Prostate cancer screening
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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 cores of the prostate are removed for closer study. 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 usually a slow-growing cancer, very common among older men. In fact, most prostate cancers never grow to the point where they cause symptoms, and most men with prostate cancer die of other causes before prostate cancer has an impact on their lives. The PSA screening test may detect these small cancers that would never become life threatening. Doing the PSA test in these men may lead to overdiagnosis, including additional testing and treatment. Follow-up tests, such as prostate biopsy, may cause pain, bleeding and infection. Prostate cancer treatments may cause urinary incontinence and erectile dysfunction. Therefore, it is essential that the risks and benefits of diagnostic procedures and treatment be carefully considered before PSA screening.
Several medical societies have not found sufficient evidence to support routine screening for prostate cancer - but the American Urological Association supports annual screening and digital examination for men over 50 years old - and starting earlier for 'men at high risk (those with a family history of prostate cancer or African American men)'. 
- In 2002, the U.S. Preventive Services Task Force (USPSTF) concluded that the evidence was insufficient to recommend for or against routine screening for prostate cancer using PSA testing or digital rectal examination (DRE). The previous 1995 USPSTF recommendation was against routine screening.
- In 1997, American Cancer Society (ACS) guidelines began recommending that beginning at age 50 (age 45 for African-American men and men with a family history of prostate cancer, and since 2001, age 40 for men with a very strong family history of prostate cancer), PSA testing and DRE be offered annually to men who have a life-expectancy of 10 or more years (average life expectancy is 10 years or more for U.S. men under age 76)along with information on the risks and benefits of screening. The previous ACS recommendations since 1980 had been for routine screening for prostate cancer with DRE annually beginning at age 40, and since 1992 had been for routine screening with DRE and PSA testing annually beginning at age 50.
- The 2007 National Comprehensive Cancer Network (NCCN) guideline recommends offering a baseline PSA test and DRE at ages 40 and 45 and annual PSA testing and DRE beginning at age 50 (with annual PSA testing and DRE beginning at age 40 for African-American men, men with a family history of prostate cancer, and men with a PSA ≥ 0.6 ng/mL at age 40 or PSA > 0.6 ng/mL at age 45) through age 80, along with information on the risks and benefits of screening. Biopsy is recommended if DRE is positive or PSA ≥ 4 ng/mL, and biopsy considered if PSA > 2.5 ng/mL or PSA velocity ≥ 0.35 ng/mL/year when PSA ≤ 2.5 ng/mL.
- Some U.S. radiation oncologists and medical oncologists who specialize in treating prostate cancer recommend obtaining a baseline PSA in all men at age 35. or beginning annual PSA testing in high risk men at age 35.
- The American Urological Association Patient Guide to Prostate Cancer.
Since there is no general agreement that the benefits of PSA screening outweigh the harms, the consensus is that clinicians use a process of shared decision-making that includes discussing with patients the risks of prostate cancer, the potential benefits and harms of screening, and involving the patients in the decision.
However, because PSA screening is widespread in the United States, following the recommendations of major scientific and medical organizations to use shared decision-making is legally perilous in some U.S. states. In 2003, a Virginia jury found a family practice residency program guilty of malpractice and liable for $1 million for following national guidelines and using shared decision-making, thereby allowing a patient (subsequently found to have a high PSA and incurable advanced prostate cancer) to decline a screening PSA test, instead of routinely ordering without discussion PSA tests in all men ≥ 50 years of age as four local physicians testified was their practice, and was accepted by the jury as the local standard of care.
An estimated 20 million PSA tests are done per year in North America and possibly 20 million more outside of North America.
- In 2000, 34.1% of all U.S. men age ≥ 50 had a screening PSA test within the past year and 56.8% reported ever having a PSA test.
- In 2000, 33.6% of all U.S. men age 50–64 and 51.3% of men age ≥ 65 had a PSA test within the past year.
- In 2005, 33.5% of all U.S. men age 50–64 had a PSA test in the past year.
- In 2000–2001, 34.1% of all Canadian men age ≥ 50 had a screening PSA test within the past year and 47.5% reported ever having a screening PSA test.
- Canadian men in Ontario were most likely to have had a PSA test within the past year and men in Alberta were least likely to have had a PSA test with the past year or ever.
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 spermatozoa to more easily navigate through the uterine cervix.
The risk of prostate cancer increases with increasing PSA levels. 4 ng/mL was chosen arbitrarily as a decision level for biopsies in the clinical trial upon which the FDA in 1994 based adding prostate cancer detection in men age 50 and over as an approved indication for the first commercially available PSA test. 4 ng/mL was used as the biopsy decision level in the PLCO trial, 3 ng/mL was used in the ERSPC and ProtecT trials, and 2.5 ng/mL is used in the 2007 NCCN guideline.
PSA levels can change for many reasons other than cancer. Two common causes of high PSA levels are enlargement of the prostate (benign prostatic hypertrophy (BPH)) and infection in the prostate (prostatitis). It can also be raised for 24 hours after ejaculation and several days after catheterization. PSA levels are lowered in men who use medications used to treat BPH or baldness. These medications, finasteride (marketed as Proscar or Propecia) and dutasteride (marketed as Avodart), may decrease the PSA levels by 50% or more.
Several other ways of evaluating the PSA have been developed to avoid the shortcomings of simple PSA screening. The use of age-specific reference ranges improves the sensitivity and specificity of the test. The rate of rise of the PSA over time, called the PSA velocity, has been used to evaluate men with PSA levels between 4 and 10 ng/ml, but 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 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 questions regarding the usefulness of these measurements limit their widespread use.
Interpreting the results of Screening Tests
Evidence for Efficacy
Randomized Controlled Trials
A secondary analysis of a randomized controlled trial suggests screening for prostate cancer every 4 years is adequate. The screening comprises a PSA blood test, a digital rectal exam, and a transrectal ultrasound. "Very few, if any, aggressive prostate cancers escape (this) screening."
In the absence of well done randomized controlled trials, a decision analysis can estimate the benefit of screening.  One analysis found that approximately 303 men would number need to be screened with a "strategy of PSA testing at ages 40 and 45 years followed by biennial testing beginning at age 50" to prevent one death from prostate cancer.
Clinical Practice Guidelines
- "the evidence is insufficient to recommend for or against routine screening for prostate cancer using prostate-specific antigen (PSA) testing or digital rectal examination (DRE). This is a grade I recommendation"
- "The PSA test and the DRE should be offered annually beginning at age 50 to men who have a life expectancy of at least 10 years. Men at high risk should begin testing at age 45. Information should be provided to patients about benefits and limitations of testing."
The ACS recommends that individual men discuss the potential benefits and risks of testing with their doctors in order to make an informed decision on whether or not to be tested. Screening should be offered annually to African-American men and those with a family history of prostate cancer upon reaching 45 years. Other racial and ethnic groups, such as Asian- and Hispanic-Americans have a lower risk of prostate cancer, and may not benefit from screening. Screening is likely not useful for men over age 70 or with other significant medical problems and a life expectancy of fewer than 10 years.
- ↑ Early Detection of Prostate Cancer, American Urological Association, Washington, D.C., revised: October 2008.Accessed: 12-01-2008
- ↑ US Preventive Services Task Force (December 2002). Screening for Prostate Cancer. Agency for Healthcare Research and Quality.
USPSTF (December 3, 2002). "Screening for prostate cancer: recommendation and rationale" (PDF). Ann Intern Med 137 (11): 915–6. PMID 12458992.
Harris R, Lohr KN (December 3, 2002). "Screening for prostate cancer: an update of the evidence for the U.S. Preventive Services Task Force" (PDF). Ann Intern Med 137 (11): 917–29. PMID 12458993.
- ↑ Arias E (April 19, 2006). "United States Life Tables, 2003" (PDF). Natl Vital Stat Rep 54 (14): 1–40. PMID 16681183.
- ↑ von Eschenbach A, Ho R, Murphy GP, Cunningham M, Lins N (September-October 1997). "American Cancer Society guideline for the early detection of prostate cancer: update 1997" (PDF). CA Cancer J Clin 47 (5): 261–4. doi:10.3322/canjclin.47.5.261. PMID 9314820.ACS (March 28, 2007). Prostate Cancer: Early Detection. Retrieved on 2007-11-19.
Smith RA, Cokkinides V, Eyre HJ (March-April 2007). "Cancer screening in the United States, 2007: a review of current guidelines, practices, and prospects" (PDF). CA Cancer J Clin 57 (2): 90–104. PMID 17392386.
Smith RA, Cokkinides V, Eyre HJ (January-February 2006). "American Cancer Society guidelines for the early detection of cancer, 2006" (PDF). CA Cancer J Clin 56 (1): 11–25. PMID 16449183.
- ↑ ACS (March 29, 2007). Chronological History of ACS Recommendations on Early Detection of Cancer.
- ↑ NCCN (May 10, 2007). Prostate Cancer Early Detection V.2.2007 (PDF). NCCN Clinical Practice Guidelines in Oncology.
- ↑ Study suggests value of regular PSA tests for tracking prostate cancer. Dana-Farber Cancer Institute (July 2004). Kladko B (August 15, 2005). "Prostate cancer test gets another look". The Boston Globe.
- ↑ Strum SB, Pogliano D (May 2005). "What every doctor who treats male patients should know" (PDF). PCRI Insights 8 (2): 4–5.
- ↑ American Urological Association (AUA) (2008). Prostate Cancer Patient Guide (PDF). AUA Patient Guidelines.
- ↑ 10.0 10.1 Ross LE, Coates RJ, Breen N, Uhler RJ, Potosky AL, Blackman D (2004). "Prostate-specific antigen test use reported in the 2000 National Health Interview Survey". Prev Med 38 (6): 732–44. doi:10.1016/j.ypmed.2004.01.005. PMID 15193893.
- ↑ Lewis MH, Gohagan JK, Merenstein DJ (2007). "The locality rule and the physician's dilemma: local medical practices vs the national standard of care". JAMA 297 (23): 2633–7. doi:10.1001/jama.297.23.2633. PMID 17579232.
- ↑ Merenstein D (2004). "Winners and losers". JAMA 291 (1): 15–6. doi:10.1001/jama.291.1.15. PMID 14709561.
- ↑ De Angelis G, Rittenhouse HG, Mikolajczyk SD, Blair Shamel L, Semjonow A (2007). "Twenty years of PSA: from prostate antigen to tumor marker". Rev Urol 9 (3): 113–23. PMID 17934568.
- ↑ Swan J, Breen N, Coates RJ, Rimer BK, Lee NC (2003). "Progress in cancer screening practices in the United States: results from the 2000 National Health Interview Survey". Cancer 97 (6): 1528–40. doi:10.1002/cncr.11208. PMID 12627518.
- ↑ Ward E, Halpern M, Schrag N, Cokkinides V, DeSantis C, Bandi P, Siegel R, Stewart A, Jemal A (Jan-Feb 2008). "Association of insurance with cancer care utilization and outcomes" (PDF). CA Cancer J Clin 58 (1): 9–31. doi:10.3322/CA.2007.0011. PMID 18096863.
- ↑ Beaulac JA, Fry RN, Onysko J (2006). "Lifetime and recent prostate specific antigen (PSA) screening of men for prostate cancer in Canada". Can J Public Health 97 (3): 171–6. PMID 16827400.
- ↑ Gibbons L, Waters C (May 2003). "Prostate cancer--testing, incidence, surgery and mortality" (PDF). Health Rep 14 (3): 9–20. PMID 12816012.
- ↑ 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.
- ↑ Krahn, MD; Mahoney JE, Eckman MH, Trachtenberg J, Pauker SG, Detsky AS (September 14 1994). "Screening for prostate cancer.. A decision analytic view". JAMA 272 (10): 773–80. doi:10.1001/jama.272.10.773. PMID 7521400.
- ↑ Catalona WJ (August 16, 2007). How I manage a patient with a newly elevated PSA (PDF). 2007 CDC Cancer Conference.
- ↑ Kolota G (May 30, 2004). "It was medical gospel, but it wasn't true". The New York Times: 4.7.
Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, Minasian LM, Ford LG, Lippman SM, Crawford ED, Crowley JJ, Coltman CA Jr (May 27, 2004). "Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter". N Engl J Med 350 (22): 2239–46. PMID 15163773.
Carter HB (May 27, 2004). "Prostate cancers in men with low PSA levels--must we find them?". N Engl J Med 350 (22): 2292–4. doi:10.1056/NEJMe048003. PMID 15163780.
Catalona WJ, Richie JP, Ahmann FR, Hudson MA, Scardino PT, Flanigan RC, deKernion JB, Ratliff TL, Kavoussi LR, Dalkin BL, et al. (May 1994). "Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: results of a multicenter clinical trial of 6,630 men". J Urol 151 (5): 1283–90. PMID 7512659.
FDA (August 29, 1994). FDA approves test for prostate cancer.
- ↑ Roobol, MJ; Kranse R, de Koning HJ, Schroder FH (February 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. doi:10.1016/j.urology.2003.09.083. PMID 14972478.
- ↑ Catalona, WJ; Richie JP, deKernion JB, Ahmann FR, Ratliff TL, Dalkin BL, Kavoussi LR, MacFarlane MT, Southwick PC (December 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.
- ↑ Hoffman, RM; Clanon DL, Littenberg B, Frank JJ, Peirce JC (October 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. doi:10.1046/j.1525-1497.2000.90907.x. PMID 11089718.
- ↑ 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 (November 2003). "Complexed prostate specific antigen improves specificity for prostate cancer detection: results of a prospective multicenter clinical trial". J Urol 170 (5): 1787–91. doi:10.1097/01.ju.0000092695.55705.dd. PMID 14532777.
- ↑ Nam RK, Toi A, Klotz LH, et al (2007). "Assessing individual risk for prostate cancer". J. Clin. Oncol. 25 (24): 3582–8. doi:10.1200/JCO.2007.10.6450. PMID 17704405.
- ↑ Thompson IM, Ankerst DP, Chi C, et al (2006). "Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial". J. Natl. Cancer Inst. 98 (8): 529–34. doi:10.1093/jnci/djj131. PMID 16622122. Online calculator
- ↑ Labrie F, Candas B, Dupont A, et al (1999). "Screening decreases prostate cancer death: first analysis of the 1988 Quebec prospective randomized controlled trial". Prostate 38 (2): 83-91. PMID 9973093.
- ↑ Schröder F, Raaijmakers R, Postma R, van der Kwast T, Roobol M (2005). "4-year prostate specific antigen progression and diagnosis of prostate cancer in the European Randomized Study of Screening for Prostate Cancer, section Rotterdam.". J Urol 174 (2): 489-94; discussion 493-4. PMID 16006878.
- ↑ Krahn MD, Mahoney JE, Eckman MH, Trachtenberg J, Pauker SG, Detsky AS (1994). "Screening for prostate cancer. A decision analytic view". JAMA 272 (10): 773-80. PMID 7521400.
- ↑ 31.0 31.1 Ross KS, Carter HB, Pearson JD, Guess HA (2000). "Comparative efficiency of prostate-specific antigen screening strategies for prostate cancer detection". JAMA 284 (11): 1399-405. PMID 10989402.
- ↑ U.S. Preventive Services Task Force (2002). "Screening for prostate cancer: recommendation and rationale". Ann. Intern. Med. 137 (11): 915-6. PMID 12458992.
- ↑ Harris R, Lohr KN (2002). "Screening for prostate cancer: an update of the evidence for the U.S. Preventive Services Task Force". Ann. Intern. Med. 137 (11): 917-29. PMID 12458993.
- ↑ U.S. Preventive Services Task Force (December 2002)). Screening for Prostate Cancer. Retrieved on 2006-09-14.
- ↑ Smith RA, von Eschenbach AC, Wender R, et al (2001). "American Cancer Society guidelines for the early detection of cancer: update of early detection guidelines for prostate, colorectal, and endometrial cancers. Also: update 2001--testing for early lung cancer detection". CA: a cancer journal for clinicians 51 (1): 38-75; quiz 77-80. PMID 11577479.
- ↑ National Guideline Clearinghouse. Recommendations from the American Cancer Society Workshop on Early Prostate Cancer Detection. Retrieved on 2006-09-14.
- ↑ American Cancer Society. What the American Cancer Society Recommends. Retrieved on 2007-01-16.
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