Update on Prostate Cancer Chemoprevention

Jennifer Fisher Lowe, PharmD; Lawrence A. Frazee, PharmD

Disclosures

Pharmacotherapy. 2006;26(3):353-359. 

In This Article

Abstract and Introduction

Abstract

Background: Prostate cancer is the most common type of cancer and the second leading cause of cancer-related deaths in American men. Its high rate of occurrence and long lead time to clinically significant disease make prostate cancer an ideal disease for pharmacologic or nutritional chemoprevention.
Methods: To identify the various chemoprevention strategies for prostate cancer, a MEDLINE search (from 1967–2005) and bibliographic search of the English-language literature were conducted.
Results: Epidemiologic and retrospective studies have assessed the effect of carotenoids (e.g., lycopene), vitamins, selenium, and nonsteroidal antiinflammatory drugs (NSAIDs) on the rate of occurrence of prostate cancer. The few published prospective trials evaluated prostate cancer as a secondary end point. Lycopene (as β-carotene) and selenium supplementation have been associated with a reduced risk of prostate cancer in nested case-control studies, but only in subgroups of men with low baseline plasma lycopene (or β-carotene) and selenium levels respectively. The Prostate Cancer Prevention Trial prospectively evaluated finasteride, a 5-α-reductase inhibitor, as chemoprevention. The results showed a 25% relative risk reduction in prostate cancer, albeit at an increased risk of invasive tumors.
Conclusion: Data regarding lycopene, vitamin E, and selenium as chemo-prevention for prostate cancer appear promising. Prospective trials such as the Selenium and Vitamin E Cancer Prevention Trial (SELECT) will clarify the role of these agents in prostate cancer prevention. The role of NSAIDs is unclear, and the long-term toxicity associated with NSAIDs may limit their usefulness. Although finasteride has decreased overall prostate cancer occurrence, the risk of invasive tumors may outweigh the benefit of this agent. The continuing Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial may help define a role for the 5-α-reductase inhibitors in cancer chemoprevention. At this time, nothing has been proven effective as chemoprevention against clinically significant prostate cancer.

Introduction

Prostate cancer is the most common type of cancer and the second leading cause of cancer-related deaths in American men. From the late 1980s to the early 1990s, greater attention was given to screening asymptomatic men by measuring concentrations of prostate-specific antigen (PSA), a protein produced by prostate tissue.[1] This led to a significant increase in detection of clinically insignificant tumors. Detection rates began to decline in the 1990s until 1996, when they started to rise again. Despite this increase, mortality due to prostate cancer has decreased every year since 1992.[2] The American Cancer Society estimated that 232,090 new cases of prostate cancer would be diagnosed and that 30,350 patients would die from the disease in 2005.[1]

Prostate cancer is a slow-growing tumor in older men; median age at diagnosis is 72 years.[3] Although its precise pathogenesis is not clear, epidemiologic evidence supports a relationship between prostate cancer and serum levels of testosterone.[4] Other risk factors include advanced age, family history, African-American ethnicity, poor diet, and cadmium exposure.[5] The frequency of prostate cancer increases exponentially with advancing age, and the natural progression to prostate cancer tends to be more aggressive in younger men and those with a family history of the disease.

On diagnosis, prostate cancer is graded based on the degree of differentiation of the primary and secondary tumors using the Gleason grading system.[3] In this 5-grade system, 1 indicates a well-differentiated, slow-growing tumor, and 5 a poorly differentiated and rapidly growing tumor. The scores for the primary and secondary tumors are added, yielding a Gleason score of 2–10; a score of 7 or greater is considered high grade.

Although controversial, strategies for decreasing prostate cancer mortality have focused on early detection. The most important tumor marker for detection and posttreatment monitoring of prostate cancer is PSA level. The presence of prostate cancer, benign prostatic hyperplasia, or prostatitis can result in increased serum PSA levels.[6] Furthermore, treatment with drugs such as 5-α-reductase inhibitors (finasteride or dutasteride) lowers the PSA level by approximately 50%.[7]

To reduce the number of unnecessary biopsies resulting from elevated levels of PSA, the sensitivity and specificity of the PSA screening tool must be increased. Proposed methods to increase sensitivity and specificity include reinterpretation of PSA levels as they change over time (PSA velocity)[8] and use of more specific markers, such as PSA level divided by prostate volume (PSA density),[9] free PSA levels,[10] and age-specific PSA ranges.[11] Current screening recommendations for asymptomatic men include serum PSA level assessment and digital rectal examination. A summary of prostate cancer detection guidelines from the American Urological Association[6] and the American Cancer Society[12] are provided in Table 1 .

The American Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial[13] and the European Randomized Study of Screening for Prostate Cancer[14] are assessing the effect of cancer screening on morbidity and mortality. The findings from these two randomized studies will yield useful information about screening recommendations, but final results are not expected for several years.

To identify the various chemoprevention strategies for prostate cancer, we conducted a MEDLINE search (from 1967–2005) and bibliographic search of the English-language literature. Search terms were prostate cancer, chemoprevention, PCPT, REDUCE, 5-α-reductase inhibitors, finasteride, dutasteride, SELECT, lycopene, nonsteroidal antiinflammatory drugs, α-tocopherol, β-carotene, and selenium.

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