Prostate cancer is a form of cancer that develops in the prostate, a gland in
the male reproductive system. The cancer cells may metastasize (spread) from the
prostate to other parts of the body, particularly the bones and lymph nodes.
Prostate cancer may cause pain, difficulty in urinating, problems during sexual
intercourse, or erectile dysfunction. Other symptoms can potentially develop
during later stages of the disease.
Rates of detection of prostate cancers vary widely across the world, with South
and East Asia detecting less frequently than in Europe, and especially the
United States.[1] Prostate cancer tends to develop in men over the age of fifty
and although it is one of the most prevalent types of cancer in men, many never
have symptoms, undergo no therapy, and eventually die of other causes. This is
because cancer of the prostate is, in most cases, slow-growing, symptom-free,
and since men with the condition are older they often die of causes unrelated to
the prostate cancer, such as heart/circulatory disease, pneumonia, other
unconnected cancers, or old age. Many factors, including genetics and diet, have
been implicated in the development of prostate cancer. The presence of prostate
cancer may be indicated by symptoms, physical examination, prostate specific
antigen (PSA), or biopsy. There is controversy about the accuracy of the PSA
test and the value of screening. Suspected prostate cancer is typically
confirmed by taking a biopsy of the prostate and examining it under a
microscope. Further tests, such as CT scans and bone scans, may be performed to
determine whether prostate cancer has spread.
Treatment options for prostate cancer with intent to cure are primarily surgery,
radiation therapy, and proton therapy. Other treatments, such as hormonal
therapy, chemotherapy, cryosurgery, and high intensity focused ultrasound (HIFU)
also exist, depending on the clinical scenario and desired outcome.
The age and underlying health of the man, the extent of metastasis, appearance
under the microscope, and response of the cancer to initial treatment are
important in determining the outcome of the disease. 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.
Classification
The prostate is a part of the male reproductive organ that 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, and rarely defecation. The prostate contains many small
glands which make about twenty percent of the fluid constituting 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,
which is converted from testosterone within the prostate itself. Androgens are
also responsible for secondary sex characteristics such as facial hair and
increased muscle mass.
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 metastasis—opposite to what is found in many other cancers that
metastasize.
Computed tomography (CT) and magnetic resonance imaging (MRI) currently do not
add any significant information in the assessment of possible lymph node
metastases in patients with prostate cancer according to a meta-analysis.[5] The
sensitivity of CT was 42% and specificity of CT was 82%. The sensitivity of MRI
was 39% and the specificity of MRI was 82%. For patients at similar risk to
those in this study (17% had positive pelvic lymph nodes in the CT studies and
30% had positive pelvic lymph nodes in the MRI studies), this leads to a
positive predictive value (PPV) of 32.3% with CT, 48.1% with MRI, and negative
predictive value (NPV) of 87.3% with CT, 75.8% with MRI.
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
Signs and symptoms
Early prostate cancer usually causes no symptoms. Often it is diagnosed during
the workup for an elevated PSA noticed during a routine checkup. It's highly
advised to avoid sexual intercourse for 3 days prior to a PSA test because that
affects the outcome of the test. 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 is associated with urinary
dysfunction as the prostate gland surrounds the prostatic urethra. Changes
within the gland, therefore, directly affect urinary function. Because the vas
deferens deposits seminal fluid into the prostatic urethra, and secretions from
the prostate gland itself are included in semen content, prostate cancer may
also cause problems with sexual function and performance, such as difficulty
achieving erection or painful ejaculation.[6]
Advanced prostate cancer can spread to other parts of the body, possibly causing
additional symptoms. The most common symptom is bone pain, often in the
vertebrae (bones of the spine), pelvis, or ribs. Spread of cancer into other
bones such as the femur is usually to the proximal part of the bone. Prostate
cancer in the spine can also compress the spinal cord, causing leg weakness and
urinary and fecal incontinence
Causes
The specific causes of prostate cancer remain unknown.[8] A man's risk of
developing prostate cancer is related to his age, genetics, race, diet,
lifestyle, medications, and other factors.[9] The primary risk factor is age.
Prostate cancer is very uncommon in men younger than 45, but becomes more common
with advancing age. The average age at the time of diagnosis is 70.[10] 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.[11] In the United States in 2005, there were an
estimated 230,000 new cases of prostate cancer and 30,000 deaths due to prostate
cancer.[12] Men with high blood pressure are more likely to develop prostate
cancer.
Genetics
Genetic background may contribute to prostate cancer risk, as suggested by
associations with race, family, and specific gene variants. In the United
States, prostate cancer more commonly affects black men than white or Hispanic
men, and is also more deadly in black men.[14][15] In contrast, the incidence
and mortality rates for Hispanic men are one third lower than for non-Hispanic
whites. Men who have a brother or father with prostate cancer have twice the
risk of developing prostate cancer.[16] Studies of twins in Scandinavia suggest
that forty percent of prostate cancer risk can be explained by inherited
factors.[17]
No single gene is responsible for prostate cancer; many different genes have
been implicated. Mutations in BRCA1 and BRCA2, important risk factors for
ovarian cancer and breast cancer in women, have also been implicated in prostate
cancer.[18] Other linked genes include the "prostate cancer gene", HPC1, the
androgen receptor, and the vitamin D receptor.[19] The TEMPRSS2-ETS fusion gene
exists in many prostate cancer cases and helps prostate cancer cells to survive
and grow.
Diet
Evidence from epidemiological studies supports a possible protective role in
reducing prostate cancer for dietary Vitamin B6,[21] selenium, vitamin E,
lycopene, and soy foods. A study in 2007 cast doubt on the effectiveness of
lycopene (found in tomatoes) in reducing the risk of prostate cancer.[22] Lower
blood levels of vitamin D may increase the risk of developing prostate
cancer.[23] This may be linked to lower exposure to ultraviolet (UV) light,
since UV light exposure can increase vitamin D in the body.[24]
Studies comparing men who live in areas of the country with high levels of
selenium to men in areas with low levels suggest that this mineral protects
against prostate cancer.[25] Selenium is believed to reduce the risk of
developing prostate cancer because it keeps cells from proliferating or dying
off in a rapid or unusual way. An analysis in 2002 of the Nutritional Prevention
of Cancer Trial revealed that the men who took selenium supplements daily were
half as likely to be diagnosed with prostate cancer.[26] However, in 2008, the
Selenium and Vitamin E Cancer Prevention Trial (SELECT) indicated that neither
selenium nor vitamin E, alone or in combination, was effective for the primary
prevention of prostate cancer.[27][28][29] Whether or not selenium helps prevent
prostate cancer, researchers at the Dana-Farber Cancer Institute in Boston found
that higher selenium levels in the blood may worsen prostate cancer in many men
who already have the disease.[29][30]
Green tea may be protective (due to its polyphenol content),[31] although the
most comprehensive clinical study indicates that it has no protective
effect.[32]
Research published in the Journal of the National Cancer Institute suggests that
taking multivitamins more than seven times a week can increase the risks of
contracting the disease.[33][34] This research was unable to highlight the exact
vitamins responsible for this increase (almost double), although they suggest
that vitamin A, vitamin E and beta-carotene may lie at its heart. It is advised
that those taking multivitamins never exceed the stated daily dose on the label.
A 2007 study published in the Journal of the National Cancer Institute found
that men eating cauliflower, broccoli, or one of the other cruciferous
vegetables, more than once a week were 40% less likely to develop prostate
cancer than men who rarely ate those vegetables.[35][36] The phytochemicals
indole-3-carbinol and diindolylmethane, found in cruciferous vegetables, has
antiandrogenic and immune modulating properties.[37][38]
Many doctors prescribe supplements to prostate cancer patients but currently the
efficacy of nutrient supplements is still unknown.[39] Supplements may not be as
beneficial to prostate health as micronutrients obatined naturally from the
diet.[39]
Folic acid supplements have recently been linked to an increase in risk of
developing prostate cancer.[40] A ten-year research study led by University of
Southern California researchers showed that men who took daily folic acid
supplements of 1 mg were three times more likely to be diagnosed with prostate
cancer than men who took a placebo.[40] Folate plays a complex role in prostate
cancer and folic acid supplements have a different effect on prostate cancer
than folate naturally found in foods.[40] The supplement form, folic acid, is
more bioavailable in the body compared with dietary sources of folate.[40]
Folate hydrolase activity is associated with prostate-specific antigen. A small
Swedish study of 254 subjects, with a median age of 64, and a follow up of 5
years suggested that folate status is not protective against prostate cancer,
however, and like folic acid may even result in a 3 fold increase in early
prostate cancer development and risk.[41] Supplements and multivitamins, alcohol
and drug consumption, GI disorders, and folate bioavailability were not analyzed
in this study.[41]
High alcohol intake may increase the risk of prostate cancer and interfere with
folate metabolism.[42] Low folate intake and high alcohol intake may increase
the risk of prostate cancer to a greater extent than the sole effect of either
one by itself.[42] A case control study consisting of 137 veterans addressed
this hypothesis and the results were that high folate intake was related to a
79% lower risk of developing prostate cancer and there was no association
between alcohol consumption by itself and prostate cancer risk.[42] Folate's
effect however was only significant when coupled with low alcohol intake.[42]
There is a significant decrease in risk of prostate cancer with increasing
dietary folate intake but this association only remains in individuals with low
levels of alcohol consumption.[42] There was no association found in this study
between folic acid supplements and risk of prostate cancer.[42]
The prostate gland has a high concentration of zinc so it has been hypothesized
that zinc plays a role in prostate cancer.[43] Recently researchers studied the
relationship between zinc supplement intake of 100 mg/day and the risk of
prostate cancer in 46 974 US men over a 14 year period and found that long term
zinc supplement intake may play a role in prostate carcinogenesis
Medication exposure
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.[44]
Use of the cholesterol-lowering drugs known as the statins may also decrease
prostate cancer risk.[45] 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.[46] Finally, obesity[47] and elevated blood
levels of testosterone[48] may increase the risk for prostate cancer. There is
an association between vasectomy and prostate cancer however more research is
needed to determine if this is a causative relationship.[9]
Research released in May 2007, found that US war veterans who had been exposed
to Agent Orange had a 48% increased risk of prostate cancer recurrence following
surgery.
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