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

## TL;DR

This study shows that muscle loss (sarcopenia) is a strong predictor of death in bladder cancer patients receiving chemotherapy and surgery, suggesting it should be assessed early to improve outcomes.

## Contribution

The study is the first to compare sarcopenia thresholds at different treatment stages in bladder cancer patients.

## Key findings

- Sarcopenia before chemotherapy and before surgery was independently linked to higher mortality risk.
- Results were consistent using two validated sarcopenia definitions (Martin and Fearon).
- Sarcopenia was associated with shorter progression-free survival.

## Abstract

This study emphasizes the importance of incorporating sarcopenia assessment into the pre-therapeutic evaluation of patients with muscle-invasive bladder cancer treated with neoadjuvant chemotherapy followed by cystectomy. We describe a radiological approach that is simple, rapid, and highly reproducible, based on a semi-automated measurement of skeletal muscle area at the L3 vertebral level on routine CT scans performed before chemotherapy and before surgery. Sarcopenia identified at each stage of treatment was shown to be an independent factor associated with increased overall and specific mortality. These findings were consistent across the two sarcopenia definitions currently validated in the literature, namely those proposed by Martin and Fearon, reinforcing the robustness of our results. These data suggest that sarcopenia represents a clinically relevant biomarker in this population. Early identification of sarcopenic patients should prompt consideration of tailored, preemptive therapeutic strategies, including nutritional and supportive interventions, with the aim of improving oncological outcomes and survival.

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.