cause life-threatening conditions in some people,
such as a drop in blood pressure; loss of consciousness;
breathing problems (e.g., shortness of breath, wheezing); and
swelling of the face, eyelids, tongue, or throat. Patients
must be monitored by a physician for at least 30 minutes after
each administration of the drug in case an adverse reaction
does occur.
Treatment involves one injection into the buttocks every 2
weeks for the first month, and every 4 weeks thereafter. Blood
tests are performed every 2 months to monitor the
effectiveness of the drug.
Common side effects include the following:
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Abnormal
breast enlargement (gynecomastia), breast tenderness and
pain
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Back pain
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Constipation
Dizziness
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Fatigue
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Headache
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Hot flashes
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Increased
urination
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Sleep
disturbances
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Swelling of
the legs and ankles (peripheral edema)
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Treatment for Bone
Metastases
Zoledronic acid (Zometa®) is a bisphosphonate prescribed to
treat hypercalcemia—excess calcium in the blood—in prostate
cancer patients who have bone metastases (secondary tumors in
bone). Patients with hypercalcemia experience dehydration,
fatigue, nausea, vomiting, confusion, and if untreated, may
result in coma.
Bone metastases cause bone tissue to break down, which
releases calcium into the bloodstream. Zoledronic acid
increases bone density, decreases bone loss, and reduces the
risk for fractures.
Patients must have completed at least one course of hormone
therapy before starting this treatment. Doses are given
intravenously for 15 minutes, every 3 to 4 weeks. A blood
sample is taken before each treatment to monitor kidney
function.
Zoledronic acid is not recommended for patients with severe
kidney disease and should be used with caution in those with
aspirin-sensitive asthma and those taking loop diuretics
(e.g., hydrochlorothiazide).
Side effects usually are mild and temporary. Patients may
experience the following:
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Anemia
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Constipation
or diarrhea
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Fatigue
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Insomnia
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Joint,
muscle, or bone pain
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Nausea
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Shortness of
breath (dyspnea)
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Vomiting
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Radiation Therapy
Two types of radiation therapy are used to treat prostate
cancer: brachytherapy and external radiation therapy (XRT).
Brachytherapy
This treatment involves implanting tiny, radioactive capsules
(called "seeds") into the cancerous prostate gland. The seeds
emit radiation that kills the malignant tumor. Men with small
tumors confined to the prostate (stage T1 or T2) are
candidates for brachytherapy.
Transrectal ultrasound (TRUS) is used to create a
three-dimensional grid map of the prostate, and a computer
calculates the volume of the gland, the number of seeds
needed, and determines where they will be placed.
The procedure is performed on an outpatient basis and takes 45
to 60 minutes. The patient is given regional anesthesia. A
needle is inserted through the perineum and into the
predetermined site(s). Fifty to 100 rice-sized seeds are
implanted into the prostate through the needle. The seeds
contain a radioactive isotope (usually palladium 103 or iodine
125) that emits radiation for about 3 months and then becomes
inert.
Recovery Brachytherapy patients are discharged the same day
and usually resume routine activity within a day or so. A
recent study has shown that most brachytherapy patients remain
free of prostate cancer 5 years after treatment.
Complications A small number of patients, generally those over
age 70, experience incontinence or impotence.
External Radiation Treatment (XRT)
XRT is recommended when the tumor has spread through the
prostate capsule to surrounding tissues. XRT usually is given
on an outpatient basis for 7 to 8 weeks. High-energy x-rays
are projected onto prostate tissue from a machine outside the
body. The radiation destroys cancer cells and shrinks tumors.
A study of 999 patients found 79% of stage T1, 66% of stage
T2, 55% of stage T3, and 22% of stage T4 prostate cancer
patients survived 10 years after XRT.
Complications
Erectile dysfunction (i.e., impotence, particularly in older
men), discomfort with urination, urinary urgency, and diarrhea
(especially during the late stages of treatment) are commonly
experienced with XRT.
Surgery
Good candidates for surgery to treat prostate cancer have one
or more of the following characteristics:
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Good health
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No spread of
cancer to bone
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Tumor
confined to the prostate gland (stage T1 and T2)
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Under the age
of 70
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Expected to
live another 10 years or longer
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Depending on the extent of the disease,
there are several surgical options for prostate cancer.
Cryosurgery
This minimally invasive outpatient procedure, also called
cryoablation, destroys cancer cells by twice rapidly freezing
and thawing cancerous tissue. It is recommended for patients
who
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cannot
tolerate surgery or radiation,
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have
prostate-confined tumors (stage T3 or lower),
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do not
respond to radiation (both external-beam and brachytherapy),
and
are elderly.
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Transrectal ultrasound and prostate biopsy
are performed prior to cryosurgery to determine the exact size
and location of the tumor(s). The procedure is performed under
regional (e.g., epidural nerve block) or general anesthesia.
With the man on his back, the surgeon inserts a warming
catheter into the urethra to protect it from freezing
temperatures. An ultrasound transducer is inserted into the
rectum, so the surgeon can see the prostate and surrounding
tissue and monitor placement of the cryoprobes. The surgeon
then makes 5 to 8 needle punctures in the perineum and
advances the needles to preselected locations in the prostate
tumor. Liquid nitrogen or argon gas circulates through the
probes and freezes cancer cells to —40°C.
The temperature in and around the prostate is monitored with
thermosensors, also inserted through the perineum. Once the
spheres of tissue surrounding the cryoprobes are covered with
ice, the liquid nitrogen or argon circulation is stopped and
the area is allowed to thaw. The freeze-thaw cycle is repeated
and then the instruments are removed. The procedure takes
about 2 hours.
Recovery
Patients usually go home the same day or the day after the
procedure. A catheter is necessary for about 3 weeks. Most
patients report very little discomfort and often recover fully
within days.
Recent studies show that 97% of cryosurgery patients are
cancer free at 1 year and 82% are cancer free at 5 years
following surgery. Cryosurgery usually can be repeated safely
if cancer returns.
Complications
The urethral warming device causes incontinence or urethral
obstruction in about 1% of patients. There is an 85% chance
that freezing will result in nerve damage and cause impotence
(erectile dysfunction). However, nerve-sparing techniques are
being developed to help reduce that risk.
High Intensity Focused Ultrasound (HIFU)
High intensity focused ultrasound (HIFU) is currently
undergoing clinical trials in the United States. HIFU is a
noninvasive treatment that uses precision-focused ultrasound
waves to heat and destroy (ablate) targeted prostatic tissue
without affecting healthy surrounding tissue. It has been
shown to effectively treat localized prostate cancer as well
as benign prostatic hyperplasia (BPH). The Food and Drug
Administration (FDA) has not yet approved this treatment in
the United States.
In clinical trials, HIFU is performed on an outpatient basis,
under anesthesia. HIFU can be repeated as necessary, and each
treatment takes 1–3 hours. Following treatment, a catheter is
necessary for about 1 week and most patients are able to
resume regular activities within days. Impotence occurs in
1–7% of patients.
Radical
Prostatectomy
Radical prostatectomy is the surgical removal of the prostate
gland and surrounding tissues, including the seminal vesicles
and the pelvic lymph nodes. Surgeons use one of two surgical
techniques, retropubic prostatectomy or perineal
prostatectomy. General anesthesia is used in both procedures.
In retropubic prostatectomy, an incision is made in the lower
abdomen. This gives the surgeon access to the prostate gland,
seminal vesicles, and the pelvic lymph nodes. In perineal
prostatectomy, the incision is made in the perineum, the space
between the scrotum and the rectum. With perineal
prostatectomy, a second procedure is required to remove the
pelvic lymph nodes (lymphadenectomy).
Recovery
Typically, patients remain in the hospital for 3 to 7 days
after surgery and are catheterized for 2 to 3 weeks.
The 10-year survival rate after radical prostatectomy ranges
from 75% to 97% for patients with well and moderately
differentiated cancers (containing normal-appearing and
slightly abnormal cells) and 60% to 86% for patients with
poorly differentiated cancers (containing very abnormal
cells).
Complications
Urinary leakage (incontinence) is common after surgery, but
most men eventually regain urinary control. Surgeons try to
avoid removing or cutting the nerves that control the ability
to achieve an erection. Depending on the patient's age and the
stage of the tumor, these nerve-sparing techniques enable
about 40% to 65% of men who were sexually potent before
surgery to remain so. There is also a risk for blood clots,
which can cause heart failure. Radiation therapy may be
recommended if cancer returns.
Laparoscopic Radical Prostatectomy
Laparoscopic radical prostatectomy is performed through
several small incisions. A device consisting of a tube and an
optical system (laparoscope) is inserted into one incision and
is used to guide the procedure. Surgical instruments are
inserted through the other incisions. This procedure is not
available in all areas, and not all surgical patients are good
candidates for the laparoscopic approach.
Laparoscopic radical prostatectomy causes less bleeding and
less postoperative pain and results in a shorter hospital stay
and recovery period. Catheterization is required for
approximately 3 days following the procedure.
Lymphadenectomy
Prostate cancer usually spreads first to the lymph nodes in
the pelvis. The physician assesses the likelihood of spread
based on the biopsy results, PSA tests, and the size of the
tumor. Lymphadenectomy is the surgical removal of lymph nodes.
There are two types of lymphadenectomy, open and laparoscopic.
General anesthesia is used in both procedures.
In an open lymphadenectomy, the lymph nodes are removed
through an incision in the lower abdomen. Laparoscopic
lymphadenectomy is performed with a laparoscope, a miniature
telescopic device connected to a monitor. The laparoscope and
other microinstruments are inserted through four small
incisions in the lower abdomen. This procedure allows the
patient to recover more quickly than open lymphadenectomy.
Prognosis
When cancer is confined to the prostate gland, the
disease is usually curable. A number of patients with locally
spread cancer die within 5 years. Once cancer has spread to
distant organs, life expectancy is usually less than 3 years.
Prevention
While prostate cancer cannot be prevented, measures can be
taken to prevent progression of the disease. It is important
for men over 40 to have an annual prostate examination. When
identified and treated early, prostate cancer has a high cure
rate.
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