Can Prostate Cancer Be Prevented?

Eric A. Klein

Disclosures

Nat Clin Pract Urol. 2005;2(1):24-31. 

In This Article

Summary and Introduction

Summary

The goal of primary chemoprevention is to decrease the incidence of a given cancer, simultaneously reducing both treatment-related adverse events and mortality. Prostate cancer is an attractive and appropriate target for primary prevention because of its incidence, prevalence, and disease-related mortality; its long latency and molecular pathogenesis; and epidemiologic data indicating that modifiable environmental factors may decrease risk. The Prostate Cancer Prevention Trial (PCPT) demonstrated that finasteride can prevent prostate cancer, albeit with an apparently increased risk of high-grade disease. A substantial amount of epidemiologic, molecular, and clinical evidence suggests that both selenium and vitamin E might also prevent prostate cancer, and this combination is being tested in the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Ultimately, the adoption of a preventive strategy hinges on its potential benefits weighed against the potential risks of the specific agents used.

Introduction

Carcinogenesis is a multistep molecular process induced by genetic and epigenetic changes that disrupt the balance between cell proliferation, apoptosis, differentiation, senescence, and the pathways controlling these cellular processes. Precursor lesions that represent intermediate stages between normal and malignant cells can arise as long as 20 years before the appearance of cancer. This, coupled with the age-dependent incidence of most cancers, suggests that the carcinogenic process occurs slowly and during a protracted interval. In theory this provides the opportunity to intervene before a malignancy is established, using either lifestyle changes such as dietary alterations, smoking cessation, exercise, or chemoprevention, defined as the use of natural or synthetic agents that reverse, inhibit, or prevent the development of cancer.[1] The goal of primary chemoprevention is to decrease the incidence of a given cancer, simultaneously reducing both treatment-related adverse events and mortality. Effective chemoprevention requires the use of nontoxic agents, usually administered orally, that inhibit specific molecular steps in the carcinogenic pathway.

Prostate cancer is an attractive and appropriate target for primary prevention because of its incidence, prevalence, and disease-related mortality. The molecular pathogenesis of prostate cancer also lends itself to a primary prevention strategy. Several histologic lesions, such as atypical small acinar proliferation , proliferative inflammatory atrophy , and prostatic intraepithelial neoplasia (PIN) , that contain both genetic and epigenetic changes intermediate between normal prostatic epithelium and prostate cancer have been described. Clinically evident prostate cancer is rare in men under 50 years of age, while PIN is apparent at autopsy in men younger than 30 years. Furthermore, the prevalence of PIN is similar across different populations, even those that have different levels of risk associated with developing clinically evident prostate cancer, suggesting that external environmental influences are important and potentially modifiable. There are numerous observations in the epidemiologic literature suggesting associations between various dietary, lifestyle, and genetic factors and the risk of developing prostate cancer.[2] The Prostate Cancer Prevention Trial (PCPT) and the Selenium and Vitamin E Cancer Prevention Trial (SELECT), two large-scale, population-based trials with the goal of preventing prostate cancer, have been launched by the National Cancer Institute and are two of the trials discussed in this review.

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