2136 EFFICACY OF DUTASTERIDE IN MEN WITH LOW PROSTATE VOLUME IN THE REDUCTION BY DUTASTERIDE OF PROSTATE CANCER EVENTS (REDUCE) STUDY

Abstract

INTRODUCTION AND OBJECTIVES: In the REDUCE study, dutasteride (DUT) compared with placebo (PBO) reduced the risk of incident prostate cancer by 23% and improved outcomes related to benign prostatic hyperplasia (BPH) in men with increased risk of PCa. Because previous DUT studies only enrolled men with enlarged prostates, and because prostate cancer has been reported to be more prevalent in men with small prostates, we now report the effect of DUT on PCa and BPH endpoints in men with low baseline prostate volume (PV) in REDUCE. METHODS: The REDUCE study was an international, randomized, double-blind, PBO-controlled study. Men received DUT (0.5 mg daily) or PBO for 4 yrs. Eligible subjects included men 50–75 yrs, with prostate specific antigen (PSA) level 2.5–10 ng/ml and a single negative prostate biopsy (6–12 cores) within 6 months of enrollment. International Prostate Symptom Score (IPSS) and serum PSA levels were measured every 6 months. PV was measured by ultrasonography at randomization and at 2 and 4 yrs. Biopsies (10 cores) were performed at 2 and 4 yrs or when clinically indicated. Two-sided P values of 0.01 indicated statistical significance in the assessment of the superiority of DUT over PBO. In the present analysis we investigate outcomes related to PCa and BPH in the subgroup of men with a baseline PV 30 cc. RESULTS: Within the REDUCE population, 774 men from the DUT group and 807 men from the PBO group had a PV 30 cc. Baseline characteristics were similar between treatment groups (Table). 225 cases of PCa were detected in the PBO group and 165 cases in the DUT group (p 0.0035), representing an incidence of 27.9% vs. 21.3%, respectively. Fewer men in the DUT group had BPH-related surgery (p 0.0014) and acute urinary retention (AUR) (p 0.00540) than in the PBO group. IPSS scores were lower than baseline at Month 48 in the DUT group, but higher than baseline in the PBO group (p 0.0001). The change in PV from baseline to Month 48 was significantly different between treatment groups (p 0.0001), however, the minimal decrease in the DUT group and large increase in the PBO group may imply a regression of the mean from baseline to follow-up PV measurements. CONCLUSIONS: In men with low PV, DUT lowered the overall incidence of PCa, led to greater improvements in IPSS scores and improved BPH-related outcomes over the 4-yr study period. Table. Baseline characteristics and PCa and BPH results in men with low prostate volume Dutasteride (n 774) Placebo (n 807) BASELINE CHARACTERISTICS Mean age (yr) 61.5 61.6 Mean total PSA (ng/ml) 5.45 5.60 Mean IPSS 7.6 7.6 Mean PV (cc) 23.6 23.5 — — — PROSTATE CANCER RESULTS Incidence (%) 165 (21.3) 225 (27.9) Relative risk reduction (95% CI) 24.1 (8.6, 36.9) — — — — BENIGN PROSTATIC HYPERPLASIA RESULTS BPH-related surgery: incidence (%) 5 (0.6) 22 (2.7) BPH-related surgery: relative risk reduction (95% CI) 76.6 (38.3, 91.2) — AUR: Incidence (%) 9 (1.2) 26 (3.2) AUR: relative risk reduction (95% CI) 64.3 (23.8, 83.3) — Change in IPSS at Month 48: adjusted mean (SE) 0.36 (0.186) 1.21 (0.181) % change in PV at Month 48: adjusted mean (SE) 0.7 (1.88) 41.4 (2.60) Use of alpha blocker (%) 74/774 (9.6) 115/807 (14.3) *Percentages based on biopsied population (placebo n 620; dutasteride n 671). CI confidence interval; SE standard error.