Abstract
BACKGROUND: Neoadjuvant immunotherapy combined with chemotherapy (NICT) has demonstrated a good pathological complete response (pCR) rate and prognosis in locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, the value and safety of postoperative radiotherapy (PORT) in the group that does not achieve pCR remain unclear. METHODS: This retrospective study included LA-ESCC patients with non-pCR after NICT. Propensity score matching (PSM) was used to balance baseline characteristics between the PORT and non-PORT groups. The outcomes assessed were disease-free survival (DFS), recurrence patterns, and treatment-related toxicity. RESULTS: In the cohort of 204 enrolled patients, 50 underwent PORT, while the remaining 154 did not, with a median follow-up of 27.0 months. 32 (20.8%) of the non-PORT patients experienced recurrence events, including locoregional recurrence (10/32, 31.3%), distant metastasis (10/32, 31.3%), and mixed patterns (12/32, 37.5%), and 71.9% of cases underwent disease progression within 12 months. With regard to patterns of locoregional recurrence, mediastinal lymph node metastasis represented the most prevalent failure pattern. In terms of distant metastasis, supraclavicular lymph node metastasis was the most commonly observed mode. By PSM analysis, DFS was improved for the patients receiving PORT (HR, 0.26; 95% CI, 0.09-0.77; P = 0.008). Subgroup and analyses revealed a significant increase in both 1- and 2-year DFS rates in patients with ypN+, ypT3-4, yp Stage III-IVA, tumor regression grade (TRG) 2-3, non-downstaging of T stage or middle/lower thoracic esophageal tumors. In patients with non-downstaging of N or TNM status, there was a notable enhancement in the 2-year DFS rate. Treatment-related adverse events (TRAEs) were predominantly grade 1-2 in the PORT group, with radiation esophagitis and myelosuppression being the most frequently observed. CONCLUSION: Mediastinal and supraclavicular lymph node metastasis remains the primary cause of treatment failure in LA-ESCC patients with non-pCR after NICT and without PORT. PORT significantly improves DFS in patients with high-risk clinicopathological features or poor response to NICT, and demonstrates a favorable safety profile, indicating an effective adjuvant treatment strategy for improving prognosis.