Does Baseline Serum Testosterone Influence Androgen Deprivation Therapy Outcomes in Hormone Naïve Patients with Advanced Prostate Cancer?

Abstract

Purpose: To study baseline serum testosterone’s prognostic value in hormone naïve advanced prostate cancer patients receiving continuous androgen deprivation therapy. Materials and Methods: The study population undergoing continuous androgen deprivation therapy (agonist or antagonist) with 1-year follow-up was pooled for post-hoc analysis from two large prospective, randomized, parallel-arm phase 3b trials (NCT00295750—Global; NCT00928434—USA). Survival end-points were evaluated for baseline serum testosterone effect as a continuous variable, and compared for low (250 ng/dL) groups based on the saturation model, using Kaplan Meier survival estimates, log rank test, and Cox proportional hazards regression models incorporating established clinically important baseline factors. Results: Limitations: On intention-to-treat analysis, 138 (16.5%) of 838 eligible men had baseline serum testosterone 20 ng/ml categories (38% each). The lowest baseline serum testosterone quartile cut-off value was <282 ng/dL (n=206). Multi-variable analysis showed a significant baseline serum testosterone effect for all survival end points. For the saturation model low cut-off <250 ng/dL, significance remained for overall (HR 2.24; p <0.02) and progression free survival (HR 1.57; p <0.02), but not for time to PSA progression (HR 1.37; p=0.2). Conclusions: Lower baseline serum testosterone was significantly associated with worse study survival end-points in hormone naïve advanced prostate cancer patients undergoing continuous medical castration. Future well-designed studies should compare continuous androgen deprivation therapy (the current gold standard) with newer alternatives, to optimize individualized management in these men.