Survival benefit of early androgen receptor inhibitor therapy in locally advanced prostate cancer: long-term follow-up of the SPCG-6 study

Eur J Cancer. 2015 Jul;51(10):1283-92. doi: 10.1016/j.ejca.2015.03.021. Epub 2015 Apr 16.


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.

Keywords: Antiandrogen; Bicalutamide; Localised; Locally advanced; Prostate cancer; Survival.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Receptor Antagonists / therapeutic use*
  • Anilides / therapeutic use
  • Disease Progression
  • Disease-Free Survival
  • Double-Blind Method
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Nitriles / therapeutic use
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Survival Analysis
  • Survival Rate
  • Tosyl Compounds / therapeutic use


  • Androgen Receptor Antagonists
  • Anilides
  • Nitriles
  • Tosyl Compounds
  • bicalutamide