Abstract
BACKGROUND: Gastroesophageal cancer is a major cause of cancer-related mortality worldwide. Treatment of both early stage and advanced disease remains highly reliant on cytotoxic chemotherapy. About 4-24% of gastroesophageal cancers are microsatellite instability high (MSI-H). The MSI-H subtype is associated with favorable prognosis, resistance to cytotoxic chemotherapy, and sensitivity to immune checkpoint inhibitors (ICI). Recent studies have demonstrated promising activity of ICIs in the MSI-H subtype, resulting in fundamental changes in the management of MSI-H gastroesophageal adenocarcinoma. PURPOSE: In this review, we discuss the prevalence, characteristics, prognosis, and management of MSI-H gastroesophageal adenocarcinoma, with a focus on recent and ongoing studies that have changed the landscape of treatment for the MSI-H subtype. We also discuss current challenges in the management of resectable and advanced MSI-H gastroesophageal cancer, including the need for more accurate biomarkers of response to ICI therapy.