SupplementOverview of Pivotal Studies for Prostate Cancer Risk Reduction, Past and Present
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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Cited by (15)
Is Testosterone Treatment Good for the Prostate? Study of Safety during Long-Term Treatment
2012, Journal of Sexual MedicineCitation Excerpt :DHT is often considered the most active androgen affecting the prostate, and benign enlargement is frequently treated with 5α‐reductase inhibitors. Recent studies suggest that these may reduce the progression of benign prostatic hyperplasia as well as PCa, although high‐grade cancer remains a concern [40-42]. Other studies indicate that circulating DHT levels and treatment with DHT do not affect the level of this hormone within the prostate [43].
Dutasteride monotherapy in men with serologic relapse following radical therapy for adenocarcinoma of the prostate: A pilot study
2012, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :These studies show dutasteride to induce phenotypic alterations in neoplastic prostate tissue supporting a chemoactive role (increased percentage of atrophic epithelium and a doubling of the stroma/gland ratio), and lower tumor volume in patients receiving dutasteride compared to control [16,31]. Further supporting a prostate cancer chemopreventive or chemoactive role for dutasteride is an analysis of the pooled data from 3 phase III clinical trials of dutasteride as BPH treatment [32]. These investigations revealed that dutasteride significantly lowered the cumulative incidence of prostate cancer compared with placebo at 24 months (1.1% vs. 1.9%) and 27 months (1.2% vs. 2.5%).
Alcohol consumption and prostate cancer incidence and progression: A Mendelian randomisation study
2017, International Journal of Cancer
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.