Treatment-related changes in body composition during maximal androgen blockade (MAB) for metastatic hormone-sensitive prostate cancer (mHSPC).

e17097 Background: Androgen deprivation therapy (ADT) combined with an androgen receptor pathway inhibitors (ARPI) +/- docetaxel is the standard of care for patients with mHSPC. ADT is known to induce adverse body composition changes, including loss of skeletal muscle and increased adiposity, which have been linked to an increased risk of obesity, sarcopenia, fracture and cardiovascular disease. However, the specific effects of MAB (ADT + ARPI) remain poorly defined. Methods: We retrospectively identified patients with mHSPC treated with MAB +/- docetaxel at the Oncology Institute of Southern Switzerland from 2019 to 2025 who underwent a computed tomography (CT) scan before hormonal therapy initiation (T0) and after 6 ± 3 months of ARPI treatment (T1). Automated CT-based body composition analysis (DAFS Express) quantified skeletal muscle area (SMA), visceral (VAT), subcutaneous (SAT), and intramuscular adipose tissue (IMAT) areas and their mean attenuation (density) at L3 level. Paired comparisons were performed between T0 and T1. A multivariable linear mixed model was fitted to assess associations between baseline clinical characteristics (Table 1) and 6-month variations in body composition parameters during treatment. Results: Overall, 192 CT scans from 86 patients were analyzed (Table 1). After six months of ARPI exposure, patients experienced a significant reduction in SMA (mean variation: -7.86 cm 2 , -7.2%, p < 0.001) and derived Skeletal muscle index (p < 0.01), and an increase in SAT (+27.62 cm 2 , +14.8%, p < 0.001) and IMAT (+1.33 cm 2 , +5.6%, p = 0.006), with heterogenous and nonsignificant VAT changes (p = 0.15). Density of SAT (CT attenuation) decreased (p = 0.001), indicating deposition of mature adipose tissue. In the multivariable model, only the specific ARPI used was independently associated with VAT variation (p = 0.017), with enzalutamide linked to a higher probability of a decrease in VAT (p = 0.0063). No other clinical factors significantly influenced the 6-month body composition results. Conclusions: In men with mHSPC, MAB induces significant skeletal muscle loss and increased adiposity within 6 months of therapy. Addition of enzalutamide was associated with a significant VAT reduction, suggesting possible distinct effects of ARPIs on these tissues. Early lifestyle modification (e.g., personalized dietary and exercise interventions) should be incorporated in the clinical routine management for men with mHSPC to actively counteract these effects. Characteristic Study population, N=86 Age, median (range), y 75.8 (54-91) BMI, median (range), kg/m² 26.4 (19.7-38.6) De novo mHSPC, n (%) 70 (81.4) CHAARTED high-volume, n (%) 53 (61.6) ARPI for mHSPC, n (%) Abiraterone 27 (31%), Darolutamide 26 (30%), Enzalutamide 20 (23%), Apalutamide 13 (15%) Added docetaxel in mHSPC to ADT+ARPI, n (%) 8 (9.3%)