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PROSTATE cancer
Prostate cancer is a disease in which cancer
develops in the prostate, a gland in the male reproductive system.
Cancer occurs when cells of the prostate mutate and begin to multiply
out of control. These cells may spread (metastasize) from the prostate
to other parts of the body, especially the bones and lymph nodes.
Prostate cancer may cause pain, difficulty in urinating, erectile
dysfunction and other symptoms.
Rates of prostate cancer vary widely across the world. Although the
rates vary widely between countries, it is least common in South and
East Asia, more common in Europe, and most common in the United States
[2]. According to the American Cancer Society, prostate cancer is
least common among Asian men and most common among black men with
figures for European men in-between [3] [4]. However, these high rates
may be affected by increasing rates of detection [5].
Prostate cancer develops most frequently in men over fifty. This
cancer can occur only in men, as the prostate is exclusively of the
male reproductive tract. It is the most common type of cancer in men
in the United States, where it is responsible for more male deaths
than any other cancer, except lung cancer. However, many men who
develop prostate cancer never have symptoms, undergo no therapy, and
eventually die of other causes. Many factors, including genetics and
diet, have been implicated in the development of prostate cancer.
Prostate cancer is most often discovered by physical examination or by
screening blood tests, such as the PSA (prostate specific antigen)
test. There is some current concern about the accuracy of the PSA test
and its usefulness. Suspected prostate cancer is typically confirmed
by removing a piece of the prostate (biopsy) and examining it under a
microscope. Further tests, such as X-rays and bone scans, may be
performed to determine whether prostate cancer has spread.
Prostate cancer can be treated with surgery, radiation therapy,
hormone therapy, occasionally chemotherapy, or some combination of
these. The age and underlying health of the man as well as the extent
of spread, appearance under the microscope, and response of the cancer
to initial treatment are important in determining the outcome of the
disease. Since prostate cancer is a disease of older men, many will
die of other causes before the prostate cancer can spread or cause
symptoms. This makes treatment selection difficult.[1] The decision
whether or not to treat localized prostate cancer (a tumor that is
contained within the prostate) with curative intent is a patient
trade-off between the expected beneficial and harmful effects in terms
of patient survival and quality of life.
The prostate
Main article: prostate
The prostate is a male reproductive organ which helps make and store
seminal fluid. In adult men a typical prostate is about three
centimeters long and weighs about twenty grams.[2] It is located in
the pelvis, under the urinary bladder and in front of the rectum. The
prostate surrounds part of the urethra, the tube that carries urine
from the bladder during urination and semen during ejaculation.[3]
Because of its location, prostate diseases often affect urination,
ejaculation, or defecation. The prostate contains many small glands
which make about twenty percent of the fluid comprising semen.[4] In
prostate cancer the cells of these prostate glands mutate into cancer
cells. The prostate glands require male hormones, known as androgens,
to work properly. Androgens include testosterone, which is made in the
testes; dehydroepiandrosterone, made in the adrenal glands; and
dihydrotestosterone, made in the prostate itself. Androgens are also
responsible for secondary sex characteristics such as facial hair and
increased muscle mass.
Symptoms
Early prostate cancer usually causes no symptoms. Often it
is diagnosed during the workup for an elevated PSA noticed during a
routine checkup. Sometimes, however, prostate cancer does cause
symptoms, often similar to those of diseases such as benign prostatic
hypertrophy. These include frequent urination, increased urination at
night, difficulty starting and maintaining a steady stream of urine,
blood in the urine, and painful urination. Prostate cancer may also
cause problems with sexual function, such as difficulty achieving
erection or painful ejaculation.[5]
Advanced prostate cancer may cause additional symptoms as the disease
spreads to other parts of the body. The most common symptom is bone
pain, often in the vertebrae (bones of the spine), pelvis or ribs,
from cancer which has spread to these bones. Prostate cancer in the
spine can also compress the spinal cord, causing leg weakness and
urinary and fecal incontinence.[6]
Pathophysiology
When normal cells are damaged beyond repair, they are eliminated by
apoptosis. Cancer cells avoid apoptosis and continue to multiply in an
unregulated manner.Prostate cancer is classified as an adenocarcinoma,
or glandular cancer, that begins when normal semen-secreting prostate
gland cells mutate into cancer cells. The region of prostate gland
where the adenocarcinoma is most common is the peripheral zone.
Initially, small clumps of cancer cells remain confined to otherwise
normal prostate glands, a condition known as carcinoma in situ or
prostatic intraepithelial neoplasia (PIN). Although there is no proof
that PIN is a cancer precursor, it is closely associated with cancer.
Over time these cancer cells begin to multiply and spread to the
surrounding prostate tissue (the stroma) forming a tumor. Eventually,
the tumor may grow large enough to invade nearby organs such as the
seminal vesicles or the rectum, or the tumor cells may develop the
ability to travel in the bloodstream and lymphatic system. Prostate
cancer is considered a malignant tumor because it is a mass of cells
which can invade other parts of the body. This invasion of other
organs is called metastasis. Prostate cancer most commonly
metastasizes to the bones, lymph nodes, rectum, and bladder.
Epidemiology
The specific causes of prostate cancer remain unknown.[7] A
man's risk of developing prostate cancer is related to his age,
genetics, race, diet, lifestyle, medications, and other factors. The
primary risk factor is age. Prostate cancer is uncommon in men less
than 45, but becomes more common with advancing age. The average age
at the time of diagnosis is 70.[8] However, many men never know they
have prostate cancer. Autopsy studies of Chinese, German, Israeli,
Jamaican, Swedish, and Ugandan men who died of other causes have found
prostate cancer in thirty percent of men in their 50s, and in eighty
percent of men in their 70s.[9] In the year 2005 in the United States,
there were an estimated 230,000 new cases of prostate cancer and
30,000 deaths due to prostate cancer.[10]
A man's genetic background contributes to his risk of developing
prostate cancer. This is suggested by an increased incidence of
prostate cancer found in certain racial groups, in identical twins of
men with prostate cancer, and in men with certain genes. In the United
States, prostate cancer more commonly affects black men than white or
Hispanic men, and is also more deadly in black men.[11] Men who have a
brother or father with prostate cancer have twice the usual risk of
developing prostate cancer.[12] Studies of twins in Scandinavia
suggest that forty percent of prostate cancer risk can be explained by
inherited factors.[13] However, no single gene is responsible for
prostate cancer; many different genes have been implicated. Two genes
(BRCA1 and BRCA2) that are important risk factors for ovarian cancer
and breast cancer in women have also been implicated in prostate
cancer.[14]
Dietary amounts of certain foods, vitamins, and minerals can
contribute to prostate cancer risk. Men with higher serum levels of
the short-chain ω-3 fatty acid linolenic acid have higher rates of
prostate cancer. However, the same series of studies showed that men
with elevated levels of long-chain ω-3 (EPA and DHA) had lowered
incidence.[15] A long-term study reports that "blood levels of trans
fatty acids, in particular trans fats resulting from the hydrogenation
of vegetable oils, are associated with an increased prostate cancer
risk."[16] Other dietary factors that may increase prostate cancer
risk include low intake of vitamin E (Vitamin E is found in green,
leafy vegetables), lycopene (found in tomatoes), omega-3 fatty acids
(found in fatty fishes like salmon), and the mineral selenium. Lower
blood levels of vitamin D also may increase the risk of developing
prostate cancer. This may be linked to lower exposure to ultraviolet
(UV) light, since UV light exposure can increase vitamin D in the
body.[17] Green tea may also be protective (due to its polyphenol
content), though the data are mixed.[18][19]
There are also some links between prostate cancer and medications,
medical procedures, and medical conditions. Daily use of
anti-inflammatory medicines such as aspirin, ibuprofen, or naproxen
may decrease prostate cancer risk.[20] Use of the cholesterol-lowering
drugs known as the statins may also decrease prostate cancer risk.[21]
Sterilization by vasectomy may increase the risk of prostate cancer,
though there are conflicting data.[22] More frequent ejaculation also
may decrease a man's risk of prostate cancer. One study showed that
men who ejaculated five times a week in their 20s had a decreased rate
of prostate cancer, though others have shown no benefit.[23][24]
Infection or inflammation of the prostate (prostatitis) may increase
the chance for prostate cancer. In particular, infection with the
sexually transmitted infections chlamydia, gonorrhea, or syphilis
seems to increase risk.[25] Finally, obesity[26] and elevated blood
levels of testosterone[27] may increase the risk for prostate cancer.
Prostate cancer risk can be decreased by modifying known risk factors
for prostate cancer, such as decreasing intake of animal fat.[28]
Several medications and vitamins may also help prevent prostate
cancer. Two dietary supplements, vitamin E and selenium, may help
prevent prostate cancer when taken daily. Estrogens from soybeans and
other plant sources (called phytoestrogens) may also help prevent
prostate cancer.[29] The selective estrogen receptor modulator drug
toremifene has shown promise in early trials.[30][31] Two medications
which block the conversion of testosterone to dihydrotestosterone,
finasteride[32] and dutasteride,[33] have also shown some promise. As
of 2006 the use of these medications for primary prevention is still
in the testing phase, and they are not widely used for this purpose.
Screening
Main article: Prostate cancer screening
Prostate cancer screening is an attempt to find unsuspected cancers.
Screening tests may lead to more specific follow-up tests such as a
biopsy, where small pieces of the prostate are removed for closer
study. As of 2006 prostate cancer screening options include the
digital rectal exam and the prostate specific antigen (PSA) blood
test. Screening for prostate cancer is controversial because it is not
clear if the benefits of screening outweigh the risks of follow-up
diagnostic tests and cancer treatments.
Prostate cancer is a slow-growing cancer, very common among older men.
In fact, most prostate cancers never grow to the point where they
cause symptoms, and most men with prostate cancer die of other causes
before prostate cancer has an impact on their lives. The PSA screening
test may detect these small cancers that would never become life
threatening. Doing the PSA test in these men may lead to overdiagnosis,
including additional testing and treatment. Follow-up tests, such as
prostate biopsy, may cause pain, bleeding and infection. Prostate
cancer treatments may cause urinary incontinence and erectile
dysfunction. Therefore, it is essential that the risks and benefits of
diagnostic procedures and treatment be carefully considered before PSA
screening.
Prostate cancer screening generally begins after age fifty, but may be
offered earlier in black men or men with a strong family history of
prostate cancer.[34] Although there is no officially recommended
cutoff, many health care providers stop monitoring PSA in men who are
older than 75 years old because of concern that prostate cancer
therapy may do more harm than good as age progresses and life
expectancy decreases.
Digital rectal examination
Digital rectal examination (DRE) is a procedure where the
examiner inserts a gloved, lubricated finger into the rectum to check
the size, shape, and texture of the prostate. Areas which are
irregular, hard or lumpy need further evaluation, since they may
contain cancer. Although the DRE only evaluates the back of the
prostate, 85% of prostate cancers arise in this part of the prostate.
Prostate cancer which can be felt on DRE is generally more
advanced.[35] The use of DRE has never been shown to prevent prostate
cancer deaths when used as the only screening test.[36]
Prostate specific antigen
Main article: Prostate specific antigen
The PSA test measures the blood level of prostate-specific antigen, an
enzyme produced by the prostate. Specifically, PSA is a serine
protease similar to kallikrein. Its normal function is to liquify
gelatinous semen after ejaculation, allowing spermatazoa to more
easily "swim" through the uterine cervix.
PSA levels under 4 ng/mL (nanograms per milliliter) are generally
considered normal, while levels over 4 ng/mL are considered abnormal
(although in men over 65 levels up to 6.5 ng/mL may be acceptable,
depending upon each laboratory's reference ranges). PSA levels between
4 and 10 ng/mL indicate a risk of prostate cancer higher than normal,
but the risk does not seem to rise within this six-point range. When
the PSA level is above 10 ng/mL, the association with cancer becomes
stronger. However, PSA is not a perfect test. Some men with prostate
cancer do not have an elevated PSA, and most men with an elevated PSA
do not have prostate cancer.
PSA levels can change for many reasons other than cancer. Two common
causes of high PSA levels are enlargement of the prostate (benign
prostatic hypertrophy (BPH)) and infection in the prostate (prostatitis).
It can also be raised for 24 hours after ejaculation and several days
after catheterization. PSA levels are lowered in men who use
medications used to treat BPH or baldness. These medications,
finasteride (marketed as Proscar or Propecia) and dutasteride
(marketed as Avodart), may decrease the PSA levels by 50% or more.
Several other ways of evaluating the PSA have been developed to avoid
the shortcomings of simple PSA screening. The use of age-specific
reference ranges improves the sensitivity and specificity of the test.
The rate of rise of the PSA over time, called the PSA velocity, has
been used to evaluate men with PSA levels between 4 and 10 ng/ml, but
as of 2006, it has not proven to be an effective screening test.[37]
Comparing the PSA level with the size of the prostate, as measured by
ultrasound or magnetic resonance imaging, has also been studied. This
comparison, called PSA density, is both costly and, as of 2006, has
not proven to be an effective screening test.[38] PSA in the blood may
either be free or bound to other proteins. Measuring the amount of PSA
which is free or bound may provide additional screening information,
but as of 2006, questions regarding the usefulness of these
measurements limit their widespread use.[39][40]
Confirming the diagnosis
Normal prostate (A) and prostate cancer (B). In prostate cancer, the
regular glands of the normal prostate are replaced by irregular glands
and clumps of cells, as seen in these pictures taken through a
microscope.When a man has symptoms of prostate cancer, or a screening
test indicates an increased risk for cancer, more invasive evaluation
is offered. The only test which can fully confirm the diagnosis of
prostate cancer is a biopsy, the removal of small pieces of the
prostate for microscopic examination. However, prior to a biopsy,
several other tools may be used to gather more information about the
prostate and the urinary tract. Cystoscopy shows the urinary tract
from inside the bladder, using a thin, flexible camera tube inserted
down the urethra. Transrectal ultrasonography creates a picture of the
prostate using sound waves from a probe in the rectum.
If cancer is suspected, a biopsy is offered. During a biopsy a
urologist obtains tissue samples from the prostate via the rectum. A
biopsy gun inserts and removes special hollow-core needles (usually
three to six on each side of the prostate) in less than a second. The
tissue samples are then examined under a microscope to determine
whether cancer cells are present, and to evaluate the microscopic
features (or Gleason score) of any cancer found. Prostate biopsies are
routinely done on an outpatient basis and rarely require
hospitalization. Fifty-five percent of men report discomfort during
prostate biopsy.[41]
Currently, an active area of research involves non-invasive methods of
prostate tumor detection. Adenoviruses modified to transfect tumor
cells with harmless yet distinct genes (such as luciferase) have
proven capable of early detection. So far, though, this area of
research has only been tested in animal and LNCaP models. [42]
Staging
Main article: Prostate cancer staging
An important part of evaluating prostate cancer is determining the
stage, or how far the cancer has spread. Knowing the stage helps
define prognosis and is useful when selecting therapies. The most
common system is the four-stage TNM system (abbreviated from
Tumor/Nodes/Metastases). Its components include the size of the tumor,
the number of involved lymph nodes, and the presence of any other
metastases.
The most important distinction made by any staging system is whether
or not the cancer is still confined to the prostate. In the TNM
system, clinical T1 and T2 cancers are found only in the prostate,
while T3 and T4 cancers have spread elsewhere. Several tests can be
used to look for evidence of spread. These include computed tomography
to evaluate spread within the pelvis, bone scans to look for spread to
the bones, and endorectal coil magnetic resonance imaging to closely
evaluate the prostatic capsule and the seminal vesicles. Bone scans
should reveal osteoblastic appearance due to increased bone density in
the areas of bone metastisis - opposite to what is found in many other
cancers that metastisize.
After a prostate biopsy, a pathologist looks at the samples under a
microscope. If cancer is present, the pathologist reports the grade of
the tumor. The grade tells how much the tumor tissue differs from
normal prostate tissue and suggests how fast the tumor is likely to
grow. The Gleason system is used to grade prostate tumors from 2 to
10, where a Gleason score of 10 indicates the most abnormalities. The
pathologist assigns a number from 1 to 5 for the most common pattern
observed under the microscope, then does the same for the second most
common pattern. The sum of these two numbers is the Gleason score. The
Whitmore-Jewett stage is another method sometimes used. Proper grading
of the tumor is critical, since the grade of the tumor is one of the
major factors used to determine the treatment recommendation.
Risk assessment
Many prostate cancers are not destined to be lethal, and
most men will ultimately die from causes other than of the disease.
Decisions about treatment type and timing may therefore be informed by
an estimation of the risk that the tumor will ultimately recur after
treatment and/or progress to metastases and mortality. Several tools
are available to help predict outcomes such as pathologic stage and
recurrence after surgery or radiation therapy. Most combine stage,
grade, and PSA level, and some also add the number or percent of
biopsy cores positive, age, and/or other information.
The D’Amico classification stratifies men to low, intermediate, or
high risk based on stage, grade, and PSA. It is used widely in
clinical practice and research settings. The major downside to the
3-level system is that it does not account for multiple adverse
parameters (e.g., high Gleason score and high PSA) in stratifying
patients.
The Partin tables predict pathologic outcomes (margin status,
extraprostatic extension, and seminal vesicle invasion) based on the
same 3 variables, and are published as lookup tables.
The Kattan nomograms predict recurrence after surgery and/or radiation
therapy, based on data available either at time of diagnosis or after
surgery. The nomograms can be calculated using paper graphs, or using
software available on a website or for handheld computers. The Kattan
score represents the likelihood of remaining free of disease at a
given time interval following treatment.
The UCSF Cancer of the Prostate Risk Assessment (CAPRA) score predicts
both pathologic status and recurrence after surgery. It offers
comparable accuracy as the Kattan preoperative nomogram, and can be
calculated without paper tables or a calculator. Points are assigned
based on PSA, Grade, stage, age, and percent of cores positive; the
sum yields a 0-10 score, with every 2 points representing roughly a
doubling of risk of recurrence. The CAPRA score was derived from
community-based data in the CaPSURE database.
Treatment
Treatment for prostate cancer may involve watchful waiting,
surgery, radiation therapy, High Intensity Focused Ultrasound (HIFU),
chemotherapy, cryosurgery, hormonal therapy, or some combination.
Which option is best depends on the stage of the disease, the Gleason
score, and the PSA level. Other important factors are the man's age,
his general health, and his feelings about potential treatments and
their possible side effects. Because all treatments can have
significant side effects, such as erectile dysfunction and urinary
incontinence, treatment discussions often focus on balancing the goals
of therapy with the risks of lifestyle alterations.
If the cancer has spread beyond the prostate, treatment options
significantly change, so most doctors who treat prostate cancer use a
variety of nomograms to predict the probability of spread. Treatment
by watchful waiting, HIFU, radiation therapy, cryosurgery, and surgery
are generally offered to men whose cancer remains within the prostate.
Hormonal therapy and chemotherapy are often reserved for disease which
has spread beyond the prostate. However, there are exceptions:
radiation therapy may be used for some advanced tumors, and hormonal
therapy is used for some early stage tumors. Cryotherapy, hormonal
therapy, and chemotherapy may also be offered if initial treatment
fails and the cancer progresses.
Watchful waiting / Active Surveillance
Watchful waiting, also called "active surveillance," refers
to observation and regular monitoring without invasive treatment.
Watchful waiting is often used when an early stage, slow-growing
prostate cancer is found in an older man. Watchful waiting may also be
suggested when the risks of surgery, radiation therapy, or hormonal
therapy outweigh the possible benefits. Other treatments can be
started if symptoms develop, or if there are signs that the cancer
growth is accelerating (e.g., rapidly rising PSA, increase in Gleason
score on repeat biopsy, etc.). Most men who choose watchful waiting
for early stage tumors eventually have signs of tumor progression, and
they may need to begin treatment within three years.[43] Although men
who choose watchful waiting avoid the risks of surgery and radiation,
the risk of metastasis (spread of the cancer) may be increased. For
younger men, a trial of active surveillance may not mean avoiding
treatment altogether, but may reasonably allow a delay of a few years
or more, during which time the quality of life impact of active
treatment can be avoided. Published data to date suggest that
carefully selected men will not miss a window for cure with this
approach. Additional health problems that develop with advancing age
during the observation period can also make it harder to undergo
surgery and radiation therapy.
Surgery
Surgical removal of the prostate, or prostatectomy, is a
common treatment either for early stage prostate cancer, or for cancer
which has failed to respond to radiation therapy. The most common type
is radical retropubic prostatectomy, when the surgeon removes the
prostate through an abdominal incision. Another type is radical
perineal prostatectomy, when the surgeon removes the prostate through
an incision in the perineum, the skin between the scrotum and anus.
Radical prostatectomy can also be performed laparoscopically, through
a series of small (1cm) incisions in the abdomen, with or without the
assistance of a surgical robot.
Radical prostatectomy is highly effective for tumors which have not
spread beyond the prostate; cure rates depend on risk factors such as
PSA level and Gleason grade. However, it may cause nerve damage that
significantly alters the quality of life of the prostate cancer
survivor. The most common serious complications are loss of urinary
control and impotence. Reported rates of both complications vary
widely depending on how they are assessed, by whom, and how long after
surgery, as well as the setting (e.g., academic series vs.
community-based or population-based data). Although penile sensation
and the ability to achieve orgasm usually remain intact, erection and
ejaculation are often impaired. Medications such as sildenafil
(Viagra), tadalafil (Cialis), or vardenafil (Levitra) may restore some
degree of potency. For most men with organ-confined disease, a more
limited "nerve-sparing" technique may help avoid urinary incontinence
and impotence.[44]
Radical prostatectomy has traditionally been used alone when the
cancer is small. In the event of positive margins or locally advanced
disease found on pathology, adjuvant radiation therapy may offer
improved survival. Surgery may also be offered when a cancer is not
responding to radiation therapy. However, because radiation therapy
causes tissue changes, prostatectomy after radiation has a higher risk
of complications.
Transurethral resection of the prostate, commonly called a "TURP," is
a surgical procedure performed when the tube from the bladder to the
penis (urethra) is blocked by prostate enlargement. TURP is generally
for benign disease and is not meant as definitive treatment for
prostate cancer. During a TURP, a small tube (cystoscope) is placed
into the penis and the blocking prostate is cut away.
In metastatic disease, where cancer has spread beyond the prostate,
removal of the testicles (called orchiectomy) may be done to decrease
testosterone levels and control cancer growth. (See hormonal therapy,
below).
Radiation therapy
Brachytherapy for prostate cancer is administered using "seeds," small
radioactive rods implanted directly into the tumor.Radiation therapy,
also known as radiotherapy, uses ionizing radiation to kill prostate
cancer cells. When absorbed in tissue, Ionizing radiation such as
Gamma and x-rays damage the DNA in cells, which increases the
probability of apoptosis (cell death). Two different kinds of
radiation therapy are used in prostate cancer treatment: external beam
radiation therapy and brachytherapy.
External beam radiation therapy uses a linear accelerator to produce
high-energy x-rays which are directed in a beam towards the prostate.
A technique called Intensity Modulated Radiation Therapy (IMRT) may be
used to adjust the radiation beam to conform with the shape of the
tumor, allowing higher doses to be given to the prostate and seminal
vesicles with less damage to the bladder and rectum. External beam
radiation therapy is generally given over several weeks, with daily
visits to a radiation therapy center.
External beam radiation therapy for prostate cancer is delivered by a
linear accelerator, such as this one.Permanent implant brachytherapy
is a popular treatment choice for patients with low to intermediate
risk features, can be performed on an outpatient basis, and is
associated with good 10-year outcomes with relatively low morbidity
[45] It involves the placement of about 100 small "seeds" containing
radioactive material (such as iodine-125 or palladium-103) with a
needle through the skin of the perineum directly into the tumor while
under spinal or general anesthetic. These seeds emit lower-energy
X-rays which are only able to travel a short distance. Although the
seeds eventually become inert, they remain in the prostate
permanently. The risk of exposure to others from men with implanted
seeds is generally accepted to be insignificant.[46]
Radiation therapy is commonly used in prostate cancer treatment. It
may be used instead of surgery for early cancers, and it may also be
used in advanced stages of prostate cancer to treat painful bone
metastases. Radiation treatments also can be combined with hormonal
therapy for intermediate risk disease, when radiation therapy alone is
less likely to cure the cancer. Some radiation oncologists combine
external beam radiation and brachytherapy for intermediate to high
risk situations. One study found that the combination of six months of
androgen suppressive therapy combined with external beam radiation had
improved survival compared to radiation alone in patients with
localized prostate cancer.[47] Others use a "triple modality"
combination of external beam radiation therapy, brachytherapy, and
hormonal therapy.
Less common applications for radiotherapy are when cancer is
compressing the spinal cord, or sometimes after surgery, such as when
cancer is found in the seminal vesicles, in the lymph nodes, outside
the prostate capsule, or at the margins of the biopsy.
Radiation therapy is often offered to men whose medical problems make
surgery more risky. Radiation therapy appears to cure small tumors
that are confined to the prostate just about as well as surgery.
However, as of 2006 some issues remain unresolved, such as whether
radiation should be given to the rest of the pelvis, how much the
absorbed dose should be, and whether hormonal therapy should be given
at the same time.
Side effects of radiation therapy might occur after a few weeks into
treatment. Both types of radiation therapy may cause diarrhea and
rectal bleeding due to radiation proctitis, as well as urinary
incontinence and impotence. Symptoms tend to improve over time.[48]
Men who have undergone external beam radiation therapy will have a
higher risk of later developing colon cancer and bladder cancer.[49]
Cryosurgery
Cryosurgery is another method of treating prostate cancer.
It is less invasive than radical prostatectomy, and general anesthesia
is less commonly used. Under ultrasound guidance, metal rods are
inserted through the skin of the perineum into the prostate. Highly
purified Argon gas is used to cool the rods, freezing the surrounding
tissue at −196 °C (−320 °F). As the water within the prostate cells
freeze, the cells die. The urethra is protected from freezing by a
catheter filled with warm liquid. Cryosurgery generally causes fewer
problems with urinary control than other treatments, but impotence
occurs up to ninety percent of the time. When used as the initial
treatment for prostate cancer, cryosurgery is not as effective as
surgery or radiation.[50] However, cryosurgery is potentially better
than radical prostatectomy for recurrent cancer following radiation
therapy.
Hormonal therapy
Hormonal therapy in prostate cancer. Diagram shows the different
organs (purple text), hormones (black text and arrows), and treatments
(red text and arrows) important in hormonal therapy.Hormonal therapy
uses medications or surgery to block prostate cancer cells from
getting dihydrotestosterone (DHT), a hormone produced in the prostate
and required for the growth and spread of most prostate cancer cells.
Blocking DHT often causes prostate cancer to stop growing and even
shrink. However, hormonal therapy rarely cures prostate cancer because
cancers which initially respond to hormonal therapy typically become
resistant after one to two years. Hormonal therapy is therefore
usually used when cancer has spread from the prostate. It may also be
given to certain men undergoing radiation therapy or surgery to help
prevent return of their cancer.[51]
Hormonal therapy for prostate cancer targets the pathways the body
uses to produce DHT. A feedback loop involving the testicles, the
hypothalamus, and the pituitary, adrenal, and prostate glands controls
the blood levels of DHT. First, low blood levels of DHT stimulate the
hypothalamus to produce gonadotropin releasing hormone (GnRH). GnRH
then stimulates the pituitary gland to produce luteinizing hormone (LH),
and LH stimulates the testicles to produce testosterone. Finally,
testosterone from the testicles and dehydroepiandrosterone from the
adrenal glands stimulate the prostate to produce more DHT. Hormonal
therapy can decrease levels of DHT by interrupting this pathway at any
point.
There are several forms of hormonal therapy:
Orchiectomy is surgery to remove the testicles. Because the testicles
make most of the body's testosterone, after orchiectomy testosterone
levels drop. Now the prostate not only lacks the testosterone stimulus
to produce DHT, but also it does not have enough testosterone to
transform into DHT.
Antiandrogens are medications such as flutamide, bicalutamide,
nilutamide, and cyproterone acetate which directly block the actions
of testosterone and DHT within prostate cancer cells.
Medications which block the production of adrenal androgens such as
DHEA include ketoconazole and aminoglutethimide. Because the adrenal
glands only make about 5% of the body's androgens, these medications
are generally used only in combination with other methods that can
block the 95% of androgens made by the testicles. These combined
methods are called total androgen blockade (TAB). TAB can also be
achieved using antiandrogens.
GnRH action can be interrupted in one of two ways. GnRH antagonists
suppress the production of GnRH directly, while GnRH agonists suppress
GnRH through the process of downregulation after an initial
stimulation effect. Abarelix is an example of a GnRH antagonist, while
the GnRH agonists include leuprolide, goserelin, triptorelin, and
buserelin. Initially, these medications increase the production of LH.
However, because the constant supply of the medication does not match
the body's natural production rhythm, production of both LH and GnRH
decreases after a few weeks.[52]
As of 2006 the most successful hormonal treatments are orchiectomy and
GnRH agonists. Despite their higher cost, GnRH agonists are often
chosen over orchiectomy for cosmetic and emotional reasons.
Eventually, total androgen blockade may prove to be better than
orchiectomy or GnRH agonists used alone.
Each treatment has disadvantages which limit its use in certain
circumstances. Although orchiectomy is a low-risk surgery, the
psychological impact of removing the testicles can be significant. The
loss of testosterone also causes hot flashes, weight gain, loss of
libido, enlargement of the breasts (gynecomastia), impotence and
osteoporosis. GnRH agonists eventually cause the same side effects as
orchiectomy but may cause worse symptoms at the beginning of
treatment. When GnRH agonists are first used, testosterone surges can
lead to increased bone pain from metastatic cancer, so antiandrogens
or abarelix are often added to blunt these side effects. Estrogens are
not commonly used because they increase the risk for cardiovascular
disease and blood clots. The antiandrogens do not generally cause
impotence and usually cause less loss of bone and muscle mass.
Ketoconazole can cause liver damage with prolonged use, and
aminoglutethimide can cause skin rashes.
Palliative care
Palliative care for advanced stage prostate cancer focuses
on extending life and relieving the symptoms of metastatic disease.
Chemotherapy may be offered to slow disease progression and postpone
symptoms. The most commonly used regimen combines the chemotherapeutic
drug docetaxel with a corticosteroid such as prednisone.[53]
Bisphosphonates such as zoledronic acid have been shown to delay
skeletal complications such as fractures or the need for radiation
therapy in patients with hormone-refractory metastatic prostate
cancer.[54]
Bone pain due to metastatic disease is treated with opioid pain
relievers such as morphine and oxycodone. External beam radiation
therapy directed at bone metastases may provide pain relief.
Injections of certain radioisotopes, such as strontium-89,
phosphorus-32, or samarium-153, also target bone metastases and may
help relieve pain.
Prognosis
Prostate cancer rates are higher and prognosis poorer in
Western societies than the rest of the world. Many of the risk factors
for prostate cancer are more prevalent in the Western world, including
longer life expectancy and diets high in animal fats. Also, where
there is more access to screening programs, there is a higher
detection rate. Prostate cancer is the ninth most common cancer in the
world, but is the number one non-skin cancer in United States men.
Prostate cancer affected eighteen percent of American men and caused
death in three percent in 2005.[55] In Japan, death from prostate
cancer was one-fifth to one-half the rates in the United States and
Europe in the 1990s.[56] In India in the 1990s, half of the people
with prostate cancer confined to the prostate died within ten
years.[57] African-American men have 50-60 times more prostate cancer
and prostate cancer deaths than men in Shanghai, China.[58] In
Nigeria, two percent of men develop prostate cancer and 64% of them
are dead after two years.[59]
In patients who undergo treatment, the most important clinical
prognostic indicators of disease outcome are stage, pre-therapy PSA
level and Gleason score. In general, the higher the grade and the
stage, the poorer the prognosis. Nomograms can be used to calculate
the estimated risk of the individual patient. The predictions are
based on the experience of large groups of patients suffering from
cancers at various stages.[60]
History
Charles B. Huggins (right), who was awarded the 1966 Nobel Prize for
his research on prostate cancer, is shown with 1937 Nobel laureate
Albert Szent-Gyorgyi.Although the prostate was first described by
Venetian anatomist Niccolò Massa in 1536, and illustrated by Flemish
anatomist Andreas Vesalius in 1538, prostate cancer was not identified
until 1853.[61] Prostate cancer was initially considered a rare
disease, probably because of shorter life expectancies and poorer
detection methods in the 19th century. The first treatments of
prostate cancer were surgeries to relieve urinary obstruction.[62]
Removal of the entire gland (radical perineal prostatectomy) was first
performed in 1904 by Hugh Young at Johns Hopkins Hospital.[63]
Surgical removal of the testes (orchiectomy) to treat prostate cancer
was first performed in the 1890s, but with limited success.
Transurethral resection of the prostate (TURP) replaced radical
prostatectomy for symptomatic relief of obstruction in the middle of
the 20th century because it could better preserve penile erectile
function. Radical retropubic prostatectomy was developed in 1983 by
Patrick Walsh.[64]
Andrzej W. Schally was awarded the 1977 Nobel prize for his research
relating to prostate cancer.This surgical approach allowed for removal
of the prostate and lymph nodes with maintenance of penile function.
In 1941 Charles B. Huggins published studies in which he used estrogen
to oppose testosterone production in men with metastatic prostate
cancer. This discovery of "chemical castration" won Huggins the 1966
Nobel Prize in Physiology or Medicine.[65] The role of the hormone
GnRH in reproduction was determined by Andrzej W. Schally and Roger
Guillemin, who both won the 1977 Nobel Prize in Physiology or Medicine
for this work. Receptor agonists, such as leuprolide and goserelin,
were subsequently developed and used to treat prostate cancer.[66][67]
Radiation therapy for prostate cancer was first developed in the early
20th century and initially consisted of intraprostatic radium
implants. External beam radiation became more popular as stronger
radiation sources became available in the middle of the 20th century.
Brachytherapy with implanted seeds was first described in 1983.[68]
Systemic chemotherapy for prostate cancer was first studied in the
1970s. The initial regimen of cyclophosphamide and 5-fluorouracil was
quickly joined by multiple regimens using a host of other systemic
chemotherapy drugs.[69]
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