Five-Year Survival Analyses on Non-Pathological Complete Response Esophageal Squamous Cell Carcinoma Patients After Neoadjuvant Regimens Plus Surgery: A Propensity Score Matching, Real-World Cohort Study.

Background: Non-pathological complete response (non-pCR) is common in esophageal squamous cell carcinoma (ESCC) patients after neoadjuvant therapy, yet evidence guiding long-term outcomes and postoperative risk stratification in the immunotherapy era remains limited.

Methods: We retrospectively enrolled consecutive ESCC patients treated with neoadjuvant immunochemotherapy (nICT) or chemotherapy alone (nCT) followed by esophagectomy and restricted analyses to non-pCR cases. Primary endpoints were five-year overall survival (OS) and event-free survival (EFS). A 1:1 optimal propensity score matching (PSM) procedure and administrative censoring at 60 months were applied. Survival outcomes were assessed using Kaplan-Meier and Cox proportional hazards analyses.

Results: Among 366 patients with non-pCR disease, 164 matched pairs were generated. After matching, nICT demonstrated a higher major pathological response (MPR) rate (19.5% vs. 6.1%), a lower ypT4 proportion (3.7% vs. 22.0%), and fewer recurrence/metastasis rate (40.2% vs. 58.5%), all p < 0.001. In the matched multivariable Cox model, nICT was independently associated with a lower risk of EFS events (HR 0.55, 95% CI 0.36-0.84; p = 0.005), whereas no independent association with OS was observed (HR 0.94, 95% CI 0.70-1.27; p = 0.707). Open esophagectomy (OE), ypN2-3 disease, and perineural invasion (PNI) were associated with worse EFS, whereas lower Ki-67 expression and postoperative adjuvant treatment were associated with better EFS. PNI was associated with worse OS, and postoperative adjuvant treatment was associated with better OS.

Conclusion: Among non-pCR ESCC patients after neoadjuvant therapy and surgery, nICT was associated with lower recurrence risk and improved five-year EFS compared with nCT, whereas a significant OS advantage was not observed. Pathological factors (PNI, high Ki-67, and residual nodal burden) and postoperative treatment may help inform risk stratification, although the observational treatment associations should be interpreted cautiously.