The first 60 days: Mismatch-repair deficient (MSI-high) colorectal cancer
Mismatch-repair deficient bowel cancer has lost its DNA spell-checker, so it carries thousands of mutations that the immune system can recognise. Immunotherapy alone controls most metastatic cases for years and makes most localised tumours disappear before surgery, sometimes so completely that no surgery is needed. Below, week by week, is what OnCo's record of Mismatch-repair deficient (MSI-high) colorectal 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: Localised colon cancer, Lynch syndrome carriers.
- SurgeonNamed in the standard of care for: Localised colon cancer, Lynch syndrome carriers.
- Medical oncologistNamed in the standard of care for: Metastatic, first line, Localised colon cancer, Rectal cancer, Lynch syndrome carriers.
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.
Neoadjuvant nivolumab plus ipilimumab for locally advanced tumours (NICHE-2) where available; surgery; adjuvant FOLFOX plus atezolizumab for stage III (ATOMIC); no fluoropyrimidine alone.
Pembrolizumab alone (KEYNOTE-177) or nivolumab plus ipilimumab (CheckMate 8HW); chemotherapy only if immunotherapy is contraindicated.
Six months of dostarlimab or another PD-1 antibody with non-operative management for complete responders (AZUR-1).
Colonoscopy every one to two years from age 25 (earlier for MLH1 and MSH2), daily aspirin (CAPP2), cascade germline testing of relatives, hysterectomy and oophorectomy after childbearing for women.
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 immunohistochemistry, Microsatellite instability by PCR or sequencing, MLH1 promoter methylation and BRAF V600E, Germline testing of mismatch repair genes, Tumour mutational burden), 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 mismatch-repair deficient, Lynch syndrome, Localised dMMR colon cancer.
- Is germline (inherited) genetic testing recommended for me or my family?Inherited variants can change treatment and matter for relatives.
Metastatic, first line
- For my situation (metastatic, first line), which of the standard options do you recommend and why?Guideline options include: Pembrolizumab alone (KEYNOTE-177) or nivolumab plus ipilimumab (CheckMate 8HW); chemotherapy only if immunotherapy is contraindicated.
- 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 KEYNOTE-177 and CheckMate 8HW apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Localised colon cancer
- For my situation (localised colon cancer), which of the standard options do you recommend and why?Guideline options include: Neoadjuvant nivolumab plus ipilimumab for locally advanced tumours (NICHE-2) where available; surgery; adjuvant FOLFOX plus atezolizumab for stage III (ATOMIC); no fluoropyrimidine alone.
- Am I a candidate for Nivolumab, Ipilimumab, Atezolizumab or related drugs, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of NICHE-2 and ATOMIC (Alliance A021502) apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Rectal cancer
- For my situation (rectal cancer), which of the standard options do you recommend and why?Guideline options include: Six months of dostarlimab or another PD-1 antibody with non-operative management for complete responders (AZUR-1).
- Am I a candidate for Dostarlimab, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of AZUR-1 apply to someone like me?Trial populations differ from individual patients; ask how closely you match.
Lynch syndrome carriers
- For my situation (lynch syndrome carriers), which of the standard options do you recommend and why?Guideline options include: Colonoscopy every one to two years from age 25 (earlier for MLH1 and MSH2), daily aspirin (CAPP2), cascade germline testing of relatives, hysterectomy and oophorectomy after childbearing for women.
- Am I a candidate for Aspirin, and what side effects should I expect?Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of WRN inhibitors: a second synthetic-lethal win for mismatch-repair cancers, EIK1005, Cadonilimab, Neoadjuvant/Adjuvant AK104 in Microsatellite Instability-high or Mismatch Repair-deficient, Resectable Colon Cancer?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 “A third of metastatic patients progress early on immunotherapy and the resistance mechanisms are only partly understood”. How does that affect my plan?Open problems are where trials and second opinions matter most.
- I read that “Whether surgery can be omitted after complete response in colon, as in rectal, cancer is untested”. How does that affect my plan?Open problems are where trials and second opinions matter most.
Trials open now for this cancer in OnCo, largest phase first. Joining a trial is a decision like any other: ask what the comparison arm is, whether a placebo is used, and what happens if you leave. The cancer page searches ClinicalTrials.gov live for more.
- A Study of Neoadjuvant QL1706 in Participants With Untreated dMMR/MSI-H Resectable Colon CancerPhase 3 · recruiting · NCT06686576A Phase Ib/III, Open-Label, Randomized Study of Neoadjuvant QL1706 Versus Standard of Care in Participants With Untreated of Microsatellite Instability-high or Mismatch Repair-deficient, Resectable Colon Cancer
- Neoadjuvant/Adjuvant AK104 in Microsatellite Instability-high or Mismatch Repair-deficient, Resectable Colon CancerPhase 3 · recruiting · NCT07412613A Randomized, Open-label, Controlled, Multicenter Phase 3 Clinical Trial of AK104 for Neoadjuvant/Adjuvant Treatment of Microsatellite Instability-high or Mismatch Repair-deficient, Resectable Colon Cancer
- Study of Perioperative Dostarlimab in Participants With Untreated T4N0 or Stage III dMMR/MSI-H Resectable Colon CancerPhase 3 · recruiting · NCT05855200A Phase 3, Open-Label, Randomized Study of Perioperative Dostarlimab Monotherapy Versus Standard of Care in Participants With Untreated T4N0 or Stage III dMMR/MSI-H Resectable Colon Cancer
- A Study of Dostarlimab in Participants With Untreated Locally Advanced Rectal Cancer in ChinaPhase 2 · active · NCT06640049A Phase 2, Single-Arm, Open-Label Study With Dostarlimab Monotherapy in Participants With Untreated Stage II/III dMMR/MSI-H Locally Advanced Rectal Cancer in China
Much of what helps in the first weeks is free if you know to ask: testing, helplines, rides and lodging, second opinions, trial travel.
- Mismatch-repair deficient (MSI-high) colorectal cancer: the full pageMismatch-repair deficient bowel cancer has lost its DNA spell-checker, so it carries thousands of mutations that the immune system can recognise. Immunotherapy alone controls most metastatic cases for years and makes most localised tumours disappear before surgery, sometimes so completely that no surgery is needed.
- 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.
- Consensus molecular subtypes (CMS1-4): The consensus molecular subtypes are four gene-expression groups of bowel cancer: immune (CMS1), canonical (CMS2), metabolic (CMS3), and mesenchymal (CMS4), with different prognoses.
- Clinical complete response (cCR): No sign of tumour on examination, endoscopy, and MRI after treatment, without surgery to confirm it.
- Tumour mutational burden (TMB): How many mutations a tumour has.
- Organ preservation (watch-and-wait, bladder-sparing, larynx preservation): Curing a cancer with drugs and radiotherapy so that the organ (rectum, bladder, larynx, limb) does not have to be removed, keeping surgery in reserve for the minority whose cancer regrows.
- 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.