RetiredUnitedHealthcarePolicy CS373LA.D

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

State-specific UnitedHealthcare Community Plan medical policy (Louisiana only) governing coverage criteria for FDA-cleared or approved companion diagnostic (CDx) tests, including genetic counseling requirements, repeat testing limits, concurrent tissue/liquid testing guidance, definitions, applicable CPT/PLA/HCPCS molecular pathology codes, and supporting evidence summaries. Effective for June 1, 2025–March 31, 2026; retired April 1, 2026.

Policy Summary

PayerUnitedHealthcare Community Plan (Louisiana)

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

Policy CodePolicy CS373LA.D

Change TypeRetired; coverage criteria revised (06/01/2025)

Effective DateJun 1, 2025

Next Review Date

Key ActionEnsure ordered companion diagnostic tests align with the drug, FDA-approved indication, and specimen on the FDA List of Cleared or Approved Companion Diagnostic Devices and document required genetic counseling in the medical record.

POLICY UPDATE CHANGES

Policy retired effective April 1, 2026.

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

Title changed and coverage guidelines revised on 06/01/2025 to define when companion diagnostic tests are proven and medically necessary, repeat testing limits, and concurrent testing criteria.

Definitions updated and CPT code 0473U noted as not on Louisiana Medicaid Fee schedule; supporting information updated.

2Cancer types with allowed concurrent testing

Up to 3

Coverage Summary

Overview: This is a Louisiana-specific UnitedHealthcare Community Plan medical policy (CS373LA.D) that governed coverage of FDA-cleared or approved companion diagnostic (CDx) testing for oncology indications. The policy was effective June 1, 2025–March 31, 2026 and the status is RETIRED effective April 1, 2026. Coverage stance was state-specific and conditional (aligned to FDA companion diagnostic listings and labeling), with requirements for alignment to FDA labeling, documentation of genetic counseling, and specified limits on repeat and concurrent testing.

Key Coverage Thresholds

Repeat CDx testing frequencyUp to three times annually

Concurrent testing ordered intervalWithin 30 days

ctDNA tumor fraction examples<1%; >=1%; >=10%; median ~2.2%

LOD badges (FoundationOne Liquid CDx)95% LOD: 0.40% VAF (select substitutions/indels); 0.37% VAF (rearrangements); 21.7% TF for copy number amplifications; 30.4% TF for copy number losses

Medical-Necessity Criteria

Companion Diagnostic Tests - Medically Necessary Criteria

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 ALL of the following are met:

ALL of the following

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 Companion Diagnostic Testing

Repeat testing on a new tissue or Liquid Biopsy specimen for therapy selection is considered proven and medically necessary up to three times annually when the CDx criteria are met AND ONE of the following:

ALL of the following

Provider Actions & Billing Impact

Prior Authorization

Align CDx with FDA labeling

Tests must be aligned with the FDA-cleared/approved companion diagnostic (CDx) listing and the labeled drug indication. Prior authorization will require documentation that the test matches the specific therapeutic product, the FDA-approved indication, and the specimen/tissue type specified on the FDA List of Cleared or Approved Companion Diagnostic Devices. Coverage depends on this alignment; tests not matching the FDA CDx listing or labeling may be denied or reviewed under alternative molecular oncology policies.

Documentation Required

Document genetic counseling

Genetic counseling is required before and after all genetic testing and must be documented in the medical record. Documentation must include: a structured family genetic history, a genetic risk assessment, and counseling provided to the enrollee and family regarding diagnosis, prognosis, and treatment options.

Obtain and document a structured family genetic history

Coding

Molecular Pathology / Genomic Testing PLA/CPT Codes listed for referencemixed

0022U	Targeted genomic sequence analysis panel, non-small cell lung neoplasia, DNA and RNA analysis, 23 genes
0037U	Targeted genomic sequence analysis, solid organ neoplasm, DNA analysis of 324 genes
0179U	Oncology (non-small cell lung cancer), cell-free DNA, targeted sequence analysis of 23 genes
0239U	Targeted genomic sequence analysis panel, solid organ neoplasm, cell-free DNA, analysis of 311+ genes
0242U	Targeted genomic sequence analysis panel, solid organ neoplasm, cell-free circulating DNA analysis of 55-74 genes
0473U	Oncology (solid tumor), NGS of DNA from FFPE tissue with matched normal, 648 genes
0543U	Oncology (solid tumor), NGS of DNA from FFPE tissue of 517 genes
81445	Solid organ neoplasm, genomic sequence analysis panel, 5-50 genes, DNA or combined DNA/RNA analysis
81449	Solid organ neoplasm, genomic sequence analysis panel, 5-50 genes, RNA analysis
81450	Hematolymphoid neoplasm or disorder, genomic sequence analysis panel, 5-50 genes, DNA or combined DNA/RNA analysis

1–10 of 15

1/2

Codes Not on Louisiana Medicaid Fee SchedulemixedNot Covered

0022U	Not on State of Louisiana Medicaid Fee Schedule (may not be covered)
0037U	Not on State of Louisiana Medicaid Fee Schedule (may not be covered)
0179U	Not on State of Louisiana Medicaid Fee Schedule (may not be covered)
0239U	Not on State of Louisiana Medicaid Fee Schedule (may not be covered)

FDA-approved companion diagnostic (examples discussed)mixed

FoundationOne Liquid CDx	FDA-approved ctDNA test for select cancer indications; 324-gene panel (named test; not a CPT/PLA code)
Guardant360 CDx	FDA-approved 55-gene ctDNA panel CDx for NSCLC, breast cancer, and general tumor mutation profiling (named test)
InVisionFirst	Liquid biopsy test using TAm-Seq technology for NSCLC (named test)

Notation re: CPTCPT

0473U

CPT code 0473U is noted as not on the State of Louisiana Medicaid Fee schedule

Background, Evidence & Definitions

Background: This Louisiana-only policy leverages the U.S. Food and Drug Administration List of Cleared or Approved Companion Diagnostic Devices to determine when companion diagnostic tests are considered proven and medically necessary; tests must align with the drug, FDA-approved indication, and specimen/tissue specified on the FDA companion diagnostic list and be used consistent with the associated drug label.

The policy requires genetic counseling before and after all genetic testing, documented in the medical record and including a structured family genetic history, genetic risk assessment, and counseling about diagnosis, prognosis, and treatment as per the LA MCO requirement.

The policy summarizes roles of Comprehensive Genomic Profiling (CGP)/NGS and liquid biopsy: CGP (broad NGS panels) can detect many alteration classes across hundreds of genes and may help match individuals with targeted therapies; liquid biopsy (ctDNA/cfDNA) is a minimally invasive approach with faster turnaround that can complement tissue testing, shorten time to molecular diagnosis, and detect alterations missed by tissue — but has limitations (variable sensitivity, false-negatives at low tumor fraction) and is generally most applicable in advanced/metastatic disease. Where no FDA CDx match exists, the policy refers providers to alternate UnitedHealthcare molecular oncology policies for Louisiana-specific guidance.

Study/Guidance	Key finding (brief)
OCTANE (Bogdan et al., OCTANE survey)
15.7% of actionable NGS results were matched to treatment (62 of 188); supports modest actionable-match rate
KEYNOTE-158 (Marabelle et al.)
29% objective response rate in TMB-high group (n=102); supported pembrolizumab TMB-high approval
Maity et al. 2023 (stage IV lung adenocarcinoma)
Simultaneous tissue+liquid reduced mean time to diagnosis (33.5 to 20.6 days) and combined testing detected actionable alterations missed by tissue alone (39% of those completing both tests)
Palmieri et al. 2022 meta-analysis
cfDNA pooled sensitivity 0.71 (95% CI 0.68-0.74) and specificity 0.93 (95% CI 0.92-0.94) for KRAS mutations
Husain et al. 2022 (FoundationOne Liquid CDx large series)
Detectable ctDNA in 94% of 23,482 samples; sensitivity near 100% for tissue-detected driver alterations when tumor fraction >=10%; median TF ~2.2%
Yang et al. 2023 (Guardant360 randomized trial)
Immediate liquid NGS shortened median time to treatment (20 vs 28 days) with no significant difference in ORR or PFS
Hayes assessments (multiple reports 2022-2024)
Hayes rates overall evidence quality low/very low for CMP via ctDNA guiding treatment/monitoring but acknowledges FDA CDx approvals for specific indications
BFAST (Dziadziuszko et al. 2021)
Blood-based NGS (Foundation ACT) identified ALK rearrangements with high investigator-assessed ORR to alectinib (87.4%) supporting blood NGS utility for ALK-positive NSCLC
Note: selected items are high-impact examples and not an exhaustive list

ASCO recommendations for genomic testing in advanced/metastatic solid tumors

ASCO provisional and updated guidance statements (2022-2024) summarize when genomic testing is recommended:

ALL of the following

Revision History

2025-06-01revision

Title change and coverage guidelines revised on 06/01/2025 to define when companion diagnostic tests are proven and medically necessary, add alignment with the FDA List of Cleared or Approved Companion Diagnostic Devices, set repeat testing limits (up to three times annually under specified clinical conditions), and permit concurrent tissue/liquid testing for stage IV breast and stage IV NSCLC. (is_material: true)

2025-06-01revision

Definitions and supporting sections updated on 06/01/2025 including Comprehensive Genomic Profiling (CGP) definition and Description of Services, Clinical Evidence, and References; CPT code 0473U noted as not on Louisiana Medicaid Fee schedule. (is_material: false)

2026-04-01retirement

Policy Summary

PayerUnitedHealthcare Community Plan (Louisiana)

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

Policy CodePolicy CS373LA.D

Change TypeRetired; coverage criteria revised (06/01/2025)

Effective DateJun 1, 2025

Next Review Date

On This Page

Concurrent Tissue-based and Liquid Biopsy CDx 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 cancer types when the CDx 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 (State-specific)

Genetic counseling before and after all genetic testing is required and must be documented in the medical record consisting of ALL of the following:

ALL of the following

Obtaining a structured family genetic history
Genetic risk assessment
Counseling of the enrollee and family about diagnosis, prognosis, and treatment (LA MCO Genetic Counseling and Testing)

Companion Diagnostic Tests - Summary of Coverage Criteria (from revision 06/01/2025)

Covered 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 the requesting provider.

Repeat Companion Diagnostic Testing (therapy selection)

Repeat testing considered medically necessary up to three times annually when criteria above are met AND ONE of the following:

ALL of the following

Criteria above for Companion Diagnostic Tests are met
One of
- The individual is experiencing disease recurrence.
- The individual's cancer has progressed or did not respond to the most recent systemic therapy.

Concurrent tissue-based and Liquid Biopsy Companion Diagnostic Testing

Concurrent testing (ordered within 30 days of each other) considered medically necessary when companion diagnostic criteria are met for the following cancer types:

ANY of the following

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

Alternate pathway when no FDA companion diagnostic match

If no cancer/diagnostic test match is found on the U.S. Food and Drug Administration (FDA) List of Cleared or Approved Companion Diagnostic Devices, refer to the following UnitedHealthcare Medical Policies:

See: 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).

Documentation Required

Limit repeat testing justification

Repeat companion diagnostic testing on a new tissue or liquid biopsy specimen for therapy selection is limited. Documentation must state the clinical rationale for repeat testing (for example: disease recurrence, disease progression, or lack of response to most recent systemic therapy). When criteria are met, up to three repeat tests per year may be considered medically necessary.

Clinical reason for repeat testing must be documented (recurrence, progression, or nonresponse)
Limit: up to three companion diagnostic tests annually when criteria met

Prior Authorization

Coverage requires alignment with FDA companion diagnostic listing and labeling

Coverage for a companion diagnostic requires that the test and its use align with the FDA companion diagnostic listing and the labeled therapeutic product. Tests that are not aligned with the FDA CDx listing or labeling should be considered under the applicable Molecular Oncology Testing policies instead of this CDx policy.

Prior Authorization

Repeat testing limits

Repeat testing limits are enforced at prior authorization: up to three companion diagnostic tests annually are allowed when the covered CDx criteria are met and a qualifying clinical criterion (recurrence, progression, or nonresponse) is documented.

Up to 3 repeat companion diagnostic tests per year when medically justified
Documentation of qualifying clinical criterion required (recurrence, progression, or nonresponse)

Documentation Required

Concurrent testing timing

Concurrent tissue-based and liquid biopsy CDx testing is allowable when both tests are ordered within 30 days and meet CDx alignment criteria. This concurrent testing is specifically allowed for stage IV (advanced/metastatic) breast cancer and stage IV non-small cell lung cancer when the CDx criteria are satisfied.

Orders must be placed within 30 days of each other
Applicable when CDx criteria are met for stage IV breast cancer and stage IV NSCLC

Documentation Required

Reflex to tissue biopsy when ctDNA fraction is low

If a liquid biopsy result is indeterminate due to low circulating tumor DNA (ctDNA) fraction, reflex testing of tissue should be performed to obtain a definitive result.

Reflex to tissue biopsy when ctDNA fraction is low or inadequate for reliable analysis

Documentation Required

Simultaneous tissue and liquid testing

Simultaneous ordering of tissue and liquid testing is acceptable in situations where both specimen types may provide complementary information or when rapid treatment decisions necessitate parallel testing. Document the clinical rationale for simultaneous testing.

Document clinical rationale when ordering tissue and liquid CDx tests concurrently

Documentation Required

Confirm negative liquid biopsy with tissue

A negative liquid biopsy (ctDNA) that would change management should be confirmed with tissue testing when feasible, especially if a therapeutic decision depends on ruling out a targetable alteration.

Confirm negative liquid biopsy with tissue testing when results would alter treatment decisions

Documentation Required

Use liquid biopsy for acquired resistance

Use liquid biopsy to evaluate for acquired resistance mechanisms when tissue is not available or when a less invasive approach is preferred; document the clinical indication and how results will impact therapy selection.

Liquid biopsy is appropriate for acquired resistance testing when tissue is unavailable or invasive sampling is not feasible
Document how results will guide subsequent therapy

Documentation Required

Use validated/CLIA-certified laboratories

Testing must be performed in validated, CLIA-certified laboratories. Documentation of laboratory accreditation and test validation should be available upon request.

Use validated/CLIA-certified laboratories for CDx testing
Maintain documentation of laboratory accreditation and test validation

Documentation Required

Prefer tissue testing when feasible

When feasible, prefer tissue-based CDx testing as the primary specimen for diagnostic accuracy. Document reasons if liquid biopsy is used instead (for example, tissue unobtainable or patient unfit for biopsy).

Prefer tissue testing when feasible for diagnostic accuracy
If liquid biopsy is used instead, document justification (e.g., tissue unobtainable, patient risk)

Documentation Required

Follow-up tissue if ctDNA negative

If ctDNA testing is negative but clinical suspicion for a targetable alteration remains, follow-up tissue testing should be pursued to ensure accurate detection of actionable biomarkers.

Follow-up tissue testing when ctDNA is negative and clinical suspicion persists

Documentation Required

Use RNA-based assays for fusion detection when indicated

Use RNA-based assays for detection of gene fusions when indicated (for example, when DNA-only panels have limited fusion detection capability). Document the rationale for RNA testing and the expected impact on treatment selection.

Use RNA-based assays for fusion detection when indicated
Document rationale and how results will affect therapy selection

ASCO recommendations for repeat genomic testing

ASCO guidance on repeat testing:

ANY of the following

Repeat genomic testing may be justified when initial sequencing used a limited NGS panel
Limited evidence supports repeat testing after prior large-panel or whole exome/genome sequencing if no treatment-induced changes are expected
Repeat testing may be undertaken for individuals who developed resistance to targeted therapies when known resistance mechanisms could affect next-line treatment

NCCN recommendations for use of NGS/ctDNA by cancer type (selected highlights)

NCCN condition-specific recommendations for tumor molecular profiling and ctDNA use:

ANY of the following

General principles for NSCLC
Tumor-type specific: Ampullary, Biliary, Bladder, Bone, Breast, Cervical, CRC, Gastric/Esophageal, GIST, Histiocytic, HCC, Melanoma, Neuroblastoma, Neuroendocrine, Occult Primary, Ovarian, Pancreatic, Prostate, SCLC, Thyroid, Uterine, Vaginal
Specific recommendations

Key points from ESMO and IASLC

Key points from ESMO and IASLC:

ALL of the following

ESMO recommends tumor NGS for individuals with advanced cancers including specified tumor types and recommends ensuring fusions are included in test panels
ESMO: ctDNA assays with sufficient sensitivity are useful for detecting actionable variations and may be used routinely when assay limitations are considered
IASLC: use clinically validated NGS platforms; consider plasma ctDNA a valid genotyping tool in advanced NSCLC and as complementary or initial approach in oncogene-addicted NSCLC

Guidance on limitations of ctDNA

Statements noting limitations and appropriate use:

ALL of the following

ctDNA testing has high specificity but considerable false-negative rates; complementary use with tissue testing is recommended
ctDNA may be less reliable for copy-number changes and some fusion detection depending on panel and partner gene
Negative ctDNA does not exclude tumor mutations; tissue testing preferred when feasible

Glossary:

• Companion Diagnostic Test: A test that provides important information for the safe and effective use of a corresponding therapeutic drug (FDA, 2024).

• Comprehensive Genomic Profiling (CGP): An NGS test able to simultaneously detect all classes of genomic alterations across hundreds of genes from a single sample.

• Liquid Biopsy: Testing of bodily fluid to identify tumor-derived DNA/RNA/cells to aid treatment selection or monitoring (NCI, 2024).

• Next Generation Sequencing (NGS): Sequencing techniques that analyze multiple DNA sections simultaneously.