Efficacy and Safety of a 5-Alpha Reductase Inhibitor, Dutasteride, Added to Bacillus Calmette-Guérin Immunotherapy for Prevention of Recurrence and Progression of Intermediate- and High-Risk Non- Muscle Invasive Bladder Cancer: A Single-Arm, Phase 2 Clinical Trial

Abstract

Objective:To assess the efficacy and safety of 5α-R inhibitor dutasteride added to standard Bacillus Calmette-Guérin (BCG) immunotherapy for preventing recurrence and progression in intermediate- and high-risk non-muscle invasive bladder cancer (NMIBC).Materials and Methods:Patients received BCG immunotherapy in accordance with the European Association of Urology guidelines and dutasteride (0.5 mg) tablet were orally administered once a day. The participants were monitored for recurrence or progression for 24 months. Androgen receptor expression assay was performed on cystoscopic biopsy materials. According to the data from retrospective studies of patients with bladder cancer, the recurrence rate was 50% in patients with BCG immunotherapy without dutasteride, and 25% in those given dutasteride, with 23 patients included in the study.Results:A total of 14 (60.9%) patients could finish the follow-up. Ten patients completed the 24 months follow-up without recurrence and 4 patients had recurrence. Nine (39.1%) patients failed to complete the follow-up. Of these patients, 28.5% had recurrence. No patient progressed to MIBC and no low-grade tumor progressed to high grade. There was no statistical significance between recurrence and non-recurrence groups for AR mRNA, ARV7 mRNA, AR protein and ARV7 protein expression. But all expressions were higher in the non-recurrence group.Conclusion:Dutasteride failed to show predicted efficacy in recurrence in this prospective study, most likely due to the limited number of patients, however the decrease in recurrences after the 6th month of dutasteride treatment and the fact that the lack of progression during the treatment is promising for future studies.

Keywords

• bladder cancer
• dutasteride
• recurrence