Impact of Sarcopenia and Pretreatment Skeletal Muscle Loss on Survival in Endometrial Cancer Patients Treated With...

Sarcopenia and cancer-related muscle wasting may affect the efficacy of immune checkpoint inhibitors (ICIs). However, their prognostic significance in endometrial cancer (EC), particularly concerning skeletal muscle status at ICI initiation and pretreatment muscle change, remains unclear. We evaluated the impact of sarcopenia at ICI initiation and pre-ICI skeletal muscle dynamics on clinical outcomes in EC.

We retrospectively analyzed 20 EC patients treated with ICIs between May 2019 and December 2024. Skeletal muscle index (SMI) was quantified using abdominal CT at the L3 level within 2 months before ICI initiation. Sarcopenia was defined as SMI < 38.5 cm²/m². Pretreatment SMI change (ΔSMI) was calculated using baseline CT before any cancer-directed therapy and CT immediately prior to ICI. Survival outcomes were assessed using Kaplan-Meier and Cox regression analyzes.

Ten patients (50%) were sarcopenic at ICI initiation and showed a trend toward poorer progression-free survival (PFS) and overall survival (OS). Pre-treatment muscle loss occurred in two-thirds of patients. Patients with decreased SMI had significantly worse OS (HR 3.64, 95% CI 1.11-11.94). In subgroup analysis, SMI decline was frequent among sarcopenic patients but did not stratify survival. In contrast, among nonsarcopenic patients, greater SMI loss was associated with poorer survival, and each 1-unit decrease in SMI significantly worsened OS (HR 1.64, 95% CI 1.05-2.63).

Sarcopenia at ICI initiation and pretreatment skeletal muscle loss are potential predictors of poor prognosis in EC. Evaluating baseline muscle mass and its trajectory may improve risk stratification and help identify patients at higher risk of ICI resistance.