• Elvira L Vos, Steven B Maron, Robert W Krell, Masaya Nakauchi, Megan Fiasconaro, Marinela Capanu, Henry S Walch, Walid K Chatila, Nikolaus Schultz, David H Ilson, Yelena Y Janjigian, Geoffrey Y Ku, Sam S Yoon, Daniel G Coit, Chad M Vanderbilt, Laura H Tang, and Vivian E Strong.
• Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
• Ann. Surg. 2023 May 1; 277 (5): 798805798-805.

ObjectiveTo evaluate the efficacy of chemotherapy in patients with microsatellite instability (MSI)-high gastric cancer.BackgroundAlthough MSI-high gastric cancer is associated with a superior prognosis, recent studies question the benefit of perioperative chemotherapy in this population.MethodsLocally advanced gastric adenocarcinoma patients who either underwent surgery alone or also received neoadjuvant, perioperative, or adjuvant chemotherapy between 2000 and 2018 were eligible. MSI status, determined by next-generation sequencing or mismatch repair protein immunohistochemistry, was determined in 535 patients. Associations among MSI status, chemotherapy administration, overall survival (OS), disease-specific survival, and disease-free survival were assessed.ResultsIn 535 patients, 82 (15.3%) had an MSI-high tumor and ∼20% better OS, disease-specific survival, and disease-free survival. Grade 1 (90%-100%) pathological response to neoadjuvant chemotherapy was found in 0 of 40 (0%) MSI-high tumors versus 43 of 274 (16%) MSS. In the MSI-high group, the 3-year OS rate was 79% with chemotherapy versus 88% with surgery alone ( P =0.48). In the MSS group, this was 61% versus 59%, respectively ( P =0.96). After multivariable interaction analyses, patients with MSI-high tumors had superior survival compared with patients with MSS tumors whether given chemotherapy (hazard ratio=0.53, 95% confidence interval: 0.28-0.99) or treated with surgery alone (hazard ratio=0.15, 95% confidence interval: 0.02-1.17).ConclusionsMSI-high locally advanced gastric cancer was associated with superior survival compared with MSS overall, despite worse pathological chemotherapy response. In patients with MSI-high gastric cancer who received chemotherapy, the survival rate was ∼9% worse compared with surgery alone, but chemotherapy was not significantly associated with survival.Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

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