Originally published as JCO Early Release 10.1200/JCO.2005.08.159 on September 12 2005

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Assessing Benefit and Risk in the Prevention of Prostate Cancer: The Prostate Cancer Prevention Trial Revisited

From the Section of Urologic Oncology, Glickman Urological Institute; Cleveland Clinic Lerner College of Medicine, Cleveland Clinic Foundation, Cleveland, OH; Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston; and Department of Urology, University of Texas Health Sciences Center, San Antonio, TX

Address reprint requests to Eric A. Klein, MD, Desk A100, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail: kleine{at}ccf.org

PURPOSE: The Prostate Cancer Prevention Trial demonstrated a 25% reduction in period prevalence of prostate cancer in men randomly assigned to 5 mg/d of finasteride. However, widespread use of finasteride for prevention is inhibited by the observed increased risk of high-grade disease. We present a model of risk and benefit that estimates the potential effects of histologic artifact in the assignment of excess risk for high-grade disease and the possible effect of overdetection bias introduced by finasteride-induced volume reduction.

METHODS: The absolute benefit/absolute risk ratio of finasteride use was estimated by calculating the ratio of absolute risk reduction in the finasteride arm to the absolute risk of excess high-grade cancers. This ratio was recalculated for assumptions that 10%, 25%, or 50% of the excess high-grade cancers were due to histologic artifact, and that there was a 25% overdetection bias in the finasteride arm.

RESULTS: For all cancers the absolute benefit/absolute risk ratio increased from 4.6:1 to 5.1:1, 6.2:1, and 9.2:1 for assumptions of 10%, 25%, or 50% histologic artifact, respectively. The ratio increased from 4.6:1 to 8.2:1 for the assumption of 25% overdetection bias, and to 9.1:1, 10.9:1, and 16.3:1 for combined assumptions of 25% overdetection bias and 10%, 25%, or 50% histologic artifact, respectively.

CONCLUSION: The adoption of a prevention strategy hinges on potential benefits weighed against potential risks. This model demonstrates the magnitude of effect for a hypothesized range of histologic artifact and overdetection bias on the assessment of risk versus benefit for finasteride.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

Related Editorial

• Rebalancing Ratios and Improving Impressions: Later Thoughts From the Prostate Cancer Prevention Trial Investigators
  James A. Talcott
  JCO 2005 23: 7388-7390 [Full Text]

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