CurrentCapital BluecrossPolicy MP 2.259

Molecular Panel Testing of Cancers to Identify Targeted Therapies

This policy governs medical necessity criteria for next‑generation sequencing gene panel testing of tumors to identify targeted cancer therapies when no more specific medical policy applies.

Policy Summary

PayerCapital Bluecross

PolicyMolecular Panel Testing of Cancers to Identify Targeted Therapies

Policy CodePolicy MP 2.259

Change TypeCoding and criteria updates

Effective DateOct 1, 2024

Next Review DateN/A

Key ActionObtain and document applicable preauthorization and ensure requested panel meets NCCN 2A+ or FDA companion diagnostic requirements before submitting claims.

SourceLink

POLICY UPDATE CHANGES

Multiple updates to criteria and references (08/07/2023).

New code 0473U added effective 7/1/2024.

New code 0448U added effective 4/1/2024.

Clinical benefit language was added in the 01/19/2024 administrative update.

New code 0409U effective 10/1/2023.

>=5Minimum targets

2A+NCCN threshold

AllowedFDA companion diagnostic

ListedInvestigational codes

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Coverage Criteria

Medically necessary criteria — Gene panel testing to identify targeted therapies is considered medically necessary when ALL of the following are met:

Gene panel testing (e.g., next generation sequencing) to identify targeted therapies is considered medically necessary when ALL of the following are met:

ALL of the following

No other genetic panel testing for targeted therapies has been performed on the individual's tumor (except when recurrent neoplastic disease following remission occasioned a new biopsy).
At least 5 targets are requested, and at least 5 of the requested targets are supported by the NCCN Biomarker Compendium at a 2A level or higher.
OR testing is required to comply with FDA label requirements as a cleared or approved companion diagnostic device (see FDA List of Cleared or Approved Companion Diagnostic Devices).
Testing that is performed solely to satisfy an FDA companion diagnostic requirement meets this criterion.

ALL of the following

The testing is used to identify targeted oncologic therapies for the individual's diagnosed cancer.
Documentation supports that results will inform therapeutic decision-making (e.g., selection of an FDA-approved targeted therapy or an NCCN-recommended targeted therapy at 2A level or higher).

ALL of the following

Prior to ordering, the provider has confirmed member benefit coverage and submitted any required prior authorization per payer-specific procedures.
See callout and billing/coding sections for investigational/ not covered procedure codes and prior authorization requirements.

ALL of the following

Expanded molecular panel testing that does not meet NCCN 2A+ support or FDA companion diagnostic requirements is considered not medically necessary due to insufficient evidence of clinical benefit.
Referenced in the policy as 'All other indications are considered not medically necessary.'

Coverage criteria (not present in this excerpt)

ALL of the following

All other indications for gene panel testing to identify targeted oncologic therapies are considered not medically necessary: there is insufficient evidence to support a general conclusion concerning the health outcomes or benefits associated with testing outside the criteria above.

ANY of the following

Investigational / not covered codes include but may not be limited to: 0009U, 0036U, 0211U, 0249U, 0391U, 0409U, 0485U, 81479.
Providers should verify coding and coverage with payer and submit medical rationale when requesting exceptions.

All other indications for gene panel testing for targeted oncologic therapies are considered not medically necessary: There is insufficient evidence to support a general conclusion concerning the health outcomes or benefits associated with this procedure.

Expanded molecular panel testing that does not meet NCCN 2A+ or FDA companion diagnostic requirements is considered not medically necessary.

When tests meet the FDA companion diagnostic designation or NCCN 2A+ support, testing may be covered if other criteria in this policy are satisfied. Providers should consult the FDA list of cleared or approved companion diagnostic devices and the NCCN Biomarker Compendium to confirm eligibility.

Covered Indications

Tumor gene panel testing — covered indications and requirements

Tumor gene panel testing to identify targeted therapies is covered when the medically necessary criteria are met and the following conditions apply:

Tumor panel prerequisites: 1) No prior genetic panel testing for targeted therapies has been performed on the tumor unless a new biopsy was obtained after disease recurrence; AND 2) The requested panel includes five or more targets, with at least five targets supported by the NCCN Biomarker Compendium at a 2A level or higher; OR 3) The requested testing is mandated by FDA companion diagnostic labeling for an associated therapy.>= 5 targets; NCCN 2A+ or FDA companion diagnostic requirement

Documentation should demonstrate prior testing status and alignment with NCCN or FDA companion diagnostic guidance.

Coding and administrative notes: Submission should use the HCPCS/CPT/PLA codes identified as covered when medically necessary; panels billed with investigational PLA or unlisted codes identified in policy may be denied.

Molecular panel testing to identify targeted therapies — policy intent

Coding

Investigational; therefore not covered when used for expanded cancer mutation panelsCPTNot Covered

0009U
0036U
0211U
0249U
0391U
0409U
0485U
81479

Covered when medically necessaryCPTCovered

0239U
0242U
0244U
0250U
0326U
0334U
0448U
0473U
81479

Covered HCPCS/U Codes (historic additions/removals)HCPCSCovered

0239U	New code added as covered with criteria
0242U	New code added as covered with criteria
0244U	New code added as covered with criteria
0326U	New code added
0339U	New code added
0334U	New code added
0391U	New code added
0409U	New code added
0448U	New code added
0473U	New code added

1–10 of 11

1/2

ICD-10 codes mentionedICD-10

C56.3

ICD-10 code added to policy

Minimum number of targets requested

Minimum targets required5 or more targets must be requested

NCCN support requirementAt least 5 of the requested targets must be supported by the NCCN Biomarker Compendium at level 2A or higher

Alternative pathway (FDA)Testing that is required to comply with FDA companion diagnostic labeling meets the coverage requirement even if NCCN 2A+ support is not met

Effective dates for codes

0239UAdded as covered with criteria; effective 1/1/2021

0242U and 0244U

Provider Actions / Requirements

Prior Authorization

Prior Authorization / Benefit Verification

Preauthorization may be required per the member's health benefit plan. Eligibility, coverage, and any prior authorization requirements are determined by the member's plan language and Capital Blue Cross preauthorization processes. Providers should verify benefits and obtain any required authorizations prior to ordering testing.

Verify member benefit coverage and preauthorization requirements before ordering testing.
If preauthorization is required, follow Capital Blue Cross preauthorization submission processes and timelines.

Billing Rule

Coverage Tied to Specific HCPCS/U Codes

Coverage for molecular panel testing is tied to specific HCPCS/ U codes. Claims submitted using codes not listed as covered under this policy or submitted as unlisted/PLA may be considered investigational and not covered when used to select targeted cancer therapies.

Definitions

Companion diagnostic — definition and role

DefinitionA companion diagnostic is a medical device, often an in vitro diagnostic (IVD), that provides information essential for the safe and effective use of a corresponding therapeutic product (FDA definition)

Primary roleIdentifies patients most likely to benefit from a particular therapeutic product

Clinical usesMay be used to monitor treatment response or identify patients at increased risk for serious side effects from a therapy

Molecular panel testing of cancers — definition / comprehensive genomic profiling

DefinitionMolecular panel testing (comprehensive genomic profiling) uses next-generation sequencing gene panels to profile tumor somatic alterations to identify targeted therapy options

Coverage linkage

Eligibility Requirements

No top-level eligibility requirement nodes are present in the excerpted inventory.

Not Covered

Expanded cancer mutation panels billed with the PLA and unlisted procedure codes identified in the policy are considered investigational and not covered when used to select targeted cancer therapies. Administrative history shows additions and removals of HCPCS/U codes over time; proper code submission consistent with the policy is necessary to avoid denial.

Specific tests or indications excluded beyond the investigational panel codes are not listed in the document excerpt provided.

Background

Targeted cancer therapy relies on identifying genetic abnormalities in a patient’s tumor to select drugs that act on those specific abnormalities. The policy distinguishes between markers that are actionable and those that are not, and ties coverage to either NCCN Biomarker Compendium support at level 2A or higher (with a minimum of 5 targets requested) or to tests required by FDA companion diagnostic labeling.

Policy Summary

PayerCapital Bluecross

PolicyMolecular Panel Testing of Cancers to Identify Targeted Therapies

Policy CodePolicy MP 2.259

Change TypeCoding and criteria updates

Effective DateOct 1, 2024

Next Review DateN/A

Key ActionObtain and document applicable preauthorization and ensure requested panel meets NCCN 2A+ or FDA companion diagnostic requirements before submitting claims.

SourceLink

On This Page

High-level intent: molecular panel testing is intended to identify targeted therapy options for cancer patients when consistent with clinical guidance and regulatory approvals.

Policy intent: Molecular panel testing of cancers is performed to identify actionable tumor biomarkers to select targeted therapies; testing should follow applicable NCCN recommendations or FDA companion diagnostic requirements.

Added as covered with criteria; effective 4/1/2021

0409UAdded as covered; effective 10/1/2023

0391UAdded as covered; effective 7/1/2023

0448UAdded as covered; effective 4/1/2024

0473UAdded as covered; effective 7/1/2024

Only submit the HCPCS/U codes included in the policy's coding section as applicable to the clinical criteria.
Expanded cancer mutation panels billed with PLA or unlisted codes (e.g., 81479 or unspecified PLA codes) for selecting targeted therapies are investigational and not covered.

Billing Rule

Administrative Coding Updates

Administrative coding updates have added or removed specific HCPCS/U codes over time. Providers must use the most current, applicable codes and review policy history or coding information to ensure proper billing. Missing or using an inappropriate code may affect coverage determinations and claims processing.

Review the policy coding section and revision history to confirm which HCPCS/U codes are currently accepted.
Be aware that codes added via administrative updates (with specific effective dates) must be used only from their effective dates onward.

Documentation Required

Required Clinical Documentation

Required provider documentation must demonstrate that no prior genetic panel testing for targeted therapies has been performed on the tumor, unless a new biopsy was obtained for recurrent disease. Documentation should also reference applicable guideline support (e.g., NCCN Biomarker Compendium) or FDA companion diagnostic labeling when relevant.

Include documentation that prior panel testing was not performed on the same tumor unless a new biopsy was obtained for recurrent disease.
Document that at least 5 targets are requested with ≥5 supported at NCCN Biomarker Compendium level 2A or higher when relying on that criterion, or that testing is required to meet FDA companion diagnostic labeling when applicable.
Reference relevant guideline or FDA companion diagnostic language in the patient's chart to support medical necessity.

Note

Policy History and Coding Additions

Policy history documents additions of specific HCPCS/U codes and references to NCCN language. Providers should reference the policy history for the effective dates of code additions and for any changes in clinical criteria (e.g., incorporation of NCCN language or FEP updates).

Policy history includes administrative updates adding codes such as 0239U, 0242U, 0244U, 0326U, 0339U, 0334U, 0391U, 0409U, 0448U, 0473U and others with specified effective dates.
Use the policy history to confirm when a code became covered (or removed) and to align billing and documentation with the policy's effective dates.

Denial Risk

Provider Action / Billing Risk

Provider action: when submitting claims, ensure coding, documentation, and any required prior authorization align with the policy's coding list and clinical criteria. Failure to follow coding updates or documentation requirements may result in claim denial as investigational/not covered.

Do not bill investigational/not covered PLA or unlisted codes for expanded cancer mutation panels used to select targeted therapies (examples listed in coding: 0009U, 0036U, 0211U, 0249U, 0391U, 0409U, 0485U, 81479).
Confirm and use codes added via administrative updates only from their stated effective dates.

Panels are covered when criteria are met: no prior panel on the tumor (unless new biopsy after recurrence) and 5 or more requested targets meeting NCCN 2A+ support or when testing is required as an FDA-cleared/approved companion diagnostic

Evidence and guidance sourcesNCCN Biomarker Compendium and FDA companion diagnostic listings guide which markers are actionable