Objectives: To assess the impact of antiandrogen withdrawal syndrome after bicalutamide withdrawal in castration-resistant prostate cancer patients treated with androgen receptor-axis targeted agents. Methods: The study cohort comprised 94 patients treated with abiraterone (n = 34) or enzalutamide (n = 60) as a first-line androgen receptor-axis targeted agent for castration-resistant prostate cancer despite combined androgen blockade by castration with bicalutamide as the first-line therapy. The association between clinicopathological factors (including antiandrogen withdrawal syndrome) and therapeutic outcome after using abiraterone and enzalutamide was investigated. Results: The decline in the prostate-specific antigen level after use of abiraterone or enzalutamide was comparable between patients with and without antiandrogen withdrawal syndrome. Antiandrogen withdrawal syndrome (hazard ratio 3.84, 95% confidence interval 1.29–11.45; P = 0.016) was associated with a higher risk of progression on multivariate analysis, but not all-cause death after abiraterone use. Progression-free survival and overall survival after enzalutamide use did not differ between patients with and without antiandrogen withdrawal syndrome. Conclusions: The present data suggest a modest therapeutic efficacy of abiraterone in castration-resistant prostate cancer patients with anti-androgen withdrawal syndrome after bicalutamide withdrawal.
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