Tumor-Type Agnostic Solid Tumor Molecular Profiling Panels - Initial
Covered when ALL of the following are met:
ALL of the following
Patient has a known or suspected solid tumor (any primary site) for which molecular profiling could inform diagnosis, prognosis, or therapeutic selection.
Testing is ordered to identify actionable somatic genomic alterations (single nucleotide variants, indels, copy number alterations, selected fusions) that could influence targeted therapy, immunotherapy eligibility, or clinical trial enrollment.
Results will be used by the treating oncology team to guide patient management; documentation of intended clinical use is present in the medical record.
Specimen adequacy: sufficient tumor content and DNA/RNA quality per laboratory requirements; if tissue is inadequate or unavailable, plasma (ctDNA) testing may be considered per liquid biopsy criteria in this policy.
ONE of
Initial broad tumor-type agnostic comprehensive genomic profiling (CGP) performed on tumor tissue when clinically indicated to identify genomic biomarkers for therapy selection or clinical trial enrollment.
Tumor-type agnostic CGP performed as reflex testing per institutional pathways for advanced, recurrent, or metastatic solid tumors when results could change first-line or subsequent treatment.
Operational notes
Single-gene tests are preferred when a specific, guideline-recommended biomarker is being evaluated and the clinical question is narrow; otherwise, CGP is preferred to maximize detection of actionable alterations.
Prior authorization may be required; submit clinical documentation showing how results will impact management.
Tumor-Type Agnostic Solid Tumor Molecular Profiling Panels - Additional Indications
Covered when ANY of the following additional indications apply:
ANY of the following
Patient has advanced or metastatic disease progressing on standard therapy and tissue CGP has not previously been performed.
Newly diagnosed advanced cancer for which guideline-recommended biomarker testing includes multi-gene profiling (e.g., to determine eligibility for targeted agents or immunotherapy).
A tumor specimen previously tested with a limited panel and additional broader testing could identify new actionable targets or clinical trial options.
Documentation requirements
Medical record must document prior testing performed (if any), prior treatments, and rationale for additional or broader testing.
Tumor-Type Agnostic Solid Tumor Molecular Profiling Panels - Repeat testing
Repeat testing covered when ALL of the following are met:
ALL of the following
There is disease progression or recurrence and results from prior testing are unavailable, inadequate, or unlikely to reflect current tumor biology (e.g., significant interval therapy).
A different specimen (new biopsy) is obtained that better represents current disease and testing may identify new actionable alterations or resistance mechanisms.
Repeat testing is not routinely covered solely for surveillance without clinical evidence of progression or change in management.
Repeat testing via tissue or ctDNA
Repeat tissue-based CGP when a new biopsy is performed and management may change based on updated genomic profile.
Targeted RNA Fusion Panels for Solid Tumors
Covered when ALL of the following are met for targeted RNA fusion panels:
ALL of the following
Testing is performed on tumor tissue (or validated alternative specimen) to detect specified gene fusions known to be clinically actionable for the tumor type (e.g., ALK, ROS1, RET, NTRK where targeted therapies are available).
The panel is a targeted RNA fusion assay designed to detect a defined set of clinically relevant fusions with sufficient analytical sensitivity and specificity documented by the laboratory.
Results will be used to determine specific targeted therapy or clinical trial eligibility; medical record documents intended use.
Appropriate use examples
Lung adenocarcinoma testing for ALK, ROS1, RET fusions when tissue-based NGS DNA-based panels lack coverage for fusions or RNA testing improves detection sensitivity.
Broad RNA Fusion Panels for Solid Tumors
Covered when ALL of the following are met for broad RNA fusion panels:
ALL of the following
Broad RNA fusion panels are used when the tumor type, histology, or prior testing indicates a high pre-test probability of uncommon or novel fusions not covered by targeted panels, and detection could change therapy.
The laboratory documents analytical validation for a wide range of fusion partners and provides reporting of novel fusions with appropriate interpretation.
Results will directly inform therapeutic selection or trial enrollment, and documentation of intended clinical use is present.
Appropriate use examples
Tumors with unusual histology or recurrent negative targeted testing where comprehensive fusion discovery may identify rare actionable fusions (e.g., certain sarcomas, gliomas, or cancers of unknown primary).
Colorectal Cancer Focused Molecular Profiling Panels
Covered when ALL of the following apply for colorectal cancer focused panels:
ALL of the following
Testing is ordered for colorectal cancer patients to identify biomarkers that guide established therapeutic decisions (e.g., KRAS/NRAS, BRAF, MSI/MMR status, HER2 as appropriate).
Panel content aligns with guideline-recommended biomarkers for colorectal cancer and results will influence management (treatment selection or clinical trial eligibility).
Lung Cancer Focused Molecular Profiling Panels
Covered when ALL of the following apply for lung cancer focused panels:
ALL of the following
Testing is performed on lung cancer (typically non-small cell lung cancer) to evaluate guideline-recommended biomarkers (e.g., EGFR, ALK, ROS1, BRAF, MET, RET, NTRK, KRAS, HER2, and PD-L1 IHC where indicated).
Panel results will be used to select FDA-approved targeted therapies, immunotherapy, or clinical trials; documentation of intended use is in the medical record.
Cutaneous Melanoma Focused Molecular Profiling Panels
Covered when ALL of the following apply for cutaneous melanoma focused panels:
ALL of the following
Testing is ordered for cutaneous melanoma to detect clinically actionable mutations (e.g., BRAF, NRAS, KIT where applicable) that guide systemic therapy selection or trial eligibility.
Panel composition matches tumor type needs and results will directly inform treatment decisions.
Tumor-specific gene/variant/protein analyses and MSI/TMB entries
Covered when ALL of the following apply for tumor-specific single-gene or small-panel analyses (BRAF, BRCA1/2, EGFR, FOLR1, IDH1/2, KIT, KRAS, MGMT, MLH1, MSI, NRAS, PD-L1, PIK3CA, TMB):
ANY of the following
BRAF variant analysis is indicated when detection of BRAF V600 or other actionable BRAF alterations would alter therapy (e.g., melanoma, colorectal cancer in context of targeted therapy).
BRCA1/2 tumor testing is indicated when results will determine use of PARP inhibitors or enrollment in relevant clinical trials; consider germline testing if tumor result suggests hereditary mutation.
EGFR variant analysis is indicated in non-small cell lung cancer and other tumor types where EGFR-targeted therapy is considered; testing methods should detect relevant activating and resistance mutations.
FOLR1 protein analysis (IHC) is indicated when folate receptor expression status is required for therapy selection or trial eligibility.
Evidence-Based Solid Tumor Minimal Residual Disease (MRD) Testing
Covered when ALL of the following are met for evidence-based MRD (Minimal Residual Disease) testing in solid tumors:
ALL of the following
MRD testing is performed using validated, tumor-informed ctDNA assays with demonstrated clinical utility in the specific cancer type and clinical context (examples include certain colorectal cancer post-operative MRD assays where evidence supports prediction of recurrence and informing adjuvant therapy).
Clinical context must match evidence-based indications: e.g., adjuvant decision-making in stage II/III colorectal cancer where prospective data support MRD-guided therapy, or surveillance following curative-intent therapy in cancer types with validated MRD assays.
Testing methodology: tumor-informed assays that use prior tumor tissue sequencing to define patient-specific variants and then monitor those variants in plasma are preferred when evidence supports improved sensitivity and specificity over tumor-naive approaches.
Timing rules: MRD testing should be performed at evidence-supported time points (e.g., a defined interval after surgery and clearance of perioperative ctDNA signal; avoid testing during the perioperative window when ctDNA shedding may confound results).
Emerging Evidence Solid Tumor MRD Testing
Not covered / Emerging evidence — tissue-based MRD and other unproven MRD applications:
ALL of the following
Tissue-based MRD assays are not supported when high-quality evidence is insufficient to demonstrate clinical utility for guiding management or improving outcomes.
Emerging MRD tests without validated clinical utility in the specific tumor type and context are considered investigational and not covered (examples include broad unvalidated tissue MRD applications and many tumor-naive ctDNA MRD approaches lacking prospective outcome data).
Billing/coding and operational notes
MRD tests intended for surveillance without validated benefit, tests lacking tumor-informed design where evidence favors tumor-informed approaches, and tests not ordered within evidence-based time frames may be denied as not medically necessary.
HPV-Related Solid Tumor MRD Testing
Covered when ALL of the following apply for HPV-related MRD testing:
ALL of the following
ctDNA MRD testing for HPV-associated tumors (e.g., oropharyngeal squamous cell carcinoma) using validated HPV-specific assays may be considered in surveillance when evidence supports its prognostic or predictive value in that cancer type.
Tissue-based HPV MRD testing is not supported where evidence is insufficient; plasma HPV ctDNA assays with validated performance are preferred for MRD surveillance when supported by data.
Testing must be performed at time points consistent with the evidence base and used to guide documented management decisions.
Appropriate use examples
Post-treatment surveillance for HPV-positive oropharyngeal cancer when validated HPV ctDNA MRD assays are used to detect molecular relapse and inform further diagnostic evaluation or therapy.
Broad Molecular Profiling Panel Tests via ctDNA (Liquid Biopsy)
Covered when ALL of the following apply for broad molecular profiling panels via ctDNA (liquid biopsy):
ALL of the following
Plasma ctDNA broad molecular profiling is indicated when tissue is unavailable or inadequate for testing, or when a less invasive approach is needed and the assay offers validated sensitivity for the intended use.
Results will influence clinical management (therapy selection, detection of resistance mutations, or trial eligibility) and documentation of the intended clinical use is present in the medical record.
Laboratory validation: the ctDNA assay must be analytically validated for the variants reported (SNVs, indels, CNAs, fusions where applicable) and the vendor provides sensitivity/specificity performance data.
Appropriate use examples
Advanced-stage solid tumor patients where tissue biopsy is unsafe or unobtainable and ctDNA testing can identify actionable alterations for therapy selection.
Lung Cancer Focused Panel Tests via ctDNA
Covered when ALL of the following apply for lung cancer–focused ctDNA panels and EGFR via ctDNA:
ALL of the following
Plasma ctDNA testing for lung cancer is reasonable when tissue is unavailable or insufficient for genotyping and a rapid result is needed to guide therapy; panels should include clinically actionable lung cancer biomarkers (EGFR, ALK [via fusion detection if validated], ROS1, BRAF, MET, RET, NTRK, KRAS, etc.).
EGFR testing via ctDNA is covered for detecting activating EGFR mutations and acquired resistance mutations (e.g., T790M) when results will guide targeted therapy; negative plasma results should prompt tissue testing if feasible.
Assays must be validated for detection of the specific EGFR variants reported and the lab must document limits of detection and clinical validation.
Use cases
Initial genotyping when tissue unavailable or insufficient and a rapid actionable EGFR result will change therapy.
BRAF, KRAS, PIK3CA via ctDNA
Covered when ALL of the following apply for ctDNA testing of specific variants (e.g., BRAF, KRAS, PIK3CA):
ALL of the following
Plasma-based testing for single-gene variants (BRAF, KRAS, PIK3CA) is covered when detection of the specific variant will directly inform therapy selection and tissue is unavailable or inadequate.
Assays must be validated for the specific variant detection and the laboratory provides performance characteristics; negative plasma results should be confirmed with tissue testing when clinically indicated.
Tumor-Specific Gene Rearrangement / Fusion / Amplification / Variant Tests (FISH/IHC/PCR/ISH)
Covered when ALL of the following apply for tumor-specific gene rearrangement / fusion / amplification / variant tests (FISH/IHC/PCR/ISH):
ANY of the following
ALK gene rearrangement testing (IHC, FISH, or validated molecular methods) is indicated in non-small cell lung cancer and other tumors per guideline recommendations to determine eligibility for ALK-targeted therapies. Laboratory methods should be validated and interpretive guidance provided.
Bladder cancer UroVysion FISH testing is indicated for evaluation of hematuria, suspicion of bladder cancer, or surveillance for recurrence per established clinical algorithms; testing must be used in the appropriate clinical context (diagnosis or recurrence surveillance) and interpreted with cystoscopy/pathology findings.
ERBB2 (HER2) testing by IHC and confirmatory FISH/CISH (or validated molecular methods) is indicated for tumor types with guideline-directed HER2-targeted therapies (e.g., breast, gastric); testing should follow recommended algorithms for reflex testing and scoring.
NTRK fusion testing is indicated in tumor types where detection of NTRK fusions would guide use of TRK inhibitors; broad or reflex testing approaches depend on tumor histology and pre-test probability (e.g., testing all advanced tumors when pan-tumor approval applies or focused testing in histologies with higher fusion rates).
Tumor-Specific Rearrangement/Fusion/Amplification Guidance (ALK, Bladder FISH, ERBB2, NTRK, RET, ROS1)
Coverage context excerpts and operational notes for select tumor-specific tests:
ALK
ALK testing (IHC/FISH/NGS) is covered for NSCLC and other indicated tumors when results will guide selection of ALK inhibitors; reflex testing algorithms per guidelines are acceptable.
Bladder FISH (UroVysion)
UroVysion FISH is covered for diagnosis or surveillance of bladder cancer when used per established clinical protocols and interpreted alongside cystoscopy and cytology results.
ERBB2 (HER2)
HER2 testing by IHC with confirmatory ISH (FISH/CISH) is covered for tumor types with guideline-recommended HER2-targeted therapies; testing and scoring should follow validated clinical algorithms.