Development and external validation of a nomogram to predict disease-free survival after neoadjuvant chemoimmunotherapy and surgery in esophageal squamous cell carcinoma: a multicenter retrospective study

Postoperative recurrence risk remains heterogeneous among patients with locally advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoimmunotherapy (NCIT) and surgery. We aimed to develop and externally validate a clinically accessible prognostic model for disease-free survival (DFS). This multicenter retrospective cohort study included patients undergoing esophagectomy after NCIT at four Chinese centers between October 2019 and December 2025. One center formed the training cohort and three independent centers formed the external validation cohort. Predictors were selected using least absolute shrinkage and selection operator-penalized Cox regression and bootstrap stability selection. Performance was evaluated by discrimination, calibration, decision curve analysis, and fixed-cutoff risk stratification and compared with ypTNM staging. Among 890 patients, 546 were included in the training cohort and 344 in external validation; DFS events occurred in 172 and 93 patients, respectively. The nomogram incorporated ypN stage, perineural invasion, major pathological response, ypT stage, sex, body mass index category, and lymphovascular invasion. The C-index was 0.741 (95% confidence interval [CI], 0.702–0.780) in training and 0.701 (0.644–0.757) in external validation. The optimism-corrected C-indices were 0.726 (0.688–0.762) for fixed-model validation and 0.706 (0.668–0.747) when predictor selection was repeated. In external validation, the C-index difference versus categorical ypTNM staging was 0.048 (0.014–0.082). External calibration showed reasonable agreement between predicted and observed DFS at 1 and 2 years, with overprediction of DFS at 3 years. Decision curve analysis showed greater net benefit than ypTNM staging within specific threshold ranges. High-risk classification using the fixed training-derived cutoff was associated with poorer DFS in training (hazard ratio [HR], 3.86; 95% CI, 2.75–5.44) and external validation (HR, 3.40; 95% CI, 2.16–5.35; both P < 0.001). This externally validated nomogram uses routinely available clinicopathological variables to provide individualized DFS estimates for patients with ESCC after NCIT and surgery and may complement ypTNM staging in postoperative risk stratification. Prospective validation is required before routine clinical use.