ModifiedUnitedHealthcarePolicy CS373KS.02

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

Policy governing coverage and medical necessity of FDA-cleared or approved molecular oncology companion diagnostic tests for members in Kansas; applies to tissue and liquid biopsy CDx tests used to guide therapy selection.

Policy Summary

PayerUnitedHealthcare

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

Policy CodePolicy CS373KS.02

Change TypeMaterial revisions and code updates

Effective DateFeb 1, 2026

Next Review Date

Key ActionWhen seeking coverage for FDA cleared or approved CDx tests, follow plan prior authorization processes and supply medical records demonstrating the member meets CDx clinical criteria and InterQual CGP criteria where applicable.

SourceLink

POLICY UPDATE CHANGES

Added notation to indicate this policy applies to tests that have been granted approval as FDA cleared or approved Companion Diagnostic (CDx) tests.

For medical necessity clinical coverage criteria for Companion Diagnostic Tests Using Comprehensive Genomic Profiling (CGP), refer to InterQual CP: Molecular Diagnostics (Comprehensive Genomic Profiling for Solid Tumor, Liquid Biopsy; Comprehensive Genomic Profiling, Tumor Tissue).

Subsequent use of an FDA cleared or approved CDx test on a new specimen for therapy selection is considered proven and medically necessary when criteria for the CDx test are met and the individual has disease recurrence or progression despite recent systemic therapy.

Concurrent testing using an FDA cleared or approved tissue-based CDx test and a liquid biopsy-based CDx test is considered proven and medically necessary for advanced or metastatic (stage IV) breast cancer and advanced or metastatic (stage IV) NSCLC when CDx criteria are met.

Due to insufficient evidence of efficacy, all other uses of the FDA cleared or approved CDx tests not specified are unproven and not medically necessary.

Added CPT codes 0211U and 0523U to Applicable Codes and removed several previously listed CPT codes.

Added and updated language about medical records documentation required to support medical necessity determinations.

Added definition of 'Concurrent Testing' and removed definitions for CGP and NGS; updated definitions for Advanced Cancer, Companion Diagnostic, and Liquid Biopsy.

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2Cancer types with specified concurrent tissue+liquid CDx coverage

5+Minimum genes detected by CDx tests covered by this policy

10 mut/MbTMB-H cutpoint

Coverage Criteria for FDA-cleared/approved Companion Diagnostics

Coverage for FDA-cleared/approved CDx tests

Covered when ALL of the following are met:

CDx test approvals and scope: The test is FDA cleared or approved as a Companion Diagnostic and is listed in the FDA List of Cleared or Approved Companion Diagnostic Devices and/or the FDA Premarket Approval Database.

Policy applies only to molecular oncology CDx tests that detect alterations in five or more genes in tumor tissue or liquid biopsy.

Intended use and linkage to therapy: The CDx test is being used to guide selection of a specific therapeutic product or group of products as stipulated in the FDA labeling for the test and the corresponding therapeutic product(s).

Use must align with FDA-approved companion diagnostic labeling.

Subsequent/new-specimen use: Subsequent use of an FDA cleared or approved CDx test on a new specimen for therapy selection is medically necessary when: the CDx criteria above are met AND the individual has disease recurrence OR the individual's cancer has progressed or did not respond to the most recent systemic therapy.

Refer to InterQual criteria where applicable.

Concurrent testing allowance: Concurrent testing using an FDA cleared/approved tissue-based CDx test and a liquid biopsy–based CDx test is medically necessary when the CDx criteria above are met AND the patient has advanced/metastatic (stage IV) breast cancer OR advanced/metastatic (stage IV) non–small cell lung cancer (NSCLC).within 30 days

Concurrent Testing defined as tissue and liquid ordered for the same clinical indication within 30 days.

Evidence summaries and coverage-relevant considerations

Key clinical findings and considerations from studies and assessments

Quality of evidence for F1LCDx: A Hayes Molecular Test Assessment identified seven studies of very poor quality; available studies suggest the test can identify treatment-eligible individuals but do not conclusively demonstrate improved clinical outcomes versus more limited testing or fully replace tissue biopsy in all cases.

(Hayes assessment; FoundationOne Liquid CDx)

Prospective study findings: Prospective studies (e.g., Bayle et al.) using FoundationOne Liquid CDx identified actionable targets in a substantial proportion of participants (64% with ≥1 actionable target) and enabled multidisciplinary tumor board–recommended matched therapy, though only a minority received matched therapy and overall survival benefit was not consistently demonstrated.

(Bayle et al. prospective cohort)

Tumor fraction and sensitivity: Sensitivity of liquid biopsy to detect tissue-identified driver alterations is highly dependent on circulating tumor DNA tumor fraction (TF); TF ≥10% is associated with near-100% sensitivity, whereas lower TF yields sensitivity ranging approximately 58%–86%.

Covered indications per tumor-specific guideline recommendations

Covered when ALL of the following are met for the listed tumor types where NCCN or guideline recommends testing:

General requirement: The test is an FDA-approved companion diagnostic or a validated FDA-cleared/approved NGS-based assay (tissue or plasma ctDNA as specified) AND the patient has the tumor type and disease stage for which NCCN or other guideline recommends testing.

References: tumor-specific NCCN recommendations and supporting guidance (ASCO, IASLC).

Specimen modality and sequencing approach: Use tissue FFPE NGS testing when tumor tissue is available; consider plasma ctDNA (liquid biopsy) when tissue is not feasible or as complementary testing; dual-modality testing may be appropriate in advanced disease per guideline recommendations.

IASLC endorses plasma ctDNA for genotyping advanced NSCLC; NCCN lists tumor-specific options below.

Primary Coverage and Delegation

Covered when ALL of the following are met:

Delegation to InterQual for CGP criteria: Medical necessity clinical coverage criteria for Companion Diagnostic Tests Using Comprehensive Genomic Profiling (CGP) are determined by InterQual CP: Molecular Diagnostics (Comprehensive Genomic Profiling for Solid Tumor, Liquid Biopsy; Comprehensive Genomic Profiling, Tumor Tissue).

Refer to InterQual for detailed CGP clinical criteria.

Subsequent Specimen Use

Subsequent use of an FDA cleared or approved CDx test on a new specimen is covered when ALL of the following are met:

Subsequent CDx testing: (1) The criteria above for the CDx test are met; AND (2) One of: the individual is experiencing disease recurrence; OR the individual's cancer has progressed or did not respond to the most recent systemic therapy.

Applies to testing on a new specimen for therapy selection.

Concurrent Testing (Tissue + Liquid)

Concurrent tissue-based and liquid biopsy-based FDA cleared or approved CDx tests are considered medically necessary when ALL of the following are met:

Concurrent CDx testing: (1) The criteria above for the CDx test are met; AND (2) The patient's cancer type is either advanced/metastatic (stage IV) breast cancer OR advanced/metastatic (stage IV) non–small cell lung cancer (NSCLC).within 30 days

Concurrent testing limited to these two cancer types per policy; concurrent defined as tissue and liquid ordered for same indication within 30 days.

All other uses of the listed FDA‑cleared or approved companion diagnostic (CDx) tests beyond the specific covered indications are considered unproven and not medically necessary. This includes concurrent tissue + liquid CDx testing for cancer types other than the two explicitly allowed (advanced/metastatic [stage IV] breast cancer and advanced/metastatic [stage IV] non‑small cell lung cancer).

Limitations in the available evidence — including small study sizes, lack of randomization, and mixed tumor‑type populations — reduce generalizability and may preclude extrapolation of benefit to broader patient groups. Larger, randomized clinical trials focused on specific tumor types are recommended before extending coverage beyond guideline‑aligned indications.

This policy does not endorse or require use of any specific commercial laboratory or proprietary assay; instead coverage is tied to tests that are FDA‑cleared or FDA‑approved as Companion Diagnostics or to validated NGS‑based assays per the policy and applicable guideline recommendations. Tests that lack FDA clearance/approval or that are not validated for the intended indication are not supported by this document.

Uses of FDA‑cleared or FDA‑approved CDx tests that are not specified in this policy (i.e., outside the listed covered indications or not meeting the CDx clinical criteria) are considered unproven and not medically necessary due to insufficient evidence of efficacy.

Where there is inadequate or low‑quality evidence to support a particular indication for a CDx test, the use is considered unproven and therefore not medically necessary. Coverage decisions rely on demonstrated clinical benefit for the intended therapy pairing and guideline or FDA support.

Absence of supportive guideline recommendations or of an FDA‑cleared/approved assay for a specified indication generally implies that the use may not be covered. FDA approval alone is informational and does not automatically guarantee coverage without meeting the policy's clinical criteria.

Uses outside the specified indications in this policy — and uses that do not meet the CDx clinical criteria or delegated InterQual CGP criteria — are considered not covered. Providers should refer to InterQual for the detailed CGP medical necessity criteria where the policy delegates that determination.

Tumor Types and Indications Covered

Use of FDA-cleared/approved molecular oncology CDx tests detecting >=5 genes

Covered when ALL of the following are met:

Panel content and intended use: Use of an FDA-cleared or approved molecular oncology companion diagnostic that detects alterations in five or more genes in tumor tissue or liquid biopsy to guide therapy selection.>= 5 genes

Policy scope specifies tests that detect five or more genes (e.g., FoundationOne panels ~311–324 genes).

Subsequent or concurrent uses included: Includes subsequent testing on new specimens for recurrence or progression when criteria are met, and concurrent tissue + liquid CDx testing for advanced/metastatic (stage IV) breast cancer and NSCLC per policy allowances.

Refer to policy concurrent testing and subsequent specimen provisions.

Use of FDA-cleared/approved liquid CDx to identify actionable genomic alterations in advanced/metastatic solid tumors

Applicable Procedure and CPT/HCPCS Codes

Applicable CPT/HCPCS Codes (group 1)CPT

0022U	Targeted genomic sequence analysis panel, non-small cell lung neoplasia, DNA and RNA analysis, 23 genes, interrogation for sequence variants and rearrangements, reported as presence or absence of variants and associated therapy(ies) to consider.
0037U	Targeted genomic sequence analysis, solid organ neoplasm, DNA analysis of 324 genes, interrogation for sequence variants, gene copy number amplifications, gene rearrangements, microsatellite instability and tumor mutational burden

Applicable CPT/HCPCS Codes (group 2)CPT

0211U	Oncology (pan-tumor), DNA and RNA by next-generation sequencing, utilizing formalin-fixed paraffin-embedded tissue, interpretative report for single nucleotide variants, copy number alterations, tumor mutational burden, and microsatellite instability, with therapy association.
0239U	Targeted genomic sequence analysis panel, solid organ neoplasm, cell-free DNA, analysis of 311 or more genes, interrogation for sequence variants, including substitutions, insertions, deletions, select rearrangements, and copy number variations.
0242U	Targeted genomic sequence analysis panel, solid organ neoplasm, cell-free circulating DNA analysis of 55-74 genes, interrogation for sequence variants, gene copy number amplifications, and gene rearrangements.
0473U	Oncology (solid tumor), next-generation sequencing (NGS) of DNA from formalin-fixed paraffin- embedded (FFPE) tissue with comparative sequence analysis from a matched normal specimen (blood or saliva), 648 genes, interrogation for sequence variants, insertion and deletion alterations, copy number variants, rearrangements, microsatellite instability, and tumor-mutation burden.
0523U	Oncology (solid tumor), DNA, qualitative, next-generation sequencing (NGS) of single-nucleotide variants (SNV) and insertion/deletions in 22 genes utilizing formalin-fixed paraffin-embedded tissue, reported as presence or absence of mutation(s), location of mutation(s), nucleotide change, and amino acid change.
0543U	Oncology (solid tumor), next-generation sequencing of DNA from formalin-fixed paraffin-embedded (FFPE) tissue of 517 genes, interrogation for single-nucleotide variants, multi-nucleotide variants, insertions and deletions from DNA, fusions in 24 genes and splice variants in 1 gene from RNA, and tumor mutation burden.
81479	Unlisted molecular pathology procedure

Named FDA-cleared/approved companion diagnostic assaysmixed

No codes listed

Applicable/Changed CPT CodesCPT

0211U	CPT code added (document lists as added)
0523U	CPT code added (document lists as added)
0179U	CPT code removed (document lists as removed)
81445	CPT code removed (document lists as removed)
81449	CPT code removed (document lists as removed)
81450	CPT code removed (document lists as removed)
81451	CPT code removed (document lists as removed)
81455	CPT code removed (document lists as removed)
81456	CPT code removed (document lists as removed)
81599	CPT code removed (document lists as removed)

Tumor Mutational Burden (TMB) — high

TMB‑High cutpoint>= 10 mut/Mb (cutpoint used by FoundationOne CDx tied to pembrolizumab approval)

Regulatory contextPremarket approval for FoundationOne CDx included a CDx indication for TMB‑high solid tumors using the 10 mut/Mb cutpoint

Clinical trial basisKEYNOTE‑158 prespecified >=10 and >=13 mut/Mb cut‑points; approval supported by response data from KEYNOTE‑158

Tumor fraction (TF) thresholds

High tumor fraction (TF) thresholdTF >= 10% — sensitivity of liquid biopsy to detect tissue‑identified driver alterations consistently near or at 100%

Provider Actions, Prior Authorization, and Documentation

Billing Rule

Applicable procedure codes (reference/prior auth may apply)

Applicable procedure and diagnosis codes are provided for reference and may be subject to prior authorization. Listing of a code does not imply coverage or guarantee payment. Providers should verify payer-specific prior authorization requirements before submitting claims.

Applicable CPT/PLA/Unlisted codes are for reference only; payer may require prior authorization.
Inclusion of a code in this policy does not guarantee coverage or reimbursement.

Prior Authorization

Prior authorization — evidence/context

Prior authorization (PA) may be required to confirm that the requested companion diagnostic (CDx) or validated NGS assay meets medical necessity criteria. When PA is requested, documentation should clearly state the test type (tissue or liquid), indication, tumor type/stage, relationship to a specified FDA-cleared/approved therapeutic product (if applicable), and prior therapies tried.

Member and Test Eligibility Requirements

Eligibility for coverage requires that the test be FDA‑cleared or FDA‑approved as a Companion Diagnostic and that the clinical scenario align with the policy's covered indications or with InterQual CGP criteria when delegated. For liquid biopsy, analytic and clinical factors such as tumor fraction (TF) and specimen adequacy influence test performance and may affect coverage decisions; when tissue is insufficient, liquid biopsy may be an appropriate alternative per guideline‑based options.

Subsequent testing on a new specimen is eligible when the CDx criteria are met and the patient has disease recurrence or progression, or did not respond to the most recent systemic therapy. Concurrent tissue and liquid CDx testing is eligible only for advanced/metastatic (stage IV) breast cancer and advanced/metastatic (stage IV) NSCLC when CDx criteria are met.

Coverage is aligned with NCCN and other guideline recommendations for specific tumor types; the test modality (tissue, plasma ctDNA, or both) should match guideline guidance and the clinical context. Medical necessity determinations for comprehensive genomic profiling using CGP are delegated to InterQual clinical criteria referenced in this policy.

Providers must maintain and make available medical record documentation that supports medical necessity. Documentation should include relevant medical history, physical examination findings, and results of pertinent diagnostic tests or procedures. When prior authorization is requested, the plan may require records demonstrating that the member meets the CDx clinical criteria and InterQual CGP criteria where applicable.

Non-covered Uses and Limitations

Molecular oncology tests that have not been cleared or approved by the FDA as Companion Diagnostics are not covered under this policy; refer to the separate Kansas molecular oncology testing policies for guidance on non‑CDx assays.

The quality of evidence for some indications is low or very low and does not consistently demonstrate a survival benefit. While some studies show detection of actionable variants and potential to shorten time to treatment, comprehensive testing has not uniformly been shown to improve clinical outcomes compared with more limited testing in all contexts.

Non‑validated assays or those not cleared/approved by the FDA for the intended companion diagnostic use are not supported by this document for the listed guideline‑recommended indications and therefore are not covered by this policy.

Even when a CDx test is FDA‑cleared or approved, use of that test for indications not specifically supported by this policy (or that fail to meet delegated InterQual criteria) is considered unproven and not medically necessary.

Background and Context

Companion diagnostics are tests that provide information essential for the safe and effective use of a corresponding therapeutic. This policy applies to FDA‑cleared or FDA‑approved molecular oncology CDx tests that detect alterations in five or more genes in tumor tissue or liquid biopsy and that are listed in the FDA's companion diagnostic device resources. Concurrent testing is defined as tissue‑based testing and liquid biopsy ordered for the same clinical indication within a 30‑day window.

Definitions

Companion Diagnostic — definition

DefinitionA Companion Diagnostic (CDx) is a test that provides information essential for the safe and effective use of a corresponding therapeutic and, as used in this policy, is FDA cleared or approved for use with a specific drug or group of drugs and eligible for listing in the FDA List of Cleared or Approved Companion Diagnostic Devices.

Regulatory tieCDx tests referenced in the policy must be FDA cleared or approved as Companion Diagnostics to be eligible for coverage under this policy.

PurposeUsed to identify patients for whom a specific therapy is safe and effective per the therapeutic labeling.

Concurrent Testing — definition

DefinitionConcurrent Testing = tissue‑based testing and liquid biopsy ordered for the same clinical indication within a 30‑day period.

Policy allowance

Policy Revision History

2026-02-01policy_revisionLatest

Added notation that the policy applies to tests granted approval as FDA cleared or approved Companion Diagnostic (CDx) tests; delegated CGP medical necessity criteria to InterQual; specified subsequent-new specimen and concurrent tissue+liquid testing rules; clarified noncovered uses for indications without sufficient evidence.

2026-02-01coding_update

Added CPT codes 0211U and 0523U to the Applicable/Changed CPT Codes list and removed several previously listed CPT codes.

2026-02-01

Policy Summary

PayerUnitedHealthcare

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

Policy CodePolicy CS373KS.02

Change TypeMaterial revisions and code updates

Effective DateFeb 1, 2026

Next Review Date

SourceLink

On This Page

TF >= 10% => near-100% sensitivity

(Husain et al.; FoundationOne Liquid CDx validation)

Analytic performance: Validation data report a 95% limit of detection of ~0.40% VAF for select substitutions/indels and high reproducibility (e.g., 99.59%) with low false positive rates for FoundationOne Liquid CDx, indicating reliable detection of SNVs, indels, fusions, CNAs, MSI, and blood TMB in many settings.LOD ~0.40% VAF (select variants)

(Woodhouse et al.; FoundationOne Liquid CDx validation)

Guardant360 CDx evidence summary: Hayes assessed Guardant360 CDx and found low- to very-low-quality evidence overall but noted implied clinical utility for identifying FDA-approved targeted treatments, evaluating TMB/MSI, and use when tissue is insufficient; prospective randomized data indicate liquid testing can shorten time to treatment though survival benefits were not demonstrated in small trials.

(Hayes assessment; Yang et al.)

Covered when ALL of the following are met:

Indication and test type: Patient has advanced or metastatic solid tumor (e.g., NSCLC, colorectal cancer, prostate cancer, breast cancer, ovarian cancer) AND an FDA-cleared or approved liquid biopsy companion diagnostic (e.g., FoundationOne Liquid CDx, Guardant360 CDx) is used to identify actionable genomic alterations to guide targeted therapy selection.

Evidence shows detection of actionable variants and potential to shorten time to treatment; clinical outcome benefit variable.

Specimen considerations: Liquid CDx may be used when tissue is insufficient or not feasible, and sensitivity is dependent on tumor fraction (TF); if TF is low or liquid results are negative but clinical suspicion remains, reflex tissue testing should be considered.TF considerations (see validation data)

(Husain et al.; Yang et al.)

Ampullary adenocarcinoma — comprehensive NGS-based assay for actionable somatic findings

Covered when ALL of the following are met:

Ampullary adenocarcinoma CGP: The patient has locally advanced or metastatic ampullary adenocarcinoma and is a candidate for anticancer therapy AND testing is performed with an FDA-approved and/or validated NGS-based assay to identify potentially actionable somatic findings (e.g., fusions, mutations, amplifications, MSI, MMR deficiency, TMB).

Per NCCN recommendation for this tumor type.

Bone cancers — consideration of CGP with validated/FDA-approved assays

Covered when ALL of the following are met:

Bone cancers CGP consideration: Individuals with metastatic chondrosarcoma, recurrent chordoma, metastatic Ewing sarcoma, or metastatic/unresectable osteosarcoma who are candidates for systemic therapy AND testing is performed with a validated and/or FDA-approved comprehensive genomic profiling assay are eligible for consideration of testing to identify potential targeted therapy opportunities.

Per NCCN as an option for select metastatic/recurrent bone tumors.

Cervical cancer — TMB testing or CGP by plasma ctDNA as options

Covered when ALL of the following are met:

Cervical cancer molecular testing: For tumors that have progressed following prior treatment or when tissue biopsy of metastatic site is not feasible, consider TMB testing by an FDA-approved assay or comprehensive genomic profiling via a validated plasma ctDNA assay to guide second-line therapy selection.

Per NCCN recommendations as option when tissue unavailable or for progressed disease.

Cutaneous melanoma — BRAF mutation testing using an FDA-approved test

Covered when ALL of the following are met:

Cutaneous melanoma BRAF testing: BRAF mutation testing using an FDA-approved test is indicated to select individuals for treatment with dabrafenib plus trametinib when clinically appropriate.

Per NCCN recommendation for BRAF-directed therapy selection.

Neuroendocrine and adrenal tumors — MSI, MMR, and TMB testing as options

Covered when ALL of the following are met:

Neuroendocrine and adrenal tumors testing: Individuals with adrenocortical carcinoma may be considered for MSI, MMR, and TMB testing by an FDA-approved test as an option to identify potential targeted therapy opportunities.

Per NCCN recommendation.

NSCLC — individualized biomarker testing per NCCN

Covered when ALL of the following are met:

NSCLC individualized biomarker testing: Individualized biomarker testing for NSCLC per NCCN recommendations using clinically validated NGS platforms (tissue or plasma ctDNA) is indicated; plasma ctDNA may be used as complementary or initial approach in select settings (e.g., when tissue biopsy is not feasible or to accelerate genotyping).

NCCN provides biomarker-specific recommendations and does not endorse specific commercial assays; ASCO guidance supports routine testing for certain mutations in advanced breast cancer context referenced elsewhere.

Occult primary (CUP) — TMB determination by validated/FDA-approved assay

Covered when ALL of the following are met:

Occult primary (CUP) TMB testing: For cancer of unknown primary, determination of tumor mutational burden (TMB) by a validated and/or FDA-approved assay is an option (NCCN Category 2B) to help identify potential targeted therapy opportunities.

Per NCCN Category 2B recommendation.

Ovarian/fallopian tube/primary peritoneal cancer — FDA-approved CDx for PARP inhibitor selection

Covered when ALL of the following are met:

Ovarian/peritoneal CDx for PARP inhibitors: Individuals with ovarian, fallopian tube, or primary peritoneal cancer who are candidates for PARP inhibitor therapy may be tested with an FDA-approved companion diagnostic as recommended by NCCN for therapy selection.

Per NCCN recommendation for selection of niraparib, olaparib, or rucaparib.

Pancreatic adenocarcinoma — testing for actionable somatic mutations, fusions, MSI/MMR/TMB

Covered when ALL of the following are met:

Pancreatic adenocarcinoma testing: Patients with locally advanced or metastatic pancreatic adenocarcinoma who are candidates for anticancer therapy may undergo testing for actionable somatic mutations, fusions, MSI/MMR, and TMB via FDA-approved and/or validated NGS assays to guide therapy selection.

Per NCCN recommendation as an option.

Uterine neoplasms — comprehensive molecular profiling and testing for NTRK, MSI, RET-fusion, TMB

Covered when ALL of the following are met:

Uterine neoplasms molecular profiling: Comprehensive molecular profiling via a validated and/or FDA-approved assay is an option in initial evaluation and testing for NTRK, MSI, RET-fusion, and TMB in metastatic uterine neoplasms to identify rare pan-tumor targeted therapy opportunities or guide systemic therapy selection.

Per NCCN recommendations for uterine neoplasms.

Vaginal cancer — TMB testing and comprehensive molecular profiling as options

Covered when ALL of the following are met:

Vaginal cancer molecular testing: For vaginal cancer that has progressed following prior treatment or in disseminated disease, TMB testing by an FDA-approved assay and comprehensive molecular profiling including MSI, NTRK, and RET testing by FDA-approved assays are options to predict rare pan-tumor targeted therapy or guide systemic therapy selection.

Per NCCN recommendation.

Vulvar cancer — comprehensive molecular profiling including MMR/MSI, TMB, NTRK

Covered when ALL of the following are met:

Vulvar cancer molecular profiling: Consider comprehensive molecular profiling by an FDA-approved assay including at least MMR/MSI, TMB, and NTRK testing as an option for individuals with metastatic vulvar cancer to identify rare targeted therapy opportunities.

Per NCCN recommendation.

Comprehensive molecular profiling or specific biomarker testing by FDA-approved assays for certain gynecologic tumors

Covered when ALL of the following are met:

Gynecologic tumors molecular profiling: Comprehensive molecular profiling or specific biomarker testing (e.g., TMB, MSI/MMR, NTRK, RET) by FDA-approved assays is an option for certain gynecologic tumors (vaginal cancer, vulvar cancer) and for predicting rare pan-tumor targeted therapy or selecting systemic therapy in disseminated disease.

NCCN recommends these tests as options; policy covers FDA-cleared/approved CDx when InterQual criteria are met for CGP.

Lower TF sensitivity range

Samples with TF < 10% showed sensitivity ranging approximately 58%–86% depending on cancer type

Median TF reportedMedian TF in the consecutive series was 2.2% (23,482 specimens evaluated)

Analytic limits of detection (LOD) — examples

VAF LOD (select substitutions/indels)95% limit of detection at 0.40% variant allele fraction for select substitutions/indels (FoundationOne Liquid CDx validation)

VAF LOD (select rearrangements)95% limit of detection at 0.37% variant allele fraction for select rearrangements

TF LOD for copy number amplifications21.7% tumor fraction required for reliable detection of copy number amplifications in validation

TF LOD for copy number losses30.4% tumor fraction required for reliable detection of copy number losses in validation

N/A

PlaceholderNo applicable threshold or value; N/A

Policy history noteSee Policy History/Revision Information for recent changes to definitions and codes

Guideline referenceNCCN tumor‑specific recommendations cited elsewhere in policy (see covered indications)

PA may be required to confirm CDx status or validated NGS assay.
If PA is required, include test type, clinical indication, tumor type and stage, and prior systemic therapies.

Denial Risk

Denial risk for non-CDx or undersized panels

Use of tests that are not FDA-cleared/approved as companion diagnostics (CDx) or use of molecular panels that detect fewer than five genes may be denied as not medically necessary. Ordering such non-CDx or undersized panels increases the risk of claim denial.

Non-FDA-cleared/approved tests used as purported CDx — denial risk.
Panels detecting fewer than five genes — increased denial risk.

Note

Specimen insufficiency risk

If tissue is insufficient for testing, a liquid biopsy (ctDNA) or repeat tissue biopsy may be indicated. Inform ordering providers that insufficient specimen may prompt alternative testing strategies and could affect coverage determinations.

Specimen insufficiency may trigger liquid biopsy or repeat tissue biopsy.
Providers should document specimen adequacy and reasoning for alternative testing.

Note

Guideline-aligned indications recommended

Ordering of CDx testing should align with current clinical guidelines (for example, NCCN, ASCO, IASLC) and with the FDA-cleared/approved indication for the companion diagnostic or validated NGS assay. Tests ordered outside guideline-recommended indications may be considered unproven and not medically necessary.

Align testing with NCCN, ASCO, IASLC, or other guideline-recommended indications.
Use FDA-cleared/approved or clinically validated assays consistent with guideline recommendations.

Denial Risk

Non-covered/Unproven Uses

Requests for uses not supported by the policy (including uses lacking sufficient evidence or outside FDA-cleared/approved indications) are considered unproven and not medically necessary and may be denied.

Non-covered/unproven uses will be considered not medically necessary.
Concurrent testing beyond specified indications is not covered unless policy criteria are met.

Documentation Required

Medical records documentation

Medical records must fully support the medical necessity for the requested testing. Documentation should be legible, retained in the patient's chart, and available upon request. Records should include relevant history, physical exam findings, prior diagnostic results, tumor type and stage, prior systemic therapies and response, and rationale for choosing the specific CDx/NGS assay.

Include relevant medical history, physical exam, diagnostic test results, tumor type/stage, prior therapies and responses.
Maintain and make available supporting documentation upon request; documentation alone does not guarantee coverage.

Documentation Required

Analytic validation documentation

Analytic validation information for the assay (for example, limit of detection, false positive rate, reproducibility, positive and negative percent agreement) may be requested to support the analytic validity of the test when coverage is being considered.

Laboratories may be asked to provide analytic validation data: LOD, FPR, reproducibility, PPA/NPA.
Analytic validation supports determination that an assay is a clinically validated/appropriate CDx.

Documentation Required

Clinical rationale and assay identification required

When seeking coverage, clearly identify the specific FDA-cleared/approved or validated NGS assay being ordered, the tumor type and stage, the clinical rationale linking the test to a specific therapeutic decision (including the targeted therapeutic product for which the CDx was approved), and whether testing is initial, repeat, or concurrent tissue/liquid testing.

Specify the assay name and manufacturer (e.g., FoundationOne Liquid CDx, Guardant360 CDx, Tempus xT CDx).
State whether the test result will directly inform use of an FDA-approved therapy (name the therapeutic when applicable).

Note

Therapy access limits

Availability of a genomic alteration or test result does not automatically guarantee access to the corresponding therapy. Clinical eligibility for treatment and drug access (e.g., formulary status, prior authorization for the drug, enrollment in a labeled indication) remain subject to separate medical necessity and coverage determinations.

Sequencing or identification of an actionable variant does not assure drug coverage; separate drug PA or benefit limits may apply.
Clinical condition and eligibility criteria for the therapy must also be met.

Concurrent tissue and liquid CDx testing within 30 days is considered medically necessary for advanced/metastatic (stage IV) breast cancer and stage IV NSCLC when CDx criteria are met.

Operational noteConcurrent Testing definition referenced for clinician ordering and coverage determinations.

Liquid Biopsy — definition

DefinitionLiquid Biopsy = testing performed on a bodily fluid sample to identify tumor‑derived cells or circulating nucleic acids (cfDNA, RNA) released from tumor cells.

ModalitiesIncludes plasma ctDNA assays used to detect genomic alterations and complex biomarkers when tissue is unavailable or as complementary testing.

Clinical roleMay be used as initial or complementary approach per guideline recommendations and assay validation.

Tumor fraction (TF) — definition

DefinitionTumor fraction (TF) = the proportion of circulating tumor DNA (ctDNA) in plasma; higher TF correlates with higher sensitivity of liquid biopsy to detect driver alterations.

Performance relationshipTF >=10% associated with near‑100% sensitivity; lower TF values correspond to reduced sensitivity (reported 58%–86% in samples with lower TF).

Typical observed TFMedian TF reported in a large clinical series was 2.2% (FoundationOne Liquid CDx cohort).

Limit of detection (LOD) — definition and examples

DefinitionLimit of detection (LOD) = the lowest variant allele fraction (VAF) that an assay can reliably detect; example: 0.40% VAF for select substitutions/indels reported in FoundationOne Liquid CDx validation.

Additional example0.37% VAF reported for select rearrangements in FoundationOne Liquid CDx validation.

CNA examplesValidation reported TF thresholds for CNAs: 21.7% TF for amplifications and 30.4% TF for copy number losses.

Companion Diagnostic (CDx) — NGS‑based CDx

DefinitionCompanion Diagnostic (CDx) — an FDA‑cleared or approved NGS‑based in vitro diagnostic test intended to detect specific genomic alterations to guide selection of targeted therapies.

ExamplesDocument lists multiple FDA‑cleared/approved NGS‑based CDx assays (e.g., oncoReveal CDx, TruSight Oncology Comprehensive, xT CDx) as examples of CDx devices.

Intended useNGS‑based CDx devices detect substitutions, indels, copy number changes, rearrangements, MSI, and may report TMB depending on the assay.

Dual‑modality genomic testing

DefinitionDual‑modality genomic testing = concurrent tissue‑based NGS and plasma ctDNA NGS testing to optimize detection of actionable mutations in advanced solid tumors.

Clinical rationaleConcurrent tissue and ctDNA profiling can identify actionable variants not found by tissue alone and may improve overall detection rates (Tempus xT CDx observational data).

Policy applicationDual‑modality or concurrent testing is supported conceptually and may be considered in advanced disease per guidelines; coverage specifics depend on CDx criteria and policy rules.

Concurrent Testing — short label

Short definitionConcurrent Testing = tissue and liquid ordered for same indication within 30 days.

Policy noteConcurrent Testing definition duplicated in definitions and policy history for clarity of coverage window.

Companion Diagnostic (CDx) — FDA list referenced; approval not sole basis for coverage

Definition and sourceCompanion Diagnostic (CDx) — FDA‑cleared or approved Companion Diagnostic tests are listed on the FDA 'List of Cleared or Approved Companion Diagnostic Devices'; FDA approval alone is not a basis for coverage (informational reference).

Coverage implicationPolicy requires CDx tests to be FDA cleared/approved as companion diagnostics for coverage consideration; providers should reference FDA listings to confirm CDx status.

Laboratory regulation noteLaboratories that perform genetic tests are regulated under CLIA; FDA CDx list is referenced for device status verification.

documentation_clarification

Added and updated language about medical records documentation required to support medical necessity determinations.

Patient medical records must fully support the medical necessity of requested testing. Documentation should be legible and include relevant medical history, physical examination findings, and results of prior diagnostic tests or procedures. Records may be requested during prior authorization or claim review and absence of adequate documentation may affect coverage determinations.