Patterns of survival and recurrence in non-pathological complete response to neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma: a real-world single-center study

Neoadjuvant immunochemotherapy (NICT) is a strategy for locally advanced esophageal squamous cell carcinoma (ESCC), yet responses vary. Survival and recurrence patterns in non-pathological complete response (non-pCR) patients remain incompletely defined. This single-center retrospective study included non-pCR thoracic ESCC patients (Jan 2020-Dec 2023) who underwent R0 esophagectomy after neoadjuvant immunochemotherapy(NICT). Patients were classified by tumor regression grade (TRG) into TRGa (0%< residual tumor ≤ 50%) and TRGb (residual tumor > 50%). Primary endpoints were disease-free survival (DFS) and overall survival (OS).Recurrence patterns and prognostic factors were also analyzed. Among 178 patients (TRGa:84, TRGb:94), the TRGb group had more aggressive features, including higher rates of ypT3-4 (77.7% vs. 26.2%, P < 0.001), perineural invasion (PNI, 44.7% vs. 6.0%, P < 0.001), and lymphovascular invasion (LVI, 63.8% vs. 27.4%, P < 0.001). The TRGb group demonstrated inferior DFS ( P = 0.038) and OS ( P = 0.003). Multivariate analysis identified ypN3(≥ 7 regional LN metastases after neoadjuvant therapy) as an independent adverse prognostic factor. The overall recurrence rate was 35.4% (63/178), with the TRGb group showing a higher distant metastasis rate (23.4% vs. 11.9%, P = 0.046). ypN+ patients had a significantly higher incidence of extra-regional lymph node metastasis than ypN0(negative pathological lymph node status after neoadjuvant therapy) patients (10.5% vs. 1.1%, P = 0.007). ypN3 was the independent predictor of poor prognosis in non-pCR ESCC; TRGb or ypN+ associates with worse survival and distant metastasis. Postoperative ypN status supports risk‑stratified adjuvant therapy and intensified surveillance for high‑risk patients.