Microsatellite instability in gastric cancer: An institutional case series analysis in patients treated with neoadjuvant therapy

Introduction: Past studies documented that microsatellite instability (MSI) is associated with improved survival in gastric cancer (GC). The aim of this study was to evaluate MSI status in a series of GCs treated with neoadjuvant therapy in relation to the tumors' characteristics and oncological outcomes. Methods: Patients with GCs treated between 2017 and 2022 at a single Italian high-volume Institution undergoing pre-operative treatment followed by resection were included if studied for their microsatellite status. Clinicopathological data were analyzed for the association with MSI. The same features were analyzing pooling the series with a subset of patients from another European trial. Secondary outcomes included the overall (OS), and disease-free (DFS) survivals comparing MSI vs microsatellite stable (MSS) GCs, and GCs presenting complete-major response (TRG1-2) vs partial response (TRG3-4) and absence of response (TRG5). Results: Among 73 patients selected, 12.3% were MSI. In the single institutional analysis, we documented a difference in the distribution of ypT stages with a prevalence of ypT0 patients in MSI vs MSS patients (ypT0 respectively 11.1% vs 1.6%, p < 0.0001). However, this difference was not of statistical value when pooling patients with those from the European trial (overall 108 patients, 9.2% MSI; ypT0 respectively 10.0% vs 2.0%, p 0.144). In the pooled analysis, a prevalence of female patients was reported in the MSI group comparing MSS (respectively, 70.0% vs 27.6%, p 0.01). At a mean follow-up of 27.7 months, OS and DFS survivals were reported similar comparing MSS and MSI (log-rank test respectively p 0.18 and p 0.96), however TRG1-2 GCs had improved OS and DFS comparing other sub-groups (TRG1-2 vs TRG3-4 vs TRG5, OS and DFS log-rank test respectively p 0.017 and p 0.0029). Conclusion: This study could not demonstrate a correlation between microsatellite status and survival in gastric cancer patients who underwent pre-operative treatment. A complete/major response was the only variable correlated with mid-term survival.