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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Microsatellite-unstable gastric cancer has lost its DNA mismatch repair machinery, carries thousands of mutations and is unusually visible to the immune system. It responds strongly to checkpoint antibodies, may gain little from chemotherapy, and in early-stage disease immunotherapy before surgery is making many tumours disappear entirely.
Mismatch repair deficiency in stomach cancer usually comes from methylation of the MLH1 promoter in older patients rather than from Lynch syndrome, though germline testing is offered when the family history suggests it. The tumours are intestinal type, distal, less likely to involve nodes and carry a better prognosis stage for stage; they are one of the four TCGA molecular groups and overlap with high PD-L1 expression. Testing by immunohistochemistry for the four repair proteins or by polymerase chain reaction or sequencing is now recommended for every gastric cancer at diagnosis.
In advanced disease the microsatellite-unstable subgroups of KEYNOTE-062, CheckMate 649 and KEYNOTE-859 showed the largest benefit of any group from PD-1 blockade, with response rates and survival far above those of chemotherapy alone, and pembrolizumab has had a tumour-agnostic approval for mismatch repair-deficient cancers since 2017. Whether chemotherapy adds anything to the antibody in these patients is uncertain, and many clinicians give a PD-1 antibody alone or with a CTLA-4 antibody.
| Setting | Approach | Guideline |
|---|---|---|
| Advanced, first line | PD-1 antibody with or without chemotherapy (nivolumab or pembrolizumab); nivolumab with ipilimumab in selected patients; the benefit exceeds that in any other subgroup. | not mapped |
| Advanced, after chemotherapy | Pembrolizumab under its tumour-agnostic approval for mismatch repair-deficient cancers. | not mapped |
| Resectable | Surgery with or without perioperative chemotherapy, whose benefit is doubtful here; neoadjuvant immunotherapy (nivolumab-ipilimumab, durvalumab-tremelimumab) in trials or where available. | not mapped |
| Hereditary risk | Germline testing and Lynch syndrome surveillance where the pattern suggests it. | not mapped |