Prostate cancer screening

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Overview

According to the AUA guidline, screening for prostate cancer by PSA is recommended every 2 years among individuals age 55 to 69 years, or younger than 55 years for individuals with high risk.[1]

Screening

Prostate cancer screening is an attempt to find unsuspected cancers. 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.

  • 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).[2]
  • 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)[3]along with information on the risks and benefits of screening.[4] 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.[5]
  • 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.[6]
  • 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.[7] or beginning annual PSA testing in high risk men at age 35.[8]
  • According to the AUA guidline, screening for prostate cancer by PSA is recommended every 2 years among individuals age 55 to 69 years, or younger than 55 years for individuals with high risk.[1]

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.[9]

Benefits

The evidence is insufficient to determine whether screening for prostate cancer with prostate-specific antigen (PSA) or digital rectal exam (DRE) reduces mortality from prostate cancer. Screening tests are able to detect prostate cancer at an early stage, but it is not clear whether this earlier detection and consequent earlier treatment leads to any change in the natural history and outcome of the disease. Observational evidence shows a trend toward lower mortality for prostate cancer in some countries, but the relationship between these trends and intensity of screening is not clear, and associations with screening patterns are inconsistent. The observed trends may be due to screening, or to other factors such as improved treatment. Results from two randomized trials show no effect on mortality through 7 years but are inconsistent beyond 7 to 10 years.[10]

Harms

Based on solid evidence, screening with PSA and/or DRE detects some prostate cancers that would never have caused important clinical problems. Thus, screening leads to some degree of overtreatment. Based on solid evidence, current prostate cancer treatments, including radical prostatectomy and radiation therapy, result in permanent side effects in many men. The most common of these side effects are erectile dysfunction and urinary incontinence. Whatever the screening modality, the screening process itself can lead to adverse psychological effects in men who have a prostate biopsy but do not have identified prostate cancer. Prostatic biopsies are associated with complications, including fever, pain, hematospermia/hematuria, positive urine cultures, and rarely sepsis.[10]

Screening Methods

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.[11] The use of DRE has never been shown to prevent prostate cancer deaths when used as the only screening test.[12]

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.[13] 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.[14] 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.[15] 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.[16] 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.[17][18]

Interpreting the results of Screening Tests

Two clinical prediction rules help predict the probability of cancer based on the the level of the prostate-specific antigen and other clinical findings.[19][20]

Evidence for Efficacy

Randomized Controlled Trials

One randomized controlled trial found significant reduction in death from screening.[21] However, the intention to treat analysis showed no benefit.

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."[22]

When all available trials are meta-analyzed, mortality from prostate cancer may be reduced among patients with sufficient duration of screening (see Forest plot) .[23]

Decision Analyses

In the absence of well done randomized controlled trials, a decision analysis can estimate the benefit of screening. [24][25] 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.[25]

Clinical Practice Guidelines

Clinical practice guidelines for prostate cancer screening are controversial because the benefits of screening may not outweigh the risks of follow-up diagnostic tests and cancer treatments:

"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.


References

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  2. US Preventive Services Task Force (2002). "Screening for Prostate Cancer". Agency for Healthcare Research and Quality. Unknown parameter |month= ignored (help) USPSTF (2002). "Screening for prostate cancer: recommendation and rationale" (PDF). Ann Intern Med. 137 (11): 915–6. PMID 12458992. Unknown parameter |month= ignored (help)
    Harris R, Lohr KN (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. Unknown parameter |month= ignored (help)
  3. Arias E (2006). "United States Life Tables, 2003" (PDF). Natl Vital Stat Rep. 54 (14): 1–40. PMID 16681183. Unknown parameter |month= ignored (help)
  4. von Eschenbach A, Ho R, Murphy GP, Cunningham M, Lins N (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. Unknown parameter |month= ignored (help)ACS (2007). "Prostate Cancer: Early Detection". Retrieved 2007-11-19. Unknown parameter |month= ignored (help)
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  6. NCCN (2007). "Prostate Cancer Early Detection V.2.2007" (PDF). NCCN Clinical Practice Guidelines in Oncology. Unknown parameter |month= ignored (help)
  7. "Study suggests value of regular PSA tests for tracking prostate cancer". Dana-Farber Cancer Institute. 2004. Unknown parameter |month= ignored (help) Kladko B (2005). "Prostate cancer test gets another look". The Boston Globe. Unknown parameter |month= ignored (help)
  8. Strum SB, Pogliano D (2005). "What every doctor who treats male patients should know" (PDF). PCRI Insights. 8 (2): 4–5. Unknown parameter |month= ignored (help)
  9. 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.
  10. 10.0 10.1 National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/publications/pdq
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  12. Krahn, MD (1994). "Screening for prostate cancer.. A decision analytic view". JAMA. 272 (10): 773–80. doi:10.1001/jama.272.10.773. PMID 7521400. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  13. Catalona WJ (2007). "How I manage a patient with a newly elevated PSA" (PDF). 2007 CDC Cancer Conference. Unknown parameter |month= ignored (help)
  14. Kolota G (2004). "It was medical gospel, but it wasn't true". The New York Times: 4.7. Unknown parameter |month= ignored (help)
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  17. Hoffman, RM (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. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
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  31. American Cancer Society. "What the American Cancer Society Recommends". Retrieved 2007-01-16.

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