Sarcopenia Predicts Mortality in Bladder Cancer with Neoadjuvant Chemotherapy: A Multicenter Study

Background: Sarcopenia is a recognized adverse prognostic factor in many cancers and can be reliably assessed using computed tomography (CT) scans. Its prognostic value in bladder cancer patients undergoing neoadjuvant chemotherapy remains underexplored. This study aimed to assess sarcopenia's impact on survival and compare different measurement thresholds. Methods: We conducted a retrospective multicenter study including patients with invasive urothelial carcinoma treated with neoadjuvant chemotherapy followed by cystectomy between 2015 and 2021. Sarcopenia was assessed by measuring the Skeletal Muscle Index on CT scans before chemotherapy (BC) and prior to surgery (BS). The primary endpoint was overall survival. Secondary endpoints included progression-free survival (PFS), pathological complete response (pCR), and treatment-related complications. Results: Seventy-four patients were included, the majority receiving the MVAC regimen (71.7%). Forty percent of patients achieved a pCR, 35% experienced disease recurrence, and the median PFS was 25 months. Sarcopenia was observed in 27% of patients BC and in 39% BS. Sarcopenia was associated with an increased risk of all-cause mortality: BC according to the definition by Martin et al. (HR 3.38; 95% CI [1.25-9.12]; p = 0.016) and Fearon et al. (HR 4.03; 95% CI [1.13-14.3]; p = 0.031); and BS according to Martin et al. (HR 3.7; 95% CI [1.12-12.2]; p = 0.032) and Fearon et al. (HR 6.08; 95% CI [1.48-24.9]; p = 0.012). Sarcopenia was an independent risk factor of shorter PFS. Conclusions: Sarcopenia represent an independent and reproducible prognostic factor for mortality in patients with bladder cancer. The study is the first study to compare threshold values at different time points.