Duration of androgen suppression before radiotherapy for localized prostate cancer: radiation therapy oncology group randomized clinical trial 9910

J Clin Oncol. 2015 Feb 1;33(4):332-9. doi: 10.1200/JCO.2014.58.0662. Epub 2014 Dec 22.

Abstract

Purpose: To determine whether prolonged androgen suppression (AS) duration before radiotherapy improves survival and disease control in prostate cancer.

Patients and methods: One thousand five hundred seventy-nine men with intermediate-risk prostate cancer were randomly assigned to 8 weeks of AS followed by radiotherapy with an additional 8 weeks of concurrent AS (16 weeks total) or to 28 weeks of AS followed by radiotherapy with an additional 8 weeks of AS (36 weeks total). The trial sought primarily to detect a 33% reduction in the hazard of prostate cancer death in the 28-week assignment. Time-to-event end points are reported for up to 10 years of follow-up.

Results: There were no between-group differences in baseline characteristics of 1,489 eligible patients with follow-up. For the 8- and 28-week assignments, 10-year disease-specific survival rates were 95% (95% CI, 93.3% to 97.0%) and 96% (95% CI, 94.6% to 98.0%; hazard ratio [HR], 0.81; P = .45), respectively, and 10-year overall survival rates were 66% (95% CI, 62.0% to 69.9%) and 67% (95% CI, 63.0% to 70.8%; HR, 0.95; P = .62), respectively. For the 8- and 28-week assignments, 10-year cumulative incidences of locoregional progression were 6% (95% CI, 4.3% to 8.0%) and 4% (95% CI, 2.5% to 5.7%; HR, 0.65; P = .07), respectively; 10-year distant metastasis cumulative incidences were 6% (95% CI, 4.0% to 7.7%) and 6% (95% CI, 4.0% to 7.6%; HR, 1.07; P = .80), respectively; and 10-year prostate-specific antigen-based recurrence cumulative incidences were 27% (95% CI, 23.1% to 29.8%) and 27% (95% CI, 23.4% to 30.3%; HR, 0.97; P = .77), respectively.

Conclusion: Extending AS duration from 8 weeks to 28 weeks before radiotherapy did not improve outcomes. A lower than expected prostate cancer death rate reduced ability to detect a between-group difference in disease-specific survival. The schedule of 8 weeks of AS before radiotherapy plus 8 weeks of AS during radiotherapy remains a standard of care in intermediate-risk prostate cancer.

Trial registration: ClinicalTrials.gov NCT00005044.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / administration & dosage
  • Androgen Antagonists / adverse effects
  • Anilides / administration & dosage
  • Anilides / adverse effects
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemoradiotherapy
  • Disease-Free Survival
  • Flutamide / administration & dosage
  • Flutamide / adverse effects
  • Follow-Up Studies
  • Goserelin / administration & dosage
  • Goserelin / adverse effects
  • Humans
  • Leuprolide / administration & dosage
  • Leuprolide / adverse effects
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Nitriles / administration & dosage
  • Nitriles / adverse effects
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • Radiotherapy / adverse effects
  • Radiotherapy / methods*
  • Time Factors
  • Tosyl Compounds / administration & dosage
  • Tosyl Compounds / adverse effects
  • Treatment Outcome

Substances

  • Androgen Antagonists
  • Anilides
  • Antineoplastic Agents, Hormonal
  • Nitriles
  • Tosyl Compounds
  • Goserelin
  • Flutamide
  • bicalutamide
  • Prostate-Specific Antigen
  • Leuprolide

Associated data

  • ClinicalTrials.gov/NCT00005044