ALCOHOL INTAKE INCREASES HIGH-GRADE PROSTATE CANCER RISK AMONG MEN TAKING DUTASTERIDE IN THE REDUCE TRIAL

INTRODUCTION AND OBJECTIVES: Although most studies found no association between alcohol intake and prostate cancer (PC) risk, an analysis of the Prostate Cancer Prevention Trial (PCPT) found high alcohol intake significantly increased PC risk, but only among men randomized to the 5a-reductase inhibitor (5-ARI) finasteride study arm. Thus, we sought to confirm the PCPT analysis to determine if alcohol use affects PC risk among men taking the 5-ARI dutasteride. METHODS: REDUCE was a randomized trial to compare PC risk after administration of dutasteride (0.5 mg/day) vs. placebo. Participants had a baseline PSA between 2.5-10.0 ng/ml and a recent negative prostate biopsy. Alcohol intake was determined by baseline questionnaire, and participants underwent a prostate biopsy to determine PC status at 2 and 4 years, regardless of PSA levels. Logistic regression was used to examine the association between alcohol intake and PC risk vs. no PC. Multinomial logistic regression was used examine the associations between alcohol intake and low-grade (Gleason <7) vs. no PC or high-grade (Gleason >7) PC vs. no PC. Results were adjusted for age, race, BMI, geographic region, family history of PC, diabetes, smoking status, PSA, TRUS prostate volume, and stratified by treatment arm. RESULTS: Of 6,374 men in the analysis, 998 (16%) low-grade and 435 (7%) high-grade PC cases were detected. Approximately 25% of participants reported no alcohol consumption, 49% were moderate drinkers (1-6 drinks/week) and 26% heavy drinkers (>7 drinks/week). Heavy drinkers were younger, more likely to be white, smokers, European, had lower BMI, and were less likely to be diabetic (all p<0.01). On multivariable analysis, alcohol intake was not associated with lowgrade, high-grade, or overall PC risk in the placebo arm, and was not associated with low-grade PC among men taking dutasteride. In contrast, heavy drinkers in the dutasteride arm were 30% more likely to be diagnosed with PC (p=0.047), and 86% more likely to be diagnosed with high-grade PC (p=0.01). Among alcohol abstainers, dutasteride was significantly associated with reduced risk of high-grade PC (OR=0.59, p=0.02). However, dutasteride was not associated with reduced high-grade PC risk among heavy drinkers (OR=0.99, p=0.95). CONCLUSIONS: Alcohol consumption negated the overall protective association between dutasteride and high-grade prostate cancer. Physicians may wish to advise patients to eliminate alcohol when taking 5ARIs if they are concerned about prostate cancer.