title: Early versus delayed endocrine treatment of T2-T3 pN1-3 M0 prostate cancer without local treatment of the primary tumour: final results of European Organisation for the Research and Treatment of Cancer protocol 30846 after 13 years of follow-up (a randomised controlled trial).
abstract: BACKGROUND
  The timing of endocrine treatment (ET) for prostate cancer (PCa) remains controversial. The issue is addressed in European Organisation for the Research and Treatment of Cancer (EORTC) protocol 30846 for patients with lymph node-positive (pN1-3) cancer without local treatment of the primary tumour.
  
  
  OBJECTIVE
  To evaluate the effect of early versus delayed treatment in pN1-3 PCa.
  
  
  METHODS
  Two hundred thirty-four patients with histologically proven PCa and nodal metastases (pN1-3) were randomized to immediate versus delayed ET without treatment of the primary tumour. ET consisted of a depot luteinising hormone-releasing hormone (LHRH) agonist and 1 mo of an anti-androgen or surgical castration. The trial's main objective was to show non-inferiority of delayed ET to immediate ET by ruling out a hazard ratio (HR) of 1.50 for overall survival (OS), with 85% power at one-sided alpha=5%.
  
  
  METHODS
  All but three patients were treated as randomized. The median follow-up is 13 yr. The median protocol treatment duration was 2.7 yr in the delayed and 3.2 yr in the immediate ET groups.
  
  
  CONCLUSIONS
  Overall, 193 patients (82.5%) have died (97 on delayed ET and 96 on immediate ET), 59.4% of them as a result of PCa. The intention-to-treat analysis shows a 22% increase in the hazard of death of those randomized to delayed treatment (HR=1.22, 95% confidence interval [CI]: 0.92, 1.62). The difference is not statistically significant, but non-inferiority is also not proved. The median OS on immediate ET is 7.6 yr (95% CI, 6.3-8.3 yr) versus 6.1 yr (95% CI, 5.7-7.3 yr) in the delayed ET group. The 10-yr cumulative incidence of death resulting from PCa was 55.6% in the delayed ET group versus 52.1% with immediate ET group. Similar conclusions hold for PCa-specific survival.
  
  
  CONCLUSIONS
  After 13 years of follow-up, survival or PCa-specific survival between immediate and delayed ET appear similar, but the trial is underpowered to reach its goal of showing non-inferiority.
authors.affiliation: Department of Urology, Erasmus MC, Rotterdam, The Netherlands. m.h.vanderlinde@erasmusmc.nl
authors.forename: Fritz H
authors.initials: FH
authors.lastname: Schröder
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Kurth
authors.forename: Sophie D
authors.initials: SD
authors.lastname: Fossa
authors.forename: Wytse
authors.initials: W
authors.lastname: Hoekstra
authors.forename: Peter P
authors.initials: PP
authors.lastname: Karthaus
authors.forename: Linda
authors.initials: L
authors.lastname: De Prijck
authors.forename: Laurence
authors.initials: L
authors.lastname: Collette
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D002369:Castration; D002985:Clinical Protocols; D005500:Follow-Up Studies; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D015996:Survival Rate; D013997:Time Factors
chemical_list: D000726:Androgen Antagonists; D007987:Gonadotropin-Releasing Hormone