Serum androgens as prognostic biomarkers in castration-resistant prostate cancer: results from an analysis of a randomized phase III trial

J Clin Oncol. 2013 Aug 1;31(22):2791-8. doi: 10.1200/JCO.2012.45.4595. Epub 2013 Jul 1.


Purpose: In the phase III study COU-AA-301, abiraterone acetate (AA) plus prednisone (P) prolonged overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel administration. In this article, we investigate the relationship between baseline serum androgen (SA) levels and OS.

Patients and methods: COU-AA-301 is a randomized, double-blind study of AA (1,000 mg every day) plus P (5 mg by mouth twice daily; n = 797) versus P alone (n = 398). Randomization was stratified by Eastern Cooperative Oncology Group performance status (0 to 1 v 2), pain (Brief Pain Inventory-Short Form over past 24 hours: 4 to 10, present; v 0 to 3, absent), prior chemotherapy (1 v 2), and progression (prostate-specific antigen v radiographic). Association of baseline SA (testosterone, androstenedione, dehydroepiandrosterone sulfate), was measured by ultrasensitive liquid-liquid extraction or protein precipitation and two-dimensional liquid chromatography coupled to mass spectrometry, with OS determined by bivariate and multivariable Cox models. OS was examined with SA as greater than median and less than or equal to the median.

Results: Median survival increased with each quartile increase in testosterone level regardless of treatment arm. SA levels at baseline strongly associated with survival (P < .0001) in bivariate and multivariable analyses. Longer survival was observed for patients with SA above median compared with below median in both the AA and P arms (eg, testosterone, AA; hazard ratio, 0.64; 95% CI, 0.53 to 0.77; P < .0001). Treatment with AA led to longer survival versus P alone in the above- or below-median group for all androgens.

Conclusion: SA, measured with a novel ultrasensitive assay in COU-AA-301, is prognostic for OS and may be useful for risk stratification in mCRPC clinical trials.

Trial registration: NCT00638690.

Publication types

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

MeSH terms

  • Abiraterone Acetate
  • Androgens / blood*
  • Androstadienes / administration & dosage*
  • Double-Blind Method
  • Humans
  • Liquid-Liquid Extraction
  • Male
  • Orchiectomy
  • Prednisone / administration & dosage*
  • Prognosis
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / mortality*
  • Prostatic Neoplasms / pathology
  • Testosterone / blood


  • Androgens
  • Androstadienes
  • Testosterone
  • Abiraterone Acetate
  • Prednisone

Associated data