Effect of BMI on efficacy of androgen receptor pathway inhibitors in patients with metastatic hormone-sensitive prostate cancer

Abstract

Body mass index (BMI) has been associated with improved outcomes in several malignancies, including prostate cancer. However, the impact of BMI on treatment efficacy, particularly with androgen receptor pathway inhibitors (ARPIs), in metastatic hormone-sensitive prostate cancer (mHSPC) remains insufficiently characterized. This study aimed to evaluate the association between BMI and radiographic progression-free survival (rPFS) in patients with mHSPC receiving first-line therapies. Methods We retrospectively analyzed 330 patients with newly diagnosed mHSPC. Patients were stratified by their treatment regime and baseline BMI. rPFS was assessed using Kaplan–Meier analysis and Cox proportional hazards models. Multivariate analyses included clinically relevant covariates and factors significant in univariate analyses. Results With a median follow-up of 47 months, median rPFS for the entire cohort was 34 months. Patients with BMI≥25 kg/m 2 demonstrated significantly longer median rPFS. Higher BMI was associated with favorable baseline characteristics, including better ECOG performance status and higher hemoglobin levels. In multivariate analysis, liver metastases, high-volume disease, low hemoglobin, elevated alkaline phosphatase, and treatment modality remained independent predictors of rPFS, whereas BMI did not retain independent significance. Among overweight patients receiving ARPIs, enzalutamide showed a numerically longer rPFS compared with abiraterone, although this difference was not statistically significant. Conclusion Higher BMI was associated with prolonged rPFS in patients with mHSPC, supporting a potential obesity paradox in this population. While BMI was not an independent predictor in multivariate analysis, it may reflect underlying patient fitness and disease biology. These findings warrant prospective validation into metabolic factors influencing ARPI efficacy.