Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial

JAMA. 2008 Jan 23;299(3):289-95. doi: 10.1001/jama.299.3.289.

Abstract

Context: Comorbidities may increase the negative effects of specific anticancer treatments such as androgen suppression therapy (AST).

Objectives: To compare 6 months of AST and radiation therapy (RT) to RT alone and to assess the interaction between level of comorbidity and all-cause mortality.

Design, setting, and patients: At academic and community-based medical centers in Massachusetts, between December 1, 1995, and April 15, 2001, 206 men with localized but unfavorable-risk prostate cancer were randomized to receive RT alone or RT and AST combined. All-cause mortality estimates stratified by randomized treatment group and further stratified in a postrandomization analysis by the Adult Comorbidity Evaluation 27 comorbidity score were compared using a log-rank test.

Main outcome measure: Time to all-cause mortality.

Results: As of January 15, 2007, with a median follow-up of 7.6 (range, 0.5-11.0) years, 74 deaths have occurred. A significant increase in the risk of all-cause mortality (44 vs 30 deaths; hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.1-2.9; P = .01) was observed in men randomized to RT compared with RT and AST. However, the increased risk in all-cause mortality appeared to apply only to men randomized to RT with no or minimal comorbidity (31 vs 11 deaths; HR, 4.2; 95% CI, 2.1-8.5; P < .001). Among men with moderate or severe comorbidity, those randomized to RT alone vs RT and AST did not have an increased risk of all-cause mortality (13 vs 19 deaths; HR, 0.54; 95% CI, 0.27-1.10; P = .08).

Conclusions: The addition of 6 months of AST to RT resulted in increased overall survival in men with localized but unfavorable-risk prostate cancer. This result may pertain only to men without moderate or severe comorbidity, but this requires further assessment in a clinical trial specifically designed to assess this interaction.

Trial registration: clinicaltrials.gov Identifier: NCT00116220.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / radiotherapy
  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / therapeutic use*
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Cause of Death
  • Chemotherapy, Adjuvant
  • Comorbidity
  • Flutamide / therapeutic use*
  • Follow-Up Studies
  • Gonadotropin-Releasing Hormone / agonists*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / radiotherapy*
  • Radiotherapy, Conformal

Substances

  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal
  • Gonadotropin-Releasing Hormone
  • Flutamide

Associated data

  • ClinicalTrials.gov/NCT00116220