AR and cancer: First, in vitro studies suggest that prostate radiation therapy (RT) can induce cellular changes such as neuroendocrine differentiation and loss of expression of androgen receptors (AR) and may result in resistance to AR-directed therapy.11,12 Furthermore, minimal residual disease after radical prostatectomy (RP) also can give rise to treatment-resistant clones through several potential mechanisms.13,14,15,16,17,18 These factors may potentially result in inferior response to subsequent systemic therapy when the cancer progresses to a nonmetastatic castration-resistant phase.