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

Background: Microsatellite instability (MSI-H) represents a small subgroup of gastric cancer (GC) with a favorable prognostic and predictive significance. This study aimed to investigate locoregional nodes involvement, overall survival (OS) and disease-free survival (DFS), and the interplay between molecular subtypes and histological profiles in relation to survival outcomes in MSI versus MSS GC.

Methods: This study included 72 GC patients treated with surgery with or without chemotherapy from 2017 to 2023. Clinicopathological characteristics, OS and DFS were compared between LN-positive and negative patients, stratified by microsatellite status, treatments, molecular profiles, tumor cell types.

Results: MSI GC was more common in older patients (79.0 versus 70.2 years, p<0.001), predominantly females (73.68% vs. 43.32%, p=0.023), and associated with intestinaltype histology (94.5% vs. 49%, p=0.002). Positive LN and lymphovascular invasion were lower in the MSI group (2.73 vs. 4.15 p=0.366; 36.8% vs. 64.5% p=0.039). MSI showed slightly better OS and DFS (84.2% vs. 66% p=0.108; 84.62% vs. 63.89% p=0.120). MSI GC also had improved OS and DFS in both LNs positive (OS 72.7% vs. 61.3% p=0.255; DFS 75% vs. 50% p=0.148) and LNs negative groups (OS 100% vs. 85.7% p=0.149; DFS 100% vs. 85.7% p=0.376). In patients not receiving chemotherapy, MSI/intestinal-type had the highest OS and DFS (77% and 87.5%), whereas MSS/mixed-type group had the poorest (25% and 100%)(p=0.024 and p=0.290). With chemotherapy, MSI/intestinal-type had the highest OS and DFS (100% and 100%), whereas MSS/mixed-type group had the poorest (66.7% and 50%)(p=0.741 and p=0.397, respectively).

Conclusions: MSI GCs have a significantly lower risk of locoregional lymph node involvement and better OS and DFS compared to MSS tumors. Secondly, treatment responses diverge based on MSI status: patients with MSI tumors benefit more from upfront surgical interventions, while 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 as well as clinical conditions of patients.