BACKGROUND: The optimal timing of endocrine therapy in non-metastatic prostate cancer (PCa) is still an issue of debate.
METHODS: A randomised, double-blind, parallel-group trial comparing bicalutamide 150mg once daily with placebo in addition to standard care in patients with hormone-naïve, non-metastatic PCa. Kaplan-Meier analysis was used to estimate overall survival (OS) and multivariate Cox proportional hazard model was performed to analyse time-to-event (death).
FINDINGS: A total of 1218 patients were included into the Scandinavian Prostate Cancer Group (SPCG)-6 study of which 607 were randomised to receive bicalutamide in addition to their standard care and 611 to receive placebo. Median follow-up was 14.6years. Overall, 866 (71.1%) patients died, 428 (70.5%) in the bicalutamide arm and 438 (71.7%) in the placebo arm, p=0.87. Bicalutamide significantly improved OS in patient with locally advanced disease (hazard ratios (HR)=0.77 (95% confidence interval (CI): 0.63-0.94, p=0.01), regardless of baseline prostate-specific antigen (PSA), with a survival benefit which was apparent throughout the study period. In contrast, survival favoured randomisation to the placebo arm in patients with localised disease (HR=1.19 (95% CI: 1.00-1.43), p=0.056). However, a survival gain from bicalutamide therapy was present in patients with localised disease and a baseline PSA greater than 28ng/mL at randomisation. In multivariate Cox proportional hazard model, only including patients managed on watchful waiting as their standard of care (n=991) OS depended on age, World Health Organisation (WHO) grade, baseline PSA, clinical stage and randomised treatment.
INTERPRETATION: Throughout the 14.6year follow-up period the addition of early bicalutamide to standard of care resulted in a significant OS benefit in patients with locally advanced PCa. In contrast, patients with localised PCa and low PSA derived no survival benefit from early bicalutamide. The optimal timing for initiating bicalutamide in non-metastatic PCa patients is dependent on disease stage and baseline PSA.
Written by:
Thomsen FB, Brasso K, Christensen IJ, Johansson JE, Angelsen A, Tammela TL, Iversen P. Are you the author?
Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Denmark; The Finsen Laboratory, Copenhagen Biocenter and Biotech Research and Innovation Centre, Rigshospitalet, University of Copenhagen, Denmark; Department of Urology, School of Health and Medical Sciences, Örebro University and Depaertment, Örebro, Sweden; Faculty of Medicine, Norwegian University of Technology and Science, Trondheim, Norway; Department of Surgery, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland.
Reference: Eur J Cancer. 2015 Jul;51(10):1283-92.
doi: 10.1016/j.ejca.2015.03.021
PubMed Abstract
PMID: 25892647