Clinical Geriatrics

American Urological Association Annual Meeting
San Francisco, CA; May 29-June 3, 2010

Effect of Dutasteride on the Detection of Prostate Cancer in Men with BPH in the CombAT Study

San Francisco, CA—The REduction by DUtasteride in prostate Cancer Events (REDUCE) study showed that dutasteride treatment resulted in 23% relative risk reduction (RRR) in biopsydetectable prostate cancer (PCa) vs. placebo in men with elevated prostate-specific antigen (PSA) and a negative baseline biopsy, who underwent scheduled biopsies at 2 and 4 years. The CombAT benign prostatic hyperplasia (BPH) study provides an opportunity to evaluate the rates of PCa in men treated with dutasteride in a typical clinical setting, with annual PSA and digital rectal examination (DRE) screening and prostate biopsies undertaken only for-cause.

CombAT was a double-blind, parallel-group study in men with moderate-to-severe BPH, age ≥ 50, International Prostate Symptom Score (IPSS) ≥ 12, prostate volume ≥ 30 cc, and serum PSA 1.5-10 ng/mL, who were randomized to receive dutasteride 0.5 mg/day (n = 1623), tamsulosin 0.4 mg/day (n = 1611), or the combination (n = 1610) for 4 years. PSA and DRE were assessed annually, with corrected (doubled) PSA values reported for men who received dutasteride, and prostate biopsies were performed on a for-cause basis, based on the investigator’s clinical judgment.

At 4 years, the cumulative PCa incidence was lower in the dutasteride and tamsulosin combination group (2.3%) than in the tamsulosin group (3.9%) and was similar to that in the dutasteride group (2.6%), with a RRR in PCa for dutasteride and tamsulosin combination vs. tamsulosin of 43% (95% CI, 15-62). The PCa RRR for combination vs. dutasteride was not significant. Men who were diagnosed with PCa had a mean PSA of 1-2 ng/mL higher at baseline than men who were not diagnosed with PCa.

PCa and biopsy rates were lower in men receiving dutasteride alone or in combination with tamsulosin vs. tamsulosin alone. There was no imbalance across treatment groups in the incidence of Gleason score 8-10 cancers. In this population of men with BPH, followed with routine PSA and DRE screening, men treated with dutasteride or the combination had fewer biopsies, and the diagnostic yield of the biopsies was slightly higher than in those treated with tamsulosin alone.

Funded by GlaxoSmithKline.

Combination Therapy with Dutasteride and Tamsulosin vs. Either Monotherapy Regardless of Prior BPH or LUT Treatment Status

San Francisco, CA—The goal of this study was to assess the efficacy and safety of dutasteride/tamsulosin combination vs. each monotherapy for improving symptoms and clinical outcomes in men with or without previous treatment (α-blockers and/or 5α-reductase inhibitors) for benign prostatic hyperplasia (BPH) or lower urinary tract (LUT) symptoms from the Combination of Avodart and Tamsulosin (CombAT) BPH study.

In this 4-year, double-blind study, 4844 men age ≥ 50 years with BPH (International Prostate Symptom Score [IPSS] ≥ 12, prostate volume [PV] ≥ 30 cc, serum PSA 1.5-10 ng/mL, Q_max 5-15 mL/s) were randomized to receive dutasteride 0.5 mg/day, tamsulosin 0.4 mg/day, or the combination. Results were reported for acute urinary retention (AUR) or BPH-related surgery, BPH clinical progression, IPSS, Q_max, and PV by treatment group in previously treated and untreated men. At baseline, 2511 men had received previous treatment with α-blockers (2444/2511; 97%) and/or 5α-reductase inhibitors (531/2511; 21%), and 2250 had not. Time to first AUR or BPH-related surgery was significantly lower for combination vs. tamsulosin in both previously treated and untreated subgroups (P < 0.001 for both), but not significant for combination vs. dutasteride in either subgroup (P = 0.23 previously treated, P = 0.43 untreated).