Perioperative chemotherapy for gastric cancer patients with microsatellite instability or deficient mismatch repair: A systematic review and meta‐analysis

Abstract Background The efficacy of perioperative chemotherapy for deficient mismatch repair or microsatellite instability–high (dMMR/MSI‐H) gastric cancer (GC) remains controversial. Methods This study was preregistered with the PROSPERO platform (CRD42023494276), and studies comparing perioperative chemotherapy with surgery alone in resectable dMMR/MSI‐H GC were included. Hazard ratios (HRs) and their 95% confidence intervals (CIs) of survival outcomes were extracted. A random‐effects model was used in the pooled analysis. Results Twenty‐two studies, which encompassed approximately 1600 patients with dMMR/MSI‐H GC, were included. The results indicated that perioperative chemotherapy does not significantly improve overall survival (OS) (HR, 0.85; 95% CI, 0.58–1.26) and disease‐free survival (DFS) (HR, 0.77; 95% CI, 0.53–1.12) in dMMR/MSI‐H GC. In the subgroup analysis, adjuvant chemotherapy was not associated with improved OS (HR, 0.83; 95% CI, 0.50–1.37) but was associated with improved DFS (HR, 0.64; 95% CI, 0.43–0.96). However, the benefit of adjuvant chemotherapy for DFS was not significant in the pooled analysis of multivariable‐adjusted results. Similar results were observed for neoadjuvant chemotherapy (OS: HR, 0.84; 95% CI, 0.44–1.57; DFS: HR, 1.13; 95% CI, 0.50–2.53). Additionally, stage stratification analysis demonstrated no significant survival benefit of adjuvant chemotherapy for stage II (OS: HR, 0.77; 95% CI, 0.31–1.90) or stage III (OS: HR, 0.72; 95% CI, 0.36–1.46) dMMR/MSI‐H GC. Conclusions Despite indications that adjuvant chemotherapy may improve DFS in the subgroup analysis, this benefit was not sustained in multivariate assessments. Overall, the pooled results indicate that perioperative chemotherapy does not significantly improve OS or DFS in patients with resectable dMMR/MSI‐H GC, and therefore such treatment may be spared in these patients.