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

Coverage Summary

Scope: This is a state-specific UnitedHealthcare (Ohio-only) medical policy (Policy CS152OH.I, effective 04/01/2026) that governs coverage and medical necessity criteria for molecular oncology testing for solid tumors, including gene expression profiling (GEP), comprehensive genomic profiling (CGP), liquid biopsy (cfDNA), and other molecular tests used for diagnosis, prognosis, and treatment decisions. The policy defines technologies and test scope (multi-gene panels, NGS, methylation, etc.), references InterQual CP criteria for many test-specific medical necessity rules, and lists extensive PLA/CPT and genomic panel codes for reference. Inclusion of codes in the policy is for reference only and does not by itself indicate coverage. Coverage stance: Mixed — specific tests and indications are stated as proven and medically necessary (for example, selected GEP tests for defined breast, lung, prostate, thyroid, and uveal melanoma indications), while numerous other tests/panels (including many named assays and MRD assays in solid tumors) are listed as unproven and not medically necessary.

Policy application: The policy applies only to Ohio and states that services identified as unproven or subject to coverage/quantity limits will be evaluated under Ohio Administrative Code 5160-101. Providers should follow the InterQual CP references and any companion diagnostic policy when applicable.

Medical Necessity Criteria (by indication)

General application and FDA companion diagnostic rule

Applies statewide in Ohio. FDA-cleared or approved companion diagnostic tests follow the Medical Policy titled “FDA Cleared or Approved Companion Diagnostic Testing (for Ohio Only).” This criteria group establishes general application and the rule that tests that are FDA-cleared/approved companion diagnostics are evaluated under that companion diagnostic policy rather than here.

ALL of the following

Policy applies only to services in the state of Ohio; requests for services listed as unproven or subject to coverage/quantity limits will be evaluated using Ohio Administrative Code 5160-101.
Tests that have an FDA-cleared or FDA-approved companion diagnostic designation are governed by the Medical Policy titled 'FDA Cleared or Approved Companion Diagnostic Testing (for Ohio Only)' and are not evaluated under this policy.
This policy addresses molecular oncology testing that is not an FDA-cleared or approved companion diagnostic; companion diagnostic use and coverage are assessed per the companion diagnostic policy.

Breast Cancer Gene Expression Profiling (GEP) — Proven and Medically Necessary

Breast cancer gene expression profiling (GEP) tests that are proven and medically necessary to inform adjuvant chemotherapy or extended endocrine therapy decisions are listed below. See InterQual CP: Molecular Diagnostics for full clinical criteria and code-level guidance.

ALL of the following

Indication: Newly diagnosed (within last 6 months)
- Tumor is invasive breast cancer; and
- Lymph node negative (including micrometastases ≤ 2 mm) OR 1–3 positive ipsilateral axillary lymph nodes; and
- No evidence of distant metastatic disease; and
- Hormone receptor–positive (ER and/or PR positive); and

Lung Cancer — cfDNA multigene profiling (NSCLC)

Multigene cfDNA (liquid biopsy) profiling for non–small cell lung cancer (NSCLC) is covered when limited to 50 genes or fewer; testing of more than 50 genes is covered only when consistent with the FDA companion diagnostic policy. See InterQual CP: Molecular Diagnostics for tissue-based CGP and tumor tissue testing criteria.

ALL of the following

Multigene molecular profiling performed via liquid biopsy (cfDNA) for NSCLC is considered proven and medically necessary when the panel interrogates no more than 50 genes; and
If testing includes >50 genes, the use is considered only when consistent with the Medical Policy titled 'FDA Cleared or Approved Companion Diagnostic Testing (for Ohio Only)' (i.e., when the larger panel is required to implement an FDA-cleared companion diagnostic or follows that policy's permitted indications).
Clinical guideline context: ASCO/CAP/IASLC/AMP guidance and NCCN recommendations support molecular testing for key NSCLC driver alterations and recognize cfDNA as an alternative when tumor tissue is unavailable or results are needed rapidly; cfDNA panels should focus on actionable biomarkers and avoid routine unnecessarily large panels that exceed clinical utility thresholds (policy operationalizes this as a ≤50 gene threshold).

Prostate Cancer GEP — Prolaris / Decipher / GPS

Prostate cancer gene expression profiling (Prolaris, Decipher, Oncotype DX GPS) are proven and medically necessary for specific clinical scenarios. See InterQual CP: Molecular Diagnostics for full clinical coverage criteria.

ALL of the following

Ordering and general requirements
- Test must be ordered by a physician specializing in treatment of organ-confined prostate cancer (urology/surgical oncology, radiation oncology, or medical oncology).
- Results must be used to inform treatment decision-making (e.g., active surveillance vs definitive therapy) or adjuvant treatment after prostatectomy as specified below.
Biopsy-proven, untreated, localized prostate adenocarcinoma
- Individual has biopsy-proven, untreated, localized prostate adenocarcinoma with no clinical evidence of metastasis or lymph node involvement; and

Thyroid nodules with indeterminate cytology

Molecular testing for indeterminate thyroid nodules can be useful to guide surgery decisions in specified circumstances. Proven examples (Afirma GSC, ThyGeNEXT/ThyraMIR) and exclusions are provided below.

ALL of the following

Covered when all of the following are met: follicular-pattern fine needle aspiration cytology is indeterminate (Bethesda III or IV); and test results will be used to inform the decision about whether to proceed with surgery (diagnostic lobectomy vs observation); and the selected molecular test is one of the validated classifiers referenced (e.g., Afirma Genomic Sequencing Classifier [GSC], ThyGeNEXT/ThyraMIR).
Comprehensive genomic profiling (CGP) of confirmed anaplastic thyroid cancer is proven and medically necessary for management of confirmed anaplastic thyroid carcinoma.
Not medically necessary: other molecular tests for indeterminate nodules or thyroid cancer that lack sufficient evidence of efficacy, including Afirma Xpression Atlas (XA) and certain CGP panels for indeterminate nodules (e.g., NeoTYPE Thyroid Profile), are considered unproven and not medically necessary.

Other molecular testing of solid tumors

Other molecular testing of solid tumors (tumor tissue or liquid biopsy) is addressed primarily via InterQual CP pathways. Providers should refer to these InterQual clinical pathways for cancer‑ and context‑specific coverage criteria for comprehensive genomic profiling (CGP) and tumor‑specific molecular tests.

ALL of the following

For medical necessity clinical coverage criteria for tumor tissue CGP, liquid biopsy CGP, and tumor‑specific tests, refer to the InterQual CP: Comprehensive Genomic Profiling for Solid Tumor, Liquid Biopsy, and tumor‑specific modules (e.g., Oncotype DX Colon Recurrence Score, colorectal prognostic and predictive testing).
Coverage of CGP and other multigene tests depends on indication, tumor type, test performance, and whether results will influence management according to guideline-based care and InterQual criteria.

Unproven and Not Medically Necessary Molecular Tests

Tests and panels determined to be unproven and not medically necessary are listed here. This includes named assays, NGS panels exceeding the policy threshold, and measurable residual disease assays for solid tumors where evidence of clinical utility is insufficient.

ALL of the following

The following are considered not medically necessary due to insufficient evidence of clinical utility: NGS panels of >50 genes or comprehensive genomic profiling (unless specifically allowed per other policy provisions); Afirma Xpression Atlas (XA); CancerTYPE ID®; Decipher® Bladder; DecisionDx®‑Melanoma, DiffDx™‑Melanoma, DecisionDx®‑SCC; DermTech PLA™; Merlin (SkylineDx); myPath® Melanoma; NavDx®; Oncotype DX Colon Recurrence Score® (except where InterQual specifies coverage); Genefx® Colon (ColDx), ColonSentry®; PancraGEN®, PancreaSeq Genomic Classifier; Percepta® GSC; solid tumor profiling that includes whole exome/genome/transcriptome sequencing (e.g., Tempus xE/xR, OncoExTra™); whole‑genome methylation profiling.
Measurable residual disease (MRD) assays in solid tumors (tumor‑informed or tumor‑naïve) such as Invitae Personalized Cancer Monitoring™, Signatera™, RaDaR®, Guardant Reveal™, Haystack MRD™ are considered not medically necessary for routine clinical use due to insufficient evidence that routine MRD testing changes outcomes.
Specific prostate cancer screening/diagnostic panels (ExoDx Prostate, MyProstateScore, ConfirmMDx, SelectMDx, TMPRSS2 fusion gene testing for screening) are considered unproven and not medically necessary for routine management in this policy.

Definitions / General Scope

Definitions and scope notes to clarify terms used in this policy and operational guidance on what is included in molecular/prognostic testing.

ALL of the following

Comparative Genome Hybridization (CGH): technology to detect copy number variations; described for context in definitions.
Comprehensive Genomic Profiling (CGP): Next‑generation sequencing capable of detecting multiple classes of genomic alterations from a single sample; coverage depends on indication and adherence to InterQual/ policy criteria.
Gene Expression Profiling (GEP): tests that analyze mRNA expression patterns to provide prognostic or predictive information (examples: Prosigna®, BCI, EndoPredict®, Prolaris®, Oncotype DX GPS, Decipher®).
Liquid Biopsy: testing of body fluids (e.g., plasma cfDNA) to detect tumor‑derived nucleic acids; cfDNA testing is an alternative when tissue is unavailable or when rapid results are needed, but cfDNA panels should be limited to clinically actionable biomarkers and, per policy, to ≤50 genes unless an exception applies.

Not Medically Necessary / Unproven Tests

The policy explicitly notes that the listing of PLA, CPT, or other procedure codes is for reference only and does not imply that a service is covered. The Applicable Codes section reiterates that inclusion of a code does not imply coverage or guarantee payment. In addition, the policy states that measurable residual disease (MRD) assays in solid tumor cancers (tumor-informed or tumor-naïve), including named examples such as Invitae Personalized Cancer Monitoring, Signatera, RaDaR, Guardant Reveal, and Haystack MRD, are considered unproven and not medically necessary due to insufficient evidence.

Coding (CPT / PLA / Proprietary codes)

Applicable PLA/other proprietary codes listed (reference only)mixed

0016M	PLA code - revised description note
0306U	Proprietary code
0307U	Proprietary code
0340U	Proprietary code
0611U	Proprietary CPT/PLA code - added
0612U	Proprietary CPT/PLA code - added
0613U	Proprietary CPT/PLA code - added
81524	Multigene expression panel - added

Not Covered / Codes referenced but may be unproven / not medically necessarymixedNot Covered

0306U	Not covered — proprietary multigene test (refer to policy rationale)
0307U	Not covered — proprietary multigene test (refer to policy rationale)
0340U	Not covered — proprietary multigene test (refer to policy rationale)

Molecular pathology / multigene panel CPT codes listedCPT

81445	Molecular pathology procedure; interpretation and report of genomic sequence analysis (eg, somatic)
81449	Molecular pathology procedure; additional genomic sequencing
81455	Molecular pathology procedure; tier 1
81456	Molecular pathology procedure; tier 2
81457	Molecular pathology procedure; tier 3
81458	Molecular pathology procedure; tier 4
81459	Molecular pathology procedure; tier 5
81460	Molecular pathology procedure; tier 6
81461	Molecular pathology procedure; tier 7
81462	Molecular pathology procedure; tier 8

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1/3

Covered / Added CPT codesmixedCovered

0611U	Covered — newly added PLA/proprietary test (effective date in header)
0612U	Covered — newly added PLA/proprietary test (effective date in header)
0613U	Covered — newly added PLA/proprietary test (effective date in header)
81524	Covered — multigene expression panel (added to coverage list)

Revised CPT descriptionmixed

0016M

Revised description — see policy notes for updated language regarding assay reporting and algorithm use.

Provider Actions / Operational Requirements

Prior Authorization

FDA companion diagnostic restriction

Multigene panels containing more than 50 genes are allowed only when their use is consistent with the Medical Policy titled "FDA Cleared or Approved Companion Diagnostic Testing (for Ohio Only)." For liquid biopsy (cfDNA) multigene profiling, panels of up to 50 genes are proven and medically necessary for non–small cell lung cancer; >50-gene panels require alignment with the companion diagnostic policy. Document the specific policy rationale when requesting authorization.

Documentation Required

Document assay results and clinical factors

Use gene expression or genomic assay results together with clinicopathologic factors to guide treatment decisions. Record the assay name and numeric/category result, the clinicopathologic variables considered (e.g., tumor size, nodal status, grade, ER/PR/HER2), and how the combined information informed adjuvant chemotherapy or extended endocrine therapy recommendations.

Background, Evidence Summaries, and Guideline Context

Background and policy context: This Ohio-only medical policy relies on InterQual CP criteria for detailed medical necessity determinations for many molecular tests and tumor-specific indications; providers are referred to the InterQual CP modules (e.g., Comprehensive Genomic Profiling for Solid Tumor, Liquid Biopsy; Thyroid Nodule Genetic Testing) for specific coverage criteria. The policy also clarifies that tests granted FDA-cleared or -approved companion diagnostic status are governed by a separate companion diagnostics policy and that use of multigene liquid biopsy panels >50 genes is restricted to situations consistent with that companion diagnostic policy. Finally, the policy reiterates that the inclusion of PLA/CPT and other procedure codes in the document is reference only and does not imply coverage.

Breast cancer — use of gene expression assays

Assay-specific evidence summaries for commonly used breast GEP assays and their comparative evidence strengths.

Assay-specific evidence summaries: Oncotype DX (21-gene RS): prognostic for distant recurrence and overall survival; strongest predictive evidence for chemotherapy benefit (TAILORx, Sparano meta-analysis, Kalinsky RCT); Prosigna (PAM50): prognostic for 10-year distant recurrence in postmenopausal N0 or N+ HR+ patients; MammaPrint (70-gene) and BluePrint: assign low/high/ultralow risk with randomized and prospective-retrospective data (MINDACT, NSABP B-42, IDEAL); EndoPredict and BCI: provide prognostic information and BCI predictive for extended endocrine therapy in pooled studies; evidence varies by assay and clinical subgroup

Summarized evidence — use in conjunction with guideline recommendations

Definitions / Glossary

Term	Definition
Comparative Genome Hybridization (CGH)	Technology to detect genomic copy number variations using labeled tumor and reference DNA hybridized on arrays.
Comprehensive Genomic Profiling (CGP)	NGS test able to detect all classes of genomic alterations including cancer biomarkers from a single sample.
Gene Expression Profiling (GEP)	Laboratory test analyzing mRNA patterns to determine gene activity; also called gene expression assay.
Liquid Biopsy / cfDNA / ctDNA	Testing on bodily fluid to identify tumor-derived cells or circulating tumor DNA/RNA to aid detection, treatment selection, or monitoring (cell-free DNA / circulating tumor DNA).
Measurable Residual Disease (MRD)	Very small number of cancer cells or genetic material detectable during/after treatment; MRD assays in solid tumors are considered unproven per policy.
Next Generation Sequencing (NGS)	High-throughput sequencing techniques that analyze multiple DNA sections simultaneously.
Multi-gene analysis	A gene panel containing five or more genes (unless exceptions noted in policy).
Recurrence Score (RS)	Numeric score produced by Oncotype DX 21-gene assay indicating risk of distant recurrence and informing chemotherapy benefit.
ROR (Risk of Recurrence)	Score provided by Prosigna/PAM50 to estimate 10-year risk of distant recurrence.
NGS panel count threshold	Policy: multigene molecular profiling including no more than 50 genes is acceptable for liquid biopsy; >50 genes allowed only when consistent with FDA Cleared/Approved Companion Diagnostic policy.
GEP/GEC/GC	Gene expression profiling / gene expression classifier / genomic classifier — tests that analyze tumor gene expression to provide prognostic or predictive information.
Tumor-informed assay	Assay designed using mutations identified in the individual's tumor profile to track ctDNA (example: Signatera).
MRD — note on policy stance	Policy states MRD assays in solid tumors (tumor-informed or tumor-naïve) are unproven and not medically necessary in general.

Revision History

2026-04-01policy_changeLatest

Added language indicating multigene molecular profiling (including no more than 50 genes, or for more than 50 genes only when used in a manner consistent with the Medical Policy titled 'FDA Cleared or Approved Companion Diagnostic Testing (for Ohio Only)') performed via Liquid Biopsy (cell-free DNA (cfDNA)) is proven and medically necessary for non-small cell lung cancer. Policy-level has_material_change = true.

2026-04-01policy_changeLatest

Replaced language to allow Prolaris Biopsy or Decipher Prostate Biopsy genomic classifier as proven and medically necessary for individuals with biopsy-proven, untreated, localized adenocarcinoma of the prostate when listed criteria are met. Policy-level has_material_change = true.

Guideline Source	Key Recommendations / Position
NCCN	Prefers 21-gene Oncotype DX for pN0 (prognostic and predictive; 'Preferred'). For pN1 (1–3 nodes) Oncotype DX predictive/prognostic; postmenopausal: preferred; premenopausal: other. MammaPrint, Prosigna, EndoPredict listed as prognostic (preference = Other). BCI predictive for extended endocrine therapy.
ASCO	Supports use of Oncotype DX, MammaPrint, BCI, and EndoPredict to guide adjuvant endocrine/chemotherapy in postmenopausal (or >50) ER+/HER2- early breast cancer (N0 or 1–3 nodes). BCI and Prosigna may be used in selected settings; BCI may be offered to inform extended endocrine therapy after 5 years of ET.
ESMO	Recommends GEP/endocrine-response assessment when uncertainty about adjuvant chemotherapy remains after clinicopathologic assessment (Level II, Grade B); individualized risk-benefit decisions including biomarkers.
NICE (2024)	EndoPredict, Oncotype DX, or Prosigna may be used to guide adjuvant chemo in postmenopausal (or appropriate hormonal profile) ER/PR+, HER2- early BC with 1–3 nodes; should not be used in premenopausal women with 1–3 nodes. MammaPrint not recommended to guide chemo in 1–3 node premenopausal women; conditions for NHS use include intended purpose and data/quality requirements.
AUA/ASTRO/AUA-SUO/ASCO (prostate)	Tissue-based genomic biomarkers (Oncotype DX Prostate/GPS, Prolaris, Decipher, ProMark) may be offered selectively when results would affect management; routine ordering not recommended. Decipher may inform post-RP adjuvant therapy when adverse features present.
ASCO/AP/IASLC/AMP (NSCLC molecular testing)	Prefer multiplexed NGS panels; cfDNA (liquid biopsy) not routine but may be used when tissue is limited/insufficient; BRAF testing for all advanced lung adenocarcinoma; include drivers in panels rather than single-gene standalone tests.