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Prostate cancer

2007 Schools Wikipedia Selection. Related subjects: Health and medicine

   CAPTION: Prostate cancer
   Classifications and external resources

     ICD- 10   C 61.
     ICD- 9    185
      OMIM     176807
   DiseasesDB  10780
   MedlinePlus 000380
    eMedicine  radio/574

   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
   . 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 . However, these high rates may be affected by
   increasing rates of detection .

   Prostate cancer develops most frequently in men over fifty. This cancer
   can only occur 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, never undergo 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. 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

   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. 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. 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. 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.

   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.

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.
   Enlarge
   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. 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. 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. 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.

   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. Men who have a
   brother or father with prostate cancer have twice the usual risk of
   developing prostate cancer. Studies of twins in Scandinavia suggest
   that forty percent of prostate cancer risk can be explained by
   inherited factors. 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.

   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.
   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." 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. Green tea may also be
   protective (due to its polyphenol content), though the data is mixed.

   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. Use of the cholesterol-lowering drugs
   known as the statins may also decrease prostate cancer risk.
   Sterilization by vasectomy may increase the risk of prostate cancer,
   though there are conflicting data. 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. Infection or
   inflammation of the prostate ( prostatitis) may increase the chance for
   prostate cancer. In particular, infection with the sexually transmitted
   infections chlamydia, gonorrhea, and syphilis seem to increase risk.
   Finally, obesity and elevated blood levels of testosterone 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. 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.
   The selective estrogen receptor modulator drug toremifene has shown
   promise in early trials. Two medications which block the conversion of
   testosterone to dihydrotestosterone, finasteride and dutasteride, 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

   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 impacts 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. 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. The use of DRE has never
   been shown to prevent prostate cancer deaths when used as the only
   screening test.

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). 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.
   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. 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.

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.
   Enlarge
   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.

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.

   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.

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

   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.
   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. Although men who choose watchful waiting avoid the
   risks of surgery and radiation, the risk of metastasis (spread of the
   cancer) may be increased. Younger men, age sixty and under, with their
   higher levels of testerone, the primary agent in the metastasis of
   prostate cancer, require more immediate and aggressive treatment, and
   do not tenably have the option of watchful waiting. 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.
   Prostatectomy can cure about seventy percent of cases of prostate
   cancer.

   Radical prostatectomy is highly effective for tumors which have not
   spread beyond the prostate. 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. As many as forty percent of men will be left
   with some urinary incontinence, usually in the form of leakage when
   they sneeze, cough or laugh. Impotence is also a common problem.
   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. In some men with smaller
   cancers, a more limited "nerve-sparing" technique may help avoid
   urinary incontinence and impotence.

   Radical prostatectomy has traditionally been used alone when the cancer
   is small. However, courses of hormone therapy prior to surgery may
   increase cure rates and are currently being studied. 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.
   Enlarge
   Brachytherapy for prostate cancer is administered using "seeds," small
   radioactive rods implanted directly into the tumor.

   Radiation therapy, also known as radiotherapy, uses Gamma-rays to kill
   prostate cancer cells. Gamma-rays are a type of ionizing radiation that
   can damage or destroy the DNA crucial to cancer cell growth. 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 Gamma-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 centre.
   External beam radiation therapy for prostate cancer is delivered by a
   linear accelerator, such as this one.
   Enlarge
   External beam radiation therapy for prostate cancer is delivered by a
   linear accelerator, such as this one.

   Brachytherapy 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.
   These seeds emit lower-energy X-rays which are only able to travel a
   short distance. Brachytherapy seeds will stay in the prostate
   permanently, but men with implanted seeds are not at risk of exposing
   others to radiation.

   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
   suppresive therapy combined with external beam radiation had improved
   survival compared to radiation alone in patients with localized
   prostate cancer. 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. Men who
   have undergone external beam radiation therapy will have a higher risk
   of later developing colon cancer and bladder cancer.

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. Liquid nitrogen is
   used to cool the rods, freezing the surrounding tissue at −196 ° C
   (−320 ° F). As the water within the prostate cells freezes, 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.
   However, cryosurgery is potentially better than radical prostatectomy
   for recurrent cancer following radiation therapy. Cryosurgery is
   reserved for localized cancer within the prostate and in cases where
   conventional therapies like surgery or radiation could not be applied.
   Advantages of cryosurgery over general surgery include less blood loss,
   less pain and shorter recovery time.

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.
   Enlarge
   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.

   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.

   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. 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.

   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. In Japan, death from prostate cancer was one-fifth to
   one-half the rates in the United States and Europe in the 1990s. In
   India in the 1990s, half of the people with prostate cancer confined to
   the prostate died within ten years. African-American men have 50-60
   times more prostate cancer and prostate cancer deaths than men in
   Shanghai, China. In Nigeria, two percent of men develop prostate cancer
   and 64% of them are dead after two years.

   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.

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.
   Enlarge
   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. 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. Removal of the entire gland (radical perineal
   prostatectomy) was first performed in 1904 by Hugh Young at Johns
   Hopkins Hospital. 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.
   Andrzej W. Schally was awarded the 1977 Nobel prize for his research
   relating to prostate cancer.
   Enlarge
   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. 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.

   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.
   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.
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