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 Content is derived from published guidelines and regulatory sources and may contain errors or outdated information.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 I
Tumor ≤4 cm, no nodal or distant metastasis (T1-T2a, N0, M0). Surgically resectable.
4 test recommendations across 1 clinical indication
Resectable Stage I adenocarcinoma. EGFR testing required for adjuvant osimertinib consideration (ADAURA trial). Broader molecular profiling recommended for complete biomarker characterization.
Required — 1 test
EGFR Mutation Analysis
EGFR
Analysis of EGFR gene for sensitizing mutations in exons 18–21 (exon 19 deletions, exon 21 L858R, exon 18 G719X/S768I/L861Q, exon 20 insertions) and resistance mutations (T790M, C797S). May be performed by PCR-based assay or as part of an NGS panel. Cobas EGFR Mutation Test v2 is FDA-approved companion diagnostic for osimertinib (Tagrisso). EGFR mutations are present in 10–15% of Caucasian patients and 30–40% of Asian patients with adenocarcinoma.
Ordering Note
ADAURA trial: adjuvant osimertinib reduces recurrence risk by 80% in EGFR-mutant resected Stage IB–IIIA NSCLC. Test before surgery if possible, or from resection specimen.
Specimen
Evidence
FDA approval: adjuvant osimertinib for EGFR-mutant resected Stage IB–IIIA NSCLC (ADAURA trial). EGFR testing required to identify eligible patients.
Recommended — 3 tests
ALK Gene Rearrangement
ALK
Detection of ALK (anaplastic lymphoma kinase) gene fusions, most commonly EML4-ALK. Testing methods include FISH (Vysis ALK Break Apart FISH Probe Kit — FDA-approved companion Dx for crizotinib/ceritinib), IHC (D5F3 clone, FDA-approved for crizotinib), and RNA-based NGS (preferred for detection of all ALK fusion variants). ALK fusions occur in 3–7% of adenocarcinoma, often in younger, never- or light-smokers.
Ordering Note
ALINA trial: adjuvant alectinib approved for ALK+ resected Stage IB–IIIA NSCLC. ALK mutation less common than EGFR in Stage I; testing as part of comprehensive panel preferred.
Specimen
Evidence
ALINA trial: adjuvant alectinib for ALK+ resected Stage IB–IIIA NSCLC. FDA approved 2024.
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 at Stage I allows complete biomarker characterization. If positive for an actionable driver, enables adjuvant targeted therapy planning. NCCN recommends broad profiling for all adenocarcinoma.
Specimen
PD-L1 Expression by Immunohistochemistry (IHC)
PD-L1 IHC
Measurement of PD-L1 (programmed death-ligand 1; CD274) protein expression on tumor cells by IHC. Reported as Tumor Proportion Score (TPS) for NSCLC. Key thresholds: TPS <1% (PD-L1 negative), TPS 1–49% (low expression), TPS ≥50% (high expression). FDA-approved companion diagnostics: 22C3 pharmDx (pembrolizumab), 28-8 pharmDx (nivolumab), SP142 (atezolizumab), SP263 (durvalumab). PD-L1 ≥50% qualifies for pembrolizumab monotherapy first-line; all TPS levels are relevant for combination chemo-immunotherapy selection.
Ordering Note
PD-L1 testing recommended for Stage IB tumors ≥4 cm — adjuvant pembrolizumab approved (PEARLS/KEYNOTE-091). For Stage IA, adjuvant pembrolizumab is not currently approved; PD-L1 testing optional at this stage.
Specimen
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 |
|---|---|---|---|---|---|---|
| EGFR | Covered | Covered | Covered | Covered | Covered | Covered |
| ALK | Covered | Covered | Covered | Covered | Covered | Covered |
| Comprehensive NGS | Covered | Covered | Covered | Prior Auth | Covered | Covered |
| PD-L1 IHC | Covered | Covered | Covered | Covered | 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.