**Higher Serum Testosterone Levels Associated with Favorable Prognosis in Enzalutamide- and Abiraterone-Treated Castration-Resistant Prostate Cancer**

**Shinichi Sakamoto 1,\*, Maihulan Maimaiti 1, Minhui Xu 1, Shuhei Kamada 2, Yasutaka Yamada 3, Hiroki Kitoh 4, Hiroaki Matsumoto 5, Nobuyoshi Takeuchi 1, Kosuke Higuchi 6, Haruhito A. Uchida 7, Akira Komiya 1, Maki Nagata 2, Hiroomi Nakatsu 3, Hideyasu Matsuyama 5, Koichiro Akakura 4 and Tomohiko Ichikawa 1**


Received: 1 March 2019; Accepted: 8 April 2019; Published: 11 April 2019

**Abstract:** Testosterone plays a significant role in maintaining the tumor microenvironment. The role of the target serum testosterone (TST) level in enzalutamide- (Enza) and abiraterone (Abi)-treated castration-resistant prostate cancer (CRPC) patients was studied. In total, 107 patients treated with Enza and/or Abi at Chiba University Hospital and affiliated hospitals were studied. The relationships between progression-free survival (PFS), overall survival (OS), and clinical factors were studied by Cox proportional hazard and Kaplan–Meier models. In the Abi and Enza groups overall, TST ≥ 13 ng/dL (median) (Hazard Ratio (HR) 0.43, *p* = 0.0032) remained an independent prognostic factor for PFS. In the Enza group, TST ≥ 13 ng/dL (median) was found to be a significant prognostic factor (HR 0.28, *p* = 0.0044), while, in the Abi group, TST ≥ 12 ng/dL (median) was not significant (HR 0.40, *p* = 0.0891). TST showed significant correlation with PFS periods (*r =* 0. 32, *p* = 0.0067), whereas, for OS, TST ≥ 13 ng/dL (median) showed no significant difference in the Abi and Enza groups overall. According to Kaplan–Meier analysis, a longer PFS at first-line therapy showed a favorable prognosis in the Enza group (*p* = 0.0429), while no difference was observed in the Abi group (*p* = 0.6051). The TST level and PFS of first-line therapy may be considered when determining the treatment strategy for CRPC patients.

**Keywords:** abiraterone; enzalutamide; prostate cancer; androgen deprivation therapy; testosterone; castration resistant prostate cancer
