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 Content is derived from published guidelines and regulatory sources and may contain errors or outdated information.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 IVA
Single extrathoracic metastatic lesion or contralateral lung nodule or pleural/pericardial involvement. Metastatic but potentially oligometastatic.
5 test recommendations across 1 clinical indication
Stage IVA metastatic rectal cancer. Full biomarker panel required: extended RAS/RAF, MSI-H/dMMR, HER2, NTRK.
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 for all metastatic rectal cancer. Extended RAS/RAF must be completed before anti-EGFR therapy consideration.
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 — encorafenib + cetuximab is FDA-approved post first-line.
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 qualifies for first-line pembrolizumab. In rectal cancer, neoadjuvant immunotherapy for MSI-H achieves complete pathologic response in >50% of cases (NICHE-2, MSKCC).
Specimen
Evidence
Recommended — 2 tests
NTRK1/2/3 Gene Fusion Analysis
NTRK fusion
Pan-tumor detection of NTRK1, NTRK2, and NTRK3 gene fusions encoding TRK (tropomyosin receptor kinase) fusion proteins. Larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) are FDA-approved pan-tumor for TRK fusion-positive cancers regardless of histology. NTRK fusions are rare in NSCLC (<1%) but the high response rate and pan-tumor approval make routine testing appropriate for all NSCLC patients. IHC screening may precede confirmatory molecular testing.
Ordering Note
Recommended for all mCRC. NTRK fusions rare but actionable with entrectinib/larotrectinib (FDA tumor-agnostic).
Specimen
Evidence
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 NGS covers all required targets efficiently; particularly important given emerging HER2-targeted options in rectal cancer.
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 |
| NTRK fusion | Covered | Unknown | 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.