Major pathologic response as a prognostic surrogate in esophageal squamous cell carcinoma patients receiving neoadjuvant chemotherapy/ chemoimmunotherapy: A multi-center cohort study

Purpose: To determine the prognostic and survival surrogate value of major pathologic response (MPR) in esophageal squamous cell carcinoma (ESCC) patients undergoing neoadjuvant chemotherapy/chemoimmunotherapy(nCT/nICT) and surgery. Method: A retrospective multi-center study cohort study enrolled 305 ESCC patients who underwent neoadjuvant chemotherapy/chemoimmunotherapy followed by esophagectomy. Endpoints included recurrence-free survival (RFS), locoregional recurrence-free survival(L-RFS), distant metastasis-free survival(D-MFS), and recurrence patterns. The Cox regression analysis and Harrell's C-index were used to analyze survival differences and surrogate endpoints. The Kaplan-Meier method was used for the subgroup analysis in two subgroups(the patients receiving nICT and patients receiving nCT) and the prognostic value analysis of adjuvant therapy in non-MPR and MPR patients. Result: Of the 305 patients, 105 achieved MPR, demonstrating a significantly improved RFS (P value < 0.001), LRFS (P value < 0.001), and D-MFS (P value = 0.003). MPR was identified as an independent risk factor for RFS (HR:0.415, 95%CI:[0.227, 0.759], P value = 0.004) and demonstrated equal predictive capacity to be a surrogate of survival endpoints with T stage and N stage(Harrell's C-index: 0.613). In subgroup analysis, patients with MPR showed better survival outcomes in subgroups that received neoadjuvant chemoimmunotherapy (P value = 0.012) and neoadjuvant chemotherapy(P value < 0.001). Additionally, adjuvant therapy did not confer additional survival benefits to both MPR and non-MPR patients. Compared with patients who achieved MPR, nonMPR patients exhibited a higher recurrence rate, although the recurrence sites were similar between the two groups. Conclusion: MPR can serve as an independent prognostic factor and a surrogate of survival endpoints in ESCC patients undergoing nCT/nICT. Besides, as a potential indicator for postoperative management, MPR can provide reference basis and evidence support in clinical practice.