CurrentunitedhealthcarePolicy CS373PA.E

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

State-specific UnitedHealthcare Community Plan medical policy governing coverage of FDA cleared or approved companion diagnostic (CDx) molecular oncology tests (tissue- or liquid-based) in Pennsylvania, including specific named CDx tests and drug/indication pairings, criteria for other FDA-cleared/approved CDx tests, subsequent use, and concurrent testing rules.

Policy Summary

Payerunitedhealthcare

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

Policy CodePolicy CS373PA.E

Change TypeMaterial and non-material edits

Effective DateMar 1, 2026

Next Review Date

Key ActionEnsure the CDx test is FDA cleared or approved for the intended therapeutic product/indication (appearing on the FDA CDx table or in an FDA PMA approval order) and document medical necessity in the patient record.

SourceLink

POLICY UPDATE CHANGES

Policy applies only to the state of Pennsylvania and references Pennsylvania-specific exceptions.

Policy applies to tests that have been granted approval as FDA cleared or approved Companion Diagnostic (CDx) tests.

Named CDx tests (e.g., Guardant360 CDx, MI Cancer Seek, Oncomine Dx Express, Oncomine Dx Target, oncoReveal CDx, TruSight Oncology Comprehensive, xT CDx) are listed as proven and medically necessary when used to inform management for specific indication/drug pairings.

Concurrent tissue and liquid CDx testing coverage for advanced/metastatic breast cancer and advanced/metastatic NSCLC.

Subsequent use of an FDA cleared or approved CDx on a new specimen is covered for recurrence or progression/no response to most recent systemic therapy.

CPT codes 0211U and 0523U added to Applicable Codes; several CPT codes removed (0179U, 81445, 81449, 81450, 81451, 81455, 81456, 81599).

FDA approval alone is not a basis for coverage; laboratory CLIA regulation noted for informational purposes.

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>=5Minimum gene count requirement for covered CDx tests

2CPT codes added

9CPT codes removed

2Cancer types allowed for concurrent tissue+liquid testing (stage IV)

MultipleNamed FDA-cleared/approved CDx tests listed (examples)

Coverage Summary

State-specific UnitedHealthcare Community Plan policy for Pennsylvania governing coverage of FDA cleared or approved Companion Diagnostic (CDx) molecular oncology tests (tissue- or liquid-based). Coverage applies only in Pennsylvania and is limited to tests that have been granted approval as FDA cleared or approved CDx tests and that are listed in the FDA's Cleared or Approved Companion Diagnostic Devices Table or have an approval order in the FDA Premarket Approval Database. The policy restricts covered CDx tests to those that detect alterations in five or more genes in tumor tissue or Liquid Biopsy. Named FDA-cleared/approved CDx tests and specific test-to-drug/indication pairings are listed as proven and medically necessary for their indicated uses. Concurrent tissue- and liquid-based CDx testing is allowed as proven and medically necessary for advanced/metastatic (stage IV) breast cancer and advanced/metastatic (stage IV) non-small cell lung cancer (NSCLC). Subsequent use (repeat testing on a new specimen) is covered when CDx criteria are met and the individual has disease recurrence or disease progression/no response to the most recent systemic therapy. All other uses not meeting these defined criteria are considered unproven and not medically necessary. Overall coverage stance: covered_with_criteria.

Key thresholds and facts

Minimum gene count for CDx tests>= 5 genes detected

Concurrent testing timeframeordered for same clinical indication within 30 days

State applicabilityPennsylvania only (policy applies to PA)

Coverage stanceCovered with criteria

Medical Necessity Criteria

General Coverage Criteria for FDA cleared/approved CDx tests

Covered when ALL of the following are met:

ALL of the following

The test is an FDA cleared or approved Companion Diagnostic (CDx) test (i.e., designated by the FDA as a companion diagnostic for use with a specific therapeutic product or group of products).
The test results will be used to inform the use of a targeted oncology therapeutic product or group of products in an individual with the corresponding clinical indication.
AND one of the following must be true:
- The test appears in the U.S. Food and Drug Administration (FDA)'s Cleared or Approved Companion Diagnostic Devices Table for use with the intended targeted therapeutic product and clinical indication.

Coding

Referenced molecular and unlisted procedure codes (for reference only)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.
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 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.
0523U	Oncology (solid tumor), DNA, qualitative, NGS of SNV and insertion/deletions in 22 genes utilizing FFPE tissue, reported as presence or absence of mutation(s), location of mutation(s), nucleotide change, and amino acid change.
0543U	Oncology (solid tumor), NGS of DNA from FFPE tissue of 517 genes, interrogation for SNV, multi-nucleotide variants, indels, fusions in 24 genes and splice variants in 1 gene from RNA, and tumor mutation burden.
81479	Unlisted molecular pathology procedure

Added CPT codesCPT

0211U	Added to Applicable Codes (policy history)
0523U	Added to Applicable Codes (policy history)

Removed CPT codesCPTNot Covered

0179U	Removed from Applicable Codes
81445	Removed from Applicable Codes
81449	Removed from Applicable Codes
81450	Removed from Applicable Codes
81451	Removed from Applicable Codes
81455	Removed from Applicable Codes
81456	Removed from Applicable Codes
81599	Removed from Applicable Codes

Provider Actions & Requirements

Documentation Required

Medical record documentation required

Patient medical record must contain documentation supporting medical necessity including relevant history, physical exam, and diagnostic test/procedure results; documentation must be legible and available upon request.

Prior Authorization

PA/case-by-case evaluation for requests not meeting PARP criteria

Any requests for services that do not meet criteria set in the PARP will be evaluated on a case-by-case basis; refer to Pennsylvania Exceptions, Pennsylvania Code, Title 55, Chapter 1101.

Background & Evidence

A Companion Diagnostic (CDx) is a test that provides information essential for the safe and effective use of a specific therapeutic product. This policy restricts coverage to FDA cleared or approved CDx tests that detect alterations in five or more genes in tumor tissue or by Liquid Biopsy and that appear in the FDA's Cleared or Approved Companion Diagnostic Devices Table or have an approval order designating them as a CDx in the FDA Premarket Approval Database. Subsequent testing on a new specimen is covered when the CDx criteria are met and the patient has disease recurrence or progression/did not respond to the most recent systemic therapy. Concurrent tissue-based CDx and Liquid Biopsy-based CDx testing is permitted for the same clinical indication within the defined timeframe and is considered medically necessary for advanced/metastatic (stage IV) breast cancer and advanced/metastatic (stage IV) NSCLC. All other uses of FDA cleared or approved CDx tests not meeting these requirements are considered unproven and not medically necessary.

Label	Value
TMB pembrolizumab KEYNOTE-158
KEYNOTE-158 showed 29% response rate in TMB-high (≥10 mut/Mb) population; FoundationOne CDx received premarket approval as a CDx for TMB-high using a cutpoint of 10 mut/Mb.
FoundationOne Liquid CDx validation
Analytical validation across >7,500 tests; 95% limit of detection ~0.40% VAF for select substitutions/indels; reproducibility 99.59%; PPA 96.3% and NPA >99.9%.
Guardant360 CDx KRAS p.G12C evidence
Clinical validation (CodeBreaK100) showed ORR in full analysis set 37.1% (46/124); Guardant360-positive cohort ORR 36.4% (28/77); disease control rate 80.6% (100/124).
Tempus xT concurrent testing study
Concurrent tissue (xT CDx) and ctDNA testing in 3,209 stage IV patients: overall concordance 66.4%; ctDNA-unique actionable variants 9.3%; tissue-unique 24.2%; demonstrated increased detection of actionable variants with concurrent testing.
ASCO 2024 recommendation
ASCO 2024 Rapid Recommendation: routine testing recommended for activating mutations in PIK3CA, AKT1, or PTEN (evidence quality: high; strength: strong).

Definitions (term → definition)

Companion DiagnosticA tool essential for safe and effective use of a corresponding therapeutic drug; as used here, an FDA cleared or approved test for use with a specific drug(s) eligible for listing in the FDA CDx devices table.

Concurrent TestingTissue-based testing and Liquid Biopsy ordered for the same clinical indication within a 30-day period.

Liquid Biopsy

Revision History

03/01/2026revisedLatest

Revised language clarifies applicability to FDA cleared/approved Companion Diagnostic (CDx) tests (material).

03/01/2026addedLatest

Multiple specific named CDx test-to-drug/indication pairings were enumerated (e.g., FoundationOne CDx, FoundationOne Liquid CDx, Guardant360 CDx, MI Cancer Seek, Oncomine Dx Express/Target, oncoReveal CDx, TruSight Oncology Comprehensive, xT CDx) and listed as proven and medically necessary for specified indication/drug pairings (material).

03/01/2026

Policy Summary

Payerunitedhealthcare

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

Policy CodePolicy CS373PA.E

Change TypeMaterial and non-material edits

Effective DateMar 1, 2026

Next Review Date

SourceLink

On This Page

The test has an approval order designating it as an FDA cleared or approved CDx test for use with the intended targeted therapeutic product and clinical indication in the FDA Premarket Approval (PMA) Database, but the approval does not yet appear in the FDA's Cleared or Approved Companion Diagnostic Devices Table.

Named CDx tests and covered indication/drug pairings (examples listed)

The following named CDx tests are proven and medically necessary for the listed example indication/drug pairings (policy body contains the full list of covered pairings). Covered when ANY of the listed pairings below apply:

ANY of the following

FoundationOne CDx pairings (examples)
- Breast cancer — trastuzumab (Herceptin), ado-trastuzumab emtansine (Kadcyla), pertuzumab (Perjeta), alpelisib (Piqray), capivasertib with fulvestrant (Truqap + Faslodex).
- Cholangiocarcinoma — pemigatinib (Pemazyre).
- Colorectal cancer — cetuximab (Erbitux), panitumumab (Vectibix).
- Low-grade glioma — tovorafenib (Ojmeda).
- Melanoma — trametinib (Mekinist), dabrafenib (Tafinlar), atezolizumab with cobimetinib and vemurafenib (Tecentriq + Cotellic + Zelboraf), vemurafenib (Zelboraf).
- Non-small cell lung cancer (NSCLC) — alectinib (Alecensa), encorafenib with binimetinib (Braftovi + Mektovi), afatinib (Gilotrif), gefitinib (Iressa), lazertinib with amivantamab (Lazcluze + Rybrevant), capmatinib (Tabrecta), dabrafenib with trametinib (Tafinlar + Mekinist), osimertinib (Tagrisso), erlotinib (Tarceva), dacomitinib (Vizimpro), crizotinib (Xalkori), ceritinib (Zykadia).
- Ovarian cancer — olaparib (Lynparza).
- Metastatic castration-resistant prostate cancer — niraparib with abiraterone acetate (Akeega), olaparib (Lynparza).
- Solid tumors — pembrolizumab (Keytruda), selpercatinib (Retevmo), entrectinib (Rozlytrek), larotrectinib (Vitrakvi).
FoundationOne Liquid CDx pairings (examples)
- Breast cancer — palbociclib with fulvestrant (Itovebi + Ibrance + Faslodex), alpelisib (Piqray).
- Metastatic colorectal cancer — encorafenib with cetuximab (Braftovi + Erbitux).
- NSCLC — alectinib (Alecensa), encorafenib with binimetinib (Braftovi + Mektovi), gefitinib (Iressa), lazertinib with amivantamab (Lazcluze + Rybrevant), capmatinib (Tabrecta), osimertinib (Tagrisso), erlotinib (Tarceva), tepotinib (Tepmetko).
- Metastatic castration-resistant prostate cancer — niraparib with abiraterone acetate (Akeega), olaparib (Lynparza), rucaparib (Rubraca).
- Solid tumors — entrectinib (Rozlytrek).
Guardant360 CDx pairings (examples)
- Breast cancer — elacestrant (Orserdu).
- NSCLC — fam-trastuzumab deruxtecan (Enhertu), sotorasib (Lumakras), amivantamab (Rybrevant), osimertinib (Tagrisso).
Other named CDx tests (examples)
- MI Cancer Seek — multiple pairings across breast, colorectal, melanoma, NSCLC, and solid tumor indications as listed in policy body.
- Oncomine Dx Express/Target — NSCLC and other listed pairings (e.g., Zegfrovy for NSCLC).
- oncoReveal CDx — colorectal and NSCLC pairings as listed in policy body.
- TruSight Oncology Comprehensive — NSCLC and larotrectinib for solid tumors.
- xT CDx — covered pairings as listed in policy body.

Subsequent use (repeat testing on new specimen)

Covered when ALL of the following are met:

ALL of the following

The criteria for an FDA cleared or approved CDx test are met (see General Coverage Criteria).
AND one of the following must be true:
- The individual is experiencing disease recurrence.
- The individual's cancer has progressed or did not respond to the most recent systemic therapy.

Concurrent tissue and liquid CDx testing

Concurrent testing is considered proven and medically necessary only when ALL of the following are met:

ALL of the following

Criteria for an FDA cleared or approved CDx test are met for each test ordered (see General Coverage Criteria).
AND the clinical indication is one of the following:
- Advanced or metastatic (stage IV) breast cancer.
- Advanced or metastatic (stage IV) non-small cell lung cancer (NSCLC).

Not medically necessary / unproven

Not medically necessary / Unproven uses:

ALL of the following

Due to insufficient evidence of efficacy, all uses of FDA cleared or approved Companion Diagnostic (CDx) tests that do not meet the criteria outlined in this policy are considered unproven and not medically necessary.

General coverage criteria for FDA cleared/approved CDx tests

Covered when ALL of the following are met:

ALL of the following

The test is an FDA cleared or approved Companion Diagnostic (CDx) test (i.e., designated by the FDA as a companion diagnostic for use with a specific therapeutic product or group of products).
The test results will be used to inform the use of a targeted oncology therapeutic product or group of products in an individual with the corresponding clinical indication.
AND one of the following must be true:
- The test appears in the U.S. Food and Drug Administration (FDA)'s Cleared or Approved Companion Diagnostic Devices Table for use with the intended targeted therapeutic product and clinical indication.
- The test has an approval order designating it as an FDA cleared or approved CDx test for use with the intended targeted therapeutic product and clinical indication in the FDA Premarket Approval (PMA) Database, but the approval does not yet appear in the FDA's Cleared or Approved Companion Diagnostic Devices Table.

Subsequent use of an FDA cleared/approved CDx on a new specimen

Subsequent use of an FDA cleared or approved CDx test on a new specimen for the purpose of assisting with therapy selection is considered proven and medically necessary when ALL of the following are met:

ALL of the following

The criteria above for the CDx test are met (see General coverage criteria for FDA cleared/approved CDx tests).
AND one of the following must be true:
- The individual is experiencing disease recurrence.
- The individual's cancer has progressed or did not respond to the most recent systemic therapy.

Concurrent testing with tissue-based CDx and liquid biopsy-based CDx

Concurrent testing using an FDA cleared or approved tissue-based CDx and a liquid biopsy-based CDx is considered proven and medically necessary when ALL of the following are met:

ALL of the following

Criteria for an FDA cleared or approved CDx test are met for each test ordered (see General coverage criteria).
AND the clinical indication is one of the following:
- Advanced or metastatic (stage IV) breast cancer.
- Advanced or metastatic (stage IV) non-small cell lung cancer (NSCLC).

Not medically necessary / Unproven uses

Not medically necessary / Unproven uses:

ALL of the following

Due to insufficient evidence of efficacy, all other uses of FDA cleared or approved Companion Diagnostic (CDx) tests that do not meet the criteria in this policy are considered unproven and not medically necessary.

Tests not FDA cleared/approved as CDx

Tests that are not FDA cleared or approved as CDx tests:

ALL of the following

For molecular oncology tests that have not been cleared or approved by the FDA as CDx tests, refer to the Medical Policy titled 'Molecular Oncology Testing for Solid Tumor Cancer Diagnosis, Prognosis, and Treatment Decisions (for Pennsylvania Only)' or 'Molecular Oncology Testing for Hematologic Cancer Diagnosis, Prognosis, and Treatment Decisions (for Pennsylvania Only)'.

Documentation Required

Medical record documentation required

Medical records may be required to assess whether the member meets clinical criteria; documentation must fully support medical necessity (medical history, physical exam, relevant diagnostic tests) and be made available upon request.

Prior Authorization

Coverage requires CDx FDA status documentation

Provider must ensure the CDx test is an FDA cleared/approved Companion Diagnostic for the intended therapeutic product and clinical indication — either appearing in the FDA's Cleared or Approved Companion Diagnostic Devices Table or having an approval order in the FDA Premarket Approval Database — to meet coverage criteria.

Documentation Required

Concurrent testing indication requirement

Concurrent tissue and liquid CDx testing is covered only for advanced/metastatic (stage IV) breast cancer and advanced/metastatic (stage IV) non-small cell lung cancer when CDx criteria are met.

Billing Rule

Applicable code updates

Report CPT codes that are currently listed as applicable, including newly added codes 0211U and 0523U; do not report CPT codes removed in the policy history.

0211U
0523U

Testing on a bodily fluid sample to identify tumor cells or tumor-derived DNA/RNA circulating in body fluids.

Advanced CancerCancer that is unlikely to be cured but that may be controlled with treatment (National Cancer Institute, 2025).

Policy-specific Concurrent Testing timeframeConcurrent testing defined as tissue and liquid CDx ordered for the same clinical indication within 30 days (policy threshold).

Concurrent tissue and liquid CDx testing coverage explicitly identified as proven and medically necessary for advanced/metastatic (stage IV) breast cancer and advanced/metastatic (stage IV) non-small cell lung cancer (NSCLC) (material).

03/01/2026addedLatest

Added criteria for subsequent use: repeat/new specimen testing with an FDA cleared or approved CDx is covered for disease recurrence or progression/no response to most recent systemic therapy (material).

03/01/2026addedLatest

Operational coding updates: CPT codes 0211U and 0523U added to Applicable Codes and several CPT codes removed (0179U, 81445, 81449, 81450, 81451, 81455, 81456, 81599) (material).

clarifiedLatest

Application section specifies Pennsylvania-only applicability and that requests not meeting PARP criteria will be evaluated case-by-case (non-material).

clarifiedLatest

Policy emphasizes that FDA approval alone is not a basis for coverage and notes CLIA regulation of laboratories (non-material).