title: Duration of androgen suppression in the treatment of prostate cancer.
abstract: BACKGROUND
  The combination of radiotherapy plus long-term medical suppression of androgens (> or = 2 years) improves overall survival in patients with locally advanced prostate cancer. We compared the use of radiotherapy plus short-term androgen suppression with the use of radiotherapy plus long-term androgen suppression in the treatment of locally advanced prostate cancer.
  
  
  METHODS
  We randomly assigned patients with locally advanced prostate cancer who had received external-beam radiotherapy plus 6 months of androgen suppression to two groups, one to receive no further treatment (short-term suppression) and the other to receive 2.5 years of further treatment with a luteinizing hormone-releasing hormone agonist (long-term suppression). An outcome of noninferiority of short-term androgen suppression as compared with long-term suppression required a hazard ratio of more than 1.35 for overall survival, with a one-sided alpha level of 0.05. An interim analysis showed futility, and the results are presented with an adjusted one-sided alpha level of 0.0429.
  
  
  RESULTS
  A total of 1113 men were registered, of whom 970 were randomly assigned, 483 to short-term suppression and 487 to long-term suppression. After a median follow-up of 6.4 years, 132 patients in the short-term group and 98 in the long-term group had died; the number of deaths due to prostate cancer was 47 in the short-term group and 29 in the long-term group. The 5-year overall mortality for short-term and long-term suppression was 19.0% and 15.2%, respectively; the observed hazard ratio was 1.42 (upper 95.71% confidence limit, 1.79; P=0.65 for noninferiority). Adverse events in both groups included fatigue, diminished sexual function, and hot flushes.
  
  
  CONCLUSIONS
  The combination of radiotherapy plus 6 months of androgen suppression provides inferior survival as compared with radiotherapy plus 3 years of androgen suppression in the treatment of locally advanced prostate cancer. (ClinicalTrials.gov number, NCT00003026.)
authors.affiliation: Centre Hospitalier Régional Universitaire de Grenoble, Grenoble, France. mbolla@chu-grenoble.fr
authors.forename: Michel
authors.initials: M
authors.lastname: Bolla
authors.forename: Theodorus M
authors.initials: TM
authors.lastname: de Reijke
authors.forename: Geertjan
authors.initials: G
authors.lastname: Van Tienhoven
authors.forename: Alphonsus C M
authors.initials: AC
authors.lastname: Van den Bergh
authors.forename: Jorg
authors.initials: J
authors.lastname: Oddens
authors.forename: Philip M P
authors.initials: PM
authors.lastname: Poortmans
authors.forename: Eliahu
authors.initials: E
authors.lastname: Gez
authors.forename: Paul
authors.initials: P
authors.lastname: Kil
authors.forename: Atif
authors.initials: A
authors.lastname: Akdas
authors.forename: Guy
authors.initials: G
authors.lastname: Soete
authors.forename: Oleg
authors.initials: O
authors.lastname: Kariakine
authors.forename: Elsbietha M
authors.initials: EM
authors.lastname: van der Steen-Banasik
authors.forename: Elena
authors.initials: E
authors.lastname: Musat
authors.forename: Marianne
authors.initials: M
authors.lastname: Piérart
authors.forename: Murielle E
authors.initials: ME
authors.lastname: Mauer
authors.forename: Laurence
authors.initials: L
authors.lastname: Collette
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D000813:Anilides / Q000009:adverse effects / Q000627:therapeutic use; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005485:Flutamide / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives*; D006331:Heart Diseases / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D011788:Quality of Life; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D014105:Tosyl Compounds / Q000009:adverse effects / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D009570:Nitriles; D014105:Tosyl Compounds; D007987:Gonadotropin-Releasing Hormone; D005485:Flutamide; C053541:bicalutamide