Genomic Sequence Analysis Panels in the Treatment of Solid Organ Neoplasms Form

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 1 (401) 274-4848 WWW.BCBSRI.COM EFFECTIVE DATE: 09|01|2025 POLICY LAST REVIEWED: 06|18|2025

OVERVIEW
The pace of discovery in the fields of immunology and cancer biology is rapidly accelerating as understanding the role of the immune system in tumor initiation, progression, and metastasis evolves. Momentum is shifting away from sequential analyte testing toward adoption of ever larger NGS panels, capable of evaluating for all classes of potentially actionable genomic alterations across hundreds of genes simultaneously. Factors include decreasing cost, proliferation of actionable biomarkers, need to detect smaller amounts of DNA variants, FDA approval of tumor-type agnostic predictive biomarkers, and most recently, so-called “pan-mutational signature” biomarkers that, almost by definition, require panels that include hundreds of genes, if not whole exome sequencing (WES). Pan-tumor biomarkers make CGP testing not just a more time, specimen, and cost-effective approach, but necessary from an analytic validity standpoint. MEDICAL CRITERIA Medicare Advantage Plans and Commercial Products Effective 9/1/2025, the following CPT code(s) are covered for Medicare Advantage Plans and Commercial Products: • 81455 • 81456 Effective 9/1/2025 for CPT codes 81445, 81449, 81457, 81458, 81459, 81462, 81463, 81464, 0048U, 0250U the medical criteria in this policy will no longer be in use. Prior Authorization requests will be reviewed using InterQual content found in the online authorization tool for Medicare Advantage Plans and Commercial Products.
Please see Related Policies section and Coding section, for more information or additional details. PRIOR AUTHORIZATION Medicare Advantage Plans and Commercial Products Prior authorization is required for Medicare Advantage Plans and recommended for Commercial Products via the online tool for participating providers for the following: • 81445 • 81449 • 81457 • 81458 • 81459 • 81462 • 81463 • 81464 • MSK-IMPACT (CPT 0048U) • PGDx elio™ tissue complete (CPT 0250U) POLICY STATEMENT Medicare Advantage Plans and Commercial Products Effective 9/1/2025, the following CPTs/test(s) may be considered medically necessary when the medical criteria in the online authorization tool for participating providers is met: Medical Coverage Policy | Genomic Sequence Analysis Panels in the Treatment of Solid Organ Neoplasms

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 2 (401) 274-4848 WWW.BCBSRI.COM

• 81445 • 81449 • 81457 • 81458 • 81459 • 81462 • 81463 • 81464 • MSK-IMPACT (CPT 0048U) • PGDx elio ™ tissue complete (CPT 0250U)

Note: Laboratories are not allowed to obtain clinical authorization or participate in the authorization process on behalf of the ordering physician. Only the ordering physician shall be involved in the authorization, appeal or other administrative processes related to prior authorization/medical necessity.

In no circumstance shall a laboratory or a physician/provider use a representative of a laboratory or anyone with a relationship to a laboratory and/or a third party to obtain authorization on behalf of the ordering physician, to facilitate any portion of the authorization process or any subsequent appeal of a claim where the authorization process was not followed and/or a denial for clinical appropriateness was issued, including any element of the preparation of necessary documentation of clinical appropriateness. If a laboratory or a third party is found to be supporting any portion of the authorization process, BCBSRI will deem the action a violation of this policy and severe action will be taken up to and including termination from the BCBSRI provider network. If a laboratory provides a laboratory service that has not been authorized, the service will be denied as the financial liability of the participating laboratory and may not be billed to the member.

Commercial Products
Some genetic testing services are not covered and a contract exclusion for any self-funded group that has excluded the expanded coverage of biomarker testing related to the state mandate, R.I.G.L. §27-19-81 described in the Biomarker Testing Mandate policy. For these groups, a list of which genetic testing services are covered with prior authorization, are not medically necessary or are not covered because they are a contract exclusion can be found in the Coding section of the Genetic Testing Services or Proprietary Laboratory Analyses policies. Please refer to the appropriate Benefit Booklet to determine whether the member’s plan has customized benefit coverage. Please refer to the list of Related Policies for more information.

COVERAGE Benefits may vary between groups and contracts. Please refer to the appropriate Benefit Booklet, Evidence of Coverage or Subscriber Agreement for applicable laboratory benefits/coverage.

BACKGROUND Not applicable

CODING Medicare Advantage Plans and Commercial Products The following CPT code(s) are covered for Medicare Advantage Plans and Commercial Products and prior authorization is not required:

81455 Solid organ or hematolymphoid neoplasm or disorder, 51 or greater genes, genomic sequence analysis panel, interrogation for sequence variants and copy number variants or rearrangements, or isoform expression or mRNA expression levels, if performed; DNA analysis or combined DNA and RNA analysis 81456 Solid organ or hematolymphoid neoplasm or disorder, 51 or greater genes, genomic sequence analysis panel, interrogation for sequence variants and copy number variants or rearrangements, or isoform expression or mRNA expression levels, if performed; RNA analysis

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 3 (401) 274-4848 WWW.BCBSRI.COM

The following CPT codes and test(s) may be considered medically necessary for Medicare Advantage Plans and Commercial Products when the medical criteria in the online authorization tool for participating providers is met:

81445 Solid organ neoplasm, genomic sequence analysis panel, 5-50 genes, interrogation for sequence
variants and copy number variants or rearrangements, if performed; DNA analysis or combined DNA and RNA analysis

81449 Solid organ neoplasm, genomic sequence analysis panel, 5-50 genes, interrogation for sequence
variants and copy number variants or rearrangements, if performed; RNA analysis

81457 Solid organ neoplasm, genomic sequence analysis panel, interrogation for sequence variants; DNA analysis, microsatellite instability

81458 Solid organ neoplasm, genomic sequence analysis panel, interrogation for sequence variants; DNA analysis, copy number variants and microsatellite instability

81462 Solid organ neoplasm, genomic sequence analysis panel, cell-free nucleic acid (eg, plasma), interrogation for sequence variants; DNA analysis or combined DNA and RNA analysis, copy number variants and rearrangements

81463 Solid organ neoplasm, genomic sequence analysis panel, cell-free nucleic acid (eg, plasma), interrogation for sequence variants; DNA analysis, copy number variants, and microsatellite instability

81459 Solid organ neoplasm, genomic sequence analysis panel, interrogation for sequence variants; DNA analysis or combined DNA and RNA analysis, copy number variants, microsatellite instability, tumor mutation burden, and rearrangements

81464 Solid organ neoplasm, genomic sequence analysis panel, cell-free nucleic acid (eg, plasma), interrogation for sequence variants; DNA analysis or combined DNA and RNA analysis, copy number variants, microsatellite instability, tumor mutation burden, and rearrangements

This code can be used for MSK-IMPACT™ (Integrated Mutation Profiling of Actionable Cancer Targets): 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)

This code can be used for PGDx elio™ tissue complete: 0250U Oncology (solid organ neoplasm), targeted genomic sequence DNA analysis of 505 genes, interrogation for somatic alterations (SNVs [single nucleotide variant], small insertions and deletions, one amplification, and four translocations), microsatellite instability and tumor-mutation burden

RELATED POLICIES Biomarker Testing Mandate
Genetic Testing Services Proprietary Laboratory Analysis (PLA) and Multianalyte Assays with Algorithmic Analyses (MAAA)

PUBLISHED Provider Update, August 2025 Provider Update, April, July 2024 Provider Update, November 2023

500 EXCHANGE STREET, PROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 4 (401) 274-4848 WWW.BCBSRI.COM

Provider Update, June 2023

REFERENCES Not applicable

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This medical policy is made available to you for informational purposes only. It is not a guarantee of payment or a substitute for your medical judgment in the treatment of your patients. Benefits and eligibility are determined by the member's subscriber agreement or member certificate and/or the employer agreement, and those documents will supersede the provisions of this medical policy. For information on member-specific benefits, call the provider call center. If you provide services to a member which are determined to not be medically necessary (or in some cases medically necessary services which are non-covered benefits), you may not charge the member for the services unless you have informed the member and they have agreed in writing in advance to continue with the treatment at their own expense. Please refer to your participation agreement(s) for the applicable provisions. This policy is current at the time of publication; however, medical practices, technology, and knowledge are constantly changing. BCBSRI reserves the right to review and revise this policy for any reason and at any time, with or without notice. Blue Cross & Blue Shield of Rhode Island is an independent licensee of the Blue Cross and Blue Shield Association. CLICK THE ENVELOPE ICON BELOW TO SUBMIT COMMENTS