RetiredUnitedHealthcarePolicy CS373LA.D

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

Coverage and criteria for FDA-cleared or approved companion diagnostic (CDx) testing for oncology for Louisiana Medicaid managed care; applies to providers ordering CDx and related molecular testing in Louisiana.

Policy Summary

PayerUnitedHealthcare

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

Policy CodePolicy CS373LA.D

Change TypeRevisions and retirement

Effective Date2025-06-01 to 2026-03-31

Next Review DateN/A

Key ActionOrder companion diagnostic tests that align with the FDA List of Cleared or Approved Companion Diagnostic Devices and document genetic counseling and test-label consistency in the medical record.

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 specific alignment and label-consistency criteria are met.

Repeat Companion Diagnostic Testing on a new tissue or liquid biopsy specimen for therapy selection 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 when criteria are met.

Policy retired effective 04/01/2026 with Louisiana plan membership disenrolled on that date.

Updated definition of 'Comprehensive Genomic Profiling (CGP)' and updated supporting sections (Description of Services, Clinical Evidence, References).

Added notation that CPT code 0473U is not on the State of Louisiana Medicaid Fee schedule.

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Coverage Criteria and Indications

inv-01: Coverage for FDA-cleared/approved Companion Diagnostic Tests

Companion Diagnostic Tests are considered proven and medically necessary when ALL of the following are met:

CDx general coverage: The oncology indication has a corresponding diagnostic test and biomarker on the U.S. FDA List of Cleared or Approved Companion Diagnostic Devices; the Companion Diagnostic Test aligns with the drug, FDA‑approved indication, and appropriate tissue/specimen on the FDA List; and use of the Companion Diagnostic Test is consistent with the label for the companion diagnostic‑associated drug as indicated by the requesting provider.

inv-03: Concurrent Tissue and Liquid Biopsy Testing

Concurrent testing covered when ALL general CDx criteria are met AND the orders are within 30 days for specified cancers:

Concurrent tissue and liquid biopsy testing: Concurrent tissue-based and Liquid Biopsy Companion Diagnostic Testing ordered within 30 days of each other is medically necessary for advanced or metastatic (stage IV) breast cancer and advanced or metastatic (stage IV) non-small cell lung cancer when the general CDx criteria are met.within 30 days

inv-04: Coverage-relevant clinical criteria and evidence summaries

Coverage-relevant findings and applicable contexts from the evidence:

TMB-guided pembrolizumab eligibility: Patient has unresectable or metastatic solid tumor AND has progressed following prior treatment with no satisfactory alternative options AND TMB determined by an FDA‑approved test (e.g., FoundationOne CDx) with TMB ≥10 mut/Mb.TMB ≥ 10 mut/Mb

Use of CGP panels for targeted therapy selection: Broad molecular profiling (e.g., FoundationOne CDx 324‑gene panel) can identify actionable variants in a subset of patients; however, randomized evidence that broad CGP‑directed therapy improves outcomes is limited.

Liquid biopsy utility and limitations: ctDNA/cfDNA testing can shorten time to molecular diagnosis and detect alterations not found in tissue; sensitivity depends on ctDNA tumor fraction and panel design (low tumor fraction reduces detection), so negative liquid biopsy results in advanced NSCLC should be confirmed with tissue when feasible.

inv-05: Coverage-context nodes (evidence summaries)

Evidence and intended uses summarized (no explicit stepwise coverage criteria present in these excerpts).

FDA-approved CDx indications: FoundationOne Liquid CDx and Guardant360 CDx have FDA companion diagnostic approvals for specified tumor‑therapy pairs; these approvals support use of those tests as CDx where indicated by the FDA labeling.

Clinical situations with supporting but limited evidence: ctDNA/CGP may identify actionable alterations and guide therapy selection in advanced/metastatic solid tumors, particularly when tissue biopsy is infeasible or insufficient; studies suggest detection of actionable targets but quality of evidence and impact on long‑term outcomes vary.

Insufficient evidence contexts: Use of liquid biopsy for early‑stage cancer screening, routine MRD surveillance to guide interventions, or other screening applications currently lacks sufficient evidence of clinical utility and is not supported for those indications.

inv-06: Guideline-aligned coverage for tumor NGS and cfDNA

Covered when ALL of the following are met (guideline-aligned indications extracted from cited guidance and evidence):

advanced_or_metastatic_tumor: Individual has advanced or metastatic solid tumor and adequate performance status.

actionable_biomarker_possible: Genomic biomarker‑associated therapies exist or testing may identify biomarker‑linked treatment options.

specimen_choice: Tissue‑based NGS is preferred; cfDNA testing is acceptable when tissue is unavailable, biopsy is infeasible, or when rapid genotyping is clinically necessary.

inv-07: Evidence-supported cfDNA use-cases

Covered when ANY of the following evidence-supported use-cases apply (Guardant360 specific evidence):

newly_diagnosed_advanced_nsclc_with_need_for_rapid_genotyping: Perform plasma ctDNA NGS at initial visit to shorten time to treatment initiation when rapid genotyping is clinically required.

post_first_line_or_prior_to_second_line: Use cfDNA NGS prior to second‑line therapy to identify actionable or emerging resistance mutations that may guide matched therapy.

when_tissue_unavailable: Use cfDNA when tumor tissue is unavailable or biopsy is not feasible; cfDNA may identify actionable mutations that obviate invasive biopsy.

inv-08: Biliary tract cancers

Covered when ALL of the following are met (biliary tract cancers):

Biliary tract CGP coverage: Individual has unresectable or metastatic biliary tract cancer and is a candidate for systemic therapy; tumor/somatic molecular profiling via an FDA‑approved or validated NGS‑based assay is performed (tissue preferred; cfDNA acceptable if tissue not feasible).

inv-09: Bladder cancer

Covered when ALL of the following are met (bladder cancer):

Bladder cancer molecular testing: Individual has stage IVA or IVB bladder cancer (consider stage IIIB) and molecular/genomic testing in a CLIA‑approved laboratory is performed to assess actionable markers (e.g., FGFR3, HER2) to inform treatment decisions.

inv-10: Colorectal cancer

Covered when ALL of the following are met (colorectal cancer):

CRC universal testing: Universal MMR/MSI testing is performed for all newly diagnosed colon or rectal cancers; for metastatic CRC, broader molecular profiling (preferably NGS) assesses KRAS/NRAS, BRAF, HER2, and MMR/MSI to guide therapy selection.

inv-11: Non-small cell lung cancer (NSCLC)

Covered when ALL of the following are met (NSCLC and general principles):

NSCLC molecular testing: Perform broad panel‑based molecular testing (NGS) when possible and include guideline‑listed biomarkers; tissue testing is preferred, with ctDNA used adjunctively or when tissue is unavailable; consider repeat/broad profiling at progression to evaluate resistance mechanisms.

inv-12: Ovarian/fallopian tube/primary peritoneal cancer

Covered when ALL of the following are met (ovarian and related cancers):

Ovarian/fallopian/primary peritoneal molecular testing: Tumor molecular analysis in a CLIA‑approved facility is performed both upfront and at recurrence to detect BRCA1/2, HRD/LOH, MSI/MMR, TMB and other actionable markers; testing on the most recent tumor tissue is preferred; ctDNA acceptable if tissue not feasible.

inv-13: Pancreatic adenocarcinoma

Covered when ALL of the following are met (pancreatic adenocarcinoma):

Pancreatic adenocarcinoma molecular testing: Individual has locally advanced or metastatic pancreatic adenocarcinoma and is a candidate for systemic therapy; tumor/somatic molecular profiling using FDA‑approved or validated NGS‑based assays (RNA‑seq preferred for fusion detection) is performed (tissue preferred; cfDNA acceptable if tissue not feasible).

inv-14: Ovarian cancer molecular testing

Ovarian/Fallopian Tube/Primary Peritoneal Cancer - tumor molecular analysis recommended

Ovarian initial setting: Perform tumor molecular analysis in a CLIA‑approved facility in the upfront setting to detect variations (including BRCA1/2, LOH, HRD) that impact therapy decisions; use most recent tumor tissue when possible; ctDNA acceptable if tissue not feasible.

inv-15: Ovarian recurrent disease testing

Ovarian recurrent disease

Ovarian recurrent: At recurrence, perform tumor molecular evaluation via validated tests to identify potential benefit of targeted agents; include BRCA1/2, HER2, HRD, MSI/MMR, TMB, BRAF, FOLR1, RET, NTRK if not previously tested; prefer most recent tumor tissue; ctDNA acceptable if tissue not clinically feasible.

inv-16: Pancreatic cancer molecular profiling

Pancreatic adenocarcinoma

Locally advanced/metastatic pancreatic adenocarcinoma: NCCN recommends tumor/somatic molecular profiling for candidates for anti‑cancer therapy to identify uncommon actionable alterations (fusions, mutations, amplifications, MSI/dMMR, TMB) using FDA‑approved or validated NGS assays; RNA‑seq preferred for fusions; tissue preferred but cfDNA may be considered if tissue not feasible.

inv-17: Prostate cancer testing

Prostate cancer

Prostate molecular evaluation: Tumor molecular and biomarker evaluation can inform treatment, genetic counseling, platinum chemotherapy use, and trial eligibility; metastatic biopsy strongly recommended; when biopsy unsafe or not feasible, plasma ctDNA is an option with preference for collection at biochemical/radiographic progression to maximize yield and with caution for CHIP interference.

inv-18: Small cell lung cancer testing

Small cell lung cancer

Selected SCLC cases: Comprehensive molecular profiling using blood, tissue, or both may be considered in select SCLC cases (extensive‑stage/relapsed, non‑smokers or light/remote smokers, diagnostic/therapeutic dilemmas) and at relapse if not previously done.

inv-19: Thyroid cancer molecular testing

Thyroid carcinoma

Anaplastic thyroid carcinoma: Molecular testing for actionable mutations (BRAF, NTRK, ALK, RET, MSI/dMMR, TMB) is recommended; BRAF IHC may be used for faster turnaround to guide systemic therapy and trial eligibility.

inv-20: Uterine neoplasms testing

Uterine neoplasms

Endometrial carcinoma molecular evaluation: Comprehensive molecular evaluation to classify molecular subgroups is strongly encouraged in initial evaluation of endometrial carcinoma; for metastatic uterine sarcoma include at minimum NTRK, MSI, and TMB to identify trial or targeted therapy options.

inv-21: Vaginal cancer testing

Vaginal cancer

Recurrent or persistent vaginal cancer: NGS and comprehensive molecular profiling are recommended for recurrent or persistent vaginal cancer to assist systemic therapy selection; tissue preferred, ctDNA acceptable if tissue unavailable or biopsy not possible.

inv-22: Covered Companion Diagnostic Testing

Companion Diagnostic Tests are considered proven and medically necessary when ALL of the following are met:

Primary criteria: The oncology indication has a corresponding diagnostic test and biomarker on the U.S. FDA List of Cleared or Approved Companion Diagnostic Devices; the Companion Diagnostic Test aligns with the drug, FDA‑approved indication, and appropriate tissue/specimen on the FDA List; and use of the test is consistent with the label for the companion diagnostic‑associated drug as indicated by the requesting provider.

Repeat testing: Repeat companion diagnostic testing on a new tissue or Liquid Biopsy specimen for therapy selection is medically necessary up to three times annually when primary criteria are met and one of: disease recurrence OR cancer progression OR lack of response to the most recent systemic therapy.up to 3 per year

Concurrent testing: Concurrent tissue‑based and Liquid Biopsy companion diagnostic testing (ordered within 30 days of each other) is medically necessary for advanced or metastatic (stage IV) breast cancer and advanced or metastatic (stage IV) non‑small cell lung cancer when primary criteria are met.

When a test–drug pairing is not found on the U.S. FDA List of Cleared or Approved Companion Diagnostic Devices, coverage under this companion diagnostic policy does not automatically apply. In those situations, providers should refer to the state-specific UnitedHealthcare Molecular Oncology Testing policies for guidance: "Molecular Oncology Testing for Solid Tumor Cancer Diagnosis, Prognosis, and Treatment Decisions (for Louisiana Only)" or "Molecular Oncology Testing for Hematologic Cancer Diagnosis, Prognosis, and Treatment Decisions (for Louisiana Only)." These alternative policies provide the applicable coverage criteria and evaluation framework for molecular tests that do not match an FDA-listed CDx for the requested drug/tissue/specimen.

Certain commercially available broad molecular profiling products (for example, CANCERPLEX, Guardant360 TissueNext, and MI Profile/MI Tumor Seek) have been evaluated in published evidence reviews and have insufficient evidence to support use as substitutes for an FDA-cleared/approved companion diagnostic when the intent is to direct therapy outside of a clinical trial. Hayes assessments and clinical studies cited in the policy indicate limited or no peer-reviewed evidence of clinical utility for these platforms as broad profiling tools to guide treatment selection, and therefore they are not considered acceptable CDx substitutes under this policy.

Liquid biopsy assays intended for population screening of early-stage colorectal cancer or detection of high-risk adenomas currently lack sufficient evidence of clinical utility. Systematic reviews and health-technology assessments cited in the policy conclude that available data do not support using plasma-based ctDNA or other liquid biopsy tests for routine CRC screening or high-risk adenoma detection.

The policy does not support routine use of circulating tumor DNA (ctDNA) testing for early-stage cancer management, minimal residual disease (MRD) surveillance, or general population screening because the majority of ctDNA assays lack demonstrated clinical validity and utility for these indications. The guidance emphasizes that ctDNA is not typically recommended in stage I–III disease and should not replace tissue testing when tumor tissue is available.

Routine comprehensive genetic profiling for hepatocellular carcinoma (HCC) is not established; molecular testing in HCC should be considered on a case-by-case basis, with priority for advanced or mixed hepatocellular-cholangiocarcinoma where actionable alterations may influence therapy or clinical trial eligibility.

FDA regulatory actions and the FDA List of Cleared or Approved Companion Diagnostic Devices are provided for informational purposes only. FDA approval alone is not sufficient to establish coverage under this policy; coverage decisions require that the test align with the drug, FDA-approved indication, and appropriate tissue/specimen and that use be consistent with the associated drug label.

When there is no match between the requested cancer/test pairing and the FDA List of Cleared or Approved Companion Diagnostic Devices, the policy directs reviewers to evaluate testing requests under the applicable UnitedHealthcare Molecular Oncology Testing policies for solid tumors or hematologic cancers (Louisiana-specific policies). These policies outline criteria for clinical utility, analytic validation, and context-specific indications when an FDA-listed CDx is not available.

Use of broad molecular profiling alone to guide clinical decision-making outside of a clinical trial has limited supporting evidence. Prospective and retrospective studies summarized in the policy show relatively low proportions of patients who received matched therapy and few objective responses when broad CGP was used solely to direct treatment, and therefore broad profiling without trial context is not supported as sufficient clinical evidence to justify coverage in those situations.

Screening applications of liquid biopsy or ctDNA—specifically for early-stage colorectal cancer and detection of high-risk adenomas—are not supported by sufficient evidence and are considered outside the scope of medically necessary use. The policy cites systematic reviews and health-technology assessments concluding that current data do not demonstrate clinical utility for screening purposes.

ctDNA assays for cancer screening and routine MRD or molecular relapse detection lack robust evidence of clinical utility in routine practice. The policy references guideline reviews and evidence summaries indicating insufficient validation and uncertain impact on patient outcomes for these uses.

ctDNA testing is generally not recommended in stage I–III disease and should not be used as a substitute for histologic tissue diagnosis when tissue is available. When tissue is unobtainable or biopsy is unsafe, validated plasma ctDNA assays may be considered, but documentation should explain the rationale and timing relative to disease progression to maximize diagnostic yield.

Companion diagnostic claims must align with an FDA-listed CDx for the specific drug, indication, tissue, and specimen and be used consistent with the drug label. Companion diagnostic testing that is not aligned with an FDA-cleared/approved companion diagnostic pairing or that is inconsistent with the companion diagnostic-associated drug label is not supported as proven and medically necessary under this policy.

Covered Indications and Uses

Provider Actions, Documentation, and Authorization

Billing Rule

Applicable procedure codes referenced

The following procedure and diagnosis codes are provided for reference and billing coordination only; inclusion does not guarantee coverage or reimbursement. Providers must bill using the appropriate CPT/HCPCS/NDC/other codes that reflect the service performed and follow plan-specific billing rules.

See Applicable Codes lists (codes include, but are not limited to: 0022U, 0037U, 0179U, 0239U, 0242U, 0473U, 0543U, 81445, 81449, 81450, 81451, 81455, 81456, 81479, 81599). Codes marked with an asterisk (*) may not be on the State of Louisiana Medicaid Fee Schedule and may not be covered by that program.

Prior Authorization

Prior authorization for TMB-directed therapy

Prior authorization (PA) is required when seeking coverage for pembrolizumab based on a tumor mutational burden (TMB)-high designation. The documented TMB result must be from an FDA-approved companion diagnostic (e.g., FoundationOne® CDx) using the FDA-specified cut-point (≥10 mut/Mb) and the clinical record must document prior progression or intolerance to standard therapies as required by the KEYNOTE-158 evidence base and FDA labeling.

Applicable Codes and Coding Details

Referenced PLA codes (selection)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.
0179U	Oncology (non-small cell lung cancer), cell-free DNA, targeted sequence analysis of 23 genes (single nucleotide variations, insertions and deletions, fusions without prior knowledge of partner/breakpoint, copy number variations), with report of significant mutation(s).
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.

Referenced CPT/PLA and molecular pathology codesmixed

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.
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.
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.
81450	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; DNA analysis or combined DNA and 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 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.
81479	Unlisted molecular pathology procedure.

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Applicable Codes / NotationCPT

0473U

CPT code noted as not on the State of Louisiana Medicaid Fee schedule

Tumor Mutational Burden (TMB) — FDA cut-point for pembrolizumab (≥ 10 mut/Mb)

TMB cut-point (FDA pembrolizumab CDx)≥ 10 mut/Mb

Assay requirementTMB must be determined by an FDA-approved test (e.g., FoundationOne CDx) when used to support pembrolizumab eligibility

Clinical context for approvalUnresectable or metastatic solid tumors after progression on prior therapy with no satisfactory alternatives (KEYNOTE-158)

TMB-high — reiterated threshold (≥ 10 mut/Mb)

TMB-high definitionTMB-high = ≥ 10 mut/Mb

Referenced CDx

Not Covered / Exclusions

Companion diagnostic testing that does not match an FDA-cleared or approved companion diagnostic pairing for the specified oncology drug, indication, and tissue/specimen is not supported for coverage under this policy. Requests for such testing should be considered under the other UnitedHealthcare molecular oncology policies referenced by the policy.

Specific commercial broad profiling tests—examples cited include CANCERPLEX, Guardant360 TissueNext, and MI Profile / MI Tumor Seek—do not have sufficient peer-reviewed evidence of clinical utility to support their use as substitutes for FDA-cleared/approved companion diagnostics for directing therapy, and are therefore listed as not covered for that intended use.

Liquid biopsy testing for population screening of early-stage colorectal cancer and detection of high-risk adenomas is considered not covered due to insufficient evidence of clinical utility as summarized in systematic reviews and technical assessments.

ctDNA testing for screening, routine MRD or molecular relapse surveillance, and for management of early-stage cancer is not covered because current evidence does not demonstrate clinical utility for these routine uses.

Routine genomic profiling for hepatocellular carcinoma is not established and therefore is generally not covered; molecular testing may be considered on a case-by-case basis for advanced mixed hepatocellular-cholangiocarcinoma or when clinical trial eligibility is the purpose.

FDA approvals and the FDA companion diagnostic list are provided for information only. FDA approval alone is not sufficient to determine coverage under this policy; coverage requires that the test align with the FDA-listed companion diagnostic pairing and use be consistent with the associated drug label.

Eligibility Requirements and Documentation

Structured family genetic history and both pre- and post-test genetic counseling are required and must be documented in the medical record for genetic testing. Documentation should include a structured family history, genetic risk assessment, counseling about diagnosis, prognosis, and treatment implications, and evidence that genetic counseling was provided as part of the testing process.

Definitions

Advanced Cancer — definition

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

Typical useContext used to define populations for companion diagnostic and comprehensive genomic profiling recommendations

ReferenceNational Cancer Institute (NCI) definition cited in policy definitions section.

Companion Diagnostic Test — definition

DefinitionCompanion Diagnostic Test: A test that provides important information for the safe and effective use of a corresponding therapeutic drug (FDA).

Coverage implicationCDx must align with the drug, FDA-approved indication, and appropriate tissue/specimen on the FDA List of Cleared or Approved Companion Diagnostic Devices to be considered medically necessary.

Background and Clinical Context

Companion diagnostic (CDx) tests identify biomarkers necessary for the safe and effective use of corresponding therapeutic drugs and guide oncology treatment selection. This policy uses the FDA List of Cleared or Approved Companion Diagnostic Devices to define CDx alignment and describes conditions for repeat and concurrent tissue and liquid biopsy CDx testing in advanced disease contexts.

Revision History and Policy Changes

2026-04-01retirementLatest

Policy retired and Louisiana plan membership disenrolled on Apr. 1, 2026.

2025-06-01material_revision

Revised coverage guidelines to require alignment with the FDA List of Cleared or Approved Companion Diagnostic Devices, added repeat testing allowance (up to three times annually) with clinical triggers, and allowed concurrent tissue and liquid biopsy CDx testing (within 30 days) for advanced/metastatic breast cancer and NSCLC.

2025-06-01

Policy Summary

PayerUnitedHealthcare

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

Policy CodePolicy CS373LA.D

Change TypeRevisions and retirement

Effective Date2025-06-01 to 2026-03-31

Next Review DateN/A

SourceLink

On This Page

Prior Authorization

Prior authorization guidance

Prior authorization decisions for molecular testing and companion diagnostics will follow FDA-approved companion diagnostic (CDx) indications and plan-specific PA processes. Tests not aligned with FDA CDx indications or used outside their labeled tissue/specimen may be denied. Providers should submit documentation of assay validation, specimen type, and clinical rationale for testing.

When requesting PA, include the FDA CDx name, specific label/indication, specimen type (tissue vs plasma), and why the selected test is appropriate for the clinical scenario.
Tests that are not listed on the FDA companion diagnostic list or that conflict with drug labeling may be subject to denial.

Prior Authorization

Clinical scenario-based prior authorization

PA expectations vary by clinical scenario. For individuals with advanced or metastatic disease, broad tumor NGS is generally recommended and may be required for PA when guideline-linked targeted therapies are being considered. If tissue is unavailable or biopsy is unsafe, document why tissue is not feasible to support consideration of ctDNA testing.

For metastatic/unresectable disease: include clinical stage, prior treatments, and whether testing is intended to guide biomarker-directed therapy.
If ctDNA is requested due to lack of tissue, provide documentation that tumor biopsy is unsafe/unfeasible and the timing of plasma collection relative to disease progression.

Prior Authorization

Prior authorization—prefer broad NGS panels

When possible, PA requests should favor broad, panel-based NGS (comprehensive genomic profiling) per guideline recommendations. Broad panels increase the likelihood of identifying actionable biomarkers and conserve limited tissue resources.

Document why a broad panel (e.g., >50 genes or CGP) is clinically indicated rather than single-gene tests.
If a limited panel is used due to tissue constraints, document the tissue limitations and the plan for future testing if clinically warranted.

Documentation Required

Medical necessity requirements for companion diagnostics

Companion diagnostic tests are considered medically necessary only when they align with an oncology drug's FDA-cleared/approved CDx indication and are used consistent with the CDx and drug labels. Repeat CDx testing on new tissue or liquid biopsy is medically necessary up to three times annually when criteria are met and disease recurrence or progression is present.

Ensure the CDx aligns with the FDA List of Cleared or Approved Companion Diagnostic Devices and with the specific drug's labeled indication and specimen type.
Concurrent tissue and liquid biopsy CDx testing ordered within 30 days is considered medically necessary for advanced/metastatic (stage IV) breast cancer and NSCLC when CDx alignment criteria are met.

Documentation Required

Analytical validation and specimen documentation

Tests must be performed in an appropriately certified laboratory and documentation submitted with PA should include analytic validation data, specimen collection details, and assay limitations. Inadequate documentation of validation or specimen handling can lead to denial.

Include laboratory certification (e.g., CLIA) and analytical validation summary (limit of detection, precision, concordance studies) with PA submissions.
Document specimen type, collection method (e.g., Streck vs EDTA tubes for plasma), timing of collection, and any pre-analytic conditions that could affect results.

Documentation Required

Required test alignment and documentation

PA submissions must document that the requested test aligns with FDA companion diagnostic listings and is consistent with the companion drug labeling. Lack of this alignment or failure to provide required documentation may result in denial.

Provide the FDA CDx name, FDA indication, and evidence that the assay is being used in a manner consistent with its FDA-approved labeling.
If no FDA CDx match exists for the drug/indication, reference the alternative UnitedHealthcare molecular oncology policies identified in the policy text.

Prior Authorization

Prior treatment requirement for pembrolizumab

The KEYNOTE-158 evidence and FDA labeling require that individuals be previously treated and have either progressed on or been intolerant to standard therapies to be eligible for pembrolizumab under a TMB-high indication. PA requests must include prior treatment history and rationale.

Document prior systemic therapies, dates, and evidence of progression or intolerance.
Include ECOG status and measurable disease documentation when available to support eligibility.

Liquid Biopsy — definition

DefinitionLiquid Biopsy: Minimally invasive testing of bodily fluids (commonly blood) to detect circulating tumor DNA/RNA, circulating tumor cells, proteins, methylation, or other tumor-derived biomarkers for detection, treatment selection, or monitoring.

Clinical roleUsed to shorten time to molecular diagnosis, as an alternative when tissue is unavailable, and for some guideline-supported indications in advanced disease.

LimitationscfDNA/ctDNA assays have variable performance for copy-number and fusion detection and overall clinical validity/utility is limited for many early-stage and monitoring uses.