Adiposity and response to ADT ± AR pathway inhibitors (ARPI) in men with metastatic hormone-sensitive prostate cancer (mHSPC).

Abstract

233 Background: Adiposity has a complex influence on prostate cancer outcomes that may be stage- and/or treatment-dependent. While linked to worse outcomes in localized disease, increased adiposity has been associated with an improved response to ARPI in metastatic castration-resistant prostate cancer (mCRPC). However, how pre-treatment (intrinsic) versus on-treatment (acquired) adiposity affects outcomes in men with mHSPC receiving ADT ± ARPI is unknown. We hypothesized that elevated intrinsic and greater acquired adiposity would improve the efficacy of ARPI in mHSPC. Methods: Men with mHSPC from a pooled cohort of three single-center, investigator-initiated trials with baseline L3 vertebra CT imaging prior to initiating ADT ± ARPI were included. An AI segmentation tool, Voronoi DAFS, measured body composition (normalized for height [m²]) on CTs obtained before and after six months of ADT ± ARPI. Response to ARPI was evaluated using 6-month PSA response, defined as PSA <0.4, 0.4–4, or >4 ng/mL, and mCRPC progression-free survival (PFS), defined as time from ADT start to development of CRPC or death. Chi-square tests, the Kaplan-Meier method, and proportional hazards regression were used for analysis. Results: In 152 men with mHSPC, median age was 66.0 years, and median PSA was 15.9 ng/mL. Antihypertensive medication use was prevalent (61.8%), 21.1% had type 2 diabetes mellitus (T2DM), and 14.5% had coronary artery disease (CAD). Intrinsic subcutaneous adiposity (SATi) was associated with 6-month PSA response (p = 0.004), with the middle tertile of intrinsic adiposity showing the most favorable response. In contrast, greater acquired SATi after six months of ADT ± ARPI was associated with an inferior 6-month PSA response (p < 0.001; Table), which persisted in a multivariable model. In a multivariable model controlling for differences across the three trials, intrinsic and acquired adiposity were not associated with PFS. Conclusions: Subcutaneous adiposity had a complex association with 6-month PSA response, but neither intrinsic nor acquired adiposity was associated with time to mCRPC. While these findings support a relationship between adiposity and PSA kinetics, a clear link between body composition and the long-term efficacy of ADT ± ARPI was not established. Association between intrinsic and acquired subcutaneous adiposity (SATi) and 6-month PSA response in men with mHSPC receiving ADT ± ARPI. 6-month PSA Univariable intrinsic SATi N PSA <0.4 PSA 0.4–4 PSA >4 p-value <43.833 37 22 (59.5%) 11 (29.7%) 4 (10.8%) 0.004 43.833 to <86.884 71 60 (84.5%) 11 (15.5%) 0 (0.0%) ≥86.884 38 24 (63.2%) 10 (26.3%) 4 (10.5%) Multivariable acquired SATi Change 0.002 Change < 15.9 79 57 (72.2%) 21 (26.6%) 1 (1.3%) Change ≥ 15.9 24 11 (45.8%) 7 (29.2%) 6 (25.0%)