Simple SummaryArtificial Intelligence (AI)-driven software that utilizes Computed Tomography (CT)images has the capability to automatically assess body composition and diagnose sarcopenia. Our research indicates that combining standardized CT staging methods with sarcopenia analysis could assist in identifying patients with advanced urothelial tumors who may benefit from customized nutritional therapies, ultimately resulting in improved outcomes and quality of life. The AI tool can represent a means to increase the clinical value of CT imaging reports and to promote the development of precision medicine.AbstractBackground: Sarcopenia is a well know prognostic factor in oncology, influencing patients’ quality of life and survival. We aimed to investigate the role of sarcopenia, assessed by a Computed Tomography (CT)-based artificial intelligence (AI)-powered-software, as a predictor of objective clinical benefit in advanced urothelial tumors and its correlations with oncological outcomes. Methods: We retrospectively searched patients with advanced urothelial tumors, treated with systemic platinum-based chemotherapy and an available total body CT, performed before and after therapy. An AI-powered software was applied to CT to obtain the Skeletal Muscle Index (SMI-L3), derived from the area of the psoas, long spine, and abdominal muscles, at the level of L3 on CT axial images. Logistic and Cox-regression modeling was implemented to explore the association of sarcopenic status and anthropometric features to the clinical benefit rate and survival endpoints. Results: 97 patients were included, 66 with bladder cancer and 31 with upper-tract urothelial carcinoma. Clinical benefit outcomes showed a linear positive association with all the observed body composition variables variations. The chances of not experiencing disease progression were positively associated with ∆_SMI-L3, ∆_psoas, and ∆_long spine muscle when they ranged from ~10–20% up to ~45–55%. Greater survival chances were matched by patients achieving a wider ∆_SMI-L3, ∆_abdominal and ∆_long spine muscle. Conclusions: A CT-based AI-powered software body composition and sarcopenia analysis provide prognostic assessments for objective clinical benefits and oncological outcomes.