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 followup was pooled for post-hoc analysis from 2 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 (less than 250 ng/dl) vs normal (250 ng/dl or greater) 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: On intention to treat analysis 138 (16.5%) of 838 eligible men had baseline serum testosterone less than 250 ng/dl. Key cancer characteristics for low vs normal baseline serum testosterone cohorts were comparable; Gleason sum 7-10 (55% vs 58%), stage and prostate specific antigen 20 ng/ml or greater categories (38% each). The lowest baseline serum testosterone quartile cutoff value was 282 ng/dl or less (206 patients). Multivariable analysis showed a significant baseline serum testosterone effect for all survival end points. For the saturation model low cutoff less than 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 prostate specific antigen 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.