Randomized non-inferiority trial of Bicalutamide and Dutasteride versus LHRH agonists for prostate volume reduction prior to I-125 permanent implant brachytherapy for prostate cancer

Abstract Objective To determine the efficacy and toxicity of a 3-month regimen of Dutasteride and Bicalutamide compared to LHRH agonists for prostate volume (PV) reduction prior to permanent implant prostate brachytherapy (PIPB). Material and methods Patients with low-risk or low-tier intermediate risk prostate cancer eligible for PIPB with a prostate volume greater than 50 cc were randomized to either Dutasteride 0.5 mg Bicalutamide 50 mg daily and Tamoxifen 10 mg daily for 3 months (D + B group) or to a 3 month dose of an LHRH agonist and Bicalutamide daily for 1 month (LHRH group). Their PV was measured at baseline and at pre-implant. Non-inferiority analysis was completed for the relative (%) PV reduction. IPSS and EPIC questionnaires were completed at baseline, pre-implant and at 1, 3, 6, 12, 18 and 24 months post-treatment. IPSS and EPIC comparisons were based on superiority analysis Results 60 patients were randomized (31 to LHRH group and 29 to D + B group). Mean relative PV reduction (SD) was 35.5% (8.9) in the LHRH group and 31.7% (9.6) in the D + B group. The upper bound of the 95% confidence for the interval for the difference between groups favouring LHRH agonists for PV reduction was 8.6 which did not cross the 10% non-inferiority margin meaning D + B is non-inferior to LHRH agonist for PV reduction, although 5/29 (17%) of those in the D + B group required longer duration of D + B to achieve adequate volume reduction. There were no statistically significant differences in IPSS scores over the entire follow-up period. EPIC sexual summary score was significantly better in the D + B group at pre-implant, 1 month, 3 months post-implant. Conclusion Dutasteride and Bicalutamide is a regimen of non-inferior efficacy to LHRH agonist based regimens for prostate volume reduction prior to permanent implant prostate brachytherapy. D + B has less sexual toxicity compared to LHRH agonists prior to implant and for the first 6 months after implant. D + B is therefore an option to be considered for prostate volume reduction prior to PIPB.