title: Survival benefit of early androgen receptor inhibitor therapy in locally advanced prostate cancer: long-term follow-up of the SPCG-6 study.
abstract: 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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Denmark. Electronic address: thomsen.frederik@gmail.com.
authors.forename: Frederik B
authors.initials: FB
authors.lastname: Thomsen
authors.affiliation: Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Brasso
authors.affiliation: The Finsen Laboratory, Copenhagen Biocenter and Biotech Research and Innovation Centre, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Ib J
authors.initials: IJ
authors.lastname: Christensen
authors.affiliation: Department of Urology, School of Health and Medical Sciences, Örebro University and Depaertment, Örebro, Sweden.
authors.forename: Jan-Erik
authors.initials: JE
authors.lastname: Johansson
authors.affiliation: Faculty of Medicine, Norwegian University of Technology and Science, Trondheim, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Angelsen
authors.affiliation: Department of Surgery, Tampere University Hospital and School of Medicine, University of Tampere, Tampere, Finland.
authors.forename: Teuvo L J
authors.initials: TL
authors.lastname: Tammela
authors.affiliation: Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Iversen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D059002:Androgen Receptor Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use; D018450:Disease Progression; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D015996:Survival Rate; D014105:Tosyl Compounds / Q000627:therapeutic use
chemical_list: D059002:Androgen Receptor Antagonists; D000813:Anilides; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide
keywords: Antiandrogen; Bicalutamide; Localised; Locally advanced; Prostate cancer; Survival