Metabolic profile and skeletal muscle as predictors of survival in testicular germ cell tumors

BACKGROUND: Testicular germ cell tumors (TGCT) are highly curable malignancies, yet the prognostic impact of host metabolic status remains underexplored, especially in non-Caucasian populations. METHODS: We analyzed 2755 Mexican patients with TGCT treated at the Instituto Nacional de Cancerología (2007-2021). A Metabolic sub-cohort (n = 586) and an Imaging sub-cohort (n = 231) with baseline CT-derived lean mass index (LMI) were evaluated. Statistical analyses included multivariate Cox regression adjusted for IGCCCG risk, principal component analysis (PCA)-based clustering, and internal validation using bootstrapping. RESULTS: Multivariate Cox regression adjusted for IGCCCG risk identified LMI (HR 0.95, 95% CI 0.90-0.99, P = .047), serum albumin (HR 0.27, 95% CI 0.18-0.42, P < .001), and HDL cholesterol (HR 0.94, 95% CI 0.91-0.96, P < .001) as independently associated factors. PCA-based metabolic-nutritional risk profiles effectively stratified 5-year survival in patients with non-seminoma (from 16.1% in depleted profiles to 97.4% in preserved profiles) and seminoma (64.0% vs 100%). A reduced prognostic model (BMI, LMI, albumin) achieved a robust optimism-corrected AUC of 0.866. CONCLUSIONS: Metabolic and body composition profiling provides prognostic discrimination complementary to the IGCCCG classification, suggesting the potential utility of incorporating objective nutritional assessments. Early identification of patients with metabolic vulnerability-specifically hypoalbuminemia, skeletal muscle depletion, and altered lipid profiles-could help guide personalized supportive strategies prioritizing nutritional and medical optimization to improve outcomes in TGCT.