Adjuvant Chemotherapy in Microsatellite Instability-High Gastric Cancer

Cancer Res Treat. 2020 Oct;52(4):1178-1187. doi: 10.4143/crt.2020.313. Epub 2020 Jun 11.

Abstract

Purpose: Microsatellite instability (MSI) status may affect the efficacy of adjuvant chemotherapy in gastric cancer. In this study, the clinical characteristics of MSI-high (MSI-H) gastric cancer and the predictive value of MSI-H for adjuvant chemotherapy in large cohorts of gastric cancer patients were evaluated.

Material and methods: This study consisted of two cohorts. Cohort 1 included gastric cancer patients who received curative resection with pathologic stage IB-IIIC. Cohort 2 included patients with MSI-H gastric cancer who received curative resection with pathologic stage II/III. MSI was examined using two mononucleotide markers and three dinucleotide markers.

Results: Of 359 patients (cohort 1), 41 patients (11.4%) had MSI-H. MSI-H tumors were more frequently identified in older patients (p < 0.001), other histology than poorly cohesive, signet ring cell type (p=0.005), intestinal type (p=0.028), lower third tumor location (p=0.005), and absent perineural invasion (p=0.027). MSI-H status has a tendency of better disease-free survival (DFS) and overall survival (OS) in multivariable analyses (hazard ratio [HR], 0.4; p=0.059 and HR, 0.4; p=0.063, respectively). In the analysis of 162 MSI-H patients (cohort 2), adjuvant chemotherapy showed a significant benefit with respect to longer DFS and OS (p=0.047 and p=0.043, respectively). In multivariable analysis, adjuvant chemotherapy improved DFS (HR, 0.4; p=0.040).

Conclusion: MSI-H gastric cancer had distinct clinicopathologic findings. Even in MSI-H gastric cancer of retrospective cohort, adjuvant chemotherapy could show a survival benefit, which was in contrast to previous prospective studies and should be investigated in a further prospective trial.

Keywords: Adjuvant chemotherapy; Microsatellite instability; Stomach neoplasms.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Gastrectomy
  • Humans
  • Male
  • Microsatellite Instability*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / prevention & control
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies
  • Stomach / pathology
  • Stomach / surgery
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / therapy*

Substances

  • Biomarkers, Tumor