Blue Cross Blue Shield RI NGS Genomic Profiling Coverage

Coverage Criteria

Somatic (Acquired) Cancer Coverage

Covered for somatic (acquired) cancer when ALL of the following are met

Somatic cancer criteria: Patient has recurrent, relapsed, refractory, metastatic, or advanced stage III or IV cancer; and the patient has decided to seek further cancer treatment (e.g., therapeutic chemotherapy); and the patient has not been previously tested with the same test using NGS for the same cancer genetic content

Germline (Inherited) Cancer Coverage

Covered for germline (inherited) cancer testing when ALL of the following are met

Germline cancer criteria: Patient has ovarian or breast cancer AND has risk factors and a clinical indication for hereditary (germline) breast or ovarian cancer testing AND has not been previously tested with the same germline test using NGS for the same germline genetic content

Germline test requirements: The NGS germline test must have FDA approval or clearance and results must be provided to the treating physician in a report template that specifies treatment options

Non-Small Cell Lung Cancer (NSCLC)

NSCLC — Covered when ALL of the following are met

NSCLC criteria: Patient is newly diagnosed with advanced (stage IIIB or IV) NSCLC not amenable to curative resection or radiation and is a suitable candidate for therapy at the time of testing; OR previously diagnosed advanced (stage IIIB or IV) NSCLC who have not responded to at least one systemic therapy or who have progressed following resection and are candidates for treatment at the time of testing

Testing evaluates tumor tissue in specified clinical circumstances; multiple actionable variants (over 40 small variants across ten genes and gene fusions) are described in policy.

Metastatic Colorectal Cancer (mCRC)

Metastatic colorectal cancer (mCRC) — Covered when ALL of the following are met

mCRC criteria: Patient has metastatic colorectal cancer AND testing is performed in a CLIA-certified laboratory qualified to perform high-complexity testing and is ordered by a treating physician AND the patient is a candidate for intensive chemotherapy with an anti-EGFR biologic agent AND the patient has not had prior RAS/BRAF testing (except testing after initiation of anti-EGFR therapy when acquired resistance is suspected)

Testing not necessary for patients considered for palliative or hospice care only; retesting may be indicated after anti-EGFR initiation if resistance develops.

General coverage rationale

Coverage stance and evidentiary summary

Evidentiary conclusions: Evidence is insufficient to determine the clinical utility of expanded molecular (comprehensive genomic) panels as a whole to direct targeted cancer treatment across cancers; the randomized SHIVA trial reported no progression-free survival benefit for an expanded-panel-directed strategy versus standard treatment. However, specific companion diagnostics with demonstrated benefit and FDA approval/clearance (and NGS tests meeting CMS criteria when performed in CLIA-certified laboratories and ordered by a treating physician) are recognized and may be used in accordance with professional guidelines and labeling. Basket trials and additional randomized studies are needed to define benefit of broad profiling compared with more limited, tumor-specific testing.

For Commercial Products, the following expanded panel tests are considered not medically necessary because the evidence is insufficient to determine clinical benefit: FoundationOne CDx (F1CDx), MSK-IMPACT, Praxis Extended RAS Panel, and myChoice CDx.

Overall, clinical utility has not been demonstrated for use of expanded molecular panels as a whole to direct targeted cancer treatment. The policy cites randomized and nonrandomized trials and systematic reviews showing that while some trials targeting a specific gene variant improved outcomes, the single published randomized trial (SHIVA) of an expanded-panel-directed strategy showed no progression-free survival benefit compared with standard treatment. Because many variants and cancer types prevent determination of clinical validity for panels in aggregate, the evidence is insufficient to support broad use of expanded panels to guide therapy across cancers.

Per this policy, the listed expanded genomic panels are not medically necessary for Commercial Products due to insufficient evidence of clinical utility. Examples explicitly named in the policy include FoundationOne CDx, MSK-IMPACT, Praxis Extended RAS Panel, and myChoice CDx and are not supported for routine use for directing targeted cancer therapy outside recognized companion diagnostic indications.

Certain CPT/PLA codes are identified as requiring prior authorization for BlueCHiP for Medicare and are also noted in this policy as not medically necessary for Commercial Products. Examples of these codes include 0022U, 0037U, 0048U, 0111U, and 0172U; many expanded panels without assigned CPT codes should be filed with an appropriate unlisted CPT code and may require authorization to determine coverage.

Covered Indications

Advanced solid organ neoplasms when comprehensive genomic profiling may inform targeted therapy decisions, and when tests are companion diagnostics with FDA approval/clearance or meet CMS NGS coverage criteria.

Advanced solid organ neoplasms: Comprehensive genomic profiling may be appropriate for advanced solid organ neoplasms when results will inform targeted therapy decisions and when the test is a companion in vitro diagnostic with FDA approval/clearance or meets CMS NGS national coverage criteria (performed in a CLIA-certified laboratory and ordered by a treating physician). Evidence supporting clinical utility is strongest for germline mutation identification in breast and ovarian cancer; some tumor-specific markers (e.g., certain NSCLC and colorectal biomarkers) are standard per guidelines.

Eligibility Requirements

Eligibility for NGS-based testing varies by indication. For germline (inherited) testing in breast or ovarian cancer, the patient must have the relevant cancer and clinical indications or risk factors for hereditary cancer, and must not have been previously tested with the same germline NGS content. For somatic (acquired) testing in advanced or metastatic cancers, the patient must have recurrent, relapsed, refractory, metastatic, or advanced stage III/IV disease, be seeking further cancer treatment, and must not have been previously tested with the same somatic NGS content. For metastatic colorectal cancer (mCRC), testing is appropriate when performed in a CLIA-certified high-complexity laboratory, ordered by a treating physician, the patient is a candidate for intensive chemotherapy with an anti-EGFR biologic agent, and prior RAS/BRAF testing has not already been performed (except when evaluating acquired resistance after anti-EGFR therapy).

Tests must be ordered by a treating physician and performed in a CLIA-certified laboratory qualified for high-complexity NGS testing. Prior testing with the same NGS test/content generally precludes repeat testing for the same indication unless clinically indicated (for example, to evaluate acquired resistance after anti-EGFR therapy in mCRC). Results should be provided to the treating physician in a report that details treatment options and management considerations.

For guideline-based tumor-specific indications such as advanced non-small cell lung cancer (NSCLC), panels may evaluate numerous variants relevant to management. NSCLC panels cited in the policy include more than 40 single nucleotide or small insertion/deletion variants across ten genes, plus gene fusions involving multiple genes. However, panel testing should be directed by clinical indication and guideline-recommended biomarkers rather than broad panel use when evidence for benefit is lacking.

Patients are eligible for covered NGS testing only when the test and clinical scenario meet the specified coverage criteria: somatic tumor profiling for advanced/recurrent/metastatic cancers when the patient is seeking further treatment and has not had the same NGS test for the same content; germline testing for hereditary breast/ovarian cancer when the patient has appropriate risk factors and clinical indication and has not had prior identical germline testing; and mCRC testing when performed in a CLIA-certified laboratory, ordered by a treating physician, the patient is a candidate for intensive chemotherapy with anti-EGFR therapy, and prior RAS/BRAF testing has not already been done (except to evaluate acquired resistance).

Coding and Billing

BlueCHiP for Medicare covered specific test HCPCS/CPT-like codesmixedCovered

0022U	Oncomine Dx Target Test
0037U	FoundationOne CDx
0111U	Praxis Extended RAS Panel
0172U	myChoice CDx

BlueCHiP for Medicare covered specific test HCPCS/CPT-like codes (source detail)mixedCovered

0022U	OncomineTM Dx Target Test
0037U	FoundationOne CDxTM (FICDx)
0111U	Praxis (TM) Extended RAS Panel
0172U	myChoice@ CDx

Additional BlueCHiP for Medicare covered test codemixedCovered

0048U

MSK-IMPACT

Additional BlueCHiP for Medicare covered test code (source detail)mixedCovered

0048U

MSK-IMPACT 0048U

Unlisted genetic testing codes requiring authorizationCPT

Unlisted CPT genetic testing codes

Use when no specific CPT exists for some services referenced

Unlisted genetic testing codes requiring authorization (note)CPT

Unlisted CPT

All Unlisted genetic testing CPT codes require authorization to determine what service is rendered and if the service is covered

Listed CPT/PLA Codes Requiring Authorization for BlueCHiP for MedicareCPTCovered

0022U	Targeted genomic sequence analysis panel, non-small cell lung neoplasia, DNA and RNA analysis, 23 genes, interrogation for sequence variants and rearrangements, reported as presence/absence of variants and associated therapy(ies) to consider
0037U	Targeted genomic sequence analysis, solid organ neoplasm, DNA analysis of 324 genes, interrogation for sequence variants, copy number amplifications, gene rearrangements, microsatellite instability and tumor mutational burden
0048U	Oncology (solid organ neoplasia), DNA, targeted sequencing of protein-coding exons of 468 cancer associated genes, including interrogation for somatic mutations and microsatellite instability, matched with normal specimens, utilizing formalin-fixed paraffin-embedded tumor tissue, report of clinically significant mutation(s)
0111U	Oncology (colon cancer), targeted KRAS (codons 12,13,and 61) and NRAS (codons 12,13,and 61) gene analysis utilizing formalin-fixed paraffin-embedded tissue
0172U	Oncology (solid tumor as indicated by the label), somatic mutation analysis of BRCA1, BRCA2 and analysis of homologous recombination deficiency pathways, DNA, formalin-fixed paraffin-embedded tissue, algorithm quantifying tumor genomic instability score

Unlisted / panels without CPTCPT

Unlisted CPT

Most expanded cancer molecular panels without assigned CPT codes should be filed with an appropriate unlisted CPT code

NSCLC — Genes and variant counts

Variants describedOver 40 single nucleotide or small insertion/deletion variants across ten genes

Gene fusionsGene fusions can involve five different genes

AmplificationAmplification is a significant recognized alteration in at least one gene

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for BlueCHiP for Medicare for the listed tests. Failure to obtain prior authorization may result in denial of coverage. For Commercial Products, prior authorization is recommended.

FoundationOne CDx (0037U)
Oncomine Dx Target Test (0022U)
MSK-IMPACT (0048U)
Praxis Extended RAS Panel (0111U)
myChoice CDx (0172U)

Prior Authorization

Prior Authorization for Unlisted and Uncoded Tests

All Unlisted genetic testing CPT codes and services that lack an assigned CPT/PLA code require prior authorization to determine what service is rendered and whether it is covered or not medically necessary. Prior authorization for BlueCHiP for Medicare is obtained via the payer's online tool for participating providers.

Use an Unlisted CPT code when no specific CPT/PLA code exists for the expanded cancer molecular panel

Not Covered / Not Medically Necessary

Not covered for Commercial Products: the policy explicitly lists several expanded panel tests as not medically necessary, including FoundationOne CDx, MSK-IMPACT, Praxis Extended RAS Panel, and myChoice CDx due to insufficient evidence that these broad panels improve health outcomes in the commercial population.

Not covered rationale: the policy states that use of expanded molecular panels to direct targeted cancer treatment lacks sufficient evidence of clinical utility overall. Because many variants and cancer types prevent clear determination of clinical validity for panels as a whole, panels that do not have established efficacy for the specific cancer under consideration are not supported as generally clinically useful.

Background

Comprehensive genomic profiling uses expanded next-generation sequencing (NGS) panels to evaluate multiple genetic markers across cancers to identify potential targeted therapies. These expanded panels can detect somatic and germline variants and may inform therapy selection when tests are companion diagnostics with demonstrated benefit. Expanded panels often identify multiple alterations per patient, but not all detected variants are clinically actionable across tumor types, and broad panel testing has uncertain clinical utility outside of validated companion diagnostic uses.

Definitions

Expanded (large) NGS panels (definition)

DefinitionExpanded (large) panels test a wide variety of genetic markers in cancers without regard to whether specific targeted treatment has demonstrated benefit

ScopeMay evaluate many genetic markers at a single time to identify potential targeted therapies

Examples in policyIncludes FoundationOne CDx, Oncomine Dx, MSK-IMPACT, myChoice CDx, Praxis Extended RAS Panel

Targeted cancer therapy

DefinitionUse of drugs that target specific genetic abnormalities identified in a patient's tumor to guide therapy selection

PurposeMatches treatments to actionable molecular alterations to improve outcomes

OpenPayer

Comprehensive Genomic Profiling for Selecting Targeted Cancer Therapies