CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

Molecular testing for indeterminate thyroid fine needle aspirates (Afirma, ThyroSeq, ThyGenX/ThyraMIR, ThyGeNEXT, RosettaGX Reveal)

Policy governing medical necessity and prior authorization for molecular assays (Afirma, RosettaGX Reveal, ThyGeNEXT, ThyraMIR, ThyroSeq) used to evaluate indeterminate thyroid FNA cytology for Medicare Advantage and Commercial products of BCBSRI.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyMolecular testing for indeterminate thyroid FNA (Afirma, ThyroSeq, ThyGenX/ThyraMIR, ThyGeNEXT, RosettaGX Reveal)

Policy CodePolicy N/A

Change TypeNo material changes

Effective DateJul 1, 2017

Next Review DateN/A

Key ActionObtain prior authorization and document medical criteria before ordering molecular testing for indeterminate thyroid FNA.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

5tests addressed in policy

20-30%equivocal cytology rate

112ThyroSeq genes

Yescode updates noted

Coverage Criteria for Molecular Testing of Indeterminate Thyroid FNAs

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Afirma (including Afirma BRAF and Afirma MTC)

Afirma may be considered medically necessary when ALL of the following are met:

Afirma medical necessity: 1) Patient has one or more thyroid nodules with a history or characteristics suggesting malignancy (examples: nodule growth over time; hoarseness, difficulty swallowing or breathing; family history of thyroid cancer; history of exposure to ionizing radiation; presence of cervical adenopathy; hard nodule compared with rest of gland consistency); AND 2) Nodule has indeterminate follicular pathology on fine needle aspiration.

Afirma BRAF and Afirma MTC are medically necessary after a positive Afirma Genomic Sequencing Classifier.

ThyraMIR / ThyGeNEXT / RosettaGX Reveal

ThyraMIR, ThyGeNEXT, and RosettaGX Reveal may be considered reasonable and necessary when ALL of the following are met:

ThyraMIR/ThyGeNEXT/RosettaGX medical necessity: Patient has one or more thyroid nodules with history or characteristics suggesting malignancy (examples: nodule growth over time; hoarseness, difficulty swallowing or breathing; family history of thyroid cancer; history of exposure to ionizing radiation; presence of cervical adenopathy; hard nodule compared with rest of gland consistency) AND an indeterminate pathology on fine needle aspiration.

ThyGeNEXT CPT code effective 4/1/2021; RosettaGX Reveal previously billed with an unlisted CPT code.

ThyroSeq and ThyGenX/ThyraMIR

ThyroSeq and ThyGenX/ThyraMIR algorithmic use:

ThyroSeq medical necessity: ThyroSeq is considered medically necessary for thyroid nodules meeting Bethesda diagnostic categories III, IV, or V to 'rule in' malignancy to guide initial surgical planning (to permit single-stage definitive surgery when appropriate).Bethesda III/IV/V

Used to guide extent of initial resection rather than staged surgery.

ThyGenX + ThyraMIR algorithm: ThyGenX (NGS panel) is used first; a positive ThyGenX result 'rules in' malignancy and informs preoperative planning. If ThyGenX is negative, reflex ThyraMIR microRNA testing is used to 'rule out' malignancy and may support active surveillance rather than surgery.

Described as a reflex/algorithmic testing sequence (ThyGenX → ThyraMIR).

Intended clinical application / testing algorithms

Clinical testing strategies and intended use described in policy:

Afirma BRAF and MTC intended use: Afirma BRAF and Afirma MTC are mRNA-expression malignancy classifiers used to detect BRAF variants or variants associated with medullary thyroid carcinoma from FNA samples; a positive result informs preoperative planning (for example, decision between hemi- versus total thyroidectomy or performance of central neck dissection).

Intended to increase pretest probability of malignancy and inform surgical approach.

ThyGenX with ThyraMIR algorithm: ThyGenX (NGS oncogene panel) is performed first to 'rule in' malignancy; if ThyGenX is negative, reflex to ThyraMIR microRNA testing is performed to 'rule out' malignancy and potentially allow active surveillance instead of surgical resection.

Reflex strategy explicitly described in policy.

Benefit limitations and coverage for laboratory tests vary by contract. Refer to the member's Benefit Booklet, Evidence of Coverage, or Subscriber Agreement to determine any limits on laboratory test coverage or when services may be considered not medically necessary.

The Afirma gene expression test code was updated: the older CPT code 81545 was deleted effective 2020-12-31. For dates of service on or after 2021-01-01, use 81546 to report Afirma testing.

This policy does not list explicit universal coverage exclusions. Note that some services that are medically necessary under clinical standards may be non-covered depending on the member's individual benefit plan; verify member-specific coverage before performing or billing tests.

Molecular tests submitted with CPT/PLA codes without documentation that the medical criteria in this policy have been met may not be considered medically necessary for Medicare Advantage and Commercial products and are subject to denial.

If services are determined to be not medically necessary (or are medically necessary but are a non-covered benefit under the member's plan), the provider may not bill the member unless the member was informed in advance and provided written agreement to assume financial responsibility.

Coding and Billing Information

Referenced test CPT/HCPCS codesCPT | mixed

81546	Afirma (new code effective 1/1/2021)
81545	Afirma (deleted effective 12/31/2020; used for dates of service to 1/1/2021)
0018U	ThyraMIR
0245U	ThyGeNEXT (code effective 4/1/2021)
0026U	ThyroSeq
Unlisted CPT	Used for some services (eg, RosettaGX Reveal prior to specific coding)

ThyGeNEXTCPTCovered

0245U

Oncology (thyroid), mutation analysis of 10 genes and 37 RNA fusions and expression of 4 mRNA markers, next-generation sequencing, fine needle aspirate, report includes associated risk of malignancy expressed as a percentage (New Code Effective 4/1/2021)

Pre-4/1/2021 ThyGeNEXT/other panelsCPTCovered

81445

Targeted genomic sequence analysis solid organ neoplasm, DNA analysis, and RNA analysis when performed, 5-50 genes (eg, ALK, BRAF, CDKN2A, EGFR, ERBB2, KIT, KRAS, NRAS, MET, PDGFRA, PDGFRB, PGR, PIK3CA, PTEN, RET), interrogation for sequence variants and copy number variants or rearrangements, if performed (use for dates of service prior to 4/1/2021)

AfirmaCPTCovered

81546	Oncology (thyroid), mRNA, gene expression analysis of 10,196 genes, utilizing fine needle aspirate, algorithm reported as a categorical result (eg, benign or suspicious) (New Code Effective 1/1/2021)
81545	Oncology (thyroid), gene expression analysis of 142 genes, utilizing fine needle aspirate, algorithm reported as a categorical result (eg, benign or suspicious) (Deleted Effective 12/31/2020) (use 81545 for dates of service prior to 1/1/2021)

ThyraMIRPLACovered

O018U

Oncology (thyroid), microRNA profiling by RT-PCR of 10 microRNA sequences, utilizing fine needle aspirate, algorithm reported as a positive or negative result for moderate to high risk of malignancy

ThyroSeqCPTCovered

0026U

Oncology (thyroid), DNA and mRNA of 112 genes, next-generation sequencing, fine needle aspirate of thyroid nodule, algorithmic analysis reported as a categorical result ("Positive, high probability of malignancy" or "Negative, low probability of malignancy")

Unlisted molecular pathologyCPT

81479

Unlisted molecular pathology procedure (may be used for any test in this policy that does not have a specific CPT code)

ThyGeNEXTCPTCovered

0245U

Oncology (thyroid), mutation analysis of 10 genes and 37 RNA fusions and expression of 4 mRNA markers next-generation sequencing, fine needle aspirate, report includes associated risk of malignancy expressed as a percentage (New Code Effective 4/1/2021)

Pre-4/1/2021 ThyGeNEXT/other panelsCPTCovered

81445

AfirmaCPTCovered

81546	Oncology (thyroid), mRNA, gene expression analysis of 10,196 genes, utilizing fine needle aspirate, algorithm reported as a categorical result (eg, benign or suspicious) (New Code Effective 1/1/2021)
81545	Oncology (thyroid), gene expression analysis of 142 genes, utilizing fine needle aspirate, algorithm reported as a categorical result (eg, benign or suspicious) (Deleted Effective 12/31/2020) (use 81545 for dates of service prior to 1/1/2021)

ThyraMIRPLACovered

O018U

Oncology (thyroid), microRNA profiling by RT-PCR of 10 microRNA sequences, utilizing fine needle aspirate, algorithm reported as a positive or negative result for moderate to high risk of malignancy

ThyroSeqCPTCovered

0026U

Unlisted molecular pathologyCPT

81479

Unlisted molecular pathology procedure (may be used for any test in this policy that does not have a specific CPT code)

Bethesda diagnostic categories for testing

Bethesda categoriesIndications limited to nodules with indeterminate or suspicious cytology corresponding to Bethesda categories III, IV, or V.

Category III (AUS/FLUS)Atypia/follicular lesion of undetermined significance (Bethesda category III).

Category IVFollicular neoplasm / suspicious for a follicular neoplasm (Bethesda category IV).

Category VSuspicious for malignancy (Bethesda category V).

CPT code effective dates

ThyGeNEXT (date-based code change)Use CPT 81445 for dates of service prior to 2021-04-01; use CPT 0245U for dates of service on or after 2021-04-01.

Afirma (date-based code change)Use CPT 81545 for dates of service prior to 2021-01-01; use CPT 81546 for dates of service on or after 2021-01-01.

Documentation requirementClaims must reflect the correct CPT/PLA code based on the date of service relative to code effective/retirement dates.

Document citations

American Thyroid AssociationHaugen BR et al., 2015 ATA Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer (published Jan 2016).

AACE/ACE GuidelinesGharib H et al., AACE/ACE Medical Guidelines for Diagnosis and Management of Thyroid Nodules — 2016 update.

NCCNNCCN Clinical Practice Guidelines in Oncology: Thyroid Carcinoma, Version 1.2019.

Selected primary studiesMultiple referenced studies evaluating molecular testing and ThyroSeq performance (e.g., Valderrabano et al. 2017; Labourier et al. 2015).

Provider Actions, Prior Authorization, and Billing Responsibilities

Prior Authorization

Prior Authorization Required

Prior authorization is required for Medicare Advantage Plans and recommended for Commercial products. Providers must verify member-specific benefits and eligibility prior to ordering services, using the member's subscriber agreement and the payer's provider portals or call center. Failure to obtain required authorization will result in denial of the laboratory service; the participating laboratory is financially liable and may not bill the member for unauthorized services.

Prior authorization required for Medicare Advantage; recommended for Commercial products
Verify member-specific benefits and eligibility via payer portals or provider call center
Unauthorized laboratory services will be denied and may not be billed to the member

Documentation Required

Authorization Ownership and Documentation

Only the ordering physician may obtain authorization, submit clinical documentation in support of medical necessity, or pursue appeals related to authorizations. Laboratories, laboratory representatives, or third parties with relationships to the laboratory must not obtain authorization on behalf of the ordering physician or participate in preparing authorization documentation. If a laboratory or related third party supports any portion of the authorization process, BCBSRI will consider this a violation and may take actions up to termination from the provider network.

Authorization and appeals must be owned and managed by the ordering physician
Laboratories and their representatives are prohibited from obtaining authorization on behalf of the ordering physician
Violations may result in sanctions, including termination from the BCBSRI provider network

Billing Rule

Coding and Date-of-Service Documentation

Claims must include the specific CPT/PLA/unique codes appropriate to the test performed and reflect the correct date of service relative to code effective or retirement dates. Using a CPT/PLA/unique code without meeting the policy's medical criteria or using an incorrect date of service may trigger claim denial.

Include the CPT/PLA/unique code that corresponds to the service performed
Ensure the date of service aligns with the code effective/retirement dates (e.g., codes effective or deleted on stated dates)
Coding without meeting medical criteria may result in denial for Medicare Advantage and Commercial products

Note

Algorithmic / Reflex Testing Sequences

Algorithmic (reflex) testing sequences are used for certain thyroid molecular diagnostics. Follow the specified testing pathway where the result of the initial test determines whether a reflex test is performed.

Algorithmic testing uses a prespecified sequence: a subsequent test is automatically obtained depending on earlier test results
Document the algorithmic pathway in the authorization and claim submission

Step Therapy

Reflex Testing Algorithm (ThyGenX → ThyraMIR)

For thyroid nodules with indeterminate cytology, ThyGenX (ThyGeNEXT) is used first to 'rule in' malignancy. A positive ThyGenX result supports surgical planning. If ThyGenX is negative, reflex testing with ThyraMIR is performed to 'rule out' malignancy; a negative ThyraMIR result supports surveillance rather than surgery.

Primary test: ThyGenX (ThyGeNEXT) — positive results 'rule in' and may guide preoperative planning
Reflex test: ThyraMIR performed only after a negative ThyGenX to 'rule out' malignancy
Document the sequence (ThyGenX → ThyraMIR when ThyGenX negative) in authorization requests

Denial Risk

Verify member-specific benefits and eligibility before performing services
Providers may not charge members for services determined not medically necessary or for non-covered benefits unless there is a prior written agreement
If a laboratory provides an unauthorized service, the service will be denied and the laboratory — not the member — is financially responsible

Definitions and Test Descriptions

Atypia/follicular lesion of undetermined significance (AUS/FLUS)

TermAtypia/follicular lesion of undetermined significance (AUS/FLUS).

Bethesda categoryBethesda diagnostic category III.

Clinical contextRepresents indeterminate cytology often requiring further molecular evaluation to clarify malignancy risk.

Bethesda diagnostic category IV

TermFollicular neoplasm / suspicious for a follicular neoplasm.

Bethesda categoryBethesda diagnostic category IV.

ImplicationClassified as indeterminate cytology and may be evaluated with molecular testing to guide surgical planning.

Bethesda diagnostic category V

TermSuspicious for malignancy.

Bethesda categoryBethesda diagnostic category V.

ImplicationHigher pretest probability of malignancy; molecular testing may be used to inform extent of surgery.

Afirma BRAF/MTC

Test typeAfirma BRAF and Afirma MTC are mRNA-expression malignancy classifiers intended to detect BRAF variants or medullary-thyroid-carcinoma–associated variants from FNA specimens.

Clinical useA positive Afirma BRAF or MTC result would inform preoperative planning such as hemi- vs total thyroidectomy or central neck dissection.

TechnologymRNA expression–based classification as adjuncts to Afirma GSC (malignancy classifiers).

ThyGenX

Test typeThyGenX is an NGS thyroid oncogene panel sequencing oncogenes to 'rule in' malignancy.

Algorithmic roleA positive ThyGenX result 'rules in' patients for surgical resection and informs preoperative planning.

Reflex pathwayWhen ThyGenX is negative, reflex to ThyraMIR for further evaluation.

ThyraMIR

Test typeThyraMIR is a microRNA expression–based classifier used as reflex testing for ThyGenX-negative indeterminate nodules to 'rule out' malignancy.

Clinical useA negative ThyraMIR result supports active surveillance and may help avoid surgery.

SpecimenPerformed on FNA specimens using microRNA profiling (PLA code O018U).

Inventory placeholderNo definition provided.

OpenPayer

Molecular testing for indeterminate thyroid fine needle aspirates (Afirma, ThyroSeq, ThyGenX/ThyraMIR, ThyGeNEXT, RosettaGX Reveal)

Coverage Criteria for Molecular Testing of Indeterminate Thyroid FNAs

Coding and Billing Information

Provider Actions, Prior Authorization, and Billing Responsibilities

Background and Clinical Context

Definitions and Test Descriptions