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

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.

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.

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).

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.