Paradoxical Effect of Obesity on Survival Outcomes in Prostate Cancer Patients Receiving Enzalutamide and Abiraterone

TL;DR

This study finds that obesity may improve survival outcomes in prostate cancer patients depending on the disease stage and treatment phase.

Contribution

The study reveals a phase-dependent obesity paradox in metastatic prostate cancer patients receiving androgen receptor-targeted therapies.

Findings

Obese patients with castration-sensitive prostate cancer had longer progression-free survival compared to normal-weight patients.

Obese patients with castration-resistant prostate cancer showed improved overall survival compared to normal-weight patients.

Obesity was identified as a protective factor for progression-free survival in castration-sensitive disease.

Abstract

Background and Objectives: Overweight and obesity is defined as a Body Mass Index (BMI) of 25.0–29.9 kg/m2 and ≥30.0 kg/m2. The prognostic significance of obesity in metastatic prostate cancer is still unclear, especially between the castration-sensitive (CSPC) and castration-resistant (CRPC) disease states. New evidence suggests that obese patients who get androgen receptor–targeted therapies may have an unexpected survival advantage. This study examined the correlation between body mass index (BMI) and survival outcomes in patients administered androgen receptor pathway inhibitors. Materials and Methods: A retrospective analysis was conducted on a cohort of 167 patients with metastatic prostate cancer treated between 2015 and 2024. BMI was analyzed as both a continuous variable and a categorical variable, which was classified as normal weight, overweight or obese. The primary goal of this study is to compare PFS and OS among BMI groups. We employed Kaplan–Meier survival analysis and Cox regression modeling to evaluate prognostic indicators. The CSPC and CRPC groups were evaluated separately. Results: PFSs for normal, overweight and obese CSPC patients were 11.3, 15.1, 19.5 months, respectively; p = 0.03 but the OS did not differ significantly between BMI groups. OS for normal, overweight and obese CRPC patients were 32.8, 47.6 and 43.4 months, respectively; p = 0.01. There was also a trend toward better PFS, but it was not statistically significant. Multivariate analysis found that obesity (BMI ≥ 30) was a separate protective factor for PFS in CSPC, while high-volume disease was a bad prognostic factor for OS in CRPC. A high Gleason score and ECOG-PS 2 were consistently associated with poor outcomes. Conclusions: Obesity has a phase-dependent prognostic influence in metastatic prostate cancer, providing a PFS advantage in CSPC and an OS benefit in CRPC. These results suggest that there may be an obesity paradox in people who are getting androgen receptor–targeted therapy. Further prospective studies are required to gain a better understanding of the biological reasons for this association.

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