Is There a Future for Chemoprevention of Prostate Cancer?

Abstract

The outcome of the Selenium and Vitamin E Cancer Prevention Trial (SELECT), demonstrating harm and no preventive activity of selenomethionine and α-tocopherol for prostate cancer, and the lack of approval by the US Food and Drug Administration for the use of 5α-reductase inhibitors to prevent prostate cancer have cast doubt about the future of chemoprevention of prostate cancer. This article attempts to critically assess whether the notion that chemoprevention of prostate cancer has no future is warranted. Risk of prostate cancer is modifiable and chemoprevention of prostate cancer, particularly fatal/lethal cancer, is both needed and possible. However, the approach to prostate cancer chemopreventive agent development has not followed a rational and systematic process. To make progress, the following steps are necessary: (1) identification of intermediate biomarkers predictive of fatal/lethal disease; (2) development of a rational approach to identification of candidate agents, including high-throughput screening and generation of information on mechanism and biology of candidate agents and potential molecular targets; and (3) systematic evaluation of the predictive value of preclinical models, Phase II trials, and intermediate biomarkers for the outcome of Phase III trials. New Phase III trials should be based on adequate preclinical and Phase II studies.

ProDiet: A Phase II Randomized Placebo-controlled Trial of Green Tea Catechins and Lycopene in Men at Increased Risk of Prostate Cancer

“…The mode of action of most chemoprevention agents remains largely unknown and the concept for prostate cancer has been deemed a failure following the SELECT and finasteride trials (44). However, preclinical evidence should be used to identify biologically active agents to enhance their likelihood of success in clinical trials (2,45). In one example, aspirin has recently been recommended for colorectal cancer prevention in the United States (46).…”

“…Prostate cancer is the commonest noncutaneous male malignancy worldwide with higher incidence in developed countries, in part due to screening with PSA (1). Around three quarters of men with an elevated PSA will not have cancer diagnosed immediately, so safe and effective chemoprevention would be beneficial as they are at the risk of future diagnosis (2). Randomized controlled trials (RCT) of prostate cancer prevention have included pharmaceutical and nutritional agents but with limited success.…”

Germline genetic variation in prostate susceptibility does not predict outcomes in the chemoprevention trials PCPT and SELECT

“…It is thought that the risk of prostate cancer development could be potentially modifiable by dietary and other lifestyle factors. Large epidemiological studies have shown that migrants who have moved from areas of low prostate cancer incidence such as Korea and Japan to the USA have developed prostate cancer rates similar to their native inhabitants [5,6]. Environmental factors are attributable to this change of risk and some of these could be potentially modifiable by dietary changes [6].…”

“…Large epidemiological studies have shown that migrants who have moved from areas of low prostate cancer incidence such as Korea and Japan to the USA have developed prostate cancer rates similar to their native inhabitants [5,6]. Environmental factors are attributable to this change of risk and some of these could be potentially modifiable by dietary changes [6]. There are also causal links between androgen exposure and the development of prostate cancer, which is also potentially modifiable [7].…”

Effectiveness of 5-Alpha-Reductase Inhibitors in Patients With Prostatic Intraepithelial Neoplasia of Peripheral Prostate Zone

“…Питання лікування пацієнтів, у яких виявлено ПІН є актуальною та невизначеною проблемою через відсутність досліджень, проведених з аналізом достатньої кількості спостережень для формулювання статистично обґрунтованих висновків. Запропоновані деякими авторами методи лікування хворих з ПІН (використання антиандрогенів, інгібіторів 5альфа-редуктази, препаратів селену, рослинного походження) мають значні розбіжності в оцінці власної ефективності [3,4,5,6]. Деякі дослідники вважають недоцільними терапевтичні заходи у пацієнтів з ПІН, вважаючи, що дана патологія має невелике клінічне значення та не загрожує життю пацієнта.…”