ModifiedUnitedHealthcarePolicy CS373ID.B

FDA Cleared or Approved Companion Diagnostic Testing (for Idaho Only)

Defines coverage and medical necessity for FDA-cleared or approved companion diagnostic tests used to guide oncology therapy selection for members in Idaho, including Idaho Medicaid Plus plans.

Policy Summary

PayerUnitedHealthcare

PolicyFDA Cleared or Approved Companion Diagnostic Testing (for Idaho Only)

Policy CodePolicy CS373ID.B

Change TypeMaterial coverage revisions and code update

Effective DateAug 1, 2025

Next Review DateN/A

Key ActionFollow Idaho-specific criteria: use FDA-listed companion diagnostics aligned with the drug label and include documentation per Idaho Medicaid handbook.

SourceLink

POLICY UPDATE CHANGES

Companion Diagnostic Tests are considered proven and medically necessary when the oncology indication has a corresponding diagnostic test and biomarker on the FDA List of Cleared or Approved Companion Diagnostic Devices and additional alignment and label-consistency criteria are met.

Repeat Companion Diagnostic Testing on a new tissue or liquid biopsy specimen is considered proven and medically necessary up to three times annually when criteria are met and disease recurrence or progression is present.

Concurrent tissue-based and liquid biopsy companion diagnostic testing ordered within 30 days is considered proven and medically necessary for advanced/metastatic (stage IV) breast cancer and advanced/metastatic (stage IV) non-small cell lung cancer.

Instruction added to refer to the Idaho Medicaid Provider Handbook, Laboratory Services, Chapter 4.8: Genetic Testing for medical necessity clinical coverage criteria for genetic testing.

CPT code 0543U was added to the applicable codes list.

up to 3repeat CDx tests allowed annually for therapy selection

30 dayswindow where concurrent tissue and liquid biopsy testing is allowed

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10 mut/MbFDA CDx cut-point for TMB-high (pembrolizumab)

Idahogeographic applicability

0543Unew CPT code added

Coverage Criteria for Companion Diagnostic and Molecular Testing

Documentation Required

inv-37: Policy note — listing of codes does not imply services are covered; operational guidance

Provider action: Applicable procedure codes (reference) — The policy includes a non-exhaustive list of applicable CPT/PLA codes (e.g., 0022U, 0037U, 0179U, 0239U, 0242U) for reference purposes only. Listing of a code does not imply that the service described is covered; benefit coverage is determined by federal, state, or contractual requirements. Providers should check contract-specific coverage and prior authorization requirements before ordering.

Covered Indications and Clinical Contexts

Eligibility Requirements

This section does not specify additional top-level eligibility criteria beyond the coverage logic tied to FDA-listed companion diagnostics and the related molecular oncology policies. Providers should follow the documented coverage criteria and the referenced state-specific guidance for Idaho when determining member eligibility.

No separate top-level eligibility nodes are provided in this policy excerpt. Eligibility for companion diagnostic testing is determined by alignment with FDA-listed companion diagnostics, clinical indication, and consistency with the associated drug label; refer to the policy and referenced state materials for operational details.

Eligibility is driven by whether the oncology indication and specimen align with a biomarker and diagnostic listed on the FDA List of Cleared or Approved Companion Diagnostic Devices and whether test use is consistent with the drug's labeling. When no FDA CDx match exists, follow the related molecular oncology testing policies referenced in this document.

No standalone eligibility checklist is provided in these chunks; the policy applies the FDA CDx alignment and label-consistency criteria as the primary eligibility determinants. Providers should document tumor type, stage, prior therapies, and the rationale for testing in the medical record.

Eligibility for repeat or concurrent companion diagnostic testing is bounded by the policy limits: repeat testing on a new specimen is allowed up to three times annually when clinical indications (recurrence or progression) are present; concurrent tissue and liquid CDx testing is allowable when ordered within 30 days for specified advanced/metastatic (stage IV) breast cancer and NSCLC cases.

When considering liquid biopsy in lieu of tissue, eligibility is contingent on tissue being unavailable or insufficient, or when rapid genotyping is clinically indicated; tests must be used consistent with FDA labeling if they are intended as companion diagnostics.

Clinical eligibility also reflects guideline recommendations: testing is appropriate for individuals with advanced or metastatic disease when results will inform FDA-approved targeted therapy selection, or when participation in clinical trials is considered and tissue testing is not feasible.

No additional state-specific eligibility nodes are provided beyond the referenced Idaho resources; providers should consult the Idaho Medicaid Provider Handbook, Chapter 4.8, as noted in policy history for further state-specific clinical coverage requirements.

Eligibility requires that the requesting provider intends to use the test in a manner consistent with the companion drug label for the indicated indication and specimen; nonaligned requests should be evaluated under the related molecular oncology policies.

Coding and Test Codes

TMB threshold for pembrolizumab CDx indication

TMB threshold for pembrolizumab CDx indication>= 10 mut/Mb

TMB threshold used in pembrolizumab monotherapy analysis

TMB threshold used in pembrolizumab monotherapy analysis (Cristescu et al.)>= 175 mutations/exome

ctDNA tumor fraction recommended threshold

ctDNA tumor fraction recommended threshold>= 1% (where detection rates are higher)

Variant allele fraction limit of detection examples

Variant allele fraction limit of detection example

Provider Actions, Documentation & Authorization

Billing Rule

Applicable procedure codes provided for reference — inclusion does not guarantee coverage

The policy includes an applicable procedure code list for claim and prior authorization processing; inclusion of CPT/HCPCS codes (including newly added codes) is for reference and does not guarantee coverage or payment.

Providers should follow UnitedHealthcare billing and prior authorization processes when submitting codes.
Added CPT code 0543U is included in the applicable codes list and should be used as appropriate in submissions.

Prior Authorization

Prior authorization may be required for CDx-associated testing

Prior authorization may be required when testing is performed to identify biomarkers tied to FDA-approved therapies; tests used as FDA-cleared or approved companion diagnostics (CDx) are intended to identify individuals for specific therapies and may trigger PA requirements.

Not Covered / Limitations

Inclusion of procedure or billing codes in this policy is for reference only and does not by itself establish coverage. Providers should be aware that listing codes does not guarantee reimbursement and that coverage determinations rely on clinical criteria and applicable federal, state, or contractual requirements.

Tests marketed as broad molecular profiling tools without peer-reviewed evidence of clinical utility (examples include CANCERPLEX, Guardant360 TissueNext, and MI Profile/MI Tumor Seek) are identified in the policy as lacking sufficient evidence to support coverage for broad profiling indications.

Liquid biopsy tests intended for population screening of early-stage colorectal cancer and other early detection uses are not supported by current evidence and are included in the policy's not-covered statements for screening purposes.

Routine use of ctDNA assays for screening, early-stage treatment monitoring, or minimal residual disease detection is considered not medically necessary in the absence of stronger evidence demonstrating clinical benefit; such uses are specifically listed as not covered in the policy.

Routine broad molecular profiling for hepatocellular carcinoma is not established as medically necessary because no molecularly defined subgroups have demonstrated differential benefit from targeted therapies; testing may be considered on a case-by-case basis or for clinical trial eligibility but is not routine covered care.

Tissue-of-origin studies and similar tissue-of-origin classifiers are not recommended and are listed among not-covered or discouraged services for occult primary cancers in this policy.

Background and Definitions

Background: Companion diagnostics (CDx) are in vitro tests that identify biomarkers necessary for the safe and effective use of corresponding therapeutic drugs. CDx inform treatment selection by indicating which individuals are most likely to benefit from a therapy, who may be at increased risk of significant adverse effects, or who require monitoring of treatment response. The FDA List of Cleared or Approved Companion Diagnostic Devices is used to determine valid CDx-drug-tissue alignments for coverage.

Definition — Advanced Cancer

DefinitionAdvanced Cancer: Cancer that is unlikely to be cured or controlled with treatment (may be called end-stage or terminal cancer)

Clinical implicationOften denotes unresectable or metastatic disease where molecular testing to guide systemic therapy may be appropriate

SourceNational Cancer Institute (NCI) definition cited in policy

Definition — Companion Diagnostic Test

Definition

Policy Revision History

08/01/2025policy_revisionLatest

Revised coverage guidelines: clarified that companion diagnostic tests are medically necessary when the oncology indication and biomarker are listed on the FDA List of Cleared or Approved Companion Diagnostic Devices and use aligns with the drug label and specimen; updated definition of Comprehensive Genomic Profiling; added instruction to refer to Idaho Medicaid Provider Handbook Chapter 4.8 for genetic testing clinical coverage criteria.

08/01/2025coverage_change

Added allowance for repeat companion diagnostic testing on a new tissue or liquid biopsy specimen up to three times annually when criteria are met and disease recurrence or progression is present.

Policy Summary

PayerUnitedHealthcare

PolicyFDA Cleared or Approved Companion Diagnostic Testing (for Idaho Only)

Policy CodePolicy CS373ID.B

Change TypeMaterial coverage revisions and code update

Effective DateAug 1, 2025

Next Review DateN/A

Key ActionFollow Idaho-specific criteria: use FDA-listed companion diagnostics aligned with the drug label and include documentation per Idaho Medicaid handbook.

SourceLink

On This Page

Concurrent ordering window

Concurrent ordering windowordered within 30 days

Repeat testing frequency

Repeat testing frequencyup to three times annually

When submitting PA requests, document that the test is an FDA-cleared/approved CDx and that use is consistent with the drug label.
Provide clinical indication, tumor type, and rationale linking the biomarker to the intended FDA-approved therapy.

Prior Authorization

Prior authorization may be required for CMP liquid biopsy

Prior authorization may be required for comprehensive molecular profiling (CMP) liquid biopsy tests when used to guide targeted therapy; documentation should include the clinical indication, tumor type, and rationale for choosing liquid versus tissue testing.

Document tumor type, clinical stage, prior treatments, and reasons tissue testing is unavailable or insufficient when requesting PA for liquid CMP.
Include evidence that the selected liquid assay is appropriate for the biomarker(s) of interest and intended therapy.

Prior Authorization

Prior authorization guidance for tumor genomic testing — document guideline-based indication

Multigene tumor sequencing or liquid biopsy may be indicated for individuals with advanced or metastatic disease when biomarker-linked therapies are available; prior authorization requests should reference guideline-based indications (e.g., NCCN, ASCO) and include clinical justification.

When requesting PA, cite relevant guideline recommendations and document how results will inform therapy selection or trial eligibility.
Provide evidence of advanced/metastatic disease status and performance status as applicable.

Prior Authorization

Prior authorization — laboratory and assay standards (CLIA/FDA validation)

Laboratory assays used to support prior authorization should be performed in appropriately certified laboratories and use FDA-cleared or validated assays when recommended; no explicit PA rules are provided here but lab certification and assay validation are required for tests informing clinical care.

Testing should be performed in CLIA-certified laboratories or using FDA-approved/validated assays when informing treatment decisions.
Submit analytical validation details (e.g., LOD, PPA/NPA, reproducibility) with PA requests when available.

Note

No explicit prior authorization requirement specified in these sections

No explicit prior authorization requirements are specified in the cited excerpts of this document; providers should follow standard UnitedHealthcare PA processes and check contractual or state-specific rules.

Absence of a stated PA rule in these sections does not eliminate PA requirements that may exist in plan contracts or state rules.

Billing Rule

Operational update: CPT 0543U added — follow standard billing/PA processes

CPT code 0543U has been added to the applicable code list; providers must follow UnitedHealthcare billing and prior authorization processes and include the new code in submissions as appropriate.

Update billing systems and PA submissions to include CPT 0543U when it accurately represents the performed service.
Inclusion of the code in the policy list is informational and does not guarantee coverage—follow plan-specific coverage rules.

Step Therapy

Step requirements for pembrolizumab (TMB-high): prior progression and label-consistent criteria

Providers should ensure patients meet label-consistent prerequisites before using TMB-high status to pursue pembrolizumab; the pembrolizumab approval requires progression following prior treatment and no satisfactory alternative options.

Confirm TMB is measured by an FDA-approved test using the labeled cut-point (≥10 mut/Mb for F1CDx) and document prior progression and lack of satisfactory alternatives when applying for therapy coverage.

Step Therapy

Testing sequence guidance — prefer tissue first; use liquid NGS when tissue not feasible

When feasible, perform tissue-based testing first; use liquid NGS (ctDNA) when tissue is unavailable, insufficient, or biopsy is not feasible — liquid testing may also be used to accelerate time to treatment in suspected advanced NSCLC.

If liquid biopsy is negative for actionable biomarkers and clinical suspicion remains, obtain reflex tissue testing.
When using liquid testing, document reasons tissue testing was not feasible or the clinical need for rapid genotyping.

Step Therapy

Repeat testing guidance — avoid routine repeat after cytotoxic chemo; allow repeat with progression

Repeat molecular testing should not be performed after standard cytotoxic chemotherapy unless clinically indicated; repeat testing may be considered after targeted therapy progression or when disease recurrence/progression is documented.

Document the clinical rationale (e.g., progression after targeted therapy) when requesting repeat testing.
Repeat companion diagnostic testing on a new tissue or liquid specimen is allowed up to three times annually when criteria are met and clinical indications exist.

Note

No step therapy rules specified — check federal/state/contract requirements

No step therapy rules are specified in this document; providers must check federal, state, or contractual benefit requirements as these may differ and govern coverage decisions.

Verify state- or contract-specific step therapy requirements before ordering testing tied to therapy selection.

Documentation Required

Medical records may be required to support coverage decisions

Medical records documentation may be required to assess whether the member meets clinical criteria for coverage; benefit coverage is determined by federal, state, or contractual requirements and applicable laws.

Submit medical records showing clinical status, prior treatments, and rationale for testing when requested.
Documentation alone does not guarantee coverage.

Documentation Required

Document clinical status and sample availability when requesting testing

Documentation should support advanced or metastatic disease status, prior progression on standard therapies when relevant to drug approvals, and availability or unavailability of tumor tissue or plasma for testing.

For pembrolizumab (TMB-high) indicate prior progression and lack of satisfactory alternatives per the drug approval.
For prostate cancer, document timing of ctDNA collection (preferably during progression) to maximize diagnostic yield.

Documentation Required

Include analytical validation metrics (LOD, PPA/NPA, reproducibility) with requests

Include analytical validation details for the assay when available (limit of detection, positive/negative percent agreement, reproducibility) to support test performance and PA requests.

Provide assay validation metrics (e.g., LOD ~0.40% VAF for select substitutions in FoundationOne Liquid CDx) when submitting testing rationale.
Analytical performance data strengthens justification for using a specific test to guide therapy.

Documentation Required

Laboratory certification required — use CLIA-certified lab or FDA-approved/validated assay

Testing used to inform clinical care must be performed in an appropriately certified laboratory; document laboratory certification (e.g., CLIA) and that the assay is FDA-approved or validated when informing treatment decisions.

Submit evidence of CLIA certification or FDA approval/validation for the performing laboratory or assay.
Document how test results will impact clinical decision-making.

Documentation Required

Laboratory and specimen documentation — CLIA-certified lab or FDA-approved assay; document tissue availability

Perform testing in a CLIA-certified/approved laboratory or use an FDA-approved/validated assay; document tumor tissue availability and, if ctDNA is used instead, the clinical reason for selecting plasma.

When ctDNA is used due to lack of feasible tissue, document why tissue biopsy was not possible and any tumor tissue previously tested.
Ensure the selected assay is appropriate for the biomarkers being evaluated (e.g., RNA-seq for fusions).

Documentation Required

Prefer most recent tumor tissue; use ctDNA only when tissue not feasible

When feasible, perform testing on the most recent tumor tissue available; use ctDNA when tissue-based testing is not clinically feasible and document the reason for using plasma.

Prefer recent tumor tissue for testing; if using ctDNA, note potential limitations (e.g., false-negatives, CHIP) in documentation.
For prostate cancer, collect plasma during biochemical or radiographic progression when possible.

Documentation Required

Required documentation: demonstrate CDx alignment with drug, FDA indication, and specimen

Documentation for companion diagnostic testing must show that the CDx aligns with the drug, the FDA-approved indication, and the appropriate specimen type as listed on the FDA List of Cleared or Approved Companion Diagnostic Devices and that use is consistent with the drug label.

Provide the FDA CDx device name or reference and the drug label showing the linked indication.
If concurrent tissue and liquid testing is requested, document that both are ordered within the allowed 30-day window when applicable.

Note

When no FDA CDx match exists, refer to related molecular oncology policies and Idaho Medicaid handbook

If no match is found on the FDA List of Cleared or Approved Companion Diagnostic Devices, providers should refer to related molecular oncology testing policies (e.g., Molecular Oncology Testing for Solid Tumor Cancer Diagnosis, Prognosis, and Treatment Decisions) and the Idaho Medicaid Provider Handbook for coverage guidance.

When an FDA-listed CDx is not available for the intended drug/indication, follow the referenced molecular oncology policies for medical necessity determination.
Refer to the Idaho Medicaid Provider Handbook, Chapter 4.8: Genetic Testing, as instructed in the policy history.

Denial Risk

Coding inclusion is not a guarantee of coverage — documentation required

Inclusion of a billing code in the policy does not imply the service described by the code is a covered or non-covered health service; lack of required documentation may lead to denial.

Use the code list as a reference only and ensure clinical documentation supports the medical necessity of the billed service.
Coverage decisions are governed by federal, state, or contractual plan terms.

Denial Risk

Insufficient evidence for broad profiling-only use — higher denial risk

Coverage requests based on broad molecular profiling tools without linkage to FDA-labeled biomarkers or actionable findings have insufficient evidence of clinical utility and may be at higher risk for denial.

When ordering broad CGP for the purpose of undirected profiling, include justification tying the test to actionable, label-supported biomarkers or clinical trial eligibility.
Evidence assessments (e.g., Hayes) identified limited clinical utility for broad profiling-only indications.

Denial Risk

Insufficient evidence for broad clinical utility may lead to denial

Tests or indications lacking evidence of clinical utility (for example, broad comprehensive molecular profiling intended to improve outcomes over limited or guideline-directed testing) may not be supported and could result in denial.

Provide indication-specific evidence that testing will inform an FDA-approved therapy or clinical trial enrollment to reduce denial risk.
Avoid using large-panel liquid biopsies for undifferentiated profiling without demonstrating actionable intent.

Denial Risk

Evidence limitations for ctDNA in screening, monitoring, and MRD — risk of denial

Evidence limitations exist for ctDNA use in certain contexts (early-stage cancer screening, routine treatment monitoring, or minimal residual disease detection); use of ctDNA for these unproven indications may lack support and risk denial.

Do not submit ctDNA for screening, early-stage disease monitoring, or MRD detection as standard coverage indications without strong supporting evidence.
When using ctDNA for therapy selection in advanced disease, document clinical context and rationale.

Denial Risk

ctDNA is not a substitute for histologic tissue diagnosis — risk of denial

Using ctDNA testing in lieu of a histologic tissue diagnosis is not supported and may trigger denial; tissue-based diagnosis is preferred in stages I–III and ctDNA is typically reserved for advanced/metastatic disease or when tissue testing is not feasible.

If ctDNA is submitted in place of a tissue diagnosis, include documentation explaining why tissue biopsy was not possible and reference clinical necessity.
Negative ctDNA results should prompt reflex tissue testing when clinical suspicion remains.

Denial Risk

FDA approval is informational only — not sole basis for coverage

FDA approval alone is informational and not a basis for coverage decisions; providers must document medical necessity per applicable benefit plan rules.

Reference FDA-cleared/approved CDx status when relevant, but ensure all other coverage criteria and documentation requirements are satisfied.

Denial Risk

Nonaligned or unlabeled CDx requests may be denied — refer to related policies/Idaho handbook

Requests for companion diagnostic testing that do not align with an oncology indication and biomarker listed on the FDA List of Cleared or Approved Companion Diagnostic Devices, or that are inconsistent with the companion drug label, may be denied; when no CDx match is found, refer to molecular oncology testing policies and the Idaho Medicaid Provider Handbook.

Ensure CDx selection and intended drug use match the FDA CDx list and drug labeling prior to submission.
If no aligned CDx exists, follow referenced policies for coverage determination.

Companion diagnostic testing requests that do not align with an oncology indication and biomarker listed on the FDA List of Cleared or Approved Companion Diagnostic Devices, or that are inconsistent with the companion drug label, are not supported by this policy and should be evaluated under other molecular oncology testing policies referenced in the document.

Companion Diagnostic Test: A test that provides important information for the safe and effective use of a corresponding therapeutic drug

Use caseIdentifies individuals most likely to benefit from a specific oncology therapeutic or at increased risk for significant side effects

Regulatory contextAlignment with FDA-approved drug labeling and the FDA List of Cleared or Approved Companion Diagnostic Devices is required for CDx coverage under this policy

Definition — Comprehensive Genomic Profiling (CGP)

DefinitionComprehensive Genomic Profiling (CGP): NGS test that simultaneously detects multiple classes of genomic alterations across hundreds of genes from a single sample

Assay examplesFDA-approved CGP example: FoundationOne CDx (analyzes 324 genes and reports TMB, MSI, gLOH where applicable)

Policy noteCGP definition was updated in this policy version (see Policy History) and CGP should be performed using FDA-approved/validated assays or CLIA-certified labs

Definition — Liquid Biopsy

DefinitionLiquid Biopsy: Minimally invasive testing of bodily fluids (commonly blood) to analyze tumor-derived biomolecules including ctDNA/cfDNA for detection, treatment selection, or monitoring

LimitationsHigh specificity but higher false-negative rate compared with tissue; should not replace histologic tissue diagnosis

Appropriate useTypically used in advanced/metastatic disease or when tissue is unavailable or would cause clinically significant delay

Definition — Next Generation Sequencing (NGS)

DefinitionNext Generation Sequencing (NGS): Sequencing techniques that can quickly analyze multiple sections of DNA at the same time

Clinical roleUsed for multigene panels, CGP, and detection of multiple variant classes (short variants, CNAs, rearrangements, TMB, MSI)

RecommendationNGS-based testing should be performed in appropriately certified laboratories and used when multiple biomarkers may inform therapy

Definition — Tumor Mutational Burden (TMB)

DefinitionTumor Mutational Burden (TMB): A quantitative measure of the number of somatic mutations per megabase in tumor DNA

Policy thresholdTMB-high defined as >= 10 mutations/Mb when measured by an FDA-approved test (e.g., F1CDx) for pembrolizumab tumor-agnostic indication

Measurement methodsTMB may be reported from targeted panels (normalized to mut/Mb) or whole exome sequencing; assay-specific cutoffs may require adjustment to align with the 10 mut/Mb standard

Definition — Liquid biopsy / ctDNA

DefinitionLiquid biopsy / ctDNA: Minimally invasive testing of circulating tumor DNA (ctDNA)/cell-free DNA (cfDNA) in plasma or other body fluids to detect tumor-derived genomic alterations

Performance characteristicsHigh specificity but variable sensitivity; detection influenced by tumor fraction and variant type (e.g., fusions, CNAs may be less reliably detected)

Clinical cautionctDNA should not be used in place of histologic diagnosis and negative ctDNA may warrant reflex tissue testing

Definition — circulating tumor DNA (ctDNA) / liquid biopsy (summary)

Definition (summary)Circulating tumor DNA (ctDNA): Cell-free tumor-derived DNA fragments in plasma used for detection of somatic genomic alterations to guide treatment selection when tissue testing is not feasible

Interpretation caveatsctDNA results can be affected by tumor fraction, CHIP (clonal hematopoiesis) may cause false positives, and certain alteration types (copy number changes, some fusions) may require higher tumor fraction for reliable detection

Recommended useUse ctDNA when tissue is unavailable/insufficient or rapid genotyping is needed; confirm negative liquid results with tissue when clinical suspicion remains

Definition — LOD (limit of detection) example

LOD example95% limit of detection approximately 0.40% VAF for select substitutions/indels (FoundationOne Liquid CDx)

Additional LOD values~0.37% VAF for select rearrangements; copy number amplifications require much higher tumor fraction (e.g., 21.7%)

Analytical validationLOD values reported from clinical and analytical validation studies involving thousands of tests and tens of thousands of variants

Definition — ctDNA / liquid biopsy (alternate)

Definition (alternate)ctDNA (cell-free tumor DNA) in plasma analyzed by NGS to identify somatic alterations when tissue biopsy is infeasible; used for treatment selection and monitoring in advanced disease

LimitationsConsider higher false-negative rate vs tissue and potential confounders such as CHIP

Operational noteCollect ctDNA during progression when possible to maximize diagnostic yield (e.g., prostate cancer guidance)

Definition — cfDNA/ctDNA (liquid biopsy) characteristics

CharacteristiccfDNA/ctDNA (liquid biopsy) is cell-free DNA in plasma used for tumor genomic profiling when tissue testing is not feasible

Diagnostic performanceHigh specificity but relatively higher false-negative rates; sensitivity varies by gene/variant type and tumor fraction

Clinical recommendationUse as alternative or complement to tissue testing; reflex to tissue testing if liquid is negative and clinical suspicion persists

Definition — RNA sequencing preference for fusion detection

Preference for fusion detectionRNA sequencing preferred for detection of gene fusions because fusions are better identified at the RNA level

Assay implicationWhen fusion detection is clinically important (e.g., ALK, NTRK, ROS1), include RNA-based NGS or orthogonal RNA testing

Policy guidanceUse RNA-seq assays when fusions will impact therapy selection; ctDNA panels may miss some fusions depending on design

Definition — RNA-sequencing assays

DefinitionRNA-sequencing assays: NGS assays that sequence RNA and have greater ability to detect gene fusions compared with DNA-only assays

Clinical useRecommended when detection of actionable fusions will inform targeted therapy decisions

Testing noteRNA assays may be incorporated into CGP or performed as reflex testing when DNA-based panels are negative for fusions

Definition — ctDNA (plasma circulating tumor DNA) interpretation caveats

Interpretation caveatsctDNA/plasma circulating tumor DNA results may be complicated by clonal hematopoiesis (CHIP), low tumor fraction, and variant-specific detection limits; negative results do not exclude actionable alterations

Clinical implicationDo not use ctDNA in lieu of histologic diagnosis; consider reflex tissue testing for negative/discordant results

Use caseAppropriate for advanced/metastatic disease or when tissue biopsy is not feasible or would cause unacceptable delay

Definition — CGP definition updated

Updated definitionComprehensive Genomic Profiling (CGP) definition was updated in this policy version to reflect NGS tests that detect multiple classes of genomic alterations across hundreds of genes

Regulatory/validation noteCGP should be performed using FDA-approved/validated assays or in CLIA-certified laboratories with appropriate analytical validation data

ExampleFoundationOne CDx cited as an FDA-approved CGP assay with extensive analytical validation

08/01/2025coverage_change

Permitted concurrent tissue-based and liquid biopsy companion diagnostic testing ordered within 30 days for advanced/metastatic (stage IV) breast cancer and advanced/metastatic (stage IV) non-small cell lung cancer when CDx criteria are met.

2025-08operational_update

Archived previous policy version CS373ID.A and updated Clinical Evidence, References, and Description of Services sections to reflect current information.

2025coding_update

Added CPT code 0543U to the applicable codes list.

Note

Refer to Idaho Medicaid Provider Handbook (Chapter 4.8) for state-specific genetic testing criteria

Refer to the Idaho Medicaid Provider Handbook, Chapter 4.8: Genetic Testing, for state-specific medical necessity clinical coverage criteria and additional guidance when FDA CDx alignment is not found.

Use the Idaho Medicaid handbook as an operational reference for Idaho Medicaid Plus and related state plan members.
The policy explicitly instructs referral to the Idaho Medicaid Provider Handbook in the summary of changes.