Postoperative radiotherapy versus systemic therapy alone for locally advanced esophageal squamous cell carcinoma following neoadjuvant chemoimmunotherapy

Objective Neoadjuvant chemoimmunotherapy (nICT) followed by radical esophagectomy is increasingly used for locally advanced esophageal squamous cell carcinoma (LA-ESCC), but the incremental value of postoperative radiotherapy (PORT) in patients who also receive postoperative systemic therapy remains uncertain. This study evaluated survival outcomes, recurrence patterns, and treatment-related toxicity associated with adding PORT after nICT and surgery. Methods We retrospectively reviewed 336 patients with LA-ESCC who underwent nICT followed by R0 esophagectomy between February 2021 and November 2024. Postoperatively, 93 patients received systemic therapy plus PORT, whereas 243 received systemic therapy alone. Propensity score matching at a 1:1 ratio was performed to balance baseline clinicopathological characteristics, yielding 71 patients in each group. Disease-free survival (DFS), overall survival (OS), recurrence patterns, and treatment-related adverse events were analyzed. Results After PSM, 142 patients (71 per group) were analyzed. The PORT group demonstrated significantly improved 2-year OS (91.0% vs. 75.5%; HR = 0.409, 95% CI: 0.181-0.925, P = 0.026) and 2-year DFS (74.2% vs. 50.1%; HR = 0.525, 95% CI: 0.303-0.911, P = 0.018) compared to the systemic therapy group. Patients with ypStage III-IV and ypN+ derived the most significant survival benefits. PORT reduced the locoregional recurrence rate from 48.1% to 32.1%, shifting the primary failure mode to distant metastasis (46.4%). Grade ≥3 treatment-related adverse events occurred in 18.3% of PORT patients (primarily hematologic), with grade 3 radiation esophagitis occurring in only 1.1%. Conclusion For LA-ESCC patients treated with nICT and surgery, adding PORT to postoperative systemic therapy improves survival and optimizes recurrence patterns with acceptable toxicity. It represents a promising intensification strategy for high-risk patients.