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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.
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.
Mismatch-repair deficiency arises when MLH1, MSH2, MSH6 or PMS2 is lost, either by sporadic MLH1 promoter methylation (typically right-sided, in older women, often with BRAF V600E) or by a germline mutation in Lynch syndrome, which is why every colorectal cancer is now tested by immunohistochemistry or microsatellite analysis at diagnosis. The tumours accumulate tens of thousands of frameshift mutations, produce abundant neoantigens and are infiltrated by T cells held in check by PD-1; they have a better prognosis when localised and do not benefit from fluorouracil alone as adjuvant therapy.
In metastatic disease KEYNOTE-177 (2020) showed that pembrolizumab alone doubled progression-free survival against chemotherapy (16.5 versus 8.2 months), with 54.8 percent of patients alive at five years and a median survival of 77.5 months; CheckMate 8HW (2024) showed that nivolumab plus ipilimumab cut progression by 79 percent against chemotherapy (median progression-free survival 54.1 versus 5.9 months) and beat nivolumab alone, and the combination was approved first line in April 2025. About a third of patients still progress early, often because of pMMR misclassification, JAK1 or B2M loss or immune-excluded biology.
| Setting | Approach | Guideline |
|---|---|---|
| Metastatic, first line | Pembrolizumab alone (KEYNOTE-177) or nivolumab plus ipilimumab (CheckMate 8HW); chemotherapy only if immunotherapy is contraindicated. | not mapped |
| Localised colon cancer | Neoadjuvant nivolumab plus ipilimumab for locally advanced tumours (NICHE-2) where available; surgery; adjuvant FOLFOX plus atezolizumab for stage III (ATOMIC); no fluoropyrimidine alone. | not mapped |
| Rectal cancer | Six months of dostarlimab or another PD-1 antibody with non-operative management for complete responders (AZUR-1). | not mapped |
| Lynch syndrome carriers | 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. | not mapped |