Medical Disclaimer
genoCDS is a clinical reference tool for qualified healthcare professionals only. Content is derived from published guidelines and regulatory sources and may contain errors or outdated information. It is not a substitute for professional medical judgment, institutional protocols, or individual patient assessment. Always verify recommendations against current primary sources before making clinical decisions. Full disclaimer →
Stage Stage IVB
Multiple extrathoracic metastases in one or more organs. Widely metastatic disease.
4 test recommendations across 1 clinical indication
Stage IVB widely metastatic colon cancer. Same biomarker requirements as Stage IVA; plasma cfDNA may supplement or replace tissue biopsy.
Required — 3 tests
Extended RAS/RAF Panel
RAS/RAF Panel
Comprehensive RAS/RAF hotspot panel detecting KRAS exons 2–4 (codons 12, 13, 59, 61, 117, 146), NRAS exons 2–4, and BRAF V600E. Extended RAS testing is mandatory before initiating anti-EGFR therapy (cetuximab, panitumumab) in metastatic CRC — any RAS mutation is a contraindication. BRAF V600E status drives eligibility for encorafenib + cetuximab (BEACON-CRC).
Ordering Note
Mandatory as for Stage IVA. Plasma cfDNA particularly useful in widely metastatic disease when tissue biopsy is not feasible.
Specimen
Evidence
BRAF V600E Mutation Analysis
BRAF V600E
Detection of BRAF V600E (p.Val600Glu) point mutation. Dabrafenib + trametinib (Tafinlar + Mekinist) is FDA-approved for BRAF V600E-mutant metastatic NSCLC. BRAF V600E occurs in 1.5–4% of NSCLC, more commonly in adenocarcinoma, and is enriched in current/former smokers. Non-V600E BRAF mutations occur more frequently but currently lack approved targeted therapy.
Ordering Note
Required. BRAF V600E mCRC has poor prognosis with standard chemotherapy; early identification enables BEACON-CRC regimen planning.
Specimen
Evidence
Microsatellite Instability / Mismatch Repair Status (MSI/MMR)
MSI/MMR
Testing for microsatellite instability (MSI) and/or mismatch repair (MMR) deficiency. Methods: PCR-based MSI testing, IHC for MMR proteins (MLH1, MSH2, MSH6, PMS2), or NGS-based MSI calculation. MSI-H (high instability) / dMMR (deficient MMR) is an FDA-approved pan-tumor biomarker for pembrolizumab and dostarlimab. MSI-H/dMMR is rare in NSCLC (<1%) but justifies routine testing given pan-tumor approval. IHC for MMR proteins can be performed on most tissue specimens.
Ordering Note
Required. MSI-H/dMMR qualifies for first-line pembrolizumab (KEYNOTE-177) with superior PFS vs. chemotherapy.
Specimen
Evidence
Recommended — 1 test
Comprehensive Solid Tumor NGS Panel
Comprehensive NGS
Next-generation sequencing panel covering ≥300 cancer-relevant genes, including all major NSCLC drivers (EGFR, ALK, ROS1, BRAF, KRAS, MET, RET, NTRK, HER2, FGFR), plus tumor mutational burden (TMB) and microsatellite instability (MSI). Examples include FoundationOne CDx, Tempus xT, Caris MI Transcriptome, and equivalent institutional panels. Preferred over single-gene sequential testing for efficiency and cost-effectiveness.
Ordering Note
Comprehensive panel preferred to capture all actionable targets (HER2, NTRK, KRAS G12C) in a single assay.
Specimen
Evidence
Payer Coverage
Payer Coverage Summary
Coverage status as of last policy review. Prior authorization requirements and coverage criteria may change. Verify directly with each payer before ordering.
| Test | Medicare (CMS) | UnitedHealth | Anthem BCBS | Humana | Cigna | Aetna |
|---|---|---|---|---|---|---|
| RAS/RAF Panel | Covered | Covered | Covered | Covered | Covered | Covered |
| MSI/MMR | Covered | Covered | Unknown | Unknown | Unknown | Unknown |
| Comprehensive NGS | Covered | Covered | Covered | Prior Auth | Covered | Covered |
Coverage data last verified via automated policy research. Always confirm current policies with each payer.
Recommendations on this page are derived from publicly available guidelines (NCCN, ASCO, ESMO, FDA, OncoKB) and are paraphrased for reference. They do not constitute medical advice. Evidence levels reflect the grading systems of each respective organization and should be interpreted in clinical context. This reference is updated periodically but may not reflect the most recent guideline revisions.