The impact of microsatellite instability in patients with locally advanced resectable gastric cancer undergoing perioperative therapy

Abstract Background According to TCGA (The Cancer Genome Atlas) and ACRG (Asian Cancer Research Group) classifications, tumors with high microsatellite instability (MSI-H) are classified as a specific group. Currently, perioperative chemotherapy is a standard of care in patients with locally advanced resectable gastric cancer (LARGC) in Western countries. Immune checkpoint inhibitors (ICIs) have shown efficacy in the treatment of metastatic gastric cancer, but their role in the neoadjuvant setting has not been studied. It is still unknown whether MSI-H tumors can benefit from perioperative therapy. Methods We analyzed patients with LARGC who had perioperative therapy from September 2019 to March 2023 at N.N.Blokhin National Medical Research Center of Oncology (Russia Federation). All patients were analyzed for MSI using PCR. Clinico-pathological factors, tumor regression grade (according to Mandard classification), disease-free (DFS), and overall survival (OS) were calculated and correlated with MSI status. Patients with MSI-H after December 2021 received perioperative chemoimmunotherapy (FOLFOX + nivolumab). Results The MSI-H phenotype was indicated in 29 (10.35%) out of 280 analyzed tumors. In 272 patients who received perioperative chemotherapy, the 2-year DFS was 51.40% in MSI-H tumors vs. 68.35% in MSS tumors (HR = 2.22, 95% CI 1.08–4.54, p = 0.028). The 2-year OS was 62.1% in MSI-H tumors vs. 83.27% in MSS tumors (HR = 2.71, 95% CI 1.12–6.53, p = 0.026). 3 (37.5%) patients out of 8 with MSI-H status who received perioperative chemoimmunotherapy had a complete pathologic response (TRG-1). Conclusion Our study shows diminished survival in patients with MSI-H gastric cancer undergoing perioperative chemotherapy. Then introduction of immunotherapy into perioperative treatment in patients with MSI-H gastric cancer demonstrates encouraging activity.