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Limitations of Basing Screening Policies on Screening Trials: The US Preventive Services Task Force and Prostate Cancer Screening

Etzioni, Ruth PhD*; Gulati, Roman MS*; Cooperberg, Matt R. MD; Penson, David M. MD; Weiss, Noel S. PhD§; Thompson, Ian M. MD

doi: 10.1097/MLR.0b013e31827da979

Background: The US Preventive Services Task Force recently recommended against prostate-specific antigen screening for prostate cancer based primarily on evidence from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial.

Objective: To examine limitations of basing screening policy on evidence from screening trials.

Methods: We reviewed published modeling studies that examined population and trial data. The studies (1) project the roles of screening and changes in primary treatment in the US mortality decline; (2) extrapolate the ERSPC mortality reduction to the long-term US setting; (3) estimate overdiagnosis based on US incidence trends; and (4) quantify the impact of control arm screening on PLCO mortality results.

Results: Screening plausibly explains 45% and changes in primary treatment can explain 33% of the US prostate cancer mortality decline. Extrapolating the ERSPC results to the long-term US setting implies an absolute mortality reduction at least 5 times greater than that observed in the trial. Approximately 28% of screen-detected cases are overdiagnosed in the United States versus 58% of screen-detected cases suggested by the ERSPC results. Control arm screening can explain the null result in the PLCO trial.

Conclusions: Modeling studies indicate that population trends and trial results extended to the long-term population setting are consistent with greater benefit of prostate-specific antigen screening—and more favorable harm-benefit tradeoffs—than has been suggested by empirical trial evidence.

*Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA

Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA

Vanderbilt University Medical Center, Nashville, TN

§Department of Epidemiology, University of Washington, Seattle, WA

Department of Urology, University of Texas, San Antonio, TX

Supported by Award Numbers R01 CA131874 and U01 CA88160 from the National Cancer Institute and Award Number U01 CA157224 from the National Cancer Institute and the Centers for Disease Control.

The authors declare no conflict of interest.

Reprints: Ruth Etzioni, PhD, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M2-B230, Seattle, WA 98109-1024. E-mail:

Copyright © 2013 Wolters Kluwer Health, Inc. All rights reserved.