Alcohol Intake Increases High-grade Prostate Cancer Risk Among Men Taking Dutasteride in the REDUCE Trial

Abstract

Background Although most studies found no association between alcohol intake and prostate cancer (PCa) risk, an analysis of the Prostate Cancer Prevention Trial found that high alcohol intake significantly increased PCa risk among men randomized to the 5a-reductase inhibitor (5-ARI) finasteride. Objective Determine whether alcohol affects PCa risk among men taking the 5-ARI dutasteride. Design, settings, and participants Reduction by Dutasteride of Prostate Cancer Events was a 4-yr, multicenter, randomized, double-blind, placebo-controlled trial to compare PCa after dutasteride administration (0.5 mg/d) with placebo. Participants had a baseline prostate-specific antigen between 2.5 and 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 PCa status at 2 yr and 4 yr of follow-up. Outcome measurements and statistical analysis Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between alcohol intake and low-grade (Gleason <7) and high-grade (Gleason >7) PCa. Results and limitations Of 6374 participants in our analysis, approximately 25% reported no alcohol consumption, 49% were moderate drinkers (one to seven drinks per week), and 26% were heavy drinkers (more than seven drinks per week). Alcohol intake was not associated with low- or high-grade PCa in the placebo arm and was not associated with low-grade PCa among men taking dutasteride. In contrast, men randomized to dutasteride and reporting more than seven drinks per week were 86% more likely to be diagnosed with high-grade PCa (p= 0.01). Among alcohol abstainers, dutasteride was associated with significantly reduced risk of high-grade PCa (OR: 0.59; 95% CI, 0.38–0.90), but dutasteride was no longer associated with reduced high-grade PCa among men reporting high alcohol intake (OR: 0.99; 95% CI, 0.67–1.45). Conclusions Alcohol consumption negated a protective association between dutaste-ride and high-grade PCa. Patient summary We confirmed a prior study that alcohol affects PCa prevention in patients taking 5-ARIs. Patients taking 5-ARIs may wish to eliminate alcohol intake if they are concerned about PCa.

Adverse effects of 5α-reductase inhibitors: What do we know, don’t know, and need to know?

“…For example, recently, it was reported that alcohol appears to increase the risk of high grade tumors in men treated with dutasteride. The exact mechanism for why alcohol may increase the risk in unknown [200].…”

Physical activity, alcohol consumption, BMI and smoking status before and after prostate cancer diagnosis in the ProtecT trial: Opportunities for lifestyle modification

“…Despite inconclusive evidence linking the development of prostate cancer to modifiable behaviours, associations with diet and lifestyle have been reported . Furthermore, sedentary behaviour, a high alcohol intake, obesity and continuing to smoke, following cancer diagnosis are associated with a worsening of prognosis. Nevertheless, there is little consistent evidence that a cancer diagnosis is associated with sustained healthy lifestyle changes .…”

Current drug therapy of patients with BPH-LUTS with the special emphasis on PDE5 inhibitors

“…The Prostate Cancer Prevention Trial study pointed out the increase in the prostate cancer incidence in men consuming a significant volume of alcohol in the group of therapy with 5-alpha reductase inhibitors [29]. Fowke et al [30] investigated the aforementioned hypothesis using the REDUCE study data. The study enrolled 6374 patients; 25% were not consuming alcohol, 49% were consuming 1 to 7 glasses per week and 26% had severe alcohol dependence (>7 glasses per week).…”

“…A similar tendency was not reported in the group of patients with severe alcohol dependence. Alcohol consumption had negative effect on the relationship between dutasteride administration and high-risk prostate cancer development [30]. Dutasteride’s effect on nocturia was investigated in several 24-month, phase III studies involving 4321 patients.…”