Background:

Prostate cancer is the most common nonskin cancer in men in the United States, and prostate cancer screening has increased in recent years. In 2002, the U.S. Preventive Services Task Force concluded that evidence was insufficient to recommend for or against screening for prostate cancer with prostate-specific antigen (PSA) testing.

Purpose:

To examine new evidence of benefits and harms of screening asymptomatic men for prostate cancer with PSA testing.

Data Sources:

English-language articles identified in PubMed and the Cochrane Library (search dates, January 2002 to July 2007), reference lists of retrieved articles, and expert suggestions.

Study Selection:

Randomized, controlled trials and meta-analyses of PSA screening and cross-sectional and cohort studies of screening harms and of the natural history of screening-detected cancer were selected to answer the following questions: Does screening for prostate cancer with PSA, as a single-threshold test or as a function of multiple tests over time, decrease morbidity or mortality? What are the magnitude and nature of harms associated with prostate cancer screening, other than overtreatment? What is the natural history of PSA-detected, nonpalpable, localized prostate cancer?

Data Extraction:

Studies were reviewed, abstracted, and rated for quality by using predefined U.S. Preventive Services Task Force criteria.

Data Synthesis:

No good-quality randomized, controlled trials of screening for prostate cancer have been completed. In 1 cross-sectional and 2 prospective cohort studies of fair to good quality, false-positive PSA screening results caused psychological adverse effects for up to 1 year after the test. The natural history of PSA-detected prostate cancer is poorly understood.

Limitations:

Few eligible studies were identified. Long-term adverse effects of false-positive PSA screening test results are unknown.

Conclusion:

Prostate-specific antigen screening is associated with psychological harms, and its potential benefits remain uncertain.

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. The American Cancer Society estimates that 27,350 men died of prostate cancer in 2006. 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.

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. 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 μg/L, a widely used cutoff value for a positive screening result. 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.

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.

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) 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:

1. Does screening for prostate cancer with PSA, as a single-threshold test or as a function of multiple tests over time, decrease morbidity or mortality?

2. What are the magnitude and nature of harms associated with prostate cancer screening other than overtreatment?

3. What is the natural history of PSA-detected, nonpalpable, localized prostate cancer?

Figure

Figure 1. Analytic Framework for Screening for Prostate Cancer.