958 CAN ANTIANDROGEN WITHDRAWAL THERAPY BE PERFORMED SAFELY FOR AGGRESSIVE PROSTATE CANCER?

INTRODUCTION AND OBJECTIVES: Antiandrogen withdrawal (AAWD) is a potential therapeutic maneuver for treating patients with castration-resistant prostate cancer (CRPC) who have undergone a combined antiandrogen blockade (CAB) therapy. However, clinicians are also concerned that, for patients with aggressive CRPC demonstrating a short PSA doubling time (PSADT), discontinuation of antiandrogens may result in even greater exacerbation of the disease. This study was designed to examine the safety of AAWD therapy. METHODS: We reviewed the medical records of patients with CRPC who received prior initial treatment with CAB therapy during the period of 2001-2011. In 95 patients, AAWD therapy (68 patients previously received bicalutamide, and 27 patients flutamide) for CRPC was performed, and we examined the changes in PSADT before and after AAWD. Serum PSA determinations were obtained 4 weeks before stopping antiandrogen therapy, immediately before (baseline PSA level), and every 4 weeks thereafter. RESULTS: A reduction in the serum PSA level after AAWD was observed in 29 of 95 patients (30.5%), and a greater than 50% decrease from the baseline serum PSA level was observed in 11 patients (10.5%). The median response duration in these 29 responders was 4.0 months. In the 66 non-responders, the mean PSADT before and after AAWD was 7.7 and 6.2 months, respectively. A shortening of PSADT after AAWD was observed in 37 patients (38.9%). Next, using a logistic regression model with stepwise forward selection, we performed univariate and multivariate analyses to identify predictors that have an influence on shortening of PSADT after AAWD (Table below). Interestingly, the results indicated that patients with a short PSADT (aggressive disease) before AAWD had a low risk of subsequent shortening of PSADT after AAWD. In 25 patients with baseline PSADT 2 months, a shortening of PSADT after AAWD was observed in only 3 patients (12.0%). Furthermore, 8 of the 25 patients (32.0%) responded to the AAWD therapy, and 2 patients (8.0%) achieved a greater than 50% decrease from the baseline PSA level. CONCLUSIONS: Our data indicate that patients with a short baseline PSADT (aggressive disease) had a low risk for worsening of the disease by AAWD, and we concluded that it should be recommended for all patients with CRPC before embarking on the next therapeutic maneuver.