This study aims to examine the recurrence patterns in patients with locally advanced esophageal squamous cell carcinoma who underwent surgery following neoadjuvant chemotherapy combined with immunotherapy. Retrospective analysis of patients with esophageal squamous cell carcinoma who received neoadjuvant Chemo-IO before surgery at Zhejiang Cancer Hospital between 2019 and 2023. The clinicopathological features, recurrence patterns, overall survival (OS), and disease-free survival (DFS) were analyzed, and the impact of postoperative adjuvant radiotherapy on prognosis was evaluated. In total, 422 patients were included in the study. After a median follow-up of 22 months, disease recurrence was observed in 89 (21.1%) patients, comprising 37 cases (8.8%) of locoregional recurrence, 30 cases (7.1%) of distant metastasis, and 22 cases (5.2%) of combined recurrence. Patients who achieved a pathologic complete response demonstrated significantly higher 3-year OS rates (90.0% vs. 72.5%
P = 0.01) and DFS rates (73.2% vs. 61.8%
P = 0.046). Univariable and multivariable analyses identified pathological lymph node staging (ypN0 vs. ypN+
HR: 1.73
95% CI: 1.01-2.99
P = 0.047) as an independent prognostic factor for locoregional recurrence. Kaplan-Meier curves for OS and DFS demonstrated that postoperative radiotherapy (PORT) significantly improved OS and DFS in ypN+ patients after propensity score matching. Additionally, PORT significantly enhanced locoregional recurrence-free survival and distant recurrence-free survival in ypN+ patients. In patients receiving neoadjuvant Chemo-IO, locoregional recurrence is the predominant recurrence pattern. For ypN+ patients, PORT significantly improved survival outcomes. However, long-term outcomes require further investigation through randomized controlled trials.