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 outcome 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). Propensity score matching analysis and 60-month censoring were used to reduce differences between groups. Cox proportional hazards model was used for analysis. Results Among 366 non-pCR patients, 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). Five-year OS rate (50.6% vs 37.2%, p = 0.014) and EFS rate (50.0% vs 31.1%, p < 0.001) were higher in nICT group. In matched multivariable Cox model, nICT was independently associated with improved EFS (P = 0.005) but not OS (P = 0.707). Adverse EFS was independently associated with open esophagectomy (OE) (p = 0.003), ypN2-3 ( p < 0.001) and perineural invasion (PNI) (p = 0.003), while lower Ki-67 (p = 0.035) and postoperative adjuvant treatment (p = 0.012) were associated with improved EFS. For OS, PNI was an adverse factor (p = 0.004), whereas postoperative adjuvant treatment was a protective one (p < 0.001). 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 were important correlates of long-term outcomes and may inform postoperative risk stratification and management.