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Lower GI: Metastatic colorectal cancer molecular markers

Free question published 27 September 2026

Lower GIMetastatic colorectal cancer molecular markers

A 64-year-old man presents with synchronous unresectable liver metastases from a left-sided sigmoid adenocarcinoma. His performance status is good and the metastases are being considered for conversion therapy. Molecular profiling shows the tumour is RAS (KRAS and NRAS) wild-type and BRAF wild-type, mismatch-repair proficient. What is the most appropriate first-line systemic option?

  1. ADoublet chemotherapy with anti-EGFR antibody (cetuximab or panitumumab)
  2. BDoublet chemotherapy combined with bevacizumab, an anti-angiogenic monoclonal antibody
  3. CSingle-agent fluoropyrimidine alone
  4. DEncorafenib plus cetuximab
  5. EPembrolizumab monotherapy

Why A is correct

ESMO recommends biomarker testing for RAS, BRAF V600E and MMR/MSI status at diagnosis, and directs treatment by primary tumour sidedness. For a RAS and BRAF wild-type, left-sided primary, ESMO preferentially recommends doublet chemotherapy plus an anti-EGFR antibody (cetuximab or panitumumab) to maximise response and conversion potential.

And why the others are not

  • BIncorrect. Bevacizumab-based doublet therapy is more commonly favoured for right-sided primaries; for a left-sided wild-type tumour anti-EGFR therapy gives the higher response rate.
  • CIncorrect. Single-agent fluoropyrimidine is inadequate for a fit patient seeking maximal response and conversion of liver metastases.
  • DIncorrect. Encorafenib plus cetuximab is for BRAF V600E-mutant disease; this tumour is BRAF wild-type.
  • EIncorrect. Pembrolizumab is reserved for mismatch-repair deficient or MSI-high tumours; this tumour is mismatch-repair proficient.

Source ESMO Clinical Practice Guideline — metastatic colorectal cancer — Cervantes A, Martinelli E, et al. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol.

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