Purpose: Phenotypic biomarkers are a high priority for patients receiving androgen deprivation therapy (ADT) for prostate cancer given the increasing number of treatment options. This study evaluates serum sex steroids as prognostic biomarkers in men receiving ADT for recurrent prostate cancer.

Experimental Design: Retrospective cohort study of Canadian patients in the PR.7 trial (accrual 1999–2005) who received continuous ADT for biochemical recurrence postradiotherapy. Patients were excluded with follow-up <2 years or who received estrogens or corticosteroids. Kaplan–Meier and multivariable Cox regression analyses adjusted for baseline prognostic factors assessed time to castration-resistant prostate cancer (CRPC), prostate cancer survival, and overall survival according to tertile of sex steroid measured by mass spectrometry.

Results: Post-ADT initiation, we measured samples in 219 patients as well as two subsequent annual samples in a subset of 101 patients. Testosterone levels correlated with androstenedione (AD) and DHT, while DHT, AD, androsterone (AST), dehydroepiandrosterone (DHEA), and androstenediol (A5diol) were highly correlated to each other and negatively associated with age. Higher tertiles of estrone (E₁) and estradiol (E₂) were significantly associated with sooner time to CRPC. In patients with longitudinal samples, increases in serum DHEA and AST were significantly associated with sooner time to CRPC. Limitations include the number of events for some groups.

Conclusions: Our data suggest the patient hormonal milieu has long-term prognostic value in men receiving ADT for recurrent prostate cancer, including increased levels of E₁ and E₂ and rising DHEA and AST levels, which predict a shorter time to CRPC. Clin Cancer Res; 24(21); 5305–12. ©2018 AACR.