Note from the National Guideline Clearinghouse (NGC): A targeted evidence review was prepared by the Agency for Healthcare Research and Quality (AHRQ) staff for use by the U.S. Preventive Services Task Force (USPSTF) (see the "Availability of Companion Documents" field).
In 2002, the USPSTF found insufficient evidence to recommend for or against routine screening for prostate cancer. The USPSTF found good evidence that prostate-specific antigen (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 (see Figure in the Evidence Update [see the "Availability of Companion Documents" field]) 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:
- 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?
After consultation with USPSTF liaisons and content experts, AHRQ staff chose a broad definition of PSA screening that included evolving prognostic measures, such as PSA velocity and doubling time. However, a comparison of the performance characteristics of such measures with traditional single-threshold PSA testing is outside the scope of this review.
Data Sources
For evidence on health outcomes associated with PSA screening, PubMed was searched for English-language articles indexed between 1 January 2002 and 12 July 2007 by using combinations of the Medical Subject Heading (MeSH) terms and keywords prostate neoplasms, screening, prostate-specific antigen, early diagnosis, PSA velocity, PSA doubling time, and prostate specific antigen doubling.
For evidence on the harms of screening for prostate cancer, PubMed was searched for English-language articles indexed between 1 January 2002, and 12 July 2007 by using combinations of the MeSH terms and keywords prostate neoplasms; screening; false positive reactions; adverse effects; mass screening/adverse effects; mass screening/psychology; anxiety; quality of life; and health knowledge, attitudes, practice.
For evidence on the natural history of PSA-detected, nonpalpable, localized prostate cancer, PubMed was searched for English-language articles indexed between 1 January 2002 and 23 August 2007 by using combinations of the MeSH terms and keywords prostatic neoplasms, natural history, epidemiology, disease progression, survival analysis, watchful waiting, active surveillance, population surveillance, expectant management, and conservative management.
Additional articles were identified through a search of the Cochrane Library, recommendations of experts, and a hand search of reference lists from major review articles and studies.
Study Selection
Two reviewers independently reviewed the title lists, abstracts, and full articles by using predetermined inclusion and exclusion criteria. Articles selected by at least 1 reviewer advanced to the next stage of review.
For key question 1, eligible studies were randomized, controlled trials (RCTs), meta-analyses, and systematic reviews that compared screening with no screening (or usual care) in general primary care populations and reported morbidity or mortality outcomes. Although the 2002 USPSTF review considered case–control studies and ecological data related to this key question, these study types were excluded from this part of the evidence update to avoid potential sources of confounding that are inherent in nonrandomized studies.
For key question 2, eligible studies were randomized or nonrandomized comparative studies that reported quantitative health or quality-of-life outcomes related to a false-positive screening result. Studies that reported only harms resulting from prostate cancer treatment were excluded.
For key question 3, eligible studies were RCTs and cohort studies that reported health outcomes of patients with stage T1c (nonpalpable, localized, PSA-detected) prostate cancer who did not receive active treatment (including patients assigned to watchful waiting or active surveillance protocols). To ensure that the most applicable information on natural history was retrieved, studies that predominantly involved patients with non–PSA-detected cancer (defined as comprising >80% of the study population), were too small to draw reliable conclusions about health outcomes (defined as <50 patients in the watchful waiting or surveillance group), or did not provide separate data on patients with stage T1c prostate cancer were excluded.