CurrentUnitedHealthcarePolicy CS152LA.AA

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

Defines UnitedHealthcare Community Plan coverage criteria for molecular and genetic testing of solid tumors for Louisiana Medicaid, including permitted gene expression profiling, next-generation sequencing, liquid biopsy, and required genetic counseling.

Policy Summary

PayerUnitedHealthcare

PolicyMolecular Oncology Testing for Solid Tumor Cancer Diagnosis, Prognosis, and Treatment Decisions (Louisiana)

Policy CodePolicy CS152LA.AA

Change TypeNo material changes

Effective DateFeb 1, 2026

Next Review Date

Key ActionDocument pre- and post-test genetic counseling, including structured family history and genetic risk assessment, in the medical record.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

LouisianaGeographic applicability

50 genesNGS panel threshold

RequiredGenetic counseling

~100+PLA/CPT/HCPCS codes listed

21Oncotype DX panel

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Coverage Criteria and Clinical Indications

inv-01: Breast Cancer Gene Expression Profiling (GEP) — Proven and medically necessary when ALL of the following are met for invasive breast cancer:

Breast Cancer Gene Expression Profiling (GEP) — Proven and medically necessary when ALL of the following are met for invasive breast cancer:

All of the following:

- Test is one of the following GEP assays: MammaPrint, Oncotype DX Breast Recurrence Score (21-gene), Prosigna (PAM50), Breast Cancer Index (BCI), or EndoPredict; and

- Testing is for an individual with newly diagnosed invasive breast cancer within the past 6 months OR for an individual currently receiving adjuvant endocrine therapy when results will be used to guide extended endocrine therapy; and

- Tumor is hormone receptor–positive (ER+ and/or PR+); and

- Tumor is HER2 receptor–negative; and

- No distant metastases are present; and

- Lymph node status is either node-negative (including micrometastases ≤ 2 mm) or 1–3 positive ipsilateral axillary lymph nodes (N0 or N1); and

- Adjuvant chemotherapy is not precluded by other non-oncologic factors (e.g., severe comorbidity, short life expectancy) and the results will be used to inform the decision to give or withhold adjuvant chemotherapy (for assays intended to predict chemotherapy benefit) or to guide consideration of extended endocrine therapy (for BCI); and

- For individuals already on adjuvant endocrine therapy, the treating clinician and patient discussed potential test outcomes prior to ordering and intend to use results to guide decisions about extended adjuvant endocrine therapy.

inv-02: Lung Cancer — Proven and medically necessary when performed as follows for non-small cell lung cancer:

Lung Cancer — Proven and medically necessary when performed as follows for non-small cell lung cancer:

All of the following:

- Multigene molecular profiling (tumor tissue-based) using a panel approach is performed to identify actionable driver alterations to guide targeted therapies; and

- When feasible, a broad, panel-based NGS approach is preferred to identify established and emerging targetable alterations; and

- If tissue is insufficient or patient is medically unfit for invasive sampling, validated plasma cfDNA/ctDNA testing may be used to identify actionable alterations, but cfDNA testing should not replace a tissue diagnosis and tissue testing should follow when an actionable driver is not identified; and

- Panel size: tests with ≤ 50 genes are acceptable; tests > 50 genes are considered medically necessary only when used consistent with applicable companion diagnostic guidance or when results would alter management per guideline recommendations.

inv-03: Prostate Cancer Gene Expression Profiling (GEP) — Proven and medically necessary when ALL of the following are met for biopsy-proven, untreated, localized adenocarcinoma:

Prostate Cancer Gene Expression Profiling (GEP) — Proven and medically necessary when ALL of the following are met for biopsy-proven, untreated, localized adenocarcinoma:

All of the following:

- Test is one of the following tissue-based genomic assays: Genomic Prostate Score (GPS/Oncotype DX Prostate), Prolaris, or Decipher (biopsy-based or as indicated for post-prostatectomy use per item below); and

- Test is ordered by a physician experienced in prostate cancer management (e.g., urology/surgical oncology, radiation oncology, or medical oncology); and

- Results will be used to assist treatment decision-making when the individual has not yet received definitive therapy and is a candidate for active surveillance versus definitive therapy; and

- Life expectancy is greater than 10 years; and

inv-04: Thyroid Cancer or Indeterminate Thyroid Nodule Testing — Proven and medically necessary when ALL of the following are met:

Thyroid Cancer or Indeterminate Thyroid Nodule Testing — Proven and medically necessary when ALL of the following are met:

All of the following:

- Fine needle aspiration cytology is indeterminate (Bethesda category III or IV) for a thyroid nodule; and

- A validated molecular classifier intended for indeterminate cytology (e.g., Afirma GSC, ThyroSeq v3, ThyGeNEXT/ThyraMIR) is ordered; and

- The results of the molecular test will be used to make decisions about further surgery (i.e., influence decision for diagnostic/diagnostic–therapeutic surgery versus observation); and

- The testing laboratory and intended test match the clinical question (rule-out vs rule-in performance characteristics considered).

inv-05: Uveal Melanoma Gene Expression Profiling (GEP) — Proven and medically necessary when ALL of the following are met:

Uveal Melanoma Gene Expression Profiling (GEP) — Proven and medically necessary when ALL of the following are met:

All of the following:

- Individual has primary, localized uveal melanoma; and

- There is no evidence of metastatic disease; and

- The individual has not previously undergone DecisionDx-UM (or equivalent validated 15-gene GEP) testing for the current diagnosis; and

- Results will be used to guide surveillance intensity and management decisions (i.e., drive high- versus low-intensity surveillance strategies).

inv-06: Coverage criteria — 0 top-level nodes (placeholder for grouped coverage logic)

Coverage criteria — summary (policy-level interpretation):

All of the following:

- Tests and indications explicitly listed as proven/medically necessary in this policy section (e.g., specified BC GEP assays, NSCLC panel testing, specified prostate/thyroid/uveal assays) are covered when the associated clinical criteria are met; and

- Tests and indications described in this policy as unproven, insufficient evidence, or explicitly listed as not medically necessary (including many other listed assays and broader applications such as routine use of MRD assays, multi-cancer early detection tests, and certain screening cfDNA tests) are not covered outside investigational or research contexts; and

- Codes marked with an asterisk in the Applicable Codes list may not be covered under some state Medicaid fee schedules (Louisiana) — check state-specific fee schedule for coverage; and

- Prosigna (PAM50) is not intended for individuals with N2 nodal status; and

inv-07: Evidence-based coverage considerations — Evidence-based findings relevant to coverage decisions

Evidence-based coverage considerations — Evidence-based findings relevant to coverage decisions:

All of the following:

- High-level evidence supports prognostic and, in some cases, predictive utility of specific GEP assays (e.g., Oncotype DX and MammaPrint have prospective trial data; Oncotype DX has the strongest evidence for predicting chemotherapy benefit in specific populations); and

- ASCO, NCCN, ESMO, and NICE guidance identify populations where selected assays may be used to inform adjuvant chemotherapy or extended endocrine therapy decisions (see guideline summaries); and

- For NSCLC, guideline panels (NCCN, ASCO-endorsed CAP/IASLC/AMP) recommend broad panel testing (NGS) to identify actionable alterations and suggest selective use of cfDNA when tissue is limited; and

- For prostate cancer, major societies endorse selective (not routine) use of tissue-based genomic classifiers when results are likely to change management decisions; and

inv-08: Assay-specific coverage considerations — Assay-specific clinical contexts and intended use

Assay-specific coverage considerations — Assay-specific clinical contexts and intended use:

All of the following:

- Oncotype DX (21-gene RS): preferred test per NCCN for ER+, HER2-, node-negative disease; validated for prognosis and prediction of chemotherapy benefit in selected populations (including guidance for pN0 and selected pN1 patients); and

- MammaPrint (70-gene): prognostic value demonstrated in MINDACT, may identify patients (including some clinically high-risk individuals) who can safely forgo chemotherapy; predictive benefit not fully established for all subgroups and age-dependent effects observed; and

- Prosigna (PAM50): provides a 10-year distant recurrence risk score for postmenopausal women with HR+, N0 or N1 disease; not intended for N2 disease; and

- BCI: may be used to inform the decision about extended endocrine therapy in individuals who have completed ~5 years of endocrine therapy with no recurrence; and

inv-09: Assay-specific coverage considerations — ASCO-based guidance and evidence summaries support assay use in specific populations

Assay-specific coverage considerations — ASCO- and guideline-based guidance and evidence summaries support assay use in specific populations:

All of the following:

- ASCO (2022) supports use of Oncotype DX, MammaPrint, BCI, and EndoPredict to guide adjuvant endocrine and chemotherapy decisions in postmenopausal individuals or those >50 with ER+, HER2- early breast cancer who are node-negative or have 1–3 positive nodes; and

- ASCO indicates BCI and Prosigna may be used in postmenopausal, node-negative ER+, HER2- disease; and BCI may aid decisions about extended endocrine therapy after 5 years of treatment; and

- NCCN prefers Oncotype DX for prognosis and prediction of chemotherapy benefit but recognizes other assays provide prognostic information; and

- NICE (2024) specifies menopausal-status distinctions for assay use in node-positive disease and outlines conditions for NHS use (data collection, clinical-risk context).

inv-10: Guideline-derived GEP indications and distinctions — recommendations and conditions for using gene expression profiling in early breast cancer

Guideline-derived GEP indications and distinctions — recommendations and conditions for using gene expression profiling in early breast cancer:

All of the following:

- Use GEP only when results will change management (e.g., decision for/against adjuvant chemotherapy or extended endocrine therapy); and

- Do not use GEP to determine need for systemic therapy in HER2-positive or triple-negative breast cancer; and

- For premenopausal individuals, Oncotype DX may be considered in node-negative disease but benefit in node-positive premenopausal women may differ (age/menopausal status can modify chemotherapy benefit); and

- GEP is not recommended for individuals with ≥4 positive nodes (N2 or higher) due to lack of validated evidence supporting its utility in this group.

inv-11: NSCLC molecular testing guidance — Guidance for molecular biomarker testing in NSCLC from multiple studies and professional society guidelines

NSCLC molecular testing guidance — Guidance for molecular biomarker testing in NSCLC from multiple guidelines:

All of the following:

- Perform comprehensive genotyping (preferably NGS panel) for advanced/metastatic NSCLC and for earlier-stage disease when results would affect neoadjuvant/adjuvant targeted therapy decisions; and

- Include testing for established targets (EGFR, ALK, ROS1, BRAF, NTRK, RET, MET, HER2, KRAS) and markers relevant for immunotherapy selection (PD-L1) as indicated; and

- Use validated plasma cfDNA testing when tissue is unavailable or insufficient, but interpret negative cfDNA results cautiously and pursue tissue testing if clinically indicated; and

- Prefer multiplexed panels to single-gene tests to conserve tissue and detect uncommon actionable alterations.

inv-12: When molecular/genomic testing is appropriate — Guideline- and evidence-based circumstances where molecular/genomic testing is recommended

When molecular/genomic testing is appropriate — Guideline- and evidence-based circumstances where molecular/genomic testing is recommended:

Any of the following:

- When test results will change management (e.g., choice of systemic therapy, selection of targeted agents, decision to omit or add chemotherapy or extend endocrine therapy); or

- When identifying an actionable alteration may enable enrollment in a clinical trial or use of an FDA-cleared/companion diagnostic therapy; or

- When test results supplement diagnostic workup in indeterminate cases (e.g., thyroid cytology Bethesda III/IV) and will influence the decision for surgery versus surveillance.

inv-13: Selective coverage vs insufficient evidence — Covered when ALL of the following are met (policy-level interpretation guidance reflected in citations):

Selective coverage vs insufficient evidence — Covered when ALL of the following are met (policy-level interpretation guidance reflected in citations):

All of the following:

- The specific assay has demonstrated analytic validity and a body of clinical evidence supporting clinical validity in the intended population; and

- Professional guidelines endorse selective use of the assay for the intended clinical question (e.g., NCCN, ASCO, NICE recommendations); and

- The treating clinician documents that test results are expected to alter management and that alternative decision-making tools were considered.

inv-14: Prostate cancer genomic classifiers — selective coverage; Covered when ALL of the following are met (per guideline consensus for selective use):

Prostate cancer genomic classifiers — selective coverage; Covered when ALL of the following are met (per guideline consensus for selective use):

All of the following:

- Test is Decipher, Oncotype DX Prostate (GPS), or Prolaris; and

- Ordered by a prostate cancer specialist; and

- Results will influence management (e.g., decision between active surveillance and definitive therapy) in men with life expectancy ≥ 10 years; and

- For post-prostatectomy adjuvant decision-making, Decipher may be used when adverse pathological features or PSA persistence/recurrence are present.

inv-15: Thyroid indeterminate nodule molecular tests — conditional coverage; Covered when ALL of the following are met:

Thyroid indeterminate nodule molecular tests — conditional coverage; Covered when ALL of the following are met:

All of the following:

- Cytology is indeterminate (Bethesda III/IV); and

- A validated molecular classifier intended for indeterminate nodules (e.g., Afirma GSC, ThyroSeq v3) is selected; and

- The test result will be used to decide between surgery and observation; and

- Patient counseling occurred regarding benefits and limitations of testing and local malignancy prevalence is considered when interpreting results.

inv-16: When molecular testing may be considered — contexts where results would alter management

When molecular testing may be considered — contexts where results would alter management:

Any of the following:

- Clarify risk to avoid unnecessary surgery (e.g., thyroid indeterminate nodules with high NPV assays); or

- Guide adjuvant systemic therapy decisions (e.g., breast GEP to inform chemotherapy use); or

- Stratify surveillance intensity (e.g., uveal melanoma GEP) or inform adjuvant therapy post-prostatectomy (Decipher).

inv-17: Cutaneous melanoma: evidence-based stance — GEP evaluated for SLNB prediction and recurrence risk with mixed evidence

Cutaneous melanoma: evidence-based stance — GEP evaluated for SLNB prediction and recurrence risk with mixed evidence:

All of the following:

- Current evidence for cutaneous melanoma GEP tests (e.g., DecisionDx-Melanoma, 31-GEP, MelaGenix, PLA) shows prognostic associations with recurrence and survival in some studies but overall clinical utility for changing management and improving outcomes has not been established; and

- NCCN does not endorse routine use of prognostic GEP tests to guide management independent of clinicopathologic factors and recommends prospective validation against established clinicopathologic models; and

- Use of tests to guide SLNB decisions or surveillance should be considered investigational or within a clinical study unless supported by prospective outcome data demonstrating improved outcomes.

inv-18: Evidence summary and coverage considerations — Coverage-relevant findings and guidance summarized from the evidence

Evidence summary and coverage considerations — Coverage-relevant findings and guidance summarized from the evidence:

All of the following:

- Coverage adheres to assay-specific evidence, regulatory/companion diagnostic status, and professional guideline recommendations; and

- Tests intended for screening or multi-cancer early detection, routine MRD surveillance without demonstrated clinical utility, and many single-use exploratory panels lack sufficient evidence and are considered not medically necessary; and

- Where guideline panels differ (e.g., menopausal status distinctions), the policy reflects conservative, evidence-aligned coverage and documents clinical criteria to limit use to populations with demonstrated benefit.

inv-19: CUP — Evidence-informed coverage considerations — Coverage considerations based on evidence and guideline statements for CUP-directed molecular testing

CUP — Evidence-informed coverage considerations — Coverage considerations based on evidence and guideline statements for CUP-directed molecular testing:

All of the following:

- Molecular tests to identify tissue of origin (GEP) or to guide site-specific therapy in CUP have variable diagnostic accuracy; randomized trials have not consistently shown survival benefit from site-specific therapy guided solely by GEP; and

- Comprehensive genomic profiling (NGS) may identify actionable alterations and trial eligibility in a subset of CUP patients and can be considered after standard histopathologic and IHC workup when results would alter therapy or enable enrollment in targeted therapy trials; and

- Routine use of GEP solely for tissue-of-origin determination without expectation of altering management is not supported.

inv-20: CRC — Evidence-informed coverage considerations — Coverage considerations for colorectal cancer molecular tests

CRC — Evidence-informed coverage considerations — Coverage considerations for colorectal cancer molecular tests:

All of the following:

- Universal tumor MMR/MSI testing is recommended for all individuals with colorectal cancer for Lynch syndrome screening and to guide immunotherapy decisions; and

- Use of multigene prognostic panels, Immunoscore, or post-surgical ctDNA for routine adjuvant decision-making is not currently recommended by NCCN due to insufficient evidence; and

- Blood-based multi-cancer early detection tests and some cfDNA screening assays currently lack sufficient evidence for population screening and are not covered for routine CRC screening.

inv-21: Coverage considerations and evidence-based criteria — Summary coverage considerations based on evidence and guideline recommendations

Coverage considerations and evidence-based criteria — Summary coverage considerations based on evidence and guideline recommendations:

All of the following:

- Cover tests and indications explicitly supported by high-quality evidence and guideline endorsement when clinical criteria in this policy are met; and

- Deny coverage for tests and uses listed as unproven or not medically necessary in this policy unless performed in the context of an IRB-approved clinical trial or with payer-approved exception; and

- Require documentation that test results will influence management and that appropriate clinical and pathologic evaluation was performed before testing; and

- Verify local/state code coverage (some CPT/HCPCS codes may be excluded from state Medicaid fee schedules).

inv-22: General Coverage Criteria and Guideline-Based Limitations — Summary of evidence-based coverage stance and clinical criteria from guidelines and technology assessments

General Coverage Criteria and Guideline-Based Limitations — Summary of evidence-based coverage stance and clinical criteria from guidelines and technology assessments:

All of the following:

- Coverage follows assay-specific inclusion criteria and professional guideline recommendations (ASCO, NCCN, ESMO, NICE, ATA, AUA/ASTRO), including menopausal and nodal-status distinctions where applicable; and

- Tests lacking sufficient evidence (extensive list in policy) are considered experimental/investigational and not medically necessary; and

- Prior authorization and documentation requirements may apply; codes with state-specific exclusions (e.g., Louisiana) should be checked before billing.

Covered Indications by Tumor Type and Test Class

Applicable Procedure Codes and Coding Notes

Applicable procedure codes (reference)mixed

0005U	Oncology (prostate) gene expression profile by real-time RT-PCR of 3 genes (ERG, PCA3, and SPDEF), urine, algorithm reported as risk score.
0011M	Oncology, prostate cancer, mRNA expression assay of 12 genes (10 content and 2 housekeeping), RT-PCR test utilizing blood plasma and urine, algorithms to predict high-grade prostate cancer risk.
0012M	Oncology (urothelial), mRNA, gene expression profiling by real-time quantitative PCR of five genes (MDK, HOXA13, CDC2 [CDK1], IGFBP5, and CXCR2), utilizing urine, algorithm reported as a risk score for having urothelial carcinoma.
0013M	Oncology (urothelial), mRNA, gene expression profiling by real-time quantitative PCR of five genes (MDK, HOXA13, CDC2 [CDK1], IGFBP5, and CXCR2), utilizing urine, algorithm reported as a risk score for having recurrent urothelial carcinoma.
0016M	Oncology (bladder), mRNA, microarray gene expression profiling of 219 genes, utilizing formalin- fixed paraffin-embedded tissue, algorithm reported as molecular subtype.
0020M	Oncology (central nervous system), analysis of 30000 DNA methylation loci by methylation array, utilizing DNA extracted from tumor tissue, diagnostic algorithm reported as probability of matching a reference tumor subclass.
0018U	Oncology (thyroid), microRNA profiling by RT-PCR of 10 microRNA sequences, utilizing fine needle aspirate, algorithm reported as a positive or negative result for moderate to high risk of malignancy.
0019U	Oncology, RNA, gene expression by whole transcriptome sequencing, formalin-fixed paraffin-embedded tissue or fresh frozen tissue, predictive algorithm reported as potential targets for therapeutic agents.
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.
0026U	Oncology (thyroid), DNA and mRNA of 112 genes, next-generation sequencing, fine needle aspirate of thyroid nodule, algorithmic analysis reported as a categorical result ('Positive, high probability of malignancy' or 'Negative, low probability of malignancy').

1–10 of 20

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Applicable molecular oncology PLA/CPT/HCPCS codes and descriptionsmixed

0022U	Targeted genomic sequence analysis panel, non-small cell lung neoplasia, DNA and RNA analysis, 23 genes
0026U	Oncology (thyroid), DNA and mRNA of 112 genes, next-generation sequencing, fine needle aspirate of thyroid nodule
0036U	Exome (somatic mutations), paired FFPE tumor and normal specimen sequence analyses
0037U	Targeted genomic sequence analysis, solid organ neoplasm, DNA analysis of 324 genes
0045U	Oncology (breast DCIS), mRNA, gene expression profiling of 12 genes, FFPE, recurrence score
0047U	Oncology (prostate), mRNA profiling of 17 genes, FFPE, risk score
0048U	Oncology (solid), DNA, targeted sequencing of 468 cancer-associated genes, matched with normal specimens
0069U	Oncology (colorectal), microRNA RT-PCR profiling of miR-31-3p, FFPE, expression score
0089U	Oncology (melanoma), gene expression profiling PRAME and LINC00518, superficial adhesive patch
0090U	Oncology (cutaneous melanoma), mRNA profiling of 23 genes, FFPE, categorical result

1–10 of 118

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Applicable CPT/HCPCS Codesmixed

81521	Oncology (breast), mRNA, microarray gene expression profiling of 70 content genes and 465 housekeeping genes, utilizing fresh frozen or formalin-fixed paraffin-embedded tissue, algorithm reported as index related to risk of distant metastasis
81522	Oncology (breast), mRNA, gene expression profiling by RT-PCR of 12 genes (8 content and 4 housekeeping), utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as recurrence risk score
81523	Oncology (breast), mRNA, next-generation sequencing gene expression profiling of 70 content genes and 31 housekeeping genes, utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as index related to risk to distant metastasis
81524	Oncology (central nervous system tumor), DNA methylation analysis of at least 10,000 methylation sites, utilizing DNA extracted from formalin-fixed tumor tissue, algorithm(s) reported as probability of matching a reference tumor family and class, and MGMT promoter methylation status, if performed
81525	Oncology (colon), mRNA, gene expression profiling by real-time RT-PCR of 12 genes (7 content and 5 housekeeping), utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as a recurrence score
81529	Oncology (cutaneous melanoma), mRNA, gene expression profiling by real-time RT-PCR of 31 genes (28 content and 3 housekeeping), utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as recurrence risk, including likelihood of sentinel lymph node metastasis
81540	Oncology (tumor of unknown origin), mRNA, gene expression profiling by real-time RT-PCR of 92 genes (87 content and 5 housekeeping) to classify tumor into main cancer type and subtype, utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as a probability of a predicted main cancer type and subtype
81541	Oncology (prostate), mRNA gene expression profiling by real-time RT-PCR of 46 genes (31 content and 15 housekeeping), utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as a disease-specific mortality risk score
81542	Oncology (prostate), mRNA, microarray gene expression profiling of 22 content genes, utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as metastasis risk score
81546	Oncology (thyroid), mRNA, gene expression analysis of 10,196 genes, utilizing fine needle aspirate, algorithm reported as a categorical result (e.g., benign or suspicious)

1–10 of 14

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No explicit billing or procedure codes listed in these chunksmixed

No codes listed

NGS panel gene-count threshold — inv-59: NGS panel gene-count threshold — NGS panels of > 50 genes or CGP are listed as unproven unless otherwise specified

Policy thresholdNGS panels of > 50 genes or comprehensive genomic profiling (CGP) are listed as unproven and not medically necessary unless explicitly specified otherwise in the policy.

Allowed exception contextPanels >50 genes may be considered only when used in a manner consistent with FDA-cleared/approved companion diagnostic testing or as otherwise specified in the policy.

Implication for orderingMultigene molecular profiling up to 50 genes is the routinely supported upper size for covered NGS panels in many indications (see lung cancer criteria).

Panel gene counts (examples) — inv-60: Panel gene counts (examples) — Examples listed range from single-gene assays up to whole genome/transcriptome and panels of 5-521+ genes

Provider Requirements, Documentation, and Operational Guidance

Prior Authorization

Align Authorization with Guideline Indications

Authorization decisions should align with ASCO-recommended indications: authorize genomic assays when results are likely to inform adjuvant endocrine or chemotherapy decisions in populations supported by ASCO/NCCN (for example, Oncotype DX, MammaPrint, BCI, EndoPredict in specified early-stage breast cancer populations). Use genomic assays within their intended purposes and ensure laboratories participate in external quality assurance programs.

Authorize tests when result will likely change management
Ensure lab QA participation and result communication by oncologist

Note

NGS Panels Preferred; cfDNA Reserved for Specific Scenarios

Prefer comprehensive NGS panels over single-gene assays where feasible for guidance of targeted therapy; reserve cfDNA (plasma/ctDNA) testing for advanced/metastatic disease or when tissue is unavailable or insufficient. cfDNA should not be used in lieu of tissue diagnosis and, when negative or indeterminate, should be followed by tissue-based testing if clinically feasible.

NGS preferred for full genotyping (NSCLC, CRC, others)

Tests and Indications Not Covered / Investigational

A broad list of named tests and categories are called out as not covered or investigational because evidence is insufficient to demonstrate clinical utility. This includes, but is not limited to, multi‑cancer early detection (MCD) assays (e.g., Galleri), tumor‑informed and tumor‑naïve MRD ctDNA assays (e.g., Signatera, Guardant Reveal), many proprietary diagnostic classifiers (e.g., CancerTYPE ID, NavDx), and routine use of whole exome/genome/transcriptome sequencing for clinical decision‑making. The policy also lists other specific proprietary and high‑complexity tests that are considered unproven for routine coverage.

Within the provided excerpts there are no additional explicit ‘not covered’ statements beyond the extensive lists of unproven tests and categories; the document instead relies on the enumerated unproven/not medically necessary lists and applicable code guidance to define noncoverage contexts.

Codes annotated with an asterisk in the policy are noted as not present on the Louisiana Medicaid Fee Schedule and therefore may not be covered for Louisiana members; coverage may vary by state fee schedules and payer‑specific rules.

EndoPredict is described in the evidence review as having limited but positive data for estimating ten‑year distant recurrence risk in ER+, HER2‑, early‑stage breast cancer; however, prospective validation is lacking and the assessment notes insufficient prospective studies to fully establish clinical validity and utility for some populations.

The policy flags that other GEP assays beyond the principal, guideline‑endorsed tests may not be covered depending on evidence — examples include Theros H/I, DCISionRT, older Oncotype DX DCIS versions, and other multi‑gene signatures lacking robust validation.

Definitions and Test Descriptions

Comprehensive Genomic Profiling (CGP) — inv-125: Comprehensive Genomic Profiling (CGP) — definition and scope

DefinitionComprehensive Genomic Profiling (CGP) is a hybrid-capture or broad NGS–based testing approach that assesses multiple genomic alteration classes (SNVs, indels, CNVs, rearrangements), and may include TMB and MSI to identify potential targeted therapies or trial eligibility.

Typical capabilitiesCGP can detect sequence variants, copy-number alterations, rearrangements, and biomarkers such as MSI or TMB from tumor tissue or cfDNA when configured for plasma testing.

Role in CUP and advanced diseaseCGP/NGS is commonly used to find actionable alterations in cancers of unknown primary or advanced/metastatic disease to support targeted therapy selection or trial enrollment, but policy notes outcome benefits are not always established.

Liquid Biopsy — inv-126: Liquid Biopsy — definition

DefinitionLiquid biopsy refers to testing performed on a bodily fluid (commonly plasma) to identify tumor-derived material such as circulating tumor DNA (ctDNA) or other analytes for detection of genomic alterations, treatment selection, or monitoring.

Eligibility Requirements and Preconditions for Coverage

The policy requires documentation of pre‑ and post‑test genetic counseling for all genetic testing. Counseling must include a structured family genetic history, genetic risk assessment, and counseling about diagnosis, prognosis, and treatment, and this documentation should be retained in the medical record.

Although the policy requires genetic counseling documentation for all genetic testing, no additional structured top‑level eligibility nodes are specified in the provided excerpts; clinicians should follow the counseling documentation requirements when ordering genetic and molecular tests.

For prostate genomic testing, guideline excerpts emphasize that patient and tumor risk factors must be fully assessed to guide decisions about testing and potential germline evaluation; the policy therefore expects documentation of the clinical rationale and baseline risk features prior to ordering select genomic assays.

NCCN guidance cited in the policy recommends universal tumor MMR/MSI testing for any individual with a personal history of colon or rectal cancer; while the policy excerpts show no top‑level eligibility nodes, this recommendation constitutes a clear practice expectation for colorectal cancer cases.

For uveal melanoma prognostic GEP (DecisionDx‑UM), eligibility requires a primary, localized uveal melanoma with no evidence of metastatic disease and that the individual has not previously had DecisionDx‑UM testing for the current diagnosis; documentation of these clinical conditions is implied.

Applicable procedure codes and gene‑panel code groupings are provided as reference; while the policy does not list additional numeric eligibility thresholds in the extracted chunks, code selection should align with the test ordered and the documented clinical indication.

Background and Evidence Context

Comprehensive genomic profiling (CGP), gene expression profiling (GEP), and liquid biopsy are commonly used in solid tumor care to assist with diagnosis, prognostication, and selection of targeted therapies. The policy differentiates evidence‑supported, clinically indicated tests (for example, specified GEP assays in defined breast cancer populations, NGS panels for NSCLC, select prostate genomic classifiers, and molecular evaluation of indeterminate thyroid nodules) from tests without sufficient evidence (including many proprietary assays, MRD assays, MCED tests, and routine whole exome/genome/transcriptome sequencing) which are considered investigational or not medically necessary for routine clinical use.

Quick Actions for Ordering Providers

Note

Revision History

2026-02-01policy_effectiveLatest

Policy effective date (CS152LA.AA) established for Louisiana Medicaid molecular oncology testing policy.

Policy Summary

PayerUnitedHealthcare

PolicyMolecular Oncology Testing for Solid Tumor Cancer Diagnosis, Prognosis, and Treatment Decisions (Louisiana)

Policy CodePolicy CS152LA.AA

Change TypeNo material changes

Effective DateFeb 1, 2026

Next Review Date

Key ActionDocument pre- and post-test genetic counseling, including structured family history and genetic risk assessment, in the medical record.

SourceLink

On This Page

- Risk group is one of: very low-risk, low-risk, or favorable intermediate-risk (GPS/Prolaris/Decipher may also be considered in unfavorable intermediate- or high-risk disease per guideline discretion).

- cfDNA (liquid biopsy) testing should not routinely replace tissue diagnosis; its use is appropriate in specific circumstances (e.g., insufficient tissue, medically unfit for biopsy) and when results would alter management per guidelines.

- For thyroid nodules with indeterminate cytology, high-sensitivity/high-NPV classifiers (e.g., ThyroSeq v3, Afirma GSC) can reduce unnecessary diagnostic surgeries when used to rule out malignancy and when results will change management.

- EndoPredict: provides EPclin score incorporating tumor size and nodal status to estimate 10-year distant recurrence risk; evidence limited in some populations and further validation recommended.

Small panels / single-gene assays

Policy references testing that can range down to single-gene assays for specific indications (e.g., single-driver tests).

Definition of multigeneFor this policy, multi-gene analysis generally refers to a gene panel containing five or more genes.

Medium panelsCPT/PLA examples and policy listings include panels in ranges such as 5–50 genes (CPT 81445/81449) and specific proprietary panels of ~23–101–257 genes in the code listings.

Large panels/whole exome/transcriptomeDocumented examples include whole-exome, whole-genome, or whole-transcriptome assays and cfDNA panels described up to 521+ genes and other WGTA/WES/WGS/WTS approaches (these are listed among broader analytic offerings).

Oncotype DX Recurrence Score risk categories (examples reported) — inv-61: Oncotype DX Recurrence Score risk categories (examples reported)

TAILORx (example cutoffs)Recurrence Score (TAILORx): <11 (low), 11–25 (intermediate), >25 (high).

Common alternative cutoffsOther commonly reported cutoffs: <18 (low), 18–30 (intermediate), >30 (high).

Clinical use noteRecurrence score categories have been used to guide adjuvant chemotherapy decisions and local-regional risk assessment in early-stage ER+/HER2- breast cancer.

Prosigna intended population nodal status — inv-62: Prosigna intended population nodal status — N0 (Stage I or II) or N+ (Stage II); not intended for N2

Intended nodal populationsProsigna (PAM50) is intended for postmenopausal women with HR+ breast cancer who are N0 (Stage I or II) or N+ (Stage II).

Not intended for N2The assay is not intended for individuals with N2 nodal status (policy explicitly states Prosigna is not for N2).

Specimen typeProsigna measures 50 genes using formalin-fixed paraffin-embedded (FFPE) breast tumor tissue.

cfDNA appropriate when tissue limited or patient unfit for biopsy

Follow-up tissue testing required if cfDNA is negative/indeterminate

Documentation Required

Clinician-Directed Test Selection

Clinician-directed test selection is expected: choose assays based on the specific clinical question (diagnosis, prognosis, or targeted therapy selection). Avoid routine or indiscriminate ordering — select tests that will provide actionable information for the individual patient's management.

Select molecular tests that address specific diagnostic or therapeutic questions
Routine ordering discouraged unless results alter management

Prior Authorization

Prior Authorization Guidance for Ancillary Molecular Testing

Prior authorization guidance for ancillary molecular testing: when tests are adjuncts to specialty pathology (e.g., dermatopathology) or are used for prognostication (e.g., GEP in melanoma or cSCC), authorization may require documentation of multidisciplinary review, intended use, and how results would change management.

Document multidisciplinary discussion for GEP use in cSCC or cutaneous melanoma
Authorization may require evidence that result would change adjuvant or surveillance plans

Documentation Required

Prior Clinical Workup and Rationale Required

Require documentation of prior clinical workup and rationale: molecular profiling (including pan-cancer NGS or GEP in CUP) should reflect guideline-recommended prior steps (histology determination, standard immunohistochemistry, imaging) and include rationale for testing.

Document prior histology/IHC and why additional molecular testing is needed
For CUP, show prior diagnostic workup before pan-cancer NGS or GEP

Billing Rule

Tumor Biomarker Testing (NGS Preferred)

Tumor biomarker testing expectations: when determining targeted therapies, tumor/somatic profiling should preferentially use NGS panels per guidelines (eg, NCCN). Ensure documentation of specimen source, receptor and nodal status, and how results will inform therapy selection.

NGS preferred methodology for actionable biomarker detection
Document tumor tissue source (FFPE, fresh/frozen) and relevant pathologic details

Note

Molecular Profiling in Pancreatic Cancer

Molecular profiling for pancreatic cancer: offer tumor/somatic profiling in metastatic or locally advanced pancreatic cancer when the patient is a candidate for anti-cancer therapy or a clinical trial. Do not use ctDNA for pancreatic cancer screening outside clinical trials.

Offer somatic profiling for advanced pancreatic cancer candidates for therapy/clinical trial
ctDNA not supported for pancreatic cancer screening outside trials

Documentation Required

Genetic Counseling and Documentation

Genetic counseling must be provided before and after all germline genetic testing and documented in the medical record: include a structured family history, genetic risk assessment, and counseling about diagnosis, prognosis, and treatment.

Pre- and post-test genetic counseling documented in record
Include structured family genetic history and risk assessment

Billing Rule

Code-Based Coverage and Eligibility Considerations

Code- and coverage-related notes: the policy lists applicable CPT/HCPCS codes for reference only — inclusion does not guarantee coverage. Claims may be subject to federal/state/contractual rules, and codes marked or excluded by state fee schedules may not be reimbursed.

Code lists are reference-only; coverage determined by contractual and statutory rules
Codes may be excluded by state fee schedules

Documentation Required

Operational Expectations and Laboratory QA

Operational expectations and laboratory standards: tests should be used within intended purposes and performed by laboratories participating in external quality assurance programs (NICE and other guidance). Companies/labs should provide timely, complete, linkable test data when required by programs.

Labs should participate in external QA programs (eg, national schemes)
Tests must be used within manufacturer/intended purpose and shared for registries when required

Denial Risk

Evidence Insufficiency and Denial Risk

Evidence insufficiency and denial risk: many commercially available assays lack sufficient evidence of clinical utility; insufficient or poor-quality evidence, high failure rates, or discordant results may lead to coverage denial. Routine use is discouraged where testing will not alter management.

Tests lacking demonstrated clinical utility may be denied
High assay failure or discordance may increase denial risk
Routine use discouraged if results won't change management

Denial Risk

Guideline-Based Limitations and Cautions

Specific test-use cautions and guideline-based limitations: prognostic GEP tests for cutaneous melanoma are discouraged for routine prognostication until clear use criteria exist; GEP-directed site-specific therapy for CUP has not shown superiority to empiric therapy and may be a basis for denial.

Do not rely on prognostic GEP for cutaneous melanoma for routine management decisions
GEP-directed site-specific therapy in CUP lacks demonstrated benefit and may be denied

Denial Risk

Assay-Specific Recommendations and Limitations

Specific assays and screening recommendations: Septin 9 (mSEPT9) blood-based testing is not recommended for colorectal cancer screening per ACG guidance; NavDx and similar tests for HPV-related cancer surveillance currently lack sufficient evidence of clinical utility.

Septin 9 not recommended for CRC screening
NavDx lacks sufficient evidence for routine surveillance use

Documentation Required

Required Documentation, Pretest Counseling, and Context

Required test documentation and pretest counseling: documentation should include tumor tissue source (FFPE, fresh/frozen), receptor status, nodal status, clinical risk group parameters (eg, PSA, Gleason/grade, clinical T stage), number/percentage of positive cores, and a statement of how test results will affect management. Pretest counseling should cover benefits, limitations, and local context (eg, institutional malignancy rates for thyroid molecular tests).

Document tumor tissue source and key pathologic/clinical features
Document how the test result will change management and evidence basis for testing
Provide pretest counseling and note local performance context

Documentation Required

Clinical Study and Assay Validation Documentation

Clinical study and validation documentation: authorization may require citation of prospective trial results, registry studies, and assay validation status (CLIA/CAP) for novel or less-established tests (eg, cfDNA HPV assays).

Provide assay validation documentation (CLIA/CAP) when applicable
Submit supporting prospective or registry evidence if required for authorization

Note

Sequencing and Clinical Context for Molecular Testing

Special clinical scenarios and sequencing of testing: sequence molecular testing after initial histologic classification; for CUP or when tissue is scarce, consider pan-cancer NGS or cfDNA only after standard diagnostic steps and with multidisciplinary input. In thyroid nodules or when thyroidectomy is already indicated, molecular testing is unnecessary.

Perform molecular profiling after initial histology/IHC determination
Avoid molecular testing when surgery is already indicated (eg, thyroidectomy)

Denial Risk

ctDNA/MRD Testing — Limited Routine Utility

ctDNA and MRD testing: current evidence for tumor-informed MRD assays (eg, Signatera) and routine post-surgical ctDNA to guide adjuvant therapy is insufficient to support routine clinical use; such tests should generally be limited to clinical trials or contexts where results will clearly change management.

Signatera and similar MRD assays lack demonstrated clinical utility for routine surveillance or adjuvant decision-making
NCCN/ESMO advise against routine ctDNA-guided adjuvant therapy decisions outside trials

Documentation Required

Multidisciplinary Documentation and Decision-Making

Multidisciplinary decision-making: encourage collaboration among pathologists, oncologists, and relevant specialists when selecting IHC, GEP, and NGS testing; document MDT discussions and rationale when used to guide adjuvant therapy or surveillance.

Document multidisciplinary tumor board or specialist consultations when tests influence major management decisions
Integrate GEP/NGS results with clinicopathologic variables in decision-making

Note

Preferred Assays and Avoidance of Standalone Single-Gene Tests

Preferred assays and test hierarchy: follow guideline-preferred assays where indicated (eg, Oncotype DX 21-gene preferred in many breast cancer adjuvant decision scenarios). Avoid routine single-gene RET/KRAS/MET testing as stand-alone assays outside trials — include these genes in broader panels instead.

Prioritize guideline-preferred assays for prognostic/predictive decisions
Do not perform single-gene RET/KRAS/MET tests routinely as stand-alone assays

Note

Prostate Genomic Assay Use — Selective and Management-Directed

Prostate and other tumor-type specific guidance: use prostate genomic assays (Decipher, Oncotype DX Prostate, Prolaris) selectively when results could change management (eg, active surveillance decisions); routine post-prostatectomy use to determine adjuvant vs salvage radiation or to initiate systemic therapy is discouraged without clear evidence.

Consider genomic assays pre-biopsy or to inform active surveillance decisions when clinically impactful
Routine post-RP genomic use to direct adjuvant radiotherapy or systemic therapy is discouraged

Step Therapy

Step Therapy — None Specified

Step therapy and lack thereof: no formal step-therapy requirements are described in these sections; decisions should be based on clinical appropriateness, guideline alignment, and evidence of management impact.

No explicit step therapy mandated in policy text
Authorize based on clinical necessity and guideline concordance

Guideline panels do not recommend GEP assays for HER2‑positive or triple‑negative breast cancer. Additionally, NICE explicitly advised against using MammaPrint to guide adjuvant chemotherapy for certain node‑positive premenopausal patients, reflecting guideline‑driven restrictions that may affect coverage decisions.

ASCO and related guideline statements advise that routine standalone single‑gene assays for alterations such as RET, KRAS, or MET are not recommended outside of clinical trials; these genes should be included within larger panel testing rather than ordered as routine single‑gene tests.

Independent technology assessments (e.g., Hayes) have identified insufficient evidence to support routine clinical use of assays such as Select mdx and Confirm mdx. Tests with very low or limited evidence are therefore considered unsupported for routine clinical use and may be excluded from coverage.

Additional molecular biomarkers and proprietary tests without adequate peer‑reviewed evidence should not be offered routinely. The policy references systematic reviews and technology assessments that identify numerous assays with limited quality evidence — these are not supported for routine clinical implementation until higher‑quality validation demonstrates clinical utility.

Hayes and other HTA assessments cited in the policy note insufficient evidence of clinical utility for a variety of proprietary tests (for example, CancerTYPE ID and NavDx). Where independent assessments conclude evidence is lacking, routine coverage is not supported.

Routine prognostic use of GEP tests for cutaneous melanoma and several proprietary prognostic assays lacks demonstrated clinical utility beyond established clinicopathologic factors. Major guideline authors and technology assessments recommend against routine use of these prognostic GEPs to guide management outside research settings.

CancerTYPE ID is specifically cited in an independent assessment (Hayes) as lacking sufficient evidence to support its effectiveness in identifying site of origin for indeterminate cancers; routine clinical use is therefore not supported by that assessment.

The policy references gastroenterology guidance and evidence assessments that do not support routine use of SEPT9 (mSEPT9/Epi proColon) as a primary colorectal cancer screening modality; ACG recommends against Septin 9 testing for CRC screening due to very low‑quality evidence. Likewise, some pancreatic cyst tests (e.g., PancraGEN) lack sufficient evidence per Hayes.

The policy treats multi‑cancer detection (MCD/MCED) tests (for example, Galleri) as investigational for population‑level screening because current evidence does not demonstrate proven clinical utility or mortality benefit; the document references systematic reviews and prospective studies showing variable sensitivity by stage and cancer type but insufficient outcome data to justify routine screening use.

NavDx is noted as having limited and low‑quality evidence according to Hayes and systematic reviews; the policy indicates insufficient evidence of clinical utility for routine diagnostic or surveillance use, and therefore treats NavDx as investigational.

Tumor‑informed MRD ctDNA assays (e.g., Signatera) and other ctDNA MRD approaches are described as lacking sufficient prospective evidence to support routine clinical use for monitoring response or surveillance after remission. Independent assessments (Hayes) and guideline summaries conclude that clinical utility remains unproven and routine coverage is not supported.

Whole exome, whole genome, and whole transcriptome sequencing approaches are considered investigational for routine use to inform clinical decision‑making because peer‑reviewed evidence demonstrating consistent clinical utility is currently insufficient.

Preferred clinical contextPolicy states cfDNA/liquid biopsy may be used when tissue is limited or unobtainable and is generally reserved for advanced/metastatic settings or adjunctive use to tissue testing.

LimitationLiquid biopsy should not replace tissue diagnosis and is discouraged as routine outside defined advanced/metastatic scenarios.

Risk groups for prostate cancer — inv-127: Risk groups for prostate cancer — definitions

Very Low / Low riskVery Low and Low risk prostate cancer categories are defined by NCCN clinical/pathological criteria (e.g., PSA, Grade Group, clinical T stage, number/percent positive cores, PSA density).

Intermediate (Favorable/Unfavorable)Favorable and Unfavorable Intermediate risk groups are differentiated by Grade Group, number of intermediate risk factors, and percent positive cores (definitions per NCCN v1.2025).

High / Very HighHigh and Very High risk prostate cancer definitions include specific combinations of T stage, Grade Group, and PSA thresholds as per NCCN guidance referenced in the policy.

cell-free DNA (cfDNA) — circulating tumor DNA isolated from plasma — inv-128: cell-free DNA (cfDNA) — circulating tumor DNA isolated from plasma

DefinitionCell-free DNA (cfDNA) refers to circulating tumor DNA fragments isolated from plasma (or other body fluids) used for genomic analysis of tumor-derived alterations.

Use casescfDNA is used in liquid biopsy to detect actionable tumor alterations when tissue is insufficient and for certain monitoring applications, though routine substitution for tissue is discouraged.

Assay constraintsAnalytic performance and clinical utility vary by indication; cfDNA-based multi-cancer detection and MRD assays are considered investigational or not supported for routine use in many contexts per policy.

CPT codes 81445-81464 correspond to genomic sequence analysis panels of varying gene counts — inv-129: CPT codes 81445-81464 correspond to genomic sequence analysis panels of varying gene counts

Relevant CPT rangeCPT codes 81445–81464 correspond to genomic sequence analysis panels of varying gene counts and specimen types (examples: 5–50 genes, 51+ genes, and cfDNA panel codes).

Examples in policyCodes listed include panel-size descriptors (e.g., 81445/81449 for 5–50 genes; 81455/81456/81459 for 51+ gene panels; 81462–81464 for cfDNA/plasma panels).

Billing noteSome PLA/PLA-like and proprietary codes (U-codes) referencing large panels or WGTA/WES/WGS are included in code listings but may be excluded from the state Medicaid fee schedule.

Multi-gene analysis — inv-130: Multi-gene analysis — panel generally refers to five or more genes

DefinitionMulti-gene analysis typically refers to a gene panel containing five or more genes; panels may return gene expression signatures, algorithmic scores, or classifications depending on assay design.

Policy applicationThis definition applies across tissue and plasma assays in the policy and informs coding distinctions for panel sizes and intended use.

Overlap with GEPMulti-gene analysis may include gene expression profiling assays (GEP) that produce algorithm-reported scores or classes for prognosis or prediction.

Algorithm-reported assay — inv-131: Algorithm-reported assay — tests that combine gene expression or methylation into algorithm outputs

DefinitionAlgorithm-reported assays combine measured gene expression or methylation features into a predefined algorithmic output such as recurrence risk score, risk class, or probability of treatment benefit.

ExamplesExamples include Oncotype DX recurrence score, Prosigna ROR score, EPclin for EndoPredict, DCISionRT Decision Score, and other multigene algorithm assays referenced in the policy.

Clinical implicationAlgorithm outputs are used to support prognostic or predictive clinical decisions when validated in the indicated populations per guideline evidence.

ROR score — inv-132: ROR score — Risk of recurrence score (Prosigna context)

DefinitionROR score (Risk of Recurrence) is the numerical output produced by the Prosigna (PAM50) assay representing ten‑year distant recurrence risk in the intended population.

Use contextROR is used with clinical features to categorize risk and inform prognostication in postmenopausal HR+ early-stage breast cancer (N0 or N+ Stage II).

Threshold reportingPolicy references ROR thresholds (e.g., ROR <57 considered low risk in some subgroup analyses) when cited in evidence summaries.

EPclin Risk Score — inv-133: EPclin Risk Score — EndoPredict combined gene expression plus clinical features

DefinitionEPclin Risk Score is the numeric EndoPredict result that combines the 12-gene molecular score with clinical features (tumor size and nodal status) to estimate ten‑year distant recurrence risk (reported range ~1.1–6.2).

CompositionEndoPredict includes eight disease genes, three normalization genes, and one DNA reference gene; EPclin integrates molecular and clinical data.

Evidence noteHayes assessment found limited but positive evidence for EPclin in ER+, HER2- early-stage disease with caveats about prospective validation and applicability to premenopausal women.

MammaPrint / 70-gene signature — inv-134: MammaPrint / 70-gene signature — definition

DefinitionMammaPrint is a 70-gene expression signature (also called the Amsterdam Signature) that classifies genomic risk of distant recurrence in early-stage breast cancer.

Intended useEvaluated in the randomized MINDACT trial to guide chemotherapy decisions in early-stage disease; often paired with BluePrint for molecular subtype information.

Panel sizeMammaPrint panel comprises 70 genes as documented in the policy and evidence summaries.

EndoPredict (EPclin) — inv-135: EndoPredict (EPclin) — definition and gene composition

DefinitionEndoPredict (EPclin) is a 12‑gene RT‑PCR assay (8 disease genes, 3 normalization genes, 1 DNA reference) combined with tumor size and nodal status to produce an EPclin score estimating recurrence risk.

Reported EPclin rangeEPclin numeric results reported between approximately 1.1 and 6.2 relating to distant recurrence risk.

Intended populationAssessed in ER+, HER2- early-stage breast cancer (N0 and some N1 analyses) with limited prospective validation per Hayes review.

Breast Cancer Index (BCI) — inv-136: Breast Cancer Index (BCI) — definition

DefinitionBreast Cancer Index (BCI) is a composite gene expression signature combining the HOXB13:IL17BR ratio and a Molecular Grade Index to prognosticate late (5–10 years) and overall (0–10 years) distant recurrence risk.

Clinical roleBCI has evidence suggesting it may predict benefit from extended endocrine therapy in select postmenopausal populations and may be offered to aid EET decisions after five years of therapy in 0–3 node patients.

Assay specimenPerformed on FFPE tumor tissue to generate a prognostic score used for late-recurrence risk assessment.

DCISionRT — inv-137: DCISionRT — molecular-clinicopathologic assay for DCIS

DefinitionDCISionRT is a molecular–clinicopathologic assay for ductal carcinoma in situ that assesses 7 genes plus clinical factors to produce a Decision Score (0–10) estimating ten‑year recurrence risk and potential radiotherapy benefit.

Score interpretationDecision Score 0–3 considered low risk; 3–10 considered elevated risk per policy description.

Evidence noteRegistry and observational data indicate DCISionRT can influence radiotherapy recommendations, but long‑term outcome data are limited and assessments find insufficient evidence for routine use.

Oncotype DX DCIS — inv-138: Oncotype DX DCIS — definition

DefinitionOncotype DX DCIS is a 12‑gene RT‑PCR assay producing a DCIS Score (0–100) estimating ten‑year local recurrence risk for patients with ductal carcinoma in situ.

Clinical evidencePolicy notes low-quality evidence per Hayes assessment with uncertain impact on long‑term outcomes and limited comparative data for the current test version.

Intended specimenPerformed on excised tumor tissue (FFPE) to generate the DCIS Score used for recurrence risk estimation.

Gene expression profiling (GEP) — inv-139: Gene expression profiling (GEP) — definition and examples

DefinitionGene expression profiling (GEP) refers to tests that evaluate expression of multiple genes to provide prognostic and/or predictive information (examples: Oncotype DX, MammaPrint, Prosigna, EndoPredict, BCI).

Clinical rolesGEP assays are used to estimate recurrence risk, predict benefit from chemotherapy or extended endocrine therapy, and inform adjuvant treatment decisions in defined early‑stage breast cancer populations.

Assay platformsGEP methods include RT‑PCR, microarray, and NGS-based expression profiling performed on FFPE tumor tissue in most commercial assays.

Multiplexed NGS panels — inv-140: Multiplexed NGS panels — definition

DefinitionMultiplexed NGS panels are broad sequencing assays that test multiple cancer-related genes simultaneously and are preferred over single-gene tests in settings like NSCLC to identify actionable driver alterations.

Clinical preferenceGuidelines (ASCO/CAP/NCCN) recommend multiplexed panels where available to detect drivers beyond single‑gene assays (EGFR, ALK, BRAF, ROS1, etc.).

Panel size considerationsPolicy limits routine coverage for NGS panels to ≤50 genes unless exceptions apply; larger CGP panels are addressed separately in CGP definitions and exclusions.

cfDNA / liquid biopsy — inv-141: cfDNA / liquid biopsy — definition and use constraints

DefinitioncfDNA / liquid biopsy refers to circulating tumor cell‑free DNA testing of plasma used to detect tumor genomic alterations when tissue is limited; it is generally reserved for advanced/metastatic disease and should not replace tissue diagnosis.

Clinical constraintsLiquid biopsy may be used adjunctively to tissue testing to expedite genotyping or when tissue is insufficient; follow‑up tissue testing is recommended if cfDNA results are negative or indeterminate and tissue access is feasible.

Limitations in screening/MRDPolicy considers many cfDNA-based multi‑cancer detection tests and MRD assays investigational or unproven for routine screening or surveillance in most settings.

Decipher genomic classifier (GC) — inv-142: Decipher genomic classifier (GC) — definition

DefinitionDecipher genomic classifier (GC) is a biopsy- or prostatectomy‑based gene expression genomic classifier used to predict risk of metastasis, biochemical recurrence, and prostate cancer–specific mortality.

Clinical evidenceRetrospective and registry analyses (including RTOG ancillary studies) show Decipher GC is independently associated with metastasis and recurrence risk, supporting prognostic validity but with limited evidence of long‑term outcome modification.

Specimen typesCan be applied to biopsy or prostatectomy FFPE tissue per test design and evidence reports.

For NSCLC, broad panel‑based NGS is preferred when feasible; the policy expects tumor genotype efforts to be prioritized and documented, particularly when prior single‑gene or limited testing was negative and broader testing may identify actionable targets.

The document emphasizes that cfDNA testing may be used in advanced/metastatic NSCLC or when tissue sampling is infeasible, but it should not replace tissue diagnosis. If cfDNA testing is used because tissue was insufficient, follow‑up tissue analysis is expected when an oncogenic driver is not identified.

Prostate genomic classifiers should be used selectively where results are likely to affect management decisions; documentation should include clinical risk group, PSA, Grade Group, clinical T stage, number/percent positive cores, and how test results will impact management.

NCCN guidance cited implies consideration of various biomarker options prior to biopsy and that ordering clinicians should document prior diagnostic steps; the policy expects ordered tests to reflect appropriate prior diagnostic workup in prostate cancer contexts.

For cancers of unknown primary (CUP), molecular testing is expected to be considered after initial histology and immunohistochemistry; testing decisions should be documented and reflect multidisciplinary input when used to identify potential tissue of origin or actionable alterations.

NCCN guidance indicates that molecular profiling for CUP should generally be considered after standard histologic workup; the policy therefore expects documentation of prior diagnostic steps and rationale when ordering advanced molecular tests for CUP.

For colorectal cancer screening alternatives and tumor biomarker testing, the policy references guideline expectations that standard screening and diagnostic pathways be considered first; for tumor testing, universal MMR/MSI testing is recommended and should be documented as part of the diagnostic record.

For pancreatic cyst fluid NGS, the policy references studies showing analytic yield and gene targets (KRAS, GNAS, TP53, PIK3CA, PTEN) and expects testing to be ordered when results will inform surgical or surveillance decisions, with prior diagnostic steps documented.

Tumor‑informed MRD assays require prior tumor sequencing to design individualized panels; the policy notes that such prior sequencing is a prerequisite for tumor‑informed ctDNA MRD testing in the assays described, and documentation of the baseline tumor sequencing is expected where relevant.