Prepared by:

Kenneth Lin, MD

Robert Lipsitz, MD, MPH

Therese Miller, DrPH

Supriya Janakiraman, MD, MPH

Agency for Healthcare Research and Quality

U.S. Department of Health and Human Services

540 Gaither Road

Rockville, MD 20850

AHRQ Publication No. 08-05121-EF-1

August 2008

This report is based on research conducted by staff of the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD. The investigators involved have declared no conflicts of interest with objectively conducting this research. The findings and conclusions in this document are those of the author(s), who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.

The information in this report is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This report is intended as a reference and not as a substitute for clinical judgment.

This report may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

This report was first published in Annals of Internal Medicine on August 5, 2008.

Suggested AHRQ Citation: Lin K, Lipsitz R, Miller T, Janakiraman S. Benefits and Harms of Prostate-Specific Cancer Screening: An Evidence Update for the U.S. Preventive Services Task Force. Evidence Synthesis No. 63. AHRQ Publication No. 08-05121-EF-1. Rockville, Maryland: Agency for Healthcare Research and Quality. August 2008.

Annals of Internal Medicine Citation: Lin K, Lipsitz R, Miller T, Janakiraman S. Benefits and harms of prostate-specific antigen screening for prostate cancer: an evidence update for the U.S. Preventive Services Task Force. Ann Intern Med. 2008:149;192199.

Prostate cancer is the most common nonskin cancer in U.S. men. An estimated 218,890 men received a new diagnosis of prostate cancer in 2007, and 1 in 6 men will receive a diagnosis in their lifetime (1). The American Cancer Society estimates that 27,350 men died of prostate cancer in 2006 (2). After peaking in 1991 (29.4 deaths per 100,000 men), the prostate cancer mortality rate has gradually decreased. Although this positive trend may be related to increased screening for prostate cancer, other factors, including new treatment approaches, could also account for some or all of the observed decline in mortality (3).

The serum prostate-specific antigen (PSA) test was approved by the U.S. Food and Drug Administration in 1986, and its use for prostate cancer screening has increased substantially since the mid-1990s (4). However, PSA testing is not specific to prostate cancer; common conditions, such as benign prostatic hyperplasia and prostatitis, also increase PSA levels. Approximately 1.5 million U.S. men age 40 to 69 years have a PSA level greater than 4.0 mg/L, a widely used cutoff value for a positive screening result (5). Refinements designed to improve the PSA test's sensitivity and specificity for prostate cancer include determination of PSA density, PSA velocity, PSA doubling time, and percentage of free PSA (69).

Potential harms from PSA screening include additional medical visits, adverse effects of prostate biopsies, anxiety, and overdiagnosis (the identification of prostate cancer that would never have caused symptoms in the patient's lifetime, leading to unnecessary treatment and associated adverse effects). Much uncertainty surrounds which cases of prostate cancer require treatment and whether earlier detection leads to improvements in duration or quality of life. Two recent systematic reviews of the comparative effectiveness and harms of therapies for localized prostate cancer concluded that no single therapy is superior to all others in all situations (10,11).

In 2002, the U.S. Preventive Services Task Force (USPSTF) found insufficient evidence to recommend for or against routine screening for prostate cancer. The USPSTF found good evidence that PSA screening can detect early-stage prostate cancer but found mixed and inconclusive evidence that screening and early detection improve health outcomes. Consequently, the USPSTF was unable to determine the balance between benefits and harms of periodic screening for prostate cancer.

The analytic framework that guided the previous USPSTF evidence review (Figure) (12) included 8 key questions about benefits and harms of prostate cancer screening and treatment. This evidence update focuses on critical gaps in the evidence that the Task Force identified in the previous review: the lack of good-quality studies linking screening to improved health outcomes; limited information about harms of screening; and a paucity of knowledge about the natural history of PSA-detected, nonpalpable, localized prostate cancer (the most common type of prostate cancer detected today). These evidence gaps produced 3 new key questions for this update: