CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

Medical Coverage Policy Genomic Sequence Analysis Panels in the Treatment of Solid Organ Neoplasms

Defines medical necessity criteria, applicable diagnoses (e.g., advanced NSCLC, metastatic colorectal cancer), testing requirements (CLIA lab, FDA-cleared or validated LDT), prior authorization expectation for Medicare Advantage and recommended for commercial, and lists covered CPT codes for genomic sequence analysis panels (tissue and plasma).

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyMedical Coverage Policy Genomic Sequence Analysis Panels in the Treatment of Solid Organ Neoplasms

Policy CodePolicy N/A

Change TypeCoding revisions and new CPT codes (effective 01/01/2024)

Effective DateJun 1, 2024

Next Review DateN/A

Key ActionObtain prior authorization for Medicare Advantage (recommended for commercial) via the online portal and ensure tests are ordered by a treating physician and performed in a CLIA-certified lab with appropriate assay validation.

SourceLink

POLICY UPDATE CHANGES

CPT code text revised 01/01/2024 and new CPT codes effective 01/01/2024 were incorporated into coding list.

Conditional by criteriaCoverage scope

12 CPT/PLACodes referenced

CLIA + physician orderOperational requirements

Coverage stance: covered_with_criteria. This policy defines medical necessity criteria for Comprehensive Genomic Profiling (CGP) using NGS panels, including general testing criteria, specific applicable diagnoses (e.g., advanced NSCLC, metastatic colorectal cancer), and documentation/operational requirements. Testing is reasonable and necessary only when performed in a CLIA-certified laboratory qualified for high-complexity testing, ordered by a treating physician, the patient has recurrent/relapsed/refractory/metastatic or advanced (stage III/IV) disease, the patient has not previously had CGP for the same genetic content, the test detects at least the minimum genomic positions listed in NCCN Biomarkers Compendium Category 1 or 2A for identification of clinically supported FDA-approved therapies, the patient is a candidate and is seeking further cancer treatment, and assays are FDA cleared/approved or, if an LDT, have peer-reviewed analytic validity evidence or NY CLEP-equivalent certification. Prior authorization is required for Medicare Advantage and recommended for Commercial products via the online portal. Covered CPT and proprietary PLA codes include tissue and plasma panel codes: 81445, 81449, 81455, 81456, 81457, 81458, 81459, 81462, 81463, 81464 and PLA codes 0048U, 0250U (report the CPT code corresponding to the panel performed).

Effective date: 2024-06-01. Policy last reviewed: 2024-02-07.

Operational facts and thresholds

Coverage scopeCoverage conditional by cancer type and clinical criteria (e.g., advanced NSCLC, metastatic CRC, other advanced cancers)

Codes referencedLists 12 CPT/PLA codes (81445, 81449, 81455, 81456, 81457, 81458, 81459, 81462, 81463, 81464, 0048U, 0250U)

Operational requirementsMust be performed in a CLIA-certified high-complexity laboratory; ordered by a treating physician; assays FDA-cleared/approved or LDTs with published analytic validity or equivalent third-party/NY CLEP certification

Threshold: TMB cutoff>= 10 mutations/megabase (TMB-H referenced with caveat that universal cutoff is limited and varies by tumor type)

Effective date / Last reviewEffective: 2024-06-01; Policy last reviewed: 2024-02-07

Medical Necessity Criteria

General Testing Criteria (CGP NGS testing)

CGP NGS testing for patients with advanced cancer is reasonable and necessary only when ALL of the following are met:

ALL of the following

Performed in a CLIA-certified laboratory qualified to perform high complexity testing
Operational requirement: CLIA certification
Ordered by a treating physician
Patient has recurrent, relapsed, refractory, metastatic, or advanced (stage III or IV) cancer
Clinical status must be documented
Patient has not been previously tested with a CGP for the same cancer genetic content
Duplicate testing for same content not covered
Test performed must detect at least the minimum genomic positions required for identification of clinically supported, FDA-approved therapies (genes/genomic positions listed in Category 1 or 2A of the most current NCCN Biomarkers Compendium)
Assay content requirement per NCCN Biomarkers Compendium
Patient has decided to seek further cancer treatment (e.g., therapeutic chemotherapy) and is a candidate for additional therapy
Patient must be a treatment candidate at time of testing
Testing assays must be FDA approved/cleared, or if a laboratory developed test (LDT), have a published, peer-reviewed study supporting analytic validity, or certification equivalent to NY CLEP review standards
Assay validation requirement; LDTs acceptable with evidence

Non-Small Cell Lung Cancer (NSCLC)

Genomic sequence analysis panels may be considered medically necessary when ALL of the following apply:

Applicable populations

Newly diagnosed advanced NSCLC: Newly diagnosed patients with advanced (stage IIIB or IV) NSCLC who are not treatable by resection or radiation with curative intent and who are suitable candidates for therapy at the time of testing
Applicable at initial presentation if candidate for therapy
Previously diagnosed progressed NSCLC: Previously diagnosed patients with advanced (stage IIIB or IV) NSCLC who have not responded to at least one systemic therapy or who have progressed following resection, and are candidates for treatment at time of testing
Post-therapy progression population
Resistant to targeted therapy NSCLC: Previously diagnosed patients with advanced (stage IIIB or IV) NSCLC who have been resistant to at least one targeted therapy, are able to undergo biopsy for testing, and are suitable candidates for additional treatment at time of testing

Metastatic Colorectal Cancer (mCRC)

Testing may be considered medically necessary when ALL of the following apply:

ALL of the following

Test performed in a CLIA-certified laboratory qualified to perform high complexity testing
Operational requirement
Ordered by a treating physician
Patient has metastatic colorectal cancer
Clinical diagnosis requirement
Patient is a candidate for intensive chemotherapy with an anti-EGFR biologic agent
Anti-EGFR candidacy required for testing consideration

Additional Clinical Considerations

Situations where CGP NGS testing is particularly relevant or limited:

ANY of the following

MSI-H / dMMR and TMB considerations: Testing to identify MSI-H/dMMR status or tumor mutational burden (TMB) when influencing immunotherapy decision-making; note that a universal TMB-H cutoff of 10 mut/Mb is questioned and evidence varies by tumor type
TMB cutoff limitations: 10 mut/Mb not universally validated
NTRK and fusion testing: Testing to identify NTRK or other actionable gene fusions where TRK inhibitor therapy is a consideration
NGS CGP preferred to detect rare fusions, RNA-based methods may be superior for NTRK detection
mCRC palliative/hospice: Testing is not necessary for mCRC patients considered only for palliative or hospice care
Testing withheld when only palliative/hospice care planned

Coding

Covered CPT codes — tissue genomic sequence analysis panelsCPTCovered

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
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
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
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

Covered CPT codes — cell-free (plasma) genomic sequence analysis panelsCPTCovered

81462	Solid organ neoplasm, genomic sequence analysis panel, cell-free nucleic acid (e.g., 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 (e.g., plasma), interrogation for sequence variants; DNA analysis, copy number variants, and microsatellite instability
81464	Solid organ neoplasm, genomic sequence analysis panel, cell-free nucleic acid (e.g., plasma), interrogation for sequence variants; DNA analysis or combined DNA and RNA analysis, copy number variants, microsatellite instability, tumor mutation burden, and rearrangements

Proprietary / PLA codes referencedCPTCovered

0048U	MSK-IMPACT (Integrated Mutation Profiling of Actionable Cancer Targets); targeted sequencing of 468 cancer-associated genes including somatic mutations and microsatellite instability
0250U	PGDx elio tissue complete; targeted genomic sequence DNA analysis of 505 genes, interrogation for somatic alterations, microsatellite instability and tumor-mutation burden

Coding change note: CPT code text was revised 01/01/2024 and new CPT codes effective 01/01/2024 were incorporated into the coding list. Proprietary PLA mappings are cited (examples: 0048U for MSK-IMPACT and 0250U for PGDx elio tissue complete) and specific CPT descriptors updated/added as noted in the coding section.

Provider Actions

Prior Authorization

Prior authorization requirement

Prior authorization is required for Medicare Advantage Plans and recommended for Commercial Products; obtained via the online portal for participating providers.

Documentation Required

Ordering and lab requirements

Testing must be ordered by a treating physician and performed in a CLIA-certified laboratory qualified for high complexity testing; assays must be FDA cleared/approved or, if an LDT, have published analytic validity evidence or equivalent third‑party certification (e.g., NY CLEP-equivalent).

CLIA-certified laboratory for high complexity testing
Ordered by a treating physician
Assays FDA cleared/approved or LDT with published analytic validity or equivalent third‑party/NY CLEP certification

Documentation Required

Clinical indications must be documented

Documentation must show the patient’s clinical status (for example stage and prior therapies), that the patient is a candidate for further treatment, and that the patient has not previously had CGP testing for the same genetic content when applicable.

Clinical status elements: stage (e.g., III/IV), prior therapies, candidacy for additional treatment
Record that prior CGP for same genetic content has not been performed when applicable

Billing Rule

Use of specific CPT codes

Report the CPT/PLA code that corresponds to the panel performed, reflecting specimen type (tissue vs plasma), gene count and analytic content (e.g., MSI, TMB, copy number, rearrangements). Proprietary PLA codes (for example 0048U, 0250U) may map to the listed CPT codes as indicated.

Affected CPT/PLA codes: 81445, 81449, 81455, 81456, 81457, 81458, 81459, 81462, 81463, 81464, 0048U, 0250U
Note tissue vs plasma when selecting code (81445–81459 = tissue panels; 81462–81464 = cell-free/plasma panels)
PLA mapping guidance: 0048U and 0250U can be reported/use the corresponding listed CPT codes as indicated

Background

Background/rationale: Comprehensive Genomic Profiling (CGP) via NGS panels identifies actionable driver mutations that can be targeted by specific therapies and detects tumor-agnostic biomarkers (e.g., MSI/dMMR, NTRK fusions, and TMB) that influence immunotherapy decisions. NGS CGP enables simultaneous evaluation of multiple classes of genomic alterations (sequence variants, copy number variants, rearrangements, MSI, and TMB) and is increasingly time- and specimen-efficient for advanced cancers and rare tumor types compared with sequential single-analyte testing. RNA-based methods can be superior for detecting certain gene fusions (e.g., NTRK).

Evidence limitations and assay validity: Current evidence does not support a universal TMB-H cutoff applied across all tumor types (the policy notes concerns about a one-size-fits-all ≥ 10 mut/Mb cutoff and variability by tumor type). The policy emphasizes that testing assays must be FDA approved/cleared, or if performed as a laboratory-developed test (LDT), must have a published, peer-reviewed study supporting analytic validity or third-party certification equivalent to New York State CLEP review standards.

Evidence sources and references

NCCN Biomarkers CompendiumReferenced as basis for required genes/genomic positions (Category 1 or 2A) to identify clinically supported, FDA-approved therapies

FDA approvalsFDA tumor-agnostic approvals cited (e.g., pembrolizumab for MSI-H/dMMR and accelerated approval for TMB-H) and other tumor-agnostic agents (TRK inhibitors for NTRK fusions)

Medicare LCD / LCALocal Coverage Determination L37810 and Local Coverage Article 456867 referenced for genomic sequence analysis coding and coverage

OpenPayer

Medical Coverage Policy Genomic Sequence Analysis Panels in the Treatment of Solid Organ Neoplasms

Coverage Summary

Medical Necessity Criteria

Coding

Provider Actions

Background

Medicare Determinations

Revision History

Type	Name	Number	Effective date
LCD	Genomic Sequence Analysis in the Treatment of Solid Organ Neoplasms	L37810
LCA	Local Coverage Article: and Coding: Genomic Sequence Analysis in the Treatment of Solid Organ Neoplasms	456867