Sarcopenia and recurrence risk in high-risk non–muscle-invasive bladder cancer: a nonlinear modeling approach

BACKGROUND: Sarcopenia and altered body composition are established prognostic markers in several malignancies, but their relevance in non-muscle-invasive bladder cancer (NMIBC) remains unclear. This study evaluated associations between body composition indices-body mass index (BMI), skeletal muscle index (SMI), and psoas muscle index (PMI)-and recurrence risk in high-risk NMIBC patients treated with intravesical Bacillus Calmette-Guérin (BCG). METHODS: Body composition was assessed on computed tomography at primary diagnosis. Sarcopenia was defined using published sex-specific cut-offs. Recurrence-free survival (RFS) was analyzed using Kaplan-Meier estimates, Cox regression with linear and spline terms, and a gradient boosted machine (GBM) model. RESULTS: A total of 118 patients (median age 71 years; 78% male) were included. Tumor stages were pTa (40%), pT1 (54%), and primary carcinoma in situ (CIS) in 6%. During a mean follow-up of 32 months, 30 patients (25.4%) developed recurrence. Median BMI was 26 kg/m². SMI and PMI were higher in men and declined with age, whereas BMI remained stable. Sarcopenia prevalence varied widely across definitions (6-66%) with low-to-moderate concordance (Cohen's κ: 0-0.58). No sarcopenia definition independently predicted recurrence. In the GBM model, BCG maintenance, tumor stage, CIS, age, BMI, SMI, and PMI were important predictors. Spline Cox models demonstrated nonlinear U-shaped associations between BMI, SMI, PMI, and recurrence risk, with increased risk at both low and high values. CONCLUSIONS: Body composition shows nonlinear associations with recurrence in high-risk NMIBC. Both low and excessive body and muscle mass may adversely affect disease control. The heterogeneity and limited prognostic value of current sarcopenia definitions highlight the need for standardized, multiparametric, and nonlinear risk modeling approaches.