Which surrogate endpoint best predict survival in locally advanced gastric cancer patients undergoing neoadjuvant chemoimmunotherapy followed by surgery? A multicenter retrospective study.

Introduction: Recent clinical researches have reported that neoadjuvant chemoimmunotherapy (NCIT) significantly improve the pathological complete response (pCR) and major pathological response (MPR) rates. However, surrogate endpoints for survival remains controversy for locally advanced gastric cancer (LAGC) after NCIT.

Methods: A retrospective analysis was performed on 84 patients with LAGC who had undergone NCIT following radical resection in three medical centers in China, between July 2020 and September 2023. Survival curves for event-free survival (EFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and the log-rank test was used to compare survival outcomes. Univariate and multivariate analyses for prognostic factors were based on Cox regression analysis.

Results: The rates of ypN0, pCR and MPR were 60.7 % (51/84), 26.2 % (22/84) and 39.3 %(33/84),respectively. Patients with ypN0 had better EFS and OS than those with ypN+ (all p < 0.05). Survival was equivalent between pCR and non-pCR group (all p > 0.05). while patients with MPR had better EFS than those with non-MPR (p = 0.028). Furthermore, a multivariate analysis revealed that the lymph nodes(LNs) status was an independent prognostic factor for the EFS (hazard ratio [HR] 5.533, 95 % confidence interval [CI] 1.186-25.804, p = 0.029) and OS (HR 5.116, 95 % CI 1.357-19.281, p = 0.016), but not pCR and MPR (all p > 0.05). Based on the status of pathologic LNs, ypN0 group showed lower depth of tumor invasion, and lower rate of perineural and vascular invasion (all p < 0.05).

Conclusion: These findings demonstrated that ypN0 may be important as a surrogate of favorable clinical outcome in LAGC patients who received NCIT plus curative surgery.