The first 60 days: 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. Below, week by week, is what OnCo's record of Microsatellite-unstable (MSI-high) gastric cancer says about the first two months: the order is typical, the timing is yours to ask about. Sections appear only where the record has something to say. Orientation, not medical advice.
What happens now
Staging tests establish exactly what and where the cancer is. Everything else follows from the answers.
Ask which of these were tested and what the results were; see the report reader for what each value means.
These specialties appear in the standard of care for this cancer. In most centres they meet weekly as a tumour board to agree each plan; you can ask when yours was discussed and what was decided.
- PathologistNamed in the standard of care for: Hereditary risk.
- SurgeonNamed in the standard of care for: Resectable.
- Medical oncologistNamed in the standard of care for: Advanced, first line, Advanced, after chemotherapy, Resectable.
A second opinion from a centre that treats many similar cases is normal, not rude; the standard of care tells you what to compare it against.
Each row is a setting from the standard of care, in the order it usually arises. Not all will apply to you; your stage and biomarkers decide which do. The guideline grade, where recorded, says how strong the evidence is.
Surgery with or without perioperative chemotherapy, whose benefit is doubtful here; neoadjuvant immunotherapy (nivolumab-ipilimumab, durvalumab-tremelimumab) in trials or where available.
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.
Germline testing and Lynch syndrome surveillance where the pattern suggests it.
Generated from this cancer's standard of care, biomarkers and open problems. Take the group that matches where you are. To tick, add your own and print, open the one-page appointment sheet.
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?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?These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?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?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?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?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?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?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?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?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?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?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?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?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?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?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?Open problems are where trials and second opinions matter most.
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Microsatellite-unstable (MSI-high) gastric cancer: the full pageMicrosatellite-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.
- One-page appointment sheetYour questions, the words you may hear, what to bring, and space for the answers. Print it.
- Treatment sequencingWhich treatment tends to follow which, line by line.
- NavigatorStandard of care for your stage, what you have tried, and trials near you.
- Gastrectomy: Removing part (subtotal) or all (total) of the stomach for stomach cancer, with the bowel joined to what remains.
- Lynch syndrome: Lynch syndrome is the most common inherited cancer syndrome: a faulty mismatch-repair gene raises lifetime bowel cancer risk to 40-80% and also endometrial and other cancers.
- Tumour-agnostic (tissue-agnostic) approval: A tumour-agnostic approval lets a drug be used for any cancer carrying a specific molecular feature, regardless of where it started.
- Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR): Microsatellite instability is the mark of a broken DNA spell-checker (loss of MLH1, MSH2, MSH6 or PMS2) that leaves thousands of mutations, so the tumour displays abnormal proteins that T cells can recognise.
Every term links to the glossary.