Neoadjuvant Immunotherapy-Based Treatment Versus Chemotherapy Alone in Resectable Locally Advanced dMMR/MSI-H Gastric...

Background: Evidence suggests dMMR/MSI-H gastric cancer patients respond better to immune checkpoint inhibitors (ICIs) than to chemotherapy, but recent trials have not consistently shown this benefit in subgroup analyses. It remains unclear whether improved the pathological response translates into survival benefit. This study compares pathological response and survival outcomes between neoadjuvant immunotherapy regimens (ICI monotherapy, ICI plus chemotherapy, or dual ICIs; group A) and chemotherapy alone (group B) in locally advanced dMMR/MSI-H gastric cancer. Methods: Between January 2020 and December 2025, 24 patients undergoing surgery were enrolled-14 in group A and 10 in group B. The primary endpoints were major pathological response (MPR), pathological complete response (pCR), event-free survival (EFS), and overall survival (OS). A meta-analysis integrating our cohort with external studies was conducted to strengthen the evidence base. Results: In our cohort, compared with group B, group A appeared to have higher rates of MPR (85.7% vs. 20%) and pCR (42.9% vs. 0%). EFS and OS in group A improved numerically (EFS: p = 0.10; OS: p = 0.12). Surgical outcomes and treatment-related adverse events were not different between the two groups. Pooled analyses implied consistent improvements in MPR (RR = 4.09) and pCR (RR = 5.38). Additionally, reconstructed individual survival data suggested that group A might have better EFS (p = 0.034) while OS (p = 0.890) showed little difference. Conclusions: Neoadjuvant immunotherapy-based regimens might show some enhancements in treatment response rates and EFS compared with chemotherapy alone, which may imply their therapeutic potential in this molecularly defined patient population.