CurrentProvidence Health PlanPolicy 352

Next Generation Sequencing for Cancer

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Defines medical necessity and coverage criteria for multi-gene/NGS tumor profiling in members with somatic cancer for Providence Health Plan commercial products. Applies to tissue-based NGS panels and excludes circulating tumor DNA/cell testing.

Policy Summary

PayerProvidence Health Plan

PolicyNext Generation Sequencing for Cancer

Policy CodePolicy 352

Change TypeNo material change

Effective DateJul 1, 2026

Last ReviewJul 1, 2026

Next Review DateMay 1, 2026

Key ActionSubmit prior authorization with test name or gene list, laboratory name, and all relevant procedure codes; requests are reviewed against NCCN guidelines and policy criteria.

SourceLink

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CurrentProvidence Health PlanPolicy 352

Next Generation Sequencing for Cancer

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Policy Summary

PayerProvidence Health Plan

PolicyNext Generation Sequencing for Cancer

Policy CodePolicy 352

Change TypeNo material change

Effective DateJul 1, 2026

Last ReviewJul 1, 2026

Next Review DateMay 1, 2026

Key ActionSubmit prior authorization with test name or gene list, laboratory name, and all relevant procedure codes; requests are reviewed against NCCN guidelines and policy criteria.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

CommercialPlan product applicability

Stage III-IVDisease stage referenced

Category 1/2ANCCN allowance

Unlisted codeBilling rule

CPT/PLA listedCodes provided

Coverage Criteria

NGS panels for somatic cancer (medical necessity)

Covered when ALL of the following are met

Main medical necessity criteria: A. Member has one of the following: (1) recurrent, relapsed, metastatic, or advanced (stage III or IV) solid tumor; OR (2) risk assessment using broad molecular testing has been validated by NCCN guidelines as a category 1 or 2A recommendation for the member's cancer type. AND B. One or more of the following: (1) genomic biomarker-linked therapies have been approved by the FDA for the specific cancer/disease site; OR (2) treatment is being considered for which there are specific genomic biomarker-based contraindications or exclusions. AND C. Member has not been previously tested with a multi-gene panel on the same tumor sample for the same indication. AND D. Results of testing will directly impact clinical decision making.

From Coverage Criteria section

Medical necessity per professional society guidance

Covered when consistent with current clinical guidance

ASCO/NCCN-guided use: NGS multigene genomic sequencing is preferred for patients with metastatic or advanced solid tumors when patients are eligible for a genomic biomarker-linked, regulatory-approved therapy; multigene panel-based testing should be used when more than one genomic biomarker is linked to an approved therapy. Testing that informs clinical care must be performed in an appropriately certified laboratory. Consider assessment of mismatch repair deficiency (dMMR)/microsatellite instability (MSI) and tumor mutational burden (TMB) using large multigene panels when results may influence immunotherapy decisions or determine candidacy for tumor-agnostic therapies. The most up-to-date NCCN guideline will be reviewed for each request.

Policy will review the most up-to-date NCCN guideline for each request.

This policy does not address circulating tumor cell/cell-free DNA (liquid biopsy) testing. See separate policy MP122 for coverage and clinical guidance related to circulating tumor cell and circulating tumor DNA assays.

If an unlisted code is submitted for services that are non-covered under this policy, the claim will be denied as not covered.

All unlisted codes submitted for services addressed in this policy are subject to review for medical necessity, correct coding, and pricing at the claim level; unlisted codes submitted for services that are non-covered under this policy will be denied as not covered.

Covered Indications

Metastatic, recurrent, relapsed, or advanced (stage III or IV) solid tumors; or cases where NCCN lists broad molecular testing as category 1 or 2A.

Indication: Member has a metastatic, recurrent, relapsed, or advanced (stage III or IV) solid tumor; OR the member's cancer type is one for which NCCN lists broad molecular testing as a category 1 or 2A recommendation.

Covered indications per ASCO/NCCN guidance.

Metastatic or advanced solid tumors where genomic biomarker-linked, regulatory-approved therapies are available; assessment of MSI/dMMR and TMB when results would influence immunotherapy decisions or tumor-agnostic therapy candidacy.

Biomarker-linked therapy / immunotherapy considerations: Indication: metastatic or advanced solid tumor for which genomic biomarker-linked, regulatory-approved therapies are available; OR testing is being used to determine candidacy for tumor-agnostic therapies. When results would influence immunotherapy decisions, assess MSI/dMMR and consider TMB testing using large multigene panels or validated methods. Testing must be performed in appropriately certified laboratories and requests will be reviewed against the current NCCN guideline for that cancer type.

From ASCO PCO and NCCN utilization guidance.

Not Covered Services

Circulating tumor cell and cell-free DNA (cfDNA) testing are not addressed by this tissue-based NGS panel policy. For coverage determinations and clinical criteria specific to liquid biopsy testing, refer to policy MP122.

Services billed using unlisted codes that correspond to non-covered services in this policy will be denied when submitted as such; providers should consult coding guidance and the policy prior to submission.

Coding and Panel Examples

Documentation — codes to submitmixed

affected codes

All relevant CPT/HCPCS codes billed (must be submitted with request)

Covered CPT/PLA examples and panel codesCPTCovered

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.
81451	Hematolymphoid neoplasm or disorder, genomic sequence analysis panel, 5-50 genes, interrogation for sequence variants, and copy number variants or rearrangements, or isoform expression or mRNA expression levels, if performed; RNA analysis.
81455	Solid organ or hematolymphoid neoplasm or disorder, 51 or greater genes, genomic sequence analysis panel, interrogation for sequence variants or 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.
81524	Oncology (central nervous system tumor), DNA methylation analysis of at least 10,000 methylation sites, utilizing DNA extracted from formalin-fixed tumor tissue, algorithm(s) reported as probability of matching a reference tumor family and class, and MGMT promoter methylation status, if performed.

PLA / proprietary panel examplesmixedCovered

0022U	Targeted genomic sequence analysis panel, non-small cell lung neoplasia, DNA and RNA analysis, 23 genes; Oncomine Dx Target Test / Guardant360 Tissue / FoundationOne CDx examples listed in PLA descriptions.
0048U	Oncology targeted sequencing of protein-coding exons of 468 cancer-associated genes including somatic mutations and MSI; MSK-IMPACT example.
0209U	Cytogenomic constitutional (genome-wide) analysis for copy number, structural changes and areas of homozygosity.
0211U	Oncology pan-tumor DNA and RNA NGS, interpretative report for SNVs, copy number alterations, TMB, and microsatellite.
0244U	Oncology DNA comprehensive genomic profiling, 257 genes, interrogation for SNVs, indels, copy number alterations, gene fusions, MSI, TMB; Oncotype MAP Pan Cancer Tissue Test example.
0274U	Hematology/genetic platelet disorder panels (examples: Versiti panels).
0313U	Oncology (pancreas) NGS of 74 genes and CEACAM5 gene expression on pancreatic cyst fluid (PancreasSeq).
0379U	Neoplasm DNA (523 genes) and RNA (55 genes) by NGS; Quest Expanded Panel example.
0391U	437 gene panel with immunotherapy response score (Strata Oncology).
0444U	Oncology targeted sequence panel of 361 genes, interrogation for gene fusions, translocations, or other rearrangements; Aventa FusionPlus example.

1–10 of 16

1/2

inv-09: Panel size for CMP — > 50 genes (Hayes CMP evidence review)

Hayes CMP panel size (evidence review)> 50 genes (comprehensive molecular profiling tests assessed in the 2022 Hayes report)

Scope of Hayes reviewExcluded CMP via liquid biopsy and targeted testing; focused on tissue-based panels assessing DNA or RNA variants in >50 genes

Implication for CMP definitionPanels with >50 genes were evaluated as broad molecular profiling tools to identify biomarkers for matched therapy

inv-10: Panel gene count — 5-50 genes and 51 or greater genes

CPT codes for 5-50 gene solid tumor panels81445, 81449, 81451 — genomic sequence analysis panels for 5-50 genes (DNA and/or RNA as specified)

Provider Actions and Requirements

Prior Authorization

Prior authorization: include test name, lab, and procedure codes

Submit a prior authorization request that includes the specific test name (or full gene list for custom tests), the performing laboratory name, and all relevant procedure (CPT/HCPCS) codes; prior authorization requests will be reviewed against NCCN guidelines and the policy clinical criteria and will be reviewed again at claim adjudication.

Provide test name or complete gene list for custom panels
Include laboratory name where testing will be performed
List all CPT/HCPCS procedure codes billed

Prior Authorization

Unlisted panel codes: prior authorization recommended

When billing a panel that does not have a specific CPT/HCPCS code, submit a prior authorization or obtain prior authorization when possible because all unlisted codes are reviewed for medical necessity, correct coding, and pricing at claim; prior authorization is recommended to avoid post-service denial.

Bill panels without a specific CPT/HCPCS code using an appropriate unlisted code

Eligibility Requirements

Inventory placeholder — no top-level eligibility requirement nodes are defined for this section.

Definitions

inv-20: Multi-gene panel testing — definition

DefinitionMulti-gene panel testing refers to a laboratory test in which many genes are studied in a sample of tissue to detect mutations and alterations that may help plan treatment or predict prognosis.

Use casePerformed on tumor tissue to identify genetic changes relevant to treatment selection or prognosis in patients with cancer.

Test outputDetects mutations and alterations across a broad selection of genes rather than single-gene assays.

inv-21: Next-generation sequencing (NGS) — definition

DefinitionNext-generation sequencing (NGS), also known as massively parallel or deep sequencing, is a technology for determining the sequence of DNA or RNA to study genetic variations associated with disease.

Capability

Background

Multi-gene or next-generation sequencing (NGS) panels analyze multiple genes in tumor tissue to detect sequence variants, copy number changes, rearrangements, and other alterations that may inform treatment selection or prognosis. Evidence and professional guidance (for example, ASCO and NCCN) support the use of tissue-based multigene NGS panels in patients with recurrent, relapsed, metastatic, or advanced (stage III or IV) solid tumors, or when NCCN lists broad molecular testing as a category 1 or 2A recommendation. This policy focuses on tissue-based assays and excludes circulating tumor cell/cfDNA testing.

Policy Summary

PayerProvidence Health Plan

PolicyNext Generation Sequencing for Cancer

Policy CodePolicy 352

Change TypeNo material change

Effective DateJul 1, 2026

Last ReviewJul 1, 2026

Next Review DateMay 1, 2026

Key ActionSubmit prior authorization with test name or gene list, laboratory name, and all relevant procedure codes; requests are reviewed against NCCN guidelines and policy criteria.

SourceLink

On This Page

CPT codes for 51+ gene panels

81455, 81456 — genomic sequence analysis panels for 51 or greater genes (solid organ or hematolymphoid neoplasm)

Comprehensive panel examples in coding list81457-81459 — panels that may include MSI, TMB, copy number variants, and combined DNA/RNA analysis

Prior authorization is recommended for unlisted codes for potentially covered services to avoid post-service denial

Documentation Required

Required documentation to submit with request

At the time of the prior authorization request, provide the specific gene, trade, or proprietary name of the test (or every gene/component for custom tests), the laboratory name, and all relevant CPT/HCPCS codes billed.

Specific gene, trade, or proprietary test name, or full gene list for custom-built tests
Name of laboratory performing the testing
All relevant CPT/HCPCS codes billed

Denial Risk

Incomplete documentation may lead to denial

Failure to submit complete documentation—specifically the test name or gene list, laboratory name, and all relevant CPT/HCPCS codes—may affect the outcome of the review and risk denial.

Incomplete documentation may lead to adverse determination at review

Note

Use appropriately certified laboratories and submit lab name

Order tests only from appropriately certified laboratories when results will inform clinical care; the policy requires submission of the laboratory name with the request.

Testing used to inform clinical care must be performed in an appropriately certified laboratory (ASCO recommendation)
Include the laboratory name on the prior authorization request

Documentation Required

Include required documentation; requests reviewed versus NCCN/policy

Ensure orders include the required documentation (test name or gene list, laboratory name, and CPT/HCPCS codes); requests will be reviewed against NCCN guidelines and the policy clinical criteria.

Requests are reviewed against NCCN guidelines and policy clinical criteria
Include all required documentation on the order

Billing Rule

Billing rule: use unlisted code (do not split into single-gene codes)

When no specific CPT or HCPCS code exists for a panel, bill using an appropriate unlisted code and do not bill the panel by submitting multiple single-gene codes as though each test were performed separately.

Use an unlisted code when no panel-specific CPT/HCPCS code exists
Do not bill the panel by splitting it across multiple single-gene codes

Denial Risk

Denial risk: unlisted codes for non-covered services will be denied

If an unlisted code is submitted for services that this policy deems non-covered, the claim will be denied as not covered.

Unlisted codes for non-covered services addressed in this policy will be denied as not covered

Note

Supplemental documentation note

See other provider action callouts in this section for additional documentation and billing requirements.

Note

Supplemental billing/prior auth note

See other provider action callouts in this section for additional prior authorization and billing guidance.

Note

Consolidated provider actions: authorization, documentation, and billing

Follow the listed provider actions: include required documentation with orders, obtain prior authorization when appropriate, and bill per coding guidance; supplemental provider action details are detailed in related callouts above.

Include test name/gene list, laboratory name, and all CPT/HCPCS codes on requests
Obtain prior authorization for unlisted codes when the service may be covered
Bill using unlisted code when no panel-specific code exists; do not split the panel into multiple single-gene codes

Permits simultaneous sequencing of many DNA/RNA fragments to identify variants across multiple genes or genomic regions.

ApplicationUsed for multigene tumor profiling (tissue-based) to assess DNA and/or RNA alterations relevant to cancer care.

inv-22: TMB / MSI / dMMR — definition and relation to multigene panels

TMB/MSI/dMMR definitions and roleTumor mutational burden (TMB) and microsatellite instability (MSI) testing assess genomic features that can predict immunotherapy response; mismatch repair deficiency (dMMR) status should be evaluated in patients who are candidates for immunotherapy.

Relation to multigene panelsASCO recommends using large multigene panel-based testing to assess MSI and validated large panels (or whole-exome analysis) to measure TMB when results may influence immunotherapy decisions.

Clinical considerationConsider prevalence of dMMR/MSI-H in tumor types and use NCCN guidance to determine when TMB/MSI assessment via panels is appropriate for tumor-agnostic or immunotherapy decisions.