The impact of low skeletal muscle index and low muscle radiodensity on the prognosis of esophageal squamous cell carcinoma: a multi-center retrospective study in China (TIMES Study)

The prognostic value of skeletal muscle mass and muscle quality in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) undergoing neoadjuvant chemoradiotherapy (NCRT) remains unclear. We investigated the association of low skeletal muscle index (SMI) and low skeletal muscle radiodensity (SMD, reflecting myosteatosis) with long-term survival. We conducted a multicenter retrospective study including consecutive LA-ESCC patients treated between 2014 and 2023 at three tertiary hospitals. SMI and SMD were measured at the third lumbar vertebral level on preoperative CT images. Optimal cutoff values were determined using time-dependent receiver operating characteristic curve analysis. Overall survival (OS) was analyzed using Kaplan–Meier curves and Cox proportional hazards models. Sex-specific analyses were conducted to explore potential effect modification. A total of 420 patients were included, with a median follow-up of 39.1 months, the 5-year OS rate was 60%. Low SMI and low SMD were both significantly associated with worse OS. In multivariable analysis, low SMI (hazard ratio [HR] 2.23, 95% CI 1.17–4.24; P = 0.015) and low SMD (HR 2.41, 95% CI 1.36–4.26; P = 0.003) remained independent predictors of OS. Patients with concomitant low SMI and low SMD had the poorest survival(56.8% vs 60.8%, P = 0.037). Sex-stratified analysis demonstrated that myosteatosis remained an independent predictor of OS in male patients (HR 1.71, 95% CI 1.16–2.52; P = 0.007). Among men, 5-year OS was 47.1% in those with myosteatosis versus 63.7% in those without (HR 1.67, P = 0.015). Both reduced muscle mass and impaired muscle quality are associated with adverse long-term outcomes in LA-ESCC patients undergoing NCRT and surgery. Myosteatosis, in particular, appears to confer a stronger prognostic impact in male patients. Assessment of skeletal muscle composition may improve risk stratification in this population.