Differences in time to disease progression do not predict for cancer-specific survival in patients receiving immediate or deferred androgen-deprivation therapy for prostate cancer: final results of EORTC randomized trial 30891 with 12 years of follow-up

Eur Urol. 2014 Nov;66(5):829-38. doi: 10.1016/j.eururo.2013.07.024. Epub 2013 Jul 24.


Background: Trials assessing the benefit of immediate androgen-deprivation therapy (ADT) for treating prostate cancer (PCa) have often done so based on differences in detectable prostate-specific antigen (PSA) relapse or metastatic disease rates at a specific time after randomization.

Objective: Based on the long-term results of European Organization for Research and Treatment of Cancer (EORTC) trial 30891, we questioned if differences in time to progression predict for survival differences.

Design, setting, and participants: EORTC trial 30891 compared immediate ADT (n=492) with orchiectomy or luteinizing hormone-releasing hormone analog with deferred ADT (n=493) initiated upon symptomatic disease progression or life-threatening complications in randomly assigned T0-4 N0-2 M0 PCa patients.

Outcome measurements and statistical analysis: Time to first objective progression (documented metastases, ureteric obstruction, not PSA rise) and time to objective castration-resistant progressive disease were compared as well as PCa mortality and overall survival.

Results and limitations: After a median of 12.8 yr, 769 of the 985 patients had died (78%), 269 of PCa (27%). For patients receiving deferred ADT, the overall treatment time was 31% of that for patients on immediate ADT. Deferred ADT was significantly worse than immediate ADT for time to first objective disease progression (p<0.0001; 10-yr progression rates 42% vs 30%). However, time to objective castration-resistant disease after deferred ADT did not differ significantly (p=0.42) from that after immediate ADT. In addition, PCa mortality did not differ significantly, except in patients with aggressive PCa resulting in death within 3-5 yr after diagnosis. Deferred ADT was inferior to immediate ADT in terms of overall survival (hazard ratio: 1.21; 95% confidence interval, 1.05-1.39; p [noninferiority]=0.72, p [difference] = 0.0085).

Conclusions: This study shows that if hormonal manipulation is used at different times during the disease course, differences in time to first disease progression cannot predict differences in disease-specific survival. A deferred ADT policy may substantially reduce the time on treatment, but it is not suitable for patients with rapidly progressing disease.

Trial registration: ClinicalTrials.gov NCT01819285.

Keywords: Androgen deprivation; Deferred treatment; Prostate cancer; Surrogate; Survival.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / administration & dosage*
  • Androgen Antagonists / adverse effects
  • Chemotherapy, Adjuvant
  • Disease Progression
  • Drug Administration Schedule
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neoplasms, Hormone-Dependent / drug therapy*
  • Neoplasms, Hormone-Dependent / mortality
  • Neoplasms, Hormone-Dependent / pathology
  • Orchiectomy* / adverse effects
  • Orchiectomy* / mortality
  • Proportional Hazards Models
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / mortality
  • Prostatic Neoplasms, Castration-Resistant / pathology
  • Risk Factors
  • Time Factors
  • Treatment Outcome


  • Androgen Antagonists

Associated data

  • ClinicalTrials.gov/NCT01819285