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

J Gastrointest Cancer. 2024 Jun;55(2):483-496. doi: 10.1007/s12029-023-01003-5. Epub 2023 Dec 22.

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

MeSH terms

  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / genetics
  • Adenocarcinoma* / pathology
  • Adenocarcinoma* / therapy
  • Biomarkers, Tumor / genetics
  • Esophageal Neoplasms* / drug therapy
  • Esophageal Neoplasms* / genetics
  • Esophageal Neoplasms* / pathology
  • Esophageal Neoplasms* / therapy
  • Esophagogastric Junction / pathology
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Microsatellite Instability*
  • Prognosis
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / pathology
  • Stomach Neoplasms* / therapy

Substances

  • Immune Checkpoint Inhibitors
  • Biomarkers, Tumor