Postoperative Pneumonia After Minimally Invasive Esophagectomy in Esophageal Squamous Cell Carcinoma: A Weighted Real-World Comparison of Neoadjuvant Treatment Strategies

Background: Postoperative pneumonia (POP) is a critical complication after minimally invasive esophagectomy (MIE) for esophageal squamous cell carcinoma (ESCC). However, the comparative odds of POP among different neoadjuvant treatment strategies remain controversial. This study aimed to compare the associations between different treatment strategies and POP in this population. Methods: A retrospective cohort of ESCC patients undergoing MIE between March 2021 and July 2025 was analyzed. Patients were divided into four groups: the surgery alone (S-alone) group (n = 282), the neoadjuvant chemotherapy (NCT) group (n = 127), the neoadjuvant chemoradiotherapy (NCRT) group (n = 60), and the neoadjuvant chemoimmunotherapy (NCIT) group (n = 71). To address baseline confounding, generalized overlap weighting (GOW) was used for the four-group comparison, and overlap weighting (OW) was used for the pairwise comparisons of NCRT versus NCT and NCIT versus NCT. Logistic regression models were used to evaluate the associations between treatment strategies and the odds of POP. Sensitivity analyses of the pairwise comparisons were performed using stabilized inverse probability of treatment weighting (S-IPTW). Results: In the four-group comparison, neither NCT nor NCRT was associated with significantly higher odds of POP than S-alone, whereas NCIT was associated with higher odds (weighted odds ratio [OR], 1.95; 95% confidence interval [CI], 1.02–3.70). In pairwise analyses, the weighted ORs were 0.45 (95% CI, 0.20–1.01) for NCRT versus NCT and 2.32 (95% CI, 1.14–4.71) for NCIT versus NCT. Sensitivity analyses were directionally consistent. Conclusions: In this single-center observational cohort, NCRT was not associated with higher odds of POP than S-alone or NCT, whereas NCIT was associated with higher odds of POP. These findings support careful perioperative respiratory management in patients receiving neoadjuvant immunotherapy.