Clinicopathologic features, treatment patterns, and outcomes of microsatellite instability–high (MSI-H) gastric (GC) and gastroesophageal junction adenocarcinoma (GEJ): A single-center retrospective analysis.

445 Background: The biologically distinct subtype of MSI-H GC/GEJ has prognostic and therapeutic implications. Immunotherapy (IO) has demonstrated clinical benefit in MSI-H disease; real-world clinical outcomes and treatment patterns are underreported. We performed a retrospective review to characterize clinicopathologic features, treatment patterns, and survival outcomes in locally advanced/metastatic GC/GEJ. Methods: We identified 35 patients (pts) with biopsy-proven MSI-H GC/GEJ treated at City of Hope between 2012 and 2025. Clinical, pathologic, molecular, and treatment data were collected. Pts were categorized as responders/non-responders based on RECIST v1.1 criteria and clinical outcomes. Survival outcomes were estimated using Kaplan–Meier curves and stratified by stage and IO response. Results: Median age was 64 years (SD 14.6); 51.4% were male. Median follow-up was 33 months. At diagnosis, pts had stage I (11.4%), stage II (26.5%), stage III (17.1%), and stage IV (45.7%) disease. Most tumors were poorly differentiated (68.6%) and HER2-negative (91.2%). 17.6% of pts had Lynch Syndrome. Tumor sites included gastric body (40%), pylorus/antrum (28.6%), cardia (20%), and GEJ (11.4%). Surgery was performed on 80% of stage I-III pts and 61.1% of stage IV pts. IO was given to 52.6% of stage II–III pts and 87.5% of stage IV pts. IO response was strongly associated with durable survival. Responders achieved 12-, 24-, and 36-month overall survival (OS) rates of 82%, 82%, and 68%, respectively (median OS not reached). In contrast, non-responders had OS rates of 67%, 33%, and