Optimizing Postoperative Management in Deficient Mismatch Repair/Microsatellite Instability-High Gastric or...

The benefit of chemotherapy in locally advanced gastroesophageal cancer with deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) remains uncertain. This study aimed to identify optimal postoperative management strategies for dMMR/MSI-H gastric or gastroesophageal junction (EGJ) adenocarcinoma.

Patients with pathologically confirmed stage II-IVA dMMR/MSI-H gastric or EGJ adenocarcinoma who underwent D2 gastrectomy between 2015 and 2022 were retrospectively enrolled from 4 centers. Postoperative management strategies included observation, chemotherapy, immune checkpoint inhibitors (ICIs), or ICIs combined with chemotherapy (ICI-chemo). The primary endpoint was 2-year event-free survival (EFS), and the secondary endpoints were EFS and overall survival (OS).

A total of 156 patients were included in the analysis. The highest 2-year EFS was observed in the ICI-chemo group (87.5%), followed by the observation group (86.7%) and the ICI monotherapy group (86.5%), whereas chemotherapy alone yielded the lowest rate (75.7%). Patients with earlier-stage disease had significantly lower risks of progression (hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.16-0.53) and death (HR, 0.30; 95% CI, 0.14-0.64). EFS improved progressively from chemotherapy to observation and further to ICI-containing regimens across stages. In stage III-IVA disease, ICI monotherapy significantly improved OS compared with chemotherapy (HR, 0.28; P=0.038), with a favorable trend observed for ICI-chemo (HR, 0.32).

Pathological stage is an independent prognostic factor in resectable dMMR/MSI-H gastric and EGJ adenocarcinoma. Adjuvant chemotherapy alone demonstrated limited benefit, whereas ICI-based regimens were associated with improved outcomes, supporting their use in high-risk patients.