Major pathologic response as a prognostic surrogate in esophageal squamous cell carcinoma patients receiving...

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.

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.

Of the 305 patients, 105 achieved MPR, demonstrating a significantly improved RFS (P value < 0.001), L-RFS (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, non-MPR patients exhibited a higher recurrence rate, although the recurrence sites were similar between the two groups.

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.