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Finasteride as a chemopreventive agent in prostate cancer: impact of the PCPT on urologic practice

Nature Clinical Practice Urology volume 3, pages 422–429 (2006)Cite this article

Abstract

Prostate cancer chemoprevention involves the use of natural and/or synthetic agents that inhibit or reverse the development of precancerous lesions or delay progression of these lesions to invasive disease. The recent completion of the first Phase III trial for prostate cancer prevention, the Prostate Cancer Prevention Trial (PCPT) using the drug finasteride, has provided the urologic community with the first evidence that a chemopreventive agent can reduce the risk of developing prostate cancer. The enthusiasm for the clear relative risk reduction in the finasteride arm of the trial has been tempered by the observation that the incidence of high-grade tumors was higher in men receiving finasteride compared to those on placebo. A question remains about whether the observed higher incidence in high-grade tumors is real or whether it is related to a pathologic or sampling artifact. The PCPT has instigated a great deal of debate, resulting in the larger urologic community being reluctant to recommend the widespread use of finasteride as a chemopreventive agent. This review summarizes the PCPT, analyzes its controversial results, and describes future prostate cancer chemoprevention studies.

Key Points

  • The recent completion of PCPT using the drug finasteride has provided the first evidence that a chemopreventive agent can reduce the risk of developing prostate cancer

  • High-grade cancers were significantly more likely to be found in the finasteride group compared to controls

  • The increase in high-grade cancers in the experimental arm might be related to a histologic or sampling artifact in the study

  • Further studies on the biopsy and prostatectomy specimens from men in the PCPT as well as the ongoing REDUCE trial should help to confirm whether 5-alpha reductase inhibitors promote higher-grade tumors; the results of these studies are needed before the use of 5-alpha reductase inhibitors can be widely accepted for prostate cancer chemoprevention

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Figure 1: Distribution of Gleason scores in men diagnosed with prostate cancer in the finasteride and placebo arms in the Prostate Cancer Prevention Trial
Figure 2: Cumulative incidence of high-grade prostate cancer diagnosed from either for-cause biopsies or biopsies taken after an interim procedure

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Authors and Affiliations

  1. Resident in Urology,

    Manlio A Goetzl & Jeffrey M Holzbeierlein

  2. Assistant Professor of Urology in the Department of Urology, University of Kansas Medical Center, Kansas City, KS, USA

    Manlio A Goetzl & Jeffrey M Holzbeierlein

Authors
  1. Manlio A Goetzl
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  2. Jeffrey M Holzbeierlein
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Correspondence to Jeffrey M Holzbeierlein.

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Competing interests

MA Goetzl has minimal stock ownership in GlaxoSmithKline.

JM Holzbeierlein receives research support from the Department of Defense, Merk and Pfizer, and is a speaker for Pfizer and Sanofi Aventis.

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Goetzl, M., Holzbeierlein, J. Finasteride as a chemopreventive agent in prostate cancer: impact of the PCPT on urologic practice. Nat Rev Urol 3, 422–429 (2006). https://doi.org/10.1038/ncpuro0574

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