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Metastatic colorectal cancer
In metastatic colorectal cancer you first test MSI, RAS, BRAF and HER2; MSI-high gets immunotherapy, left-sided RAS wild-type gets an anti-EGFR antibody, and the rest get doublet chemotherapy with bevacizumab — and you always ask whether the metastases are resectable.
Why it matters in the exam
This is one of the most frequent topics in the GI part of the oncology exam. Stems show a patient with liver metastases and molecular results, and ask about first-line therapy, the drug for a given mutation, the role of tipiracil in TAS-102, or the toxicity of irinotecan, oxaliplatin, 5-FU and anti-EGFR antibodies.
A common distractor is giving an anti-EGFR antibody to a patient with a KRAS or NRAS mutation, or for a right-sided tumour. Another is forgetting DPD deficiency testing before 5-FU, or UGT1A1 testing before irinotecan in a patient with a high indirect bilirubin.
Key points
- Molecular testing before first line: MSI, RAS, BRAF and HER2.
- MSI-high — immunotherapy; left-sided RAS wild-type — anti-EGFR; otherwise — bevacizumab.
- A BRAF V600E tumour is treated with encorafenib plus cetuximab, because a BRAF inhibitor alone fails in the colon due to EGFR reactivation.
- Resectable liver or lung metastases are a chance for cure, so every such patient should be presented to a multidisciplinary team with a surgeon.
- Toxicities: DPD with 5-FU, UGT1A1 and diarrhoea with irinotecan, cold neuropathy with oxaliplatin.
Summary table
| Finding | First line | Notes |
|---|---|---|
| MSI-high or dMMR | Pembrolizumab, or nivolumab with ipilimumab | Better than chemotherapy; durable responses |
| RAS and BRAF wild-type, left side | FOLFOX or FOLFIRI with cetuximab or panitumumab | Acneiform rash and hypomagnesaemia; the rash relates to response |
| RAS-mutant or right side | FOLFOX, CAPOX or FOLFIRI with bevacizumab | Bevacizumab: hypertension, proteinuria, bleeding, perforation and delayed wound healing |
| BRAF V600E | Encorafenib with cetuximab (with FOLFOX in first line) | Poor prognosis; a BRAF inhibitor alone does not work in the colon |
| HER2 amplification | Trastuzumab with tucatinib, or T-DXd | Only in RAS wild-type |
| Later lines | TAS-102 with bevacizumab, regorafenib or fruquintinib | Tipiracil blocks the breakdown of trifluridine and raises its blood level |
| Resectable or convertible liver metastases | Perioperative chemotherapy and resection, or local ablation for small metastases | The decision is made by a multidisciplinary team with a liver surgeon, sometimes after treatment that shrinks the metastases |
In the full version for subscribers
- A simple algorithm
- Memory aid
- Exam traps
- 5 review cards
- Enough for IMLE
The full version is open to subscribers of: Oncology, Internal medicine, Medical licensing exam (IMLE), General surgery.
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Sources
- NCCN Clinical Practice Guidelines in Oncology: Colon Cancer, 2026 — Systemic therapy for advanced or metastatic disease
- ESMO Clinical Practice Guideline: Metastatic colorectal cancer, 2023 — Diagnosis, treatment and follow-up
- DeVita, Hellman and Rosenberg's Cancer: Principles and Practice of Oncology, 12th ed. (2023) — Cancer of the colon
Sources are given for further reading; the text is written afresh and not copied from them.
Reviewed by the Examqo AI Professor · 2026-11-06. The text may contain errors; when in doubt, check the source.