Background: Bicalutamide blocks androgen action and is frequently used in men with non-metastatic, castration-resistant prostate cancer (CRPC). By reducing intracellular dihydrotestosterone, dutasteride (dual 5-alpha reductase inhibitor) could increase the effectiveness of bicalutamide in this setting. The objective of the study is therefore to prospectively evaluate dutasteride plus bicalutamide in men with asymptomatic, non-metastatic CRPC with rising prostate-specific antigen (PSA).

Methods: Prostate cancer patients with rising PSA whilst on first-line androgen deprivation therapy (ADT) were randomised (1:1) in a double-blind trial to receive bicalutamide 50mg plus placebo or bicalutamide 50mg plus dutasteride 3.5mg once daily for 18 months. Randomisation was stratified by centre; treatment assignments were generated using GlaxoSmithKline's RandAll System. Subjects who completed 18 months could participate in the 2-year extension. Central laboratory and study sites/monitors remained treatment-blinded. Primary end-point was time to disease progression (TDP) up to 42 months (defined as PSA progression from baseline or nadir, radiographic disease progression, death from prostate cancer or receipt of rescue medication).

Findings: There was no statistically significant difference in TDP in 127 men treated with bicalutamide/dutasteride (n=62) compared with bicalutamide/placebo (n=65) (hazard ratio (HR)=0.94 [95% confidence interval (CI) 0.61, 1.46]; p=0.79). The estimated median TDP was 425 days (95% CI 302, 858) in the bicalutamide/placebo group and 623 days (95% CI 369, 730) in the bicalutamide/dutasteride group. There was no statistically significant difference between the treatment groups for any secondary efficacy end-points, including time to treatment failure or PSA response. In the multivariate analysis, age, non-White race, higher baseline testosterone and lower baseline PSA were associated with longer TDP. Adverse events were comparable between treatment groups.

Interpretation: In men with non-metastatic CRPC, adding dutasteride to bicalutamide did not significantly prolong TDP. Prospective data are provided concerning the common practice of using bicalutamide in this setting.