Osteosarcopenia Predicts Mortality in Metastatic Prostate Cancer: A Longitudinal Analysis of Opportunistic CT Imaging

Background/Objectives: Osteoporosis and sarcopenia are associated with fractures, falls, and mortality. In prostate cancer, aging, advanced disease, and androgen deprivation therapy may accelerate concurrent bone and muscle loss. This study characterized longitudinal CT-derived musculoskeletal biomarkers in metastatic prostate cancer and evaluated the association between baseline osteosarcopenia and overall survival. Methods: This retrospective single-centre cohort included patients treated from 2009 to 2022, with follow-up imaging through 2024. An automated deep-learning pipeline quantified lumbar trabecular bone mineral density (BMD), psoas muscle volume (PV), psoas muscle density (PD), and volumetric psoas muscle index (vPMI). Osteosarcopenia was defined as concurrent osteoporosis (BMD < 135 HU) and sarcopenia (vPMI < 30). Survival from baseline CT was assessed using Kaplan-Meier analysis and multivariable Cox regression. Results: Among 437 patients with 3389 CT scans, osteoporosis, sarcopenia, and osteosarcopenia increased from 29.6%, 46.9%, and 17.2% at baseline to 54.0%, 82.8%, and 45.5% at final imaging. BMD declined by 2.1-3.7% annually, PD by 3.2-3.9%, and PV by 3.6-4.6% (all p < 0.0001). In the final year of life, PD declined by 12.0% and PV by 9.3%. Baseline osteosarcopenia remained independently associated with mortality after adjustment for age, time from diagnosis to baseline CT, PSA, and Gleason risk group (HR 2.11, 95% CI 1.50-2.99; p < 0.001). Conclusions: Osteosarcopenia is common and progressive in metastatic prostate cancer, and muscle loss accelerates near death. Baseline osteosarcopenia independently identifies patients at increased mortality risk. Automated analysis of routine surveillance CT may enable longitudinal musculoskeletal assessment and prognostic risk stratification.