Genetic testing — gene expression (coverage criteria)
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Medicaid clinical coverage policy describing gene expression testing (definitions, coverage framework, and requirements) for beneficiaries enrolled in NC Medicaid PHPs. This part of the document provides background, definitions, and table-of-contents level structure affecting providers, labs, and prior authorization processes.
Added coverage for AlloMap.
Non-coverage criteria added for AlloMap.
Procedure codes updated and code for AlloMap added.
Coverage Criteria and Clinical Indications
Coverage framework (structure only)
Policy sections outline when covered, specific criteria, Medicaid-specific criteria, and prior approval requirements.
Detailed coverage rules not present in this excerpt
Breast cancer — general recurrence/chemo decision assays
Covered when ALL of the following are met (Oncotype DX, EndoPredict, Prosigna, Breast Cancer Index, MammaPrint):
Exact assay list: Oncotype DX Breast Recurrence Score, EndoPredict, Prosigna, Breast Cancer Index, MammaPrint
Oncotype DX — node-positive postmenopausal
Covered when ALL of the following are met:
Extended adjuvant hormonal therapy decision — EndoPredict/Prosigna/Breast Cancer Index
Covered when ALL of the following are met:
Applies to EndoPredict, Prosigna, or Breast Cancer Index to aid decisions about extending adjuvant hormonal therapy beyond 5 years.
Breast Cancer Index — extended therapy for node-positive
Covered when ALL of the following are met:
Applies for beneficiaries with 1–3 positive lymph nodes.
Thyroid nodule gene expression testing
Covered when ALL of the following are met:
AlloMap — heart transplant rejection surveillance
Covered when ALL of the following are met:
Additional universal requirements for all covered gene expression tests
All covered gene expression profiling tests require ALL of the following:
Refer to Subsections 1.1.5 and 6.2 for counseling reference.
Not Medically Necessary / Specific Not Covered Indications
Tests are not covered for the following specific situations
Derived from Section 4.2.1
Derived from Section 4.2.1
Derived from Section 4.2.1
Covered with Criteria
Covered when billed according to listed unit limits and frequency guidance:
See chunk 55 for codes and limits.
See chunk 56 for codes and limits.
See chunk 57 for schedule.
See chunk 58.
The policy Table of Contents identifies a When Not Covered section (Section 4.0) with subsections for General Criteria Not Covered (4.1) and Specific Criteria Not Covered (4.2, including 4.2.1 and 4.2.2). However, the excerpt provided contains only the section headings and structure; explicit exclusion condition text is present elsewhere in the policy and is summarized in the specific not-covered blocks below.
Gene expression profiling is not covered to predict response to specific chemotherapy regimens, and is not covered for beneficiaries with known metastatic cancer. The policy also prohibits coverage when results would not affect clinical management (for example, if management decisions such as biopsy are already planned) and when the general Section 3.0 coverage criteria are not met. These limitations are listed under the policy's Specific Not Covered and General Not Covered subsections.
Thyroid nodule gene expression testing is covered only when the criteria in Subsection 3.2.2 are met (including age ≥21 and an ultrasound nodule ≥1 cm with indeterminate cytology). The policy expressly states that thyroid nodule profiling is not covered when the Section 3.2.2 requirements are not satisfied.
The policy excludes the use of breast gene expression profiling to manage Ductal Carcinoma in Situ (DCIS) when DCIS is the sole breast cancer histology. Gene expression assays listed for invasive disease are not intended to guide management when DCIS is the only histologic finding.
The policy explicitly excludes using gene expression profiling to predict response to specific chemotherapy regimens. Such predictive use is identified as a non-covered indication for the listed breast prognostic assays (Oncotype DX, EndoPredict, Prosigna, Breast Cancer Index, MammaPrint) when Section 3.0 criteria are not met or when used for that purpose.
When a procedure, product, or service does not have an assigned, specific CPT or HCPCS code, providers must report it with the appropriate unlisted procedure or service code and submit the required special report documentation per the current CPT/HCPCS instructions for use. The policy directs providers to follow CPT/HCPCS guidance for unlisted codes and supporting documentation.
The policy includes a When Not Covered section (Section 4.0) that defines conditions under which services are considered not medically necessary. The policy instructs that detailed not-medically-necessary statements and examples are set out in that section and related subsections; providers should consult Section 4.0 for the full list of NMN conditions.
Services are considered not medically necessary when the beneficiary fails to meet eligibility in Section 2.0, does not meet the coverage criteria in Section 3.0, when the service duplicates another provider's service, or when the procedure is experimental, investigational, or part of a clinical trial. The policy further specifies that tests are not medically necessary when results will not alter clinical management.
The policy states that tests which would not impact clinical management are not covered as medically necessary. Examples include situations where a biopsy or other management step is already planned based on other clinical data; in such cases gene expression testing would not change the planned care and is therefore not covered.
Covered Indications by Test and Use Case
Claims, CPT/PLA, and Billing Rules
| No codes listed |
| 81518 | CPT code listed in policy (breast cancer gene expression test) |
| 81519 | CPT code listed in policy (breast cancer gene expression test) |
| 81520 | CPT code listed in policy (breast cancer gene expression test) |
| 81521 | CPT code listed in policy (breast cancer gene expression test) |
| 81522 | CPT code listed in policy (breast cancer gene expression test) |
| 81523 | CPT code listed in policy (breast cancer gene expression test) |
| 81595 | Transplant rejection monitoring gene expression code |
| 96041 | Medical geneticist or genetic counselor counseling; 1 unit = 30 minutes |
| Unlisted CPT/HCPCS | Use appropriate unlisted procedure or service code when no specific code exists and provide special report per current CPT/HCPCS instructions |
Provider Responsibilities, Prior Authorization, and Documentation
Prior approval required when exceeding Attachment A limits
Prior approval is required when exceeding unit limitations found in Attachment A, Section C; providers must follow the prior approval requirements documented in Subsection 5.2 and submit the prior approval request and supporting health records to the DHHS Utilization Review Contractor.
- Submit the prior approval request and all health records supporting that the beneficiary meets the specific criteria in Subsection 3.2.
EPSDT does not waive prior approval
If a service requires prior approval, EPSDT does not waive that requirement for beneficiaries under age 21; the ordering provider must ensure prior approval is obtained when applicable and counseling/consent are documented.
- EPSDT does not eliminate prior approval requirements; see NCTracks and EPSDT resources for additional guidance.
Prior approval required for requests exceeding Attachment A unit limits
Prior approval is not required generally for gene expression profiling tests, but prior approval is required when requesting services that exceed the unit limitations in Attachment A, Section C.
- When requesting additional units beyond the listed unit limits, follow Subsection 5.2 and provide supporting documentation per Subsection 5.3.2.
Follow Attachment A unit limits and frequency guidance
Providers must follow the unit limitations and frequency guidance for the listed CPT/PLA codes in Attachment A when billing gene expression tests; requests for additional units must be justified per the documentation requirements.
- Breast panels (CPT 81518–81523): 1 unit once per primary cancer occurrence.
- Thyroid panels (81546, 0018U, 0026U, 0245U, 0287U): 1 unit once per primary cancer occurrence.
- Transplant monitoring (81595): specified intervals (monthly starting at 2 months post-transplant in year 1; every 3–6 months in years 1–5; beyond 5 years as needed).
- Genetic counseling (96041): limited to 3 units (90 minutes).
No step therapy specified; follow transplant monitoring intervals for 81595
No step therapy is specified in this portion of the policy; transplant rejection monitoring (CPT 81595) uses defined monitoring intervals rather than stepwise therapy requirements.
- Policy states no step therapy is specified for gene expression profiling tests.
- Use the monitoring schedule for 81595 (see Attachment A) to guide ongoing testing post-transplant.
Follow specified AlloMap monitoring intervals (81595)
Transplant rejection monitoring with AlloMap (CPT 81595) must follow the specified post-transplant monitoring schedule: monthly starting at >55 days (≈2 months) post-transplant in the first year, then every 3–6 months in years 1–5 depending on stability, and thereafter as clinically indicated.
- Do not use AlloMap outside the validated heart transplant rejection monitoring indications (see non-coverage rules).
Document genetic counseling elements and informed consent
When genetic counseling is provided by a licensed provider instead of a certified genetic counselor, the provider must document counseling elements and informed consent in the beneficiary's health record as described in the genetic counseling definition.
- Document structured family medical and genetic history, multi-generation pedigree, analysis for genetic risk assessment, discussion of natural history and recurrence risk, testing/screening/monitoring options, and that informed consent was obtained.
Document counseling, consent, non-duplication, and EPSDT justification
Providers must document pre- and post-test genetic counseling, documented informed consent, and that the test is not duplicative; for beneficiaries under 21, EPSDT requirements do not waive prior approval and documentation must support medical necessity.
- Maintain records showing counseling occurred, informed consent was obtained, and the test is not a duplicate of another performed test.
- For additional units or EPSDT exceptions, include prior related lab results and justification per Subsection 5.3.2.
Submit prior approval request with full supporting documentation
For prior approval requests, submit the prior approval request plus all health records and supporting documentation that the beneficiary meets the criteria in Subsection 3.2; when requesting additional units, include the reason for the test, previous related lab results, how results improve outcomes, and how results alter treatment.
- Include clinical records and any prior test results demonstrating indications and how results will affect management.
Use unlisted code + special report when no specific code exists
When no specific CPT or HCPCS code exists, providers must report the service with the appropriate unlisted procedure or service code and comply with CPT/HCPCS instructions for unlisted codes, including submission of the required special report documentation.
- Follow the Instructions for Use in the current CPT and HCPCS editions for unlisted procedure or service codes and submit a special report as required.
Prior approval referenced — lack of required prior approval may cause denial
Prior approval is referenced as a requirement area; services lacking required prior approval (when exceeding Attachment A limits) may be subject to denial.
- Verify whether the requested service exceeds Attachment A unit limits and obtain prior approval if required.
General denial triggers — eligibility, criteria, duplication, experimental
Services are not covered when the beneficiary does not meet eligibility (Section 2.0), does not meet the coverage criteria (Section 3.0), the service duplicates another provider's service, or the service is experimental/investigational.
- Confirm beneficiary eligibility and that all Section 3.0/Subsection 3.2 criteria are met before ordering.
Specific denial triggers — listed non-covered indications
Specific denial triggers include use of gene expression profiling to predict response to specific chemotherapy regimens, testing in beneficiaries with known metastatic cancer, duplicate or multisite testing of the same tumor, testing when results would not change chemotherapy decisions, and use of assays outside the listed approved tests.
- Avoid ordering tests for the listed non-covered indications to prevent claim denial.
Non-covered indications for breast gene expression tests
Breast gene expression tests (Oncotype DX, EndoPredict, Prosigna, Breast Cancer Index, MammaPrint) are not covered when used to predict response to specific chemotherapy regimens, for beneficiaries with known metastatic cancer, when DCIS is the sole histology, for testing the same tumor or multiple sites in multifocal primaries, when results will not affect chemotherapy decisions, or when a different, unlisted gene expression test is used.
- Do not order these breast assays for the enumerated non-covered indications.
Non-covered indications for AlloMap
AlloMap is not covered for beneficiaries with a history of antibody-mediated rejection, for any use outside heart transplant rejection monitoring, or when results would not impact clinical management (for example, when a biopsy is already planned).
- Do not use AlloMap for antibody-mediated rejection surveillance or non-transplant indications; follow coverage criteria in Subsection 3.2.1 for appropriate use.
Non-covered indications for thyroid gene expression tests when Section 3.2.2 criteria unmet
Thyroid nodule gene expression profiling is not covered when the specific criteria in Section 3.2.2 are not met (e.g., beneficiary age, nodule size, and indeterminate cytology requirements).
- Ensure all Section 3.2.2 criteria are documented before ordering thyroid gene expression tests.
Report the most specific CPT/HCPCS code; use unlisted code + special report if none
Providers shall report the most specific CPT or HCPCS code that accurately and completely describes the procedure, product, or service provided; failure to do so may affect payment and claims processing.
- Use the current CPT, HCPCS, and UB-04 Data Specifications Manual editions in effect at time of service.
- If no specific code exists, report the service with the appropriate unlisted code and include a special report.
Beneficiary and Test Eligibility Requirements
When requesting services, providers must include supporting clinical documentation. Specifically, if additional testing units are requested beyond standard limits, providers should submit prior related laboratory results and rationale demonstrating how the additional results will alter clinical management and improve outcomes; these prior results serve as supporting documentation for the authorization request.
Definitions and Background
Gene expression describes the process by which genetic information is transcribed into RNA and proteins, functioning as on/off switches and modulators of the timing, location, and amount of gene products. Assessing gene expression evaluates the functional activity of gene products or associated phenotypes and is clinically relevant in conditions such as cancer where markers like ER, PR, and HER2 inform treatment decisions.
Not Covered / Exclusions
The policy's Not Covered section (Section 4.0) includes both general and specific non-coverage lists and identifies Medicaid-specific additional criteria not covered (Subsections 4.2, 4.2.1, and 4.2.2). The excerpt provides the structure and specific statements for many exclusions and also instructs the use of unlisted codes where no specific CPT/HCPCS code exists.
Specific non-covered indications include using gene expression tests to predict response to particular chemotherapy regimens, performing testing for beneficiaries with known metastatic cancer, using gene expression profiling when DCIS is the sole breast histology, duplicate or multisite testing of the same tumor, and investigational or otherwise unsupported uses. These non-coverage rules apply to the listed breast prognostic assays and AlloMap where noted.
The policy reiterates that breast gene expression profiling is not covered to predict response to specific chemotherapy regimens, is not covered for known metastatic disease, and is specifically excluded when DCIS is the only histology. Duplicate testing or testing of multiple sites for a multifocal primary is also not covered, as are uses that would not change clinical management.
The Not Covered section does not provide an exhaustive enumeration of every possible test that might be excluded; rather, it lists the specific non-covered indications. When no specific CPT or HCPCS code exists for a service, the policy requires use of the appropriate unlisted code and submission of the special report per CPT/HCPCS instructions to support adjudication.
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