Management of Microsatellite Instability High (MSI-H) Gastroesophageal Adenocarcinoma

J Gastrointest Cancer. 2023 Dec 22. doi: 10.1007/s12029-023-01003-5. Online ahead of print.

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.

Keywords: Gastroesophageal adenocarcinoma; Immunotherapy; Microsatellite instability; Molecular biomarkers.

Publication types

  • Review