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

Baike Liu West China Hospital, Chengdu, Sichuan, China info_outline Baike Liu, Zhaolun Cai, Yuan Yin, Jingjing Wang, Chaoyong Shen, Xiaonan Yin, Tianxiang Jiang, Yihui Han, Bo Zhang

Authors Baike Liu West China Hospital, Chengdu, Sichuan, China info_outline Baike Liu, Zhaolun Cai, Yuan Yin, Jingjing Wang, Chaoyong Shen, Xiaonan Yin, Tianxiang Jiang, Yihui Han, Bo Zhang Organizations West China Hospital, Chengdu, Sichuan, China, West China Hospital, Sichuan University, Chengdu, China, Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China Abstract Disclosures Research Funding No funding sources reported Background: Currently, the efficacy of perioperative chemotherapy for gastric cancer (GC) patients with deficient mismatch repair or microsatellite instability-high (dMMR/MSI-H) remains controversial. It is still inconclusive whether chemotherapy can be spared for dMMR/MSI-H GC patients. Meanwhile, in the different therapeutic settings (e.g. neoadjuvant, adjuvant, or both), the efficacy of chemotherapy remains to be clarified. Therefore, a systematic review and meta-analysis in this regard was conducted. Methods: Studies comparing perioperative chemotherapy with surgery alone in resectable dMMR/MSI-H GCs (up to December 1, 2023) were included. The hazard ratio (HR) and its 95% confidence interval (CI) of survival outcomes were extracted from the original research or recalculated using Kaplan-Meier curves if the number of patients at risk was provided. In the pooled analysis, a random-effects model was employed. Subgroup analyses (perioperative chemotherapy in stage II and stage III diseases) and sensitivity analysis including studies reporting the results from multivariable analyses were conducted. This study was previously registered on PROSPERO platform (CRD42023494276). Results: Nineteen studies, encompassing over 1500 dMMR/MSI-H GC patients, were included in this study. The results revealed that perioperative chemotherapy (including neoadjuvant and adjuvant chemotherapy) did not significantly improve the overall survival (OS) (HR 0.86, 95% CI 0.57–1.31) and disease-free survival (DFS) (HR 0.70, 95% CI 0.46–1.05) in dMMR/MSI-H GCs. Furthermore, adjuvant chemotherapy did not confer a significant survival advantage for dMMR/MSI-H GCs (OS, HR 0.83, 95% CI 0.50–1.37) and (DFS, HR 0.67, 95% CI 0.41–1.07). Similar results were observed for neoadjuvant chemotherapy (OS, HR 1.09, 95% CI 0.55–2.15). In addition, 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 GCs. In the sensitivity analysis, the results remained consistent. Conclusions: Perioperative (including adjuvant and/or neoadjuvant) chemotherapy does not significantly improve survival in resectable dMMR/MSI-H GC patients. Immunotherapy may be better suitable for these patients in the future.