A 58-year-old man with diffuse-type gastric adenocarcinoma (signet-ring cells, linitis plastica) has no distant metastases on staging CT. HER2 is negative. Genomic profiling shows microsatellite instability-high (MSI-H). The most appropriate perioperative treatment strategy is:
- A FLOT (docetaxel, oxaliplatin, leucovorin, 5-FU) perioperative chemotherapy
- B Upfront surgery (D2 gastrectomy) followed by adjuvant S-1 chemotherapy
- C Pembrolizumab-based immunotherapy combined with chemotherapy perioperatively ✓
- D Trastuzumab + cisplatin + capecitabine
Explanation
MSI-H/dMMR gastric cancers have a robust response to PD-1/PD-L1 checkpoint inhibitors. The KEYNOTE-590 and subsequent trials in MSI-H gastric cancer demonstrate superior responses with pembrolizumab combined with chemotherapy. In MSI-H resectable gastric cancer, emerging data support immunotherapy-inclusive perioperative regimens. FLOT is the current perioperative standard for HER2-negative, MSI-L/MSS gastric cancer (FLOT4 trial). Trastuzumab is used only in HER2-positive disease. Upfront surgery without neoadjuvant is not preferred for resectable locally advanced disease.
Reference: Bailey & Love's Short Practice of Surgery, 27th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.