Neoadjuvant immunotherapy followed by surgery versus non-operative management in dMMR/MSI gastroesophageal adenocarcinomas: a case series and review of the literature

Background Deficient mismatch repair (dMMR)/microsatellite instable (MSI) gastric adenocarcinomas and gastroesophageal junction adenocarcinomas (GEAs) constitute a biologically distinct subgroup characterized by high immunogenicity and limited benefit from fluoropyrimidine-based chemotherapy. Recent phase II trials, such as NEONIPIGA and INFINITY, have demonstrated unprecedented pathological complete response (pCR) rates with neoadjuvant immune checkpoint blockade, raising the question of whether chemotherapy and surgery could be safely omitted in this population. Material and methods We retrospectively analyzed all consecutive patients with localized dMMR/MSI GEA treated with neoadjuvant immunotherapy between January 2024 and July 2025 at Paoli-Calmettes Institute (Marseille, France). Clinical, endoscopic, radiologic, and pathological data were prospectively collected and retrospectively reviewed. Pathologically documented response was assessed on surgical specimens when available, and clinical complete response (cCR) was defined by the absence of detectable disease on endoscopy or imaging. Results Ten patients were included in this retrospective review (median age 70.5 years; six males, four females). Nine of them received neoadjuvant dual immunotherapy, and one received chemoimmunotherapy. Six patients underwent surgery, four achieving pCR; one patient achieved partial regression (TRG1), and one TRG2. Four patients were managed non-operatively with two obtaining complete clinical response, and all ultimately achieved cCR following individualized treatment continuation. After a median follow-up of 19.5 months (range 10-22), all patients were alive and disease-free. Conclusions These preliminary real-world data suggest that neoadjuvant immunotherapy may be safe and feasible in selected patients with localized dMMR/MSI GEA, and that non-operative management warrants further evaluation.