Blue Cross RI NGS/CDx Coverage & Prior Auth

Coverage and Medical Necessity Criteria

inv-01: Somatic (Acquired) cancer — initial coverage criteria

Covered when ALL of the following are met

Somatic (Acquired) Cancer criteria: 1. Patient has recurrent, relapsed, refractory, metastatic, or advanced stage III or IV cancer AND has decided to seek further cancer treatment (e.g., therapeutic chemotherapy). 2. The patient has not been previously tested with the same NGS test for the same cancer genetic content. 3. The diagnostic NGS test is performed in a CLIA-certified laboratory and ordered by a treating physician. 4. The NGS test has FDA approval or clearance as a companion in vitro diagnostic or an FDA-approved/cleared indication for use in that patient's cancer, and results are provided to the treating physician using a report template that specifies treatment options.

Derived from combined statements in chunks 2,4,5,6

inv-02: Germline breast/ovarian cancer — coverage criteria

Covered when ALL of the following are met

Germline breast/ovarian cancer criteria: 1. Patient has ovarian or breast cancer. 2. Patient has a risk factor for germline (inherited) breast or ovarian cancer and there is a clinical indication for germline testing for hereditary breast or ovarian cancer. 3. The patient has not been previously tested with the same germline NGS test for the same germline genetic content. 4. The diagnostic germline NGS test has FDA approval or clearance, and results are provided to the treating physician using a report template that specifies treatment options.

From chunk 5 and 6

inv-03: General coverage stance

Covered when medical criteria are met and testing is used to guide targeted cancer therapy:

Evidence and utility requirements: Evidence for expanded/comprehensive genomic profiling is limited. A randomized controlled trial (SHIVA) reported no progression-free survival benefit; overall clinical utility of broad panels across many variants and tumor types has not been demonstrated. Use of these tests to guide targeted therapy may be considered when the medical criteria above are met and when results will directly inform targeted cancer treatment decisions.

Policy states insufficient evidence for broad benefit across tumor types; targeted use based on known tumor-specific variants has stronger evidence.

The policy explicitly identifies specific proprietary tests that are not covered for Medicare Advantage Plans or are not medically necessary for Commercial Products due to insufficient evidence of improved net health outcomes. Examples listed include: HeproDx, OncoTarget/OncoTreat, EXaCT-1 Whole Exome Test, MI Cancer Seek NGS Analysis, and a LC‑MS/MS Targeted Proteomic Assay.

The policy states that “The following CPT codes are not covered for Medicare Advantage Plans and not medically necessary for Commercial Products” (section heading present in the source). Specific CPT code examples calling out this non‑coverage status are presented elsewhere in the policy under coding and exclusions; providers should refer to the coding section and payer tools for the exact list of non‑covered codes.

For both Medicare Advantage and Commercial Products, several named tests are considered not covered or not medically necessary because the evidence is insufficient to demonstrate an improvement in net health outcomes. The document specifically cites insufficient evidence as the reason these services are excluded from coverage determinations.

The policy notes that use of expanded or large genomic panels to direct targeted cancer treatment has not demonstrated clinical utility in many settings. Evidence reviewed includes one randomized controlled trial (the SHIVA trial) that showed no progression‑free survival benefit for broad profiling versus standard treatment, and the policy concludes that the evidence is insufficient to determine improved net health outcomes for comprehensive genomic profiling across diverse tumor types and variants.

Indications Where Testing May Be Covered

inv-33: Advanced/recurrent/metastatic/relapsed/refractory stage III/IV cancers being considered for further treatment; germline testing for breast or ovarian cancer when risk factors and clinical indication present.

Covered indications (advanced or recurrent disease; germline testing): Advanced/recurrent/relapsed/refractory (stage III/IV) cancers being considered for further cancer-directed treatment are eligible for targeted genomic sequence analysis when the somatic criteria are met. Germline testing for breast or ovarian cancer is eligible when risk factors and a clinical indication for hereditary testing are present and the germline criteria are met.

Synthesizes covered-indication statements from chunks 4–6

inv-34: Targeted genomic sequence analysis for solid organ neoplasms or cell-free DNA to identify variants potentially actionable for targeted therapy — includes mapping of proprietary tests to CPT/PLA codes

Targeted genomic sequence analysis (proprietary CDx and cfDNA): Targeted genomic sequence analysis of tumor tissue or cell-free DNA to identify variants potentially actionable for targeted therapy may be considered medically necessary when the medical criteria in this policy are met. Examples of proprietary/companion diagnostic assays mapped to CPT/PLA codes include: FoundationOne CDx (0037U; 324 genes), FoundationOne Liquid CDx (0239U; 311+ genes), Guardant360 CDx (0242U; 55–74 genes), and XT CDx (0473U; 648 genes). Tests must be used to guide targeted cancer therapy and meet the policy's laboratory, FDA-approval/clearance, and reporting requirements.

CPT / PLA / Proprietary Test Codes

Covered CPT/PLA Codes (examples)CPTCovered

0022U

Targeted genomic sequence analysis panel, non-small cell neoplasia, DNA and RNA analysis, 23 genes, interrogation for sequence variants and rearrangements, reported as presence or absence of variants and associated therapy(ies) to consider

Covered CPT/PLA Codes (examples)CPTCovered

0037U

Targeted genomic sequence analysis, solid organ neoplasm, DNA analysis of 324 genes, interrogation for sequence variants, gene copy number amplifications, gene rearrangements, microsatellite instability and tumor mutational burden

Covered CPT/PLA Codes (examples)CPTCovered

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

Covered CPT/PLA Codes (examples)CPTCovered

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

Covered/considered medically necessary (when criteria met)CPTCovered

0022U	Targeted genomic sequence analysis panel, non-small cell neoplasia, DNA and RNA analysis, 23 genes
0037U	Targeted genomic sequence analysis, solid organ neoplasm, DNA analysis of 324 genes (FoundationOne CDx)
O111U	Oncology (colon cancer), targeted KRAS and NRAS gene analysis
0172U	myChoice CDx: somatic mutation analysis of BRCA1/BRCA2 and homologous recombination deficiency pathways

Covered/considered medically necessary (when criteria met)CPTCovered

0239U

Targeted genomic sequence analysis panel, solid organ neoplasm, cell-free DNA, analysis of 311 or more genes

Covered/considered medically necessary (when criteria met)CPTCovered

0242U

Targeted genomic sequence analysis panel, solid organ neoplasm, cell-free circulating DNA analysis of 55-74 genes

Covered/considered medically necessary (when criteria met)CPTCovered

0473U

Next-generation sequencing of DNA with matched normal specimen, 648 genes (XT CDx)

Listed proprietary/other tests (explicitly noted in policy)CPT

0006M	mRNA expression levels of 161 genes (HepatoPredict/Hepro Dx)
0019U	RNA whole transcriptome sequencing with predictive algorithm (OncoTarget/OncoTreat)
0036U	Exome (somatic mutations), paired tumor and normal specimen (EXaCT-1)
0174U	LC-MS/MS targeted proteomic assay, 30 protein targets with prognostic/predictive algorithm
0211U	Oncology pan-tumor DNA and RNA NGS with interpretative report and therapy association (MI Cancer Seek NGS Analysis)

Coding — selected code notes

0022UTargeted genomic sequence analysis panel, non-small cell neoplasia (Oncomine Dx Target Test) — DNA and RNA analysis, 23 genes

0037UTargeted genomic sequence analysis, solid organ neoplasm (FoundationOne CDx) — DNA analysis of 324 genes

0111UOncology (colon cancer) — targeted KRAS and NRAS gene analysis (Praxis Extended RAS Panel)

0172UmyChoice CDx — somatic mutation analysis of BRCA1/BRCA2 and homologous recombination deficiency pathways

Provider Responsibilities and Authorization

Prior Authorization

Prior Authorization Required / Recommended

Prior authorization is required for Medicare Advantage plans and recommended for Commercial products. Providers must obtain prior authorization via the payer's online portal for participating providers before ordering the listed tests. Lack of prior authorization may result in claim denials or reduced coverage depending on the member's plan.

Affected tests include: Oncomine™ Dx Target Test; FoundationOne CDx™ (F1CDx); Praxis™ Extended RAS Panel; FoundationOne Liquid CDx; myChoice® CDx; Guardant360® CDx; XT CDx.
Operational detail: use the payer's online prior authorization tool for submission.

Denial Risk

Coverage and Denial Risk

Tests and CPT/Proprietary codes referenced in this policy are covered only when the policy's medical criteria are met. If the clinical criteria and documentation requirements are not satisfied, the test may be considered not medically necessary and will not be covered.

Member and Clinical Eligibility

Eligibility requirements for coverage decisions are defined by the medical criteria in this policy (see Somatic and Germline coverage criteria). These include clinical stage and treatment intent, absence of prior identical testing for the same genetic content, laboratory and ordering requirements, and FDA approval/clearance or companion diagnostic status where applicable.

Providers must confirm member eligibility and benefits prior to testing. Coverage is determined by whether the patient’s clinical scenario meets the policy’s medical criteria (for example advanced/recurrent/metastatic disease or germline testing indications) and by any applicable contractual exclusions noted in the member’s benefit booklet.

Tests and Codes Not Covered

The policy lists specific proprietary or specialty tests that are not covered or not medically necessary based on available evidence. Named examples include: HeproDx, OncoTarget/OncoTreat, EXaCT‑1 Whole Exome Testing, MI Cancer Seek NGS Analysis, and a LC‑MS/MS Targeted Proteomic Assay.

The policy indicates that certain CPT codes are explicitly designated as not covered for Medicare Advantage Plans and not medically necessary for Commercial Products. The section heading announces this non‑coverage status; providers should consult the policy coding tables and payer resources to identify the specific CPT codes subject to these exclusions.

Background and Rationale

Comprehensive genomic profiling evaluates multiple genetic markers simultaneously—often via broad next‑generation sequencing (NGS) panels or proprietary assays—to identify potentially targetable alterations. Unlike traditional selection based on tumor site and stage, these large panels interrogate many genes or biomarkers at once to uncover actionable variants; however, clinical utility depends on validated links between detected variants and effective targeted therapies, regulatory (FDA) companion diagnostic status where relevant, and appropriate clinical context.

The policy’s evidence summary emphasizes that expanded/large panels have limited demonstrated clinical utility across many settings. The document cites one randomized trial (SHIVA) that found no progression‑free survival benefit for comprehensive profiling versus standard therapy and concludes that overall evidence is insufficient to show that broad molecular profiling improves net health outcomes for all tumor types or variants.

Definitions and Terminology

Expanded/large genomic panels — definition

DefinitionMolecular tests that assess a wide variety of genetic markers in cancers without regard for whether a specific targeted treatment has demonstrated benefit

PurposeEvaluate multiple genetic markers simultaneously to identify potential targeted cancer treatments

Clinical implicationMay identify treatments different from those selected based on tumor type and stage; clinical utility for broad panels not established across all cancers

NGS diagnostic test — definition and lab/ordering note

DefinitionNext-Generation Sequencing (NGS) diagnostic test performed in a CLIA-certified laboratory and ordered by a treating physician

Coverage note

Document History

2024-01-01policy_effectiveLatest

Policy effective date established for Comprehensive Genomic Profiling for Selecting Targeted Cancer Therapies.

2023-09-06policy_review

Policy last reviewed on this date (routine review of medical coverage policy).