Perioperative outcomes of neoadjuvant immunochemoradiotherapy versus immunochemotherapy followed by surgery in elderly patients with locally advanced esophageal squamous cell carcinoma.

Abstract

Esophageal squamous cell carcinoma is a leading cause of cancer-related mortality, with elderly patients (≥65 years) representing a growing but underserved population because of limited evidence on neoadjuvant immunotherapy regimens. The choice between neoadjuvant immunochemotherapy and neoadjuvant immunochemoradiotherapy remains unresolved in this vulnerable group. This retrospective cohort study included 257 elderly patients with locally advanced esophageal squamous cell carcinoma who underwent neoadjuvant immunochemotherapy (n = 194) or neoadjuvant immunochemoradiotherapy (n = 63), followed by radical esophagectomy at Sichuan Cancer Hospital between January 2021 and April 2025. The propensity score-based inverse probability weighting method was used to balance confounding factors. Perioperative outcomes were compared. Sensitivity analysis using entropy balancing weighting and propensity score matching was performed. The study revealed that compared with neoadjuvant immunochemotherapy , neoadjuvant immunochemoradiotherapy achieved a higher pathologic complete response rate (16% vs 41.3%; P < .001), whereas neoadjuvant immunochemoradiotherapy was associated with prolonged surgical duration (median, interquartile range, 3.8 h, 3.0 h-4.7 h vs 4.5 h, 4.0 h-5.0 h; P < .001), increased intraoperative blood loss (170 mL, 100-220 mL vs 210 mL, 140 mL-250 mL), higher blood transfusion requirements (3.6% vs 12.7%, P = .007), and elevated risks of cardiac complications (odds ratio, 3.21; 95% confidence interval, 1.34-7.69; P = .009) and major cardiac complications (odds ratio, 6.59; 95% confidence interval, 1.75-24.73; P = .005). No significant differences were observed in terms of pulmonary complications, anastomotic complications, pneumonia, anastomotic leakage, hospital length of stay, or in-hospital mortality between the 2 groups (all P > .05). The results were consistent after inverse probability weighting adjustment and in the sensitivity analysis. For elderly patients with locally advanced esophageal squamous cell carcinoma, neoadjuvant immunochemoradiotherapy provides superior pathologic downstaging but is associated with increased surgical complexity and cardiac complication risks compared with neoadjuvant immunochemotherapy. These results support personalized treatment decision-making to balance local tumor control and toxicity.