Prostate cancer

From Wikipedia, the free encyclopedia

**Prostate cancer**
*Classifications and external resources*
Image:Prostatelead.jpg
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 [1]. 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 [2] [3]. However, these high rates may be affected by increasing rates of detection [4].

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 thus 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.<ref>Detailed Guide: prostate cancer. American Cancer Society webpage.</ref> 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.

[edit] 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.<ref>Aumüller, G. (1979). Prostate Gland and Seminal Vesicles. Berlin-Heidelberg: Springer-Verlag.</ref> 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.<ref>Moore, K., Dalley, A. (1999). Clinically Oriented Anatomy. Baltimore, Maryland: Lippincott Williams & Wilkins.</ref> 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.<ref>Steive, H. (1930). “Männliche Genitalorgane”, Handbuch der mikroskopischen Anatomie des Menschen. Vol. VII Part 2. Berlin: Springer, 1-399.</ref> 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.

[edit] 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.<ref>Miller, DC, Hafez, KS, Stewart, A, et al (2003). "Prostate carcinoma presentation, diagnosis, and staging: an update form the National Cancer Data Base". Cancer 98: 1169. PMID 12973840.</ref> There also may be unexplained pain in the lower abdomen and/or pelvis.

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.<ref>van der Cruijsen-Koeter, IW, Vis AN, Roobol MJ, Wildhagen MF, de Koning HJ, van der Kwast TH, Schroder FH (Jul 2005). "Comparison of screen detected and clinically diagnosed prostate cancer in the European randomized study of screening for prostate cancer, section rotterdam". Urol 174 (1): 121-5. PMID 15947595.</ref>

[edit] 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.

[edit] Epidemiology

The specific causes of prostate cancer remain unknown.<ref>Hsing, Ann W., Anand P. Chokkalingam (May 1 2006). "Prostate cancer epidemiology". Frontiers in Bioscience 11: 1388-1413.</ref> 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.<ref>Hankey, BF, Feuer EJ, Clegg LX, Hayes RB, Legler JM, Prorok PC, Ries LA, Merrill RM, Kaplan RS (Jun 16 1999). "Cancer surveillance series: interpreting trends in prostate cancer--part I: Evidence of the effects of screening in recent prostate cancer incidence, mortality, and survival rates". J Natl Cancer Inst 91 (12): 1017-24. PMID 10379964.</ref> 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.<ref>Breslow, N, Chan CW, Dhom G, Drury RA, Franks LM, Gellei B, Lee YS, Lundberg S, Sparke B, Sternby NH, Tulinius H. (Nov 15 1977). "Latent carcinoma of prostate at autopsy in seven areas. The International Agency for Research on Cancer, Lyons, France". Int J Cancer 20 (5): 680-8. PMID 924691.</ref> 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.<ref>Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ (Jan-Feb 2005). "Cancer statistics, 2005". CA Cancer J Clin 55 (1): 10-30. PMID 15661684. Erratum in: CA Cancer J Clin. 2005 Jul-Aug;55(4):259</ref>

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.<ref>Hoffman, RM, Gilliland FD; Eley JW; Harlan LC; Stephenson RA; Stanford JL; Albertson PC; Hamilton AS; Hunt WC; Potosky AL (Mar 7 2001). "Racial and ethnic differences in advanced-stage prostate cancer: the Prostate Cancer Outcomes Study". J Natl Cancer Inst 93 (5): 388-95. PMID 11238701.</ref> Men who have a brother or father with prostate cancer have twice the usual risk of developing prostate cancer.<ref>Steinberg, GD, Carter BS; Beaty TH; Childs B; Walsh PC (1990). "Family history and the risk of prostate cancer". Prostate 17 (4): 337-47. PMID 2251225.</ref> Studies of twins in Scandinavia suggest that forty percent of prostate cancer risk can be explained by inherited factors.<ref>Lichtenstein, P, Holm NV; Verkasalo PK; Iliadou A; Kaprio J; Koskenvuo M; Pukkala E; Skytthe A; Hemminki K (Jul 13 2000). "Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland". N Engl J Med 343 (2): 78-85. PMID 10891514.</ref> 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.<ref>Struewing, JP, Hartge P; Wacholder S; Baker SM; Berlin M; McAdams M; Timmerman MM; Brody LC; Tucker MA (May 15 1997). "The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews". N Engl J Med 336 (20): 1401-8. PMID 9145676.</ref>

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.<ref>Gann, PH and Giovannucci (2005). Prostate Cancer and Nutrition. Retrieved on February 20, 2006. in .pdf format.</ref> 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."<ref>Chavarro et al., "A prospective study of blood trans fatty acid levels and risk of prostate cancer," Proc. Amer. Assoc. Cancer Res., Volume 47, 2006 [5]. See also Ledesma 2004 Nutrition & prostate cancer.</ref> 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.<ref>Schulman, CC, Ekane S; Zlotta AR (Sep 2001). "Nutrition and prostate cancer: evidence or suspicion?". Urology 58 (3): 318-34. PMID 11549473.</ref> Green tea may also be protective (due to its polyphenol content), though the data is mixed.<ref>Lee AH, Fraser ML, Meng X, Binns CW. Protective effects of green tea against prostate cancer. Expert Rev Anticancer Ther. 2006 Apr;6(4):507-13. Review. PMID 16613539</ref><ref>Kikuchi N, Ohmori K, Shimazu T, Nakaya N, Kuriyama S, Nishino Y, Tsubono Y, Tsuji I. No association between green tea and prostate cancer risk in Japanese men: the Ohsaki Cohort Study. Br J Cancer. 2006 Aug 7;95(3):371-3. Epub 2006 Jun 27. PMID 16804523 </ref>

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.<ref>Jacobs, EJ, Rodriguez C, Mondul AM, Connell CJ, Henley SJ, Calle EE, Thun MJ (Jul 6 2005). "A large cohort study of aspirin and other nonsteroidal anti-inflammatory drugs and prostate cancer incidence". J Natl Cancer Inst 97 (13): 975-80. PMID 15998950.</ref> Use of the cholesterol-lowering drugs known as the statins may also decrease prostate cancer risk.<ref>Shannon, J, Tewoderos S, Garzotto M, Beer TM, Derenick R, Palma A, Farris PE (Aug 15 2005). "Statins and prostate cancer risk: a case-control study". Am J Epidemiol 162 (4): 318-25. PMID 16014776. Epub 2005 Jul 13</ref> Sterilization by vasectomy may increase the risk of prostate cancer, though there are conflicting data.<ref>Giovannucci, E, Tosteson TD, Speizer FE, Ascherio A, Vessey MP, Colditz GA (Feb 17 1993). "A retrospective cohort study of vasectomy and prostate cancer in US men". JAMA 269 (7): 878-82. PMID 8123059.</ref> 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.<ref>Giles, GG, Severi G; English DR; McCredie MR; Borland R; Boyle P; Hopper JL (Aug 2003). "Sexual factors and prostate cancer". BJU Int 92 (3): 211-6. PMID 12887469.</ref><ref>Leitzmann, Michael F. (April 7 2004). "Ejaculation Frequency and Subsequent Risk of Prostate Cancer". JAMA 291 (13): 1578-86. 2004;291:1578-1586.PMID: 15069045</ref> 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.<ref>Dennis, LK, Lynch CF; Torner JC (Jul 2002). "Epidemiologic association between prostatitis and prostate cancer". Urology 60 (1): 78-83. PMID 12100928.</ref> Finally, obesity<ref>Calle, EE, Rodriguez C, Walker-Thurmond K, Thun MJ (Apr 24 2003). "Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults". N Engl J Med 348 (17): 1625-38. PMID 12711737.</ref> and elevated blood levels of testosterone<ref>Gann, PH, Hennekens CH, Ma J, Longcope C, Stampfer MJ (Aug 21 1996). "Prospective study of sex hormone levels and risk of prostate cancer". J Natl Cancer Inst 88 (16): 1118-26. PMID 8757191.</ref> 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.<ref> (2003) "Position of the American Dietetic Association and Dietitians of Canada: Vegetarian diets". J Am Diet Assoc 103 (6): 748-65. PMID 12778049.</ref> 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.<ref>Strom, SS, Yamamura Y, Duphorne CM, Spitz MR, Babaian RJ, Pillow PC, Hursting SD (1999). "Phytoestrogen intake and prostate cancer: a case-control study using a new database". Nutr Cancer 33 (1): 20-5. PMID 10227039. Erratum in: Nutr Cancer 2000;36(2):243.</ref> The selective estrogen receptor modulator drug toremifene has shown promise in early trials.<ref>Steiner, MS, Pound, CR, Gingrich, JR, et al. (2002). "Acapodene (GTx-006) reduces high-grade prostatic intraepithelial neoplasia in phase II clinical trial (abstract)". Proc Am Soc Clin Oncol 21: 180a.</ref><ref>Price, D, Stein, B, Goluboff, E, et al. (2005). "Double-blind, placebo-controlled trial of toremifene for the provention of prostate cancer in men with high-grade prostatic intrapeithelial neoplasia (abstract)". J Clin Oncol 23: 106s.</ref> Two medications which block the conversion of testosterone to dihydrotestosterone, finasteride<ref>Thompson, IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, Crowley JJ, Coltman CA Jr. (Jul 17 2003). "The influence of finasteride on the development of prostate cancer". N Engl J Med 349 (3): 215-24. PMID 12824459.</ref> and dutasteride,<ref>Andriole, GL, Roehrborn C, Schulman C, Slawin KM, Somerville M, Rittmaster RS (Sep 2004). "Effect of dutasteride on the detection of prostate cancer in men with benign prostatic hyperplasia". Urology 64 (3): 537-41; discussion 542-3. PMID 15351586.</ref> 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.

[edit] 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 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.<ref>Grubb, RL, Roehl KA, Antenor JA, Catalona WJ (Aug 2005). "Results of compliance with prostate cancer screening guidelines". J Urol 174 (2): 668-72; discussion 672. PMID 16006944.</ref> 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.

[edit] 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.<ref>Chodak, GW, Keller P, Schoenberg HW (May 1989). "Assessment of screening for prostate cancer using the digital rectal examination". J Urol 141 (5): 1136-8. PMID 2709500.</ref> The use of DRE has never been shown to prevent prostate cancer deaths when used as the only screening test.<ref>Krahn, MD, Mahoney JE, Eckman MH, Trachtenberg J, Pauker SG, Detsky AS (Sep 14 1994). "Screening for prostate cancer. A decision analytic view". JAMA 272 (10): 773-80. PMID 7521400.</ref>

[edit] 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.<ref>Roobol, MJ, Kranse R, de Koning HJ, Schroder FH (Feb 2004). "Prostate-specific antigen velocity at low prostate-specific antigen levels as screening tool for prostate cancer: results of second screening round of ERSPC (ROTTERDAM)". Urology 63 (2): 309-13; discussion 313-5. PMID 14972478.</ref> 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.<ref>Catalona, WJ, Richie JP, deKernion JB, Ahmann FR, Ratliff TL, Dalkin BL, Kavoussi LR, MacFarlane MT, Southwick PC (Dec 1994). "Comparison of prostate specific antigen concentration versus prostate specific antigen density in the early detection of prostate cancer: receiver operating characteristic curves". J Urol 152 (6 Pt 1): 2031-6. PMID 7525994.</ref> 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.<ref>Hoffman, RM, Clanon DL, Littenberg B, Frank JJ, Peirce JC (Oct 2000). "Using the free-to-total prostate-specific antigen ratio to detect prostate cancer in men with nonspecific elevations of prostate-specific antigen levels". J Gen Intern Med 15 (10): 739-48. PMID 11089718.</ref><ref>Partin, AW, Brawer MK; Bartsch G; Horninger W; Taneja SS; Lepor H; Babaian R; Childs SJ; Stamey T; Fritsche HA; Sokoll L; Chan DW; Thiel RP; Cheli CD (Nov 2003). "Complexed prostate specific antigen improves specificity for prostate cancer detection: results of a prospective multicenter clinical trial". J Urol 170 (5): 1787-91. PMID 14532777.</ref>

[edit] Confirming the diagnosis

Image:Prostatehistopath.jpg

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.<ref>Essink-Bot, ML, de Koning HJ, Nijs HG, Kirkels WJ, van der Maas PJ, Schroder FH (Jun 17 1998). "Short-term effects of population-based screening for prostate cancer on health-related quality of life". J Natl Cancer Inst 90 (12): 925-31. PMID 9637143.</ref>

[edit] 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.

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.

[edit] 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.

[edit] 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.<ref>Wu, H, Sun L, Moul JW, Wu HY, McLeod DG, Amling C, Lance R, Kusuda L, Donahue T, Foley J, Chung A, Sexton W, Soderdahl D (Mar 2004). "Watchful waiting and factors predictive of secondary treatment of localized prostate cancer". J Urol 171 (3): 1111-6. PMID 14767282.</ref> 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.

[edit] 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.<ref>Gerber, GS, Thisted RA, Scardino PT, Frohmuller HG, Schroeder FH, Paulson DF, Middleton AW Jr, Rukstalis DB, Smith JA Jr, Schellhammer PF, Ohori M, Chodak GW (Aug 28 1996). "Results of radical prostatectomy in men with clinically localized prostate cancer". JAMA 276 (8): 615-9. PMID 8773633.</ref>

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.<ref>Ward JF, Zincke H (2003). "Radical prostatectomy for the patient with locally advanced prostate cancer". Curr Urol Rep 4 (3): 196-204. PMID 12756082.</ref> 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).

[edit] Radiation therapy

Image:Brachytherapy.jpg

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 center.

Image:Linacprostate.jpg

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.<ref>Perez, CA, Hanks GE, Leibel SA, Zietman AL, Fuks Z, Lee WR (Dec 1 1993). "Localized carcinoma of the prostate (stages T1B, T1C, T2, and T3). Review of management with external beam radiation therapy". Cancer 72 (11): 3156-73. PMID 7694785. Review.</ref>

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.<ref>D'Amico AV, Manola J, Loffredo M, Renshaw AA, DellaCroce A, Kantoff PW (2004). "6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial". JAMA 292 (7): 821-7. PMID 15315996.</ref> 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.<ref>Lawton, CA, Won M, Pilepich MV, Asbell SO, Shipley WU, Hanks GE, Cox JD, Perez CA, Sause WT, Doggett SR, et al (Sep 1991). "Long-term treatment sequelae following external beam irradiation for adenocarcinoma of the prostate: analysis of RTOG studies 7506 and 7706". Int J Radiat Oncol Biol Phys 21 (4): 935-9. PMID 1917622.</ref> Men who have undergone external beam radiation therapy will have a higher risk of later developing colon cancer and bladder cancer.<ref>Brenner, DJ, Curtis RE, Hall EJ, Ron E (Jan 15 2000). "Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery". Cancer 88 (2): 398-406. PMID 10640974.</ref>

[edit] 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.<ref>Bahn, DK, Lee F, Badalament R, Kumar A, Greski J, Chernick M (Aug 2002). "Targeted cryoablation of the prostate: 7-year outcomes in the primary treatment of prostate cancer". Urology 60 (2 Suppl 1): 3-11. PMID 12206842.</ref> 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<ref>CCS Cancer Curable Society. Retrieved 2006-11-12.</ref>.

[edit] Hormonal therapy

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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.<ref>Robson, M, Dawson N (Jun 1996). "How is androgen-dependent metastatic prostate cancer best treated?". Hematol Oncol Clin North Am 10 (3): 727-47. PMID 8773508. Review.</ref>

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.<ref>Loblaw, DA, Mendelson DS, Talcott JA, Virgo KS, Somerfield MR, Ben-Josef E, Middleton R, Porterfield H, Sharp SA, Smith TJ, Taplin ME, Vogelzang NJ, Wade JL Jr, Bennett CL, Scher HI; American Society of Clinical Oncology (Jul 15 2004). "American Society of Clinical Oncology recommendations for the initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer". J Clin Oncol 22 (14): 2927-41. PMID 15184404. Erratum in: J Clin Oncol. 2004 Nov 1;22(21):4435.</ref>

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.

[edit] 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.<ref>Tannock, IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Theodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA; TAX 327 Investigators (Oct 7 2004). "Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer". N Engl J Med 351 (15): 1502-12. PMID 1547021.</ref> 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.<ref>Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Chen B (2002). "A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma". J Natl Cancer Inst 94 (19): 1458-68. PMID 12359855.</ref>

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.

[edit] 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.<ref>Jemal, A, Murray T; Ward E; Samuels A; Tiwari RC; Ghafoor A; Feuer EJ; Thun MJ (Jan-Feb 2005). "Cancer statistics, 2005". CA Cancer J Clin 55 (1): 10-30. PMID 15661684. Erratum in: CA Cancer J Clin. 2005 Jul-Aug;55(4):259.</ref> In Japan, death from prostate cancer was one-fifth to one-half the rates in the United States and Europe in the 1990s.<ref>Wakai, K (Feb 2005). "Descriptive epidemiology of prostate cancer in Japan and Western countries". Nippon Rinsho 63 (2): 207-12. PMID 15714967. Review. (Japanese)</ref> In India in the 1990s, half of the people with prostate cancer confined to the prostate died within ten years.<ref>Yeole, BB, Sunny L (Jun-Dec 2001). "Population based survival from prostate cancer in Mumbai (Bombay), India". Indian J Cancer 38 (2-4): 126-32. PMID 1259345.</ref> African-American men have 50-60 times more prostate cancer and prostate cancer deaths than men in Shanghai, China.<ref>Hsing, AW, Tsao L, Devesa SS (Jan 1 2000). "International trends and patterns of prostate cancer incidence and mortality". Int J Cancer 85 (1): 60-7. PMID 10585584.</ref> In Nigeria, two percent of men develop prostate cancer and 64% of them are dead after two years.<ref>Osegbe, DN (Apr 1997). "Prostate cancer in Nigerians: facts and nonfacts". J Urol 157 (4): 1340-3. PMID 9120935.</ref>

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.<ref>Di Blasio CJ, Rhee AC, Cho D, Scardino PT, Kattan MW (2003). "Predicting clinical end points: treatment nomograms in prostate cancer". Semin Oncol 30 (5): 567-86. PMID 14571407.</ref>

[edit] History

Image:Hugginsprostate.jpg

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.<ref>Adams, J. The case of scirrhous of the prostate gland with corresponding affliction of the lymphatic glands in the lumbar region and in the pelvis. Lancet 1, 393 (1853).</ref> 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.<ref>Lytton, B. Prostate cancer: a brief history and the discovery of hormonal ablation treatment. J. Urol. 165, 1859-1862</ref> Removal of the entire gland (radical perineal prostatectomy) was first performed in 1904 by Hugh Young at Johns Hopkins Hospital.<ref>Young, H. H. Four cases of radical prostatectomy. Johns Hopkins Bull. 16, 315 (1905).</ref> 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.<ref>Walsh, P. C., Lepor, H. & Eggleston, J. C. Radical prostatectomy with preservation of sexual function: anatomical and pathological considerations. Prostate 4, 473-485 (1983). PMID 6889192</ref>

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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.<ref>Huggins, C. B. & Hodges, C. V. Studies on prostate cancer: 1. The effects of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res. 1, 203 (1941).</ref> 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.<ref>Schally, A. V., Kastin, A. J. & Arimura, A. Hypothalamic FSH and LH-regulating hormone. Structure, physiology and clinical studies. Fertil. Steril. 22, 703-721 (1971).</ref><ref>Tolis G, Ackman D, Stellos A, Mehta A, Labrie F, Fazekas AT, Comaru-Schally AM, Schally AV. Tumor growth inhibition in patients with prostatic carcinoma treated with luteinizing hormone-releasing hormone agonists. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1658-62 PMID 6461861</ref>

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.<ref>Denmeade SR, Isaacs JT. A History of Prostate Cancer Treatment. Nature Reviews Cancer 2, 389-396 (2002). PMID 12044015</ref> 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.<ref>Scott, W. W. et al. Chemotherapy of advanced prostatic carcinoma with cyclophosphamide or 5-fluorouracil: results of first national randomized study. J. Urol. 114, 909-911 (1975). PMID 1104900</ref>