Real-World Role of Adjuvant Radiotherapy after Neoadjuvant Treatment for Thoracic Esophageal Cancer

Background Patients with locally advanced esophageal squamous cell carcinoma (ESCC) undergoing surgery after neoadjuvant chemotherapy (NCT) or neoadjuvant chemoimmunotherapy (NICT) remain at risk of disease progression. Currently, adjuvant radiotherapy (ART) is not recommended following these treatment sequences due to a lack of high-level evidence supporting its efficacy. This real-world study preliminarily evaluates the potential role of ART in this clinical setting. Methods A sum of 324 ESCC patients who had surgery following NCT or NICT were included and divided into two groups: the neoadjuvant therapy with surgery (NA+S) group and the neoadjuvant therapy with surgery followed by adjuvant radiotherapy (NA+S+RT) group. The primary outcomes assessed were the two-year recurrence free survival (RFS) and overall survival (OS). The Kaplan-Meier method was utilized for survival analysis, while the Cox regression model was applied to determine the clinical factors linked to prognosis. Results The NA+S group (n=180) and the NA+S+RT group (n=144) showed no statistically significant differences in 2‑year RFS (71.8% vs 68.8%, P=0.661, 95% CI: 55.52‑63.95) or 2‑year OS (80.7% vs 74.3%, P=0.162, 95% CI: 60.44‑68.17), indicating that ART did not provide a survival benefit. Subgroup analysis showed no significant survival difference between patients with major pathological response (MPR) and those without (non-MPR). However, among ypN+ patients, RFS was significantly improved in the NA+S+RT group (60.6% vs 41.8%, P=0.005, 95% CI: 37.65‑50.90). Similarly, ypT3‑4 patients showed a survival benefit in 2‑year RFS after ART (65% vs 44.4%, P<0.05, 95% CI: 38.42‑52.33). The incidence of distant metastasis, especially to the lung, bone, and pleura, was notably greater in the NA+S+RT group than in the NA+S group (P<0.05). The results of the multivariate analysis identified ypN+ and non‑MPR as independent risk factors for both RFS and OS. Conclusion ART did not improve survival outcomes in the entire neoadjuvant therapy cohort; however, it conferred a survival benefit in patients with ypN+ disease or ypT3‑4 tumors.