Published online Nov 15, 2026. doi: 10.4251/wjgo.123400
Revised: June 8, 2026
Accepted: July 2, 2026
Published online: November 15, 2026
Processing time: 163 Days and 20.6 Hours
Definitive chemoradiotherapy is the standard treatment for advanced esophageal squamous cell carcinoma (ESCC); however, marked prognostic heterogeneity exists and simple predictive biomarkers are lacking. Although skeletal muscle density (SMD) reflects muscle quality, its posttreatment prognostic value and age-dependent modifying effect in ESCC remain unclear.
To explore the prognostic significance of post-treatment SMD (post-SMD) and to clarify the age-related interaction in patients with ESCC undergoing definitive chemoradiotherapy.
Altogether, 255 eligible ESCC patients were retrospectively enrolled. Post-SMD was calculated using L3 vertebral-level abdominal computed tomography images. Additionally, multivariate logistic regression and restricted cubic spline were util
In the entire cohort, lower post-SMD was significantly associated with worse survival (P = 0.034). A nonlinear relationship was identified between age and post-SMD, with 64 years established as the inflection point (P = 0.016). Consequently, the prognostic impact of post-SMD was highly age-dependent. It served as a significant predictor of poor survival exclusively in patients aged < 64 years (P = 0.020) but not in those ≥ 64 years (P = 0.439). Multivariate analysis confirmed that higher post-SMD was an independent protective factor for survival (hazard ratio = 0.633, P = 0.006). Based on these findings, we developed a prognostic model incorporating post-SMD specifically for patients under 64 years. This model demonstrated excellent performance in distinguishing high-risk patients (P < 0.001), exhibiting high discriminatory power [12-month area under the curve (AUC) = 0.820; 36-month AUC = 0.867], good calibration, and providing a positive net clinical benefit in decision curve analysis.
In this study cohort, post-SMD is a vital prognostic biomarker, and age acts as a core effect modifier in evaluating its prognostic significance. This finding can provide references for precise risk stratification and individualized management of the corresponding population.
Core Tip: This study enrolled 255 esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy to explore the prognostic role of post-treatment skeletal muscle density (post-SMD). We innovatively identified a nonlinear correlation between age and post-SMD, with 64 years as the optimal cut-off inflection point. Post-SMD exhibited an age-dependent prognostic modifying effect: Reduced post-SMD independently predicted inferior survival exclusively in patients aged < 64 years, while no significant prognostic correlation was observed in elderly patients ( ≥ 64 years). A tailored prognostic model incorporating post-SMD was established for young ESCC patients, which presented favorable discrimination, calibration, and net clinical benefit.