Preoperative Nutritional Risk Defines Treatment Tolerance and Guides Adjuvant Immunotherapy in Resectable Esophageal...

Malnutrition is a critical determinant of treatment tolerance in esophageal squamous cell carcinoma (ESCC). However, its utility in guiding dynamic perioperative decision-making and adjuvant immunotherapy selection remains undefined.

This study evaluated 498 locally advanced ESCC patients receiving neoadjuvant chemoimmunotherapy and planned esophagectomy. A classification and regression tree (CART) model stratified patients by baseline PG-SGA score. The primary endpoint was treatment tolerance as defined by a composite Neoadjuvant Therapy Tolerance Grade (NAT-TG) that integrated therapy completion and surgical feasibility. The secondary endpoints included postoperative morbidity and survival outcomes. Additionally, dynamic preoperative nutritional trajectories were longitudinally tracked.

The CART model identified three distinct nutritional risk strata. Increasing nutritional risk was strongly associated with impaired treatment tolerance, reflected by reduced surgical completion (97.1% vs 93.3% vs 76.7%; P < 0.001) and higher-grade (≥3) toxicities. High-risk patients experienced significantly more severe postoperative complications (38.2% vs 18.0%; P < 0.001). Longitudinal monitoring showed that a persistent-severe dynamic nutritional trajectory independently predicted major postoperative complications (odds ratio, 3.21; P < 0.001). At a median follow-up period of 41 months, baseline high nutritional risk independently predicted inferior overall survival (hazard ratio, 2.03; P < 0.001). Notably, within the cohort that underwent resection, adjuvant immunotherapy significantly improved 3-year overall survival for high-risk patients, from 41.7% to 65.8% (P = 0.043), whereas no such benefit was observed in lower-risk groups.

Integrating baseline nutritional triage with dynamic longitudinal monitoring effectively predicts treatment tolerance and prognosis in ESCC. This framework identifies a high-risk subset that derives substantial survival benefit from adjuvant immunotherapy consolidation.