What molecular tests and imaging do I need before deciding first-line treatment for metastatic colorectal cancer?

For newly diagnosed unresectable/metastatic CRC where first-line systemic treatment is being chosen:

Molecular tests

Minimum routine tests

• RAS status: KRAS/NRAS exons 2, 3 and 4
• BRAF V600E
  NICE says to test these in all people with metastatic CRC suitable for systemic anticancer treatment [1].

Strongly advisable before first-line choice

• MSI-H / dMMR status, because it can make the patient eligible for first-line immunotherapy
  ESMO recommends testing dMMR/MSI-H at mCRC diagnosis [2].

Useful if you are doing a broader upfront panel

• HER2 amplification/overexpression (mainly for later-line targeted options)
• Consider multigene NGS if available, with NTRK fusions and other actionable alterations (e.g. POLE/POLD1) where relevant [2].

Imaging

Baseline staging

• Contrast-enhanced CT of thorax/chest, abdomen and pelvis [2].

Add if needed

• Liver MRI with hepatobiliary contrast if liver lesions are indeterminate on CT or the patient may be eligible for liver-directed/locoregional therapy [2].
• PET-CT only in selected cases; not routine [2].

If the primary is rectal

• Pelvic MRI is important for local staging / MDT planning, though it is more about local than systemic strategy [2].

Practical “before first-line” set

If you want a pragmatic order set, I’d do:

1. CT chest/abdomen/pelvis with contrast
2. KRAS/NRAS exons 2–4
3. BRAF V600E
4. MSI/MMR
5. Add liver MRI if liver disease may be potentially resectable or CT is equivocal
6. Consider expanded NGS/HER2 if available and it won’t delay treatment