Resectable gastric cancer: should we apply a tailored surgical strategy according to microsatellite status?

Background: High microsatellite instability (MSI) represents a small subgroup of gastric cancer (GC) with favorable prognostic and predictive significance. This study aimed to investigate locoregional lymph node (LN) involvement, overall survival (OS), disease-free survival (DFS), and the interplay between molecular subtypes and histologic profiles regarding survival outcomes in MSI GC vs microsatellite stability (MSS) GC. Methods: This study included 72 patients with GC who underwent surgery with or without chemotherapy from 2017 to 2023. Clinicopathologic characteristics, OS, and DFS were compared between LN-positive and LN-negative patients stratified by microsatellite status, treatments, molecular profiles, and tumor cell types. Results: MSI GC was more common in older patients (79.0 vs 70.2 years; P <.001), more common in females (73.68% vs 43.32%; P =.023), and associated with intestinal-type histology (94.5% vs 49.0%; P =.002). Positive LN involvement and lymphovascular invasion (LVI) were lower in the MSI group than in the MSS group (positive LN: 2.73 vs 4.15, respectively; P =.366; LVI: 36.8% vs 64.5%, respectively; P =.039). Patients with MSI showed slightly better OS and DFS than those with MSS (OS: 84.20% vs 66.00%, respectively; P =.108; DFS: 84.62% vs 63.89%, respectively; P =.120). In addition, compared with patients with MSS GC, those with MSI GC had improved OS and DFS in the LN-positive group (OS: 72.7% vs 61.3%, respectively; P =.255; DFS: 75.0% vs 50.0%, respectively; P =.148) and LN-negative group (OS: 100.0% vs 85.7%, respectively; P =.149; DFS: 100.0% vs 85.7%, respectively; P =.376). In patients not receiving chemotherapy, the MSI/intestinal-type group had the highest OS and DFS (77.0% and 87.5%, respectively; P =.024), whereas the MSS/mixed-type group had the lowest OS and DFS (25.0% and 100.0%, respectively; P =.290). In patients receiving chemotherapy, the MSI/intestinal-type group had the highest OS and DFS (100.0% and 100.0%, respectively; P =.741), whereas the MSS/mixed-type group had the lowest OS and DFS (66.7% and 50.0%, respectively; P =.397). Conclusion: First, patients with MSI GC have a significantly lower risk of locoregional LN involvement and better OS and DFS than those with MSS GC. Second, treatment responses differ based on MSI status: patients with MSI tumors benefit more from upfront surgical interventions, whereas those with MSS, particularly mixed histotypes, demonstrate improved outcomes with preoperative chemotherapy. These results advocate for a tailored therapeutic approach that considers microsatellite status, Lauren classification, and patient clinical conditions.