Microsatellite-unstable (MSI-high) gastric cancer
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.
Overview
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.
In resectable disease post hoc analyses of the MAGIC and CLASSIC trials and a 2019 meta-analysis suggested that perioperative chemotherapy gives little or no benefit in microsatellite-unstable tumours, and neoadjuvant immunotherapy trials have followed: NEONIPIGA (nivolumab and ipilimumab) produced pathological complete responses in 59 percent of patients, and INFINITY (durvalumab and tremelimumab) and DANTE reported similar findings. Organ-preserving strategies that omit surgery after a complete response are being tested, following the same path as rectal cancer.
State of the art
- Microsatellite-unstable gastric cancer is the clearest immunotherapy success story in the disease, with long remissions in metastatic patients.
- Neoadjuvant checkpoint blockade produces complete pathological responses in more than half of localised tumours.
- The evidence that chemotherapy adds little has changed how these patients are treated before surgery.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowHypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Check before combiningFood and drink: Pembrolizumab
No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
- Good to knowImmune-related endocrinopathies (thyroiditis, hypophysitis)
Immunotherapy can attack hormone-producing glands: most often the thyroid (usually ending in an under-active thyroid needing lifelong tablets), and less often the pituitary (hypophysitis) or adrenal glands, which can be life-threatening if missed.
- Good to knowImmune-mediated colitis and diarrhoea
Inflammation of the bowel caused by immunotherapy releasing the immune system against the gut lining, producing diarrhoea that can be severe. It is the commonest serious side effect of CTLA-4 antibodies and is treated with steroids and, if needed, infliximab.
See all on the product pages:DurvalumabFLOT (5-FU, leucovorin, oxaliplatin, docetaxel)IpilimumabNivolumabPembrolizumabTremelimumab·Printable cards in the navigator
Anatomy and lymph node drainage
- Upper and middle oesophagus (squamous)
- Lower oesophagus and junction (adenocarcinoma)
- Cardia and fundus
- Body (diffuse or intestinal type)
- Antrum and pylorus
- Muscle wall (GIST)
- Nodes: perigastric (greater and lesser curve)
- Nodes: coeliac and hepatic
- Nodes: mediastinal
- Nodes: cervical (upper oesophagus)
Squamous cancers sit in the upper and middle oesophagus, adenocarcinomas at the junction and in the stomach; the stomach wall also gives rise to GIST from its pacemaker cells.
- Upper and middle oesophagus (squamous)
- Lower oesophagus and junction (adenocarcinoma)
- Cardia and fundus
- Body (diffuse or intestinal type)Sporadic MSI-high gastric cancer (MLH1 promoter methylation, older patients, distal stomach) · MSI-high intestinal type · Localised MSI-high (neoadjuvant immunotherapy trials) · Metastatic MSI-high (checkpoint blockade)
- Antrum and pylorusSporadic MSI-high gastric cancer (MLH1 promoter methylation, older patients, distal stomach)
- Muscle wall (GIST)
- perigastric (greater and lesser curve)
- coeliac and hepatic
- mediastinal
- cervical (upper oesophagus)
Same organ: Gastric & gastro-oesophageal junction cancer, HER2-positive gastric cancer, Claudin 18.2-positive gastric cancer, PD-L1-high gastric cancer, Early gastric cancer, Oesophageal squamous cell carcinoma, Oesophageal and junctional adenocarcinoma, Oesophageal cancer, Gastrointestinal stromal tumour (GIST), KIT exon 11-mutant GIST, PDGFRA D842V-mutant GIST, Imatinib-resistant GIST
Around one in five localised gastric cancers in Western series but only about one in twenty at the metastatic stage, because these tumours spread less; they occur in older patients, in the distal stomach and in intestinal-type histology.
- Liquid biopsy (ctDNA)Standard of care
Nothing recorded yet.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
PD-1 antibody with or without chemotherapy (nivolumab or pembrolizumab); nivolumab with ipilimumab in selected patients; the benefit exceeds that in any other subgroup.
Pembrolizumab under its tumour-agnostic approval for mismatch repair-deficient cancers.
Surgery with or without perioperative chemotherapy, whose benefit is doubtful here; neoadjuvant immunotherapy (nivolumab-ipilimumab, durvalumab-tremelimumab) in trials or where available.
Germline testing and Lynch syndrome surveillance where the pattern suggests it.
Subtypes & biomarkers
top- Sporadic MSI-high gastric cancer (MLH1 promoter methylation, older patients, distal stomach)
- Lynch syndrome-associated gastric cancer
- MSI-high intestinal type
- Localised MSI-high (neoadjuvant immunotherapy trials)
- Metastatic MSI-high (checkpoint blockade)
How often this target appears
- 2014TCGA classifies gastric cancer into four molecular groups including MSI-high
- 2017Pembrolizumab receives tumour-agnostic approval for mismatch repair-deficient cancers
- 2019Meta-analysis of MAGIC, CLASSIC, ARTIST and ITACA-S: no chemotherapy benefit in MSI-high tumours
- 2021CheckMate 649 and KEYNOTE-062 subgroups: large gains from PD-1 blockade in MSI-high disease
- 2023NEONIPIGA: neoadjuvant nivolumab and ipilimumab give pathological complete response in 59 percent
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 8 changes by month →- 2026-09-17This recordMicrosatellite-unstable (MSI-high) gastric cancerFacts on this page last checked
When this page itself was last checked or edited.
- 2023Trial resultKEYNOTE-859KEYNOTE-859 reported
OS HR 0.
- 2023MilestoneNivolumabNEONIPIGA: neoadjuvant nivolumab and ipilimumab give pathological complete response in 59 percent
A milestone in how this cancer is treated.
- 2021MilestoneCheckMate 649CheckMate 649 and KEYNOTE-062 subgroups: large gains from PD-1 blockade in MSI-high disease
A milestone in how this cancer is treated.
- 2020Trial resultCheckMate 649CheckMate 649 reported
CPS ≥5: OS 14.
- 2019MilestoneMicrosatellite-unstable (MSI-high) gastric cancerMeta-analysis of MAGIC, CLASSIC, ARTIST and ITACA-S: no chemotherapy benefit in MSI-high tumours
A milestone in how this cancer is treated.
What is in development for Microsatellite-unstable (MSI-high) gastric cancer, drawn from the whole corpus: 1 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Trials reported · 1
- CheckMate 649 · phase 3 · 2020 · positive
Open problems and what is being done
Whether surgery can be omitted after a complete response to neoadjuvant immunotherapy.
Whether chemotherapy should be dropped altogether in metastatic disease.
and how the field plans to fix it →What is being done about thisAdvanced and metastatic diseaseAvailable now- Liquid biopsy (ctDNA)Standard of care
- MRD / molecular residual disease testingEstablished
In trialsNothing recorded yet.
Ideas and roadmapsNothing recorded yet.
Also on OnCo: Atlas of advanced disease · Invasion and metastasis.
A minority of MSI-high tumours do not respond, and the reasons are unclear.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Shanghai · hospital | China | none recorded | 0 | 2,872 | 31,534 | - | |
London · hospital | United Kingdom | none recorded | 0 | 2,376 | 28,940 | - | |
Beijing · hospital | China | none recorded | 0 | 1,784 | 18,230 | - | |
Miami, FL · cancer center | United States | 0 | 1,607 | 15,145 | - | ||
Rozzano (Milan) · hospital | Italy | none recorded | 0 | 1,031 | 10,720 | - | |
L'Hospitalet de Llobregat · cancer center | Spain | 0 | 988 | 14,310 | - | ||
Naples · cancer center | Italy | none recorded | 0 | 961 | 15,028 | - | |
Madrid · hospital | Spain | none recorded | 0 | 764 | 13,767 | - | |
Philadelphia, PA · cancer center | United States | 0 | 755 | 12,225 | - | ||
Pamplona · cancer center | Spain | none recorded | 0 | 751 | 10,993 | - | |
Philadelphia, PA · hospital | United States | none recorded | 0 | 695 | 9,931 | - | |
Nagaizumi, Shizuoka · cancer center | Japan | none recorded | 0 | 657 | 3,545 | - | |
Helsinki · cancer center | Finland | none recorded | 0 | 558 | 5,920 | - | |
Lund · hospital | Sweden | none recorded | 0 | 521 | 4,154 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Microsatellite-unstable (MSI-high) gastric cancer but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Microsatellite-unstable (MSI-high) gastric cancer
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Mismatch repair proteins by immunohistochemistry, Microsatellite instability by polymerase chain reaction or sequencing, Tumour mutational burden, PD-L1 combined positive score, Germline mismatch repair genes where Lynch syndrome is suspected), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Sporadic MSI-high gastric cancer, Lynch syndrome-associated gastric cancer, MSI-high intestinal type.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Advanced, first line
- For my situation (advanced, first line), which of the standard options do you recommend and why?Why: Guideline options include: PD-1 antibody with or without chemotherapy (nivolumab or pembrolizumab); nivolumab with ipilimumab in selected patients; the benefit exceeds that in any other subgroup.
- Am I a candidate for Pembrolizumab, Nivolumab, Ipilimumab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of CheckMate 649 and KEYNOTE-859 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Advanced, after chemotherapy
- For my situation (advanced, after chemotherapy), which of the standard options do you recommend and why?Why: Guideline options include: Pembrolizumab under its tumour-agnostic approval for mismatch repair-deficient cancers.
- Am I a candidate for Pembrolizumab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Resectable
- For my situation (resectable), which of the standard options do you recommend and why?Why: Guideline options include: Surgery with or without perioperative chemotherapy, whose benefit is doubtful here; neoadjuvant immunotherapy (nivolumab-ipilimumab, durvalumab-tremelimumab) in trials or where available.
- Am I a candidate for Nivolumab, Ipilimumab, Durvalumab or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Hereditary risk
- For my situation (hereditary risk), which of the standard options do you recommend and why?Why: Guideline options include: Germline testing and Lynch syndrome surveillance where the pattern suggests it.
Any stage
- Are there clinical trials I could join, for example of Nivolumab, Ipilimumab, Durvalumab, Tremelimumab?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Whether surgery can be omitted after a complete response to neoadjuvant immunotherapy”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Whether chemotherapy should be dropped altogether in metastatic disease”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Microsatellite-unstable (MSI-high) gastric cancer, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
6targets
3drugs
6companies
3pathways
1terms
4trials
2Latest papers
topQuery for this cancer: (TITLE:"Microsatellite-unstable MSI-high gastric cancer" OR ABSTRACT:"Microsatellite-unstable MSI-high gastric cancer" OR TITLE:"MSI-H gastric cancer" OR ABSTRACT:"MSI-H gastric cancer" OR TITLE:"Mismatch repair-deficient gastric cancer" OR ABSTRACT:"Mismatch repair-deficient gastric cancer" OR TITLE:"dMMR gastric cancer" OR ABSTRACT:"dMMR gastric cancer") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Microsatellite-unstable (MSI-high) gastric cancer, not a curated reading list.
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