Abstract
OBJECTIVES: Prostate cancer prognostication has traditionally emphasized tumor-related factors (e.g., Gleason score and metastatic burden). Emerging evidence suggests that physical (host) factors influence outcomes. This study evaluated whether physical factors, including myosteatosis and sarcopenia, are prognostic factors in patients with androgen receptor signaling inhibitor-naïve, castration-resistant prostate cancer. METHODS: We retrospectively analyzed 117 androgen receptor signaling inhibitor-naïve patients with castration-resistant prostate cancer who received enzalutamide treatment at The University of Osaka Hospital between 2014 and 2024. Myosteatosis and sarcopenia were derived from pretreatment abdominal computed tomography. The primary endpoint was failure-free survival. Multivariate Cox proportional hazards analysis was performed to identify independent prognostic factors. RESULTS: Myosteatosis and sarcopenia were present in 49 (42%) and 46 (39%) patients, respectively. In univariate analyses, the Charlson comorbidity index, body mass index, and sarcopenia demonstrated no significant association with failure-free survival, whereas myosteatosis and distant metastasis were associated with a shorter failure-free survival. In multivariable analysis, myosteatosis remained an independent predictor of shorter failure-free survival (hazard ratio 1.91, 95% confidence interval 1.22-2.99, p < 0.01). The median failure-free survival was 6 and 17 months with and without myosteatosis, respectively (p < 0.01). CONCLUSIONS: Myosteatosis is an independent failure-free survival predictor in patients with androgen receptor signaling inhibitor-naïve castration-resistant prostate cancer treated with enzalutamide. Computed tomography-based evaluation of muscle quality may be useful for predicting the outcome of androgen receptor signaling inhibitors in patients with castration-resistant prostate cancer.