RetiredUnitedHealthcarePolicy CS373LA.D

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

State-specific UnitedHealthcare Community Plan medical policy for Louisiana governing coverage criteria for FDA-cleared or approved companion diagnostic (CDx) tests, genetic counseling requirements, limits on repeat testing and concurrent tissue/liquid testing for specific cancers, and lists applicable procedure codes. Effective for June 1, 2025 - March 31, 2026 with retirement date April 1, 2026.

Policy Summary

PayerUnitedHealthcare

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

Policy CodePolicy CS373LA.D

Change TypeRetired; coverage criteria revised/added

Effective DateJun 1, 2025

Next Review Date

Key ActionGenetic counseling must be performed before and after all genetic testing and documented in the medical record, and providers must order a CDx that aligns with the drug, FDA-approved indication, appropriate tissue/specimen per the FDA list and consistent with the drug label.

POLICY UPDATE CHANGES

Policy applies only to the state of Louisiana and reflects Louisiana Medicaid coverage requirements, including genetic counseling and state-specific coverage criteria.

Document header indicates policy retired April 1, 2026 and effective June 1, 2025 - March 31, 2026.

Revised coverage guidelines to indicate 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 specified alignment and labeling 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/nonresponse 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.

Retired policy; Louisiana plan membership disenrolled on Apr. 1, 2026.

Supporting information, description of services, clinical evidence, and references updated; notation that some procedure codes (e.g., 0473U and others marked with *) are not on the Louisiana Medicaid Fee Schedule.

2Cancers with specified concurrent testing allowance

Up to 3Allowed repeat CDx tests per year

ManyApplicable procedure codes listed (some excluded from LA fee schedule)

94%Detectable ctDNA in FoundationOne Liquid CDx cohort

64%Percent with ≥1 actionable target (Bayle/F1LCDx)

2026-04-01Retirement Effective Date (LA)

Coverage Summary and Scope

This Louisiana-specific UnitedHealthcare Community Plan policy (Policy CS373LA.D) addresses coverage for FDA-cleared or -approved Companion Diagnostic (CDx) testing; it was effective 2025-06-01 through 2026-03-31 and was retired effective 2026-04-01. The policy leverages the FDA List of Cleared or Approved Companion Diagnostic Devices and incorporates Louisiana Medicaid Managed Care Organization requirements (including genetic counseling) and state-specific coverage criteria for CDx tests, repeat testing limits, and allowances for concurrent tissue and liquid biopsy testing in selected cancer types.

Coverage / Medical Necessity Criteria

General Companion Diagnostic Test Coverage (Medically Necessary)

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

ALL of the following

The oncology indication has a corresponding diagnostic test and biomarker on the U.S. Food and Drug Administration (FDA) List of Cleared or Approved Companion Diagnostic Devices.
The Companion Diagnostic Test must align with the drug, FDA-approved indication, and appropriate tissue/specimen in the FDA List of Cleared or Approved Companion Diagnostic Devices.
The use of the Companion Diagnostic Test must be consistent with the label for the Companion Diagnostic-associated drug indicated by requesting provider.

Repeat Testing Criteria

Repeat Companion Diagnostic Testing (for therapy selection)

Repeat testing on a new tissue or Liquid Biopsy specimen is considered proven and medically necessary when general criteria above are met and any ONE of the following:

ANY of the following

One of: The individual is experiencing disease recurrence.
The individual's cancer has progressed or did not respond to the most recent systemic therapy.

Usage limit: Repeat Companion Diagnostic Testing is limited to up to three times annually.Up to three times annually

Concurrent Tissue and Liquid Biopsy Testing Criteria

Concurrent Tissue-based and Liquid Biopsy Companion Diagnostic Testing

Concurrent tissue-based and Liquid Biopsy CDx testing (ordered within 30 days of each other) is considered proven and medically necessary for the following when general criteria above are met:

ANY of the following

Advanced or metastatic (stage IV) breast cancer.
Advanced or metastatic (stage IV) non-small cell lung cancer.

Genetic Counseling Requirement (Louisiana MCO)

Genetic Counseling Requirement (State-specific LA MCO)

Required documented elements for genetic counseling (LA MCO):

Document genetic counseling including a structured family history, risk assessment, and counseling about diagnosis, prognosis, and treatment.

Documentation Required

Document genetic counseling

Document genetic counseling in the medical record. At minimum, include: the structured family genetic history, the genetic risk assessment, and counseling provided to the enrollee and family about diagnosis, prognosis, and treatment. When ordering and interpreting molecular testing, providers should: use CLIA‑approved/validated tests; prefer tissue-based testing when feasible; consider liquid biopsy (ctDNA) as complementary to tissue testing and for evaluation of acquired resistance or when tissue is unavailable; interpret negative ctDNA results cautiously and confirm negative liquid biopsy with tissue testing if absence of an actionable result would change management; consider repeat testing at disease progression or at emergence of resistance; align use of companion diagnostics with the FDA List of Cleared or Approved Companion Diagnostic Devices and the drug label; and if no FDA-listed companion diagnostic matches the intended therapy, refer to the Molecular Oncology Testing policies (solid tumor or hematologic cancer) for further guidance.

Clinical Guidance, Society Recommendations, and Definitions

General recommendations for genomic testing in advanced/metastatic cancers

Recommendations from multiple oncology societies for when to perform genomic/ctDNA testing:

ALL of the following

Individuals with advanced or metastatic cancer and adequate performance status should be tested with genomic sequencing when genomic biomarker-associated therapies exist which have been approved for the individual's cancer.
Multigene panel tests (NGS) should be performed when the individual has metastatic or advanced solid tumor and is eligible for genomic biomarker-linked, approved therapy.
Testing used to inform clinical care must be done in an appropriately certified/CLIA laboratory.
Consider repeat testing when

Coverage Pathway When No FDA Companion Diagnostic Match Exists

When No FDA Companion Diagnostic Match Exists

If no cancer/diagnostic test match is found on the FDA List of Cleared or Approved Companion Diagnostic Devices, refer to applicable molecular oncology medical policies:

ANY of the following

Molecular Oncology Testing for Solid Tumor Cancer Diagnosis, Prognosis, and Treatment Decisions (for Louisiana Only)
Molecular Oncology Testing for Hematologic Cancer Diagnosis, Prognosis, and Treatment Decisions (for Louisiana Only)

Applicable Procedure Codes and Notations

Applicable Procedure Codes (reference list)mixed

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.
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, 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 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.

1–10 of 15

1/2

Notation / Applicable Codes MentionedCPT

0473U

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

Provider Actions and Operational Guidance

Prior Authorization

Ensure CDx test matches FDA labeling

Provider must order a Companion Diagnostic (CDx) test that aligns with the drug and the FDA-approved indication, and that uses the appropriate tissue/specimen listed on the FDA List of Cleared or Approved Companion Diagnostic Devices. Use of the test must also be consistent with the CDx-associated drug label.

Billing Rule

Check state fee schedule coverage

Verify coverage and reimbursement under the State of Louisiana Medicaid Fee Schedule before billing: several listed procedure codes are noted as not on the Louisiana Medicaid fee schedule and may not be covered.

0022U
0037U
0179U

Evidence Summary and Key Studies

Evidence summary (high-level introduction): The policy cites clinical trials, validation studies, systematic reviews, and assessment reports that evaluate analytic performance, diagnostic concordance, and clinical impact of tissue- and plasma-based genomic testing and specific CDx assays; selected key evidence items and one-line findings are listed below.

KEYNOTE-158 — Pembrolizumab approval for TMB-high (≥10 mut/Mb) tumors based on response-rate evidence supporting a CDx indication for TMB-high status.

TRITON2 — Rucaparib showed efficacy in mCRPC with BRCA alterations, supporting genomic testing to identify PARP inhibitor benefit.

Maity et al. (2023) — Simultaneous tissue plus liquid genotyping shortened time to diagnosis (mean 20.6 vs 33.5 days), liquid detected alterations when tissue insufficient, and 39% of paired cases had informative alterations found by only one test.

Palmieri et al. (2022) meta-analysis — Pooled cfDNA sensitivity for KRAS versus tissue was 0.71 (95% CI 0.68–0.74) and specificity 0.93 (95% CI 0.92–0.94).

Hayes assessments — Reports indicate generally low to very low quality evidence for broad circulating CMP clinical utility, with guideline support for metastatic/advanced disease when tissue is not feasible.

Husain et al. (2022, F1LCDx) — In >23,000 liquid biopsies, ctDNA was detectable in 94% with median tumor fraction 2.2%; sensitivity approached ~100% at tumor fraction ≥10% and was substantially lower at lower TF.

Woodhouse et al. (2020) — FoundationOne Liquid CDx analytical validation reported high reproducibility (99.59%), PPA ~96.3%, NPA >99.9%, and low false-positive rate (0.013%).

BFAST (Dziadziuszko et al. 2021) — Blood-based NGS identified ALK+ NSCLC and showed high investigator-assessed ORR to alectinib (87.4%), supporting clinical actionability of plasma-detected alterations.

Revision History and Policy Changes

2025-06-01revised

Policy effective date changed; revised coverage guidelines to indicate 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 the CDx must align with the drug, FDA-approved indication, and appropriate tissue/specimen and be consistent with the drug label. (Material change)

2025-06-01revised

Document header reflects Louisiana-only application and incorporation of Louisiana Medicaid Managed Care Organization requirements for genetic counseling (state-specific criteria). (Material change)

2025-06-01added

Policy Summary

PayerUnitedHealthcare

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

Policy CodePolicy CS373LA.D

Change TypeRetired; coverage criteria revised/added

Effective DateJun 1, 2025

Next Review Date

On This Page

Document: structured family history, genetic risk assessment, counseling about diagnosis/prognosis/treatment
Use CLIA‑approved/validated tests
Prefer tissue testing when feasible; use liquid biopsy as complementary to tissue testing
Consider liquid biopsy for acquired resistance or when tissue is unavailable
Interpret negative ctDNA cautiously; confirm negative liquid biopsy with tissue when absence of an actionable result impacts management
Consider repeat testing at progression or when resistance emerges
Align companion diagnostic selection with the FDA List of Cleared or Approved Companion Diagnostic Devices and the drug label
If no FDA companion diagnostic match, refer to the Molecular Oncology Testing policies

initial sequencing was done with a limited NGS panel

individual has developed resistance to targeted therapies and acquired resistance mechanisms might impact next-line treatment choice

there is clinical or radiologic progression where repeat testing may identify new targets

ctDNA (plasma) testing may be used routinely when tissue is unavailable, biopsy is infeasible, or rapid results are needed; tissue testing is preferred in many settings, especially stage I-III disease.

ctDNA testing should not replace histologic tissue diagnosis.

NCCN site-specific recommendations (selected highlights)

NCCN recommends tumor/somatic molecular profiling (preferably tissue NGS) for many tumor types; cfDNA may be considered when tissue is unavailable or biopsy is not feasible. Key tumor-specific points:

ANY of the following

Ampullary adenocarcinoma: tumor/somatic molecular profiling for locally advanced/metastatic disease; test for fusions (ALK, NRG1, NTRK, ROS1, FGFR2, RET), mutations (BRAF, BRCA1/2, KRAS, PALB2), amplifications (HER2), MSI, dMMR, TMB; RNA sequencing preferred for fusions; cfDNA can be considered if tissue testing not feasible.
Biliary tract cancers: comprehensive molecular profiling for unresectable or metastatic disease; cfDNA may be considered but may not reliably identify fusions depending on panel.
Bladder cancer (stages IVA/IVB): molecular/genomic testing including FGFR and HER2 testing recommended; early testing ideally at diagnosis of advanced disease.
Breast cancer: recurrent unresectable or stage IV: tumor or ctDNA testing for PIK3CA and other biomarkers; if liquid biopsy is negative for PIK3CA, tumor tissue testing is recommended.
CRC: universal MMR/MSI testing for all newly diagnosed; metastatic CRC should include RAS (KRAS/NRAS), BRAF, HER2, MMR/MSI; NGS preferred; tissue preferred but blood-based NGS acceptable.
Gastric/Esophageal cancers: IHC/ISH/PCR first-line then NGS; when biopsy not feasible consider CGP with validated NGS assay; cfDNA may be considered in metastatic or monitoring contexts, interpret negatives cautiously.
Various other tumor types: NCCN recommends molecular profiling (NGS/CGP) in specified advanced/metastatic or recurrence contexts; tissue preferred, ctDNA acceptable when tissue not available; specific marker lists provided per disease.
NSCLC: broad panel-based molecular testing preferred (NGS); ctDNA can be complementary to tissue testing in metastatic disease; tissue biopsy for progression on targeted therapy is recommended; ctDNA not typical in stages I-III.

Society guidance on ctDNA / liquid biopsy

Key consensus points from ASCO, ESMO, IASLC and others:

ALL of the following

ctDNA assays with sufficient sensitivity are useful to detect actionable variations in advanced cancers and can be used routinely when assay limitations are considered.
ctDNA is most useful when tissue is unavailable or biopsy is not feasible; complementary use with tissue testing increases detection and reduces turnaround time.
There is insufficient evidence of clinical validity/utility of ctDNA for early-stage cancer, treatment monitoring, residual disease detection, or screening for most assays.
Fusion detection and copy-number changes may be harder to assess in ctDNA; RNA-based assays are preferred for fusion detection.

Key definitions relevant to clinicians: Companion Diagnostic Test — a test that provides information necessary for the safe and effective use of a corresponding therapeutic drug (FDA); Comprehensive Genomic Profiling (CGP) — NGS tests that detect multiple classes of genomic alterations across hundreds of genes from a single sample; Liquid Biopsy — testing of bodily fluids to identify tumor-derived DNA/RNA or other circulating tumor molecules; ctDNA — circulating tumor DNA in plasma used for genomic profiling; and CLIA — Clinical Laboratory Improvement Amendments certification required for clinical laboratory testing.

Documentation Required

Consider tissue biopsy when ctDNA tumor fraction is low

If ctDNA tumor fraction is low (examples and data reported), consider reflex tumor tissue biopsy because sensitivity of liquid biopsy decreases at low tumor fraction and actionable alterations may be missed.

Examples noted: reflex tissue biopsy advised when ctDNA tumor fraction < 1%
Median ctDNA tumor fraction reported ~2.2%; sensitivity approaches 100% at TF ≥10% but is substantially lower at lower TF

Guardant randomized (Yang et al. 2023) and Powell et al. (2024) — Immediate liquid NGS shortened time to treatment (median 20 vs 28 days) though small randomized data showed no significant ORR/PFS differences; observational GuardantINFORM data associated CGP-directed optimal first-line therapy with longer time to next treatment and fewer ED/outpatient visits.

Added criteria defining repeat Companion Diagnostic Testing on a new tissue or Liquid Biopsy specimen is considered proven and medically necessary up to three times annually for therapy selection when criteria are met and the patient has disease recurrence or progression/nonresponse. (Material change)

2025-06-01added

Added allowance for concurrent tissue-based and Liquid Biopsy Companion Diagnostic Testing (ordered within 30 days) as proven and medically necessary for advanced/metastatic (stage IV) breast cancer and advanced/metastatic (stage IV) non-small cell lung cancer. (Material change)

2025-06-01clarified

Supporting information, description of services, clinical evidence, references, and definitions updated; Comprehensive Genomic Profiling (CGP) definition updated and notation added that CPT code 0473U is not on the Louisiana Medicaid fee schedule. (Non-material clarification)

2026-04-01removedLatest

Policy retired for Louisiana plan membership; Louisiana plan membership disenrolled effective April 1, 2026. (Material change)