Elsevier

Urology

Volume 73, Issue 5, Supplement, May 2009, Pages S36-S43
Urology

Supplement
Overview of Pivotal Studies for Prostate Cancer Risk Reduction, Past and Present

https://doi.org/10.1016/j.urology.2009.02.017Get rights and content

Prostate cancer (PCa), with its potentially long latency, generally late-age onset, and high prevalence, is an ideal target for risk reduction and disease prevention strategies. Treatment of the disease is currently associated with significant side effects and reduced quality of life. Encouraging results are emerging in PCa risk reduction with 5α-reductase inhibitors (5-ARIs). The pivotal Prostate Cancer Prevention Trial (PCPT) with finasteride established the efficacy of 5-ARIs in reducing the period prevalence of PCa. Ongoing trials that will further clarify the role of 5-ARIs in preventing and treating PCa include the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) with dutasteride in PCa risk reduction; the Reduction by Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) trial on the effect of dutasteride on disease progression in low-grade localized PCa; and the Therapeutic Assessment of Rising PSAs [prostate-specific antigens] (TARP) trial on dutasteride in asymptomatic recurrent cancer. The data from these trials might initiate a paradigm shift in the attitudes of clinicians, healthcare policymakers, and patients to the benefits of PCa risk reduction strategies and their potential effect on a patient's health and quality of life.

Section snippets

5-ARIs and PCa

With progress in the understanding of the biology of PCa, multiple signaling targets have been identified that are involved in the development and progression of the disease (see report by Crawford in this supplement). Although testosterone is the main circulating androgen in men, dihydrotestosterone (DHT) is the primary prostatic androgen.5 In addition, DHT has a greater affinity to the androgen receptor,5, 6 making it the predominant agonist of the androgen receptor pathway that leads to

Study Design

The Prostate Cancer Prevention Trial (PCPT) was the first large-scale PCa risk reduction study (Fig. 2). It was a 7-year randomized, double-blind, placebo-controlled trial of finasteride for PCa risk reduction in healthy men. Participants in the study were healthy men with a low risk of PCa as determined by a prostate-specific antigen (PSA) level of ≤3.0 ng/mL and normal digital rectal examination (DRE) findings at enrollment. After a 3-month placebo run-in, 18 882 men ≥55 years old were

Rationale

PCa development is a complicated process, involving multiple cell signaling pathways and a myriad of molecular components. In addition to the action of 5-ARIs through the androgen receptor pathway, some dietary items have shown potential in PCa risk reduction, according to evidence from secondary analyses of large-scale trials of other potential risk reduction agents for other cancers. In the Nutritional Prevention of Cancer study of the effect of selenium on skin cancer, the patients in the

Conclusions

In the past decade, significant strides have been made in our understanding of PCa development and progression. The results from the PCPT, the first large-scale, long-term, prospective PCa risk reduction clinical trial, have established the promise of 5α-reductase inhibitors in reducing PCa events.

Dutasteride, a potent, dual 5-ΑRI, is being investigated for PCa risk reduction in the REDUCE trial. Large prospective studies are also underway to determine the effect of dutasteride on PCa

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    G. L. Andriole serves as a consultant to Aeterna Zentaris, Nema Steba, Onconome, and GlaxoSmithKline and has received research funding from Envisioneering, Ferring Pharmaceuticals, GlaxoSmithKline, Veridex, Viking Medical, and Zeneca.

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