ModifiedCentenePolicy N/A

CONCERT GENETIC ONCOLOGY: CYTOGENETIC TESTING

Coverage and medical necessity criteria for cytogenetic and tumor-specific genetic testing (FISH, CISH, IHC, PCR, NGS fusion panels) used to diagnose, classify, and guide treatment of solid tumors and hematologic malignancies for Centene-affiliated health plans.

Policy Summary

PayerCentene

PolicyCONCERT GENETIC ONCOLOGY: CYTOGENETIC TESTING

Policy CodePolicy N/A

Change TypeCriteria additions and coverage expansions (added RET, FOLR1, PML‑RARA codesstage-language revisions)

Effective DateN/A

Next Review DateN/A

Key ActionCheck the Concert Platform and payer-specific prior authorization processes before ordering tumor-specific IHC or FISH assays and document the tumor type and treatment rationale.

SourceLink

POLICY UPDATE CHANGES

Added Tumor Specific RET Gene Rearrangement (FISH) and related criteria.

Added Tumor Specific FOLR1 Protein Analysis and related content.

Replaced references to 'advanced or metastatic' disease with specific stage language (e.g., Stage IB or higher) for some tumor-specific tests including PD-L1.

Added PML-RARA (qualitative FISH and PCR) testing codes 81315 and 81316 to criteria.

Expanded coverage criteria for multiple fusion/rearrangement tests (ALK, ROS1, RET, NTRK) to include additional tumor types per updated NCCN guidance.

multipledistinct tumor-specific cytogenetic/IHC/NGS test sections included

frequency limitsbladder FISH monitoring frequency specified

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage and Medical Necessity Criteria

Tumor-specific covered testing

Covered when indications align with NCCN guideline recommendations or FDA companion diagnostic approvals:

ANY of the following

Tumor molecular testing that matches an FDA-cleared or -approved companion diagnostic indication for a specific therapy (e.g., PD-L1 IHC companion diagnostics where FDA approval exists).
Include testing methods and companion diagnostic designation in documentation.
Tumor types and clinical states for which NCCN treatment guidelines recommend testing to inform selection of targeted or immuno-oncology therapies (examples below).
See specific tumor-type criteria groups elsewhere in this policy for detailed lists and required diagnostic stages.
Operational requirement
- Testing must be ordered by or in consultation with an appropriate oncology specialist and for the explicit purpose of guiding treatment selection or prognosis (not routine screening).
- Results must be reported on a per-tumor basis with methodology (e.g., IHC, FISH, CISH, PCR, NGS) and analytical validity evidence when available.
Illustrative tumor-specific examples referenced in this policy
- PD-L1 protein analysis by IHC for cancers and clinical settings with FDA-cleared companion diagnostics or NCCN-recommended testing (e.g., selected head and neck, urothelial, and triple negative breast cancers).
  See Tumor Specific PD-L1 Protein Analysis criteria group.
- FOLR1 (Folate Receptor alpha) IHC when mirvetuximab soravtansine is being considered for treatment of platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
  See Tumor Specific FOLR1 Protein Analysis criteria group.
- RET, ROS1, ALK, NTRK, and other fusion detection (FISH/NGS/IHC as appropriate) for tumor types and stages where NCCN recommends fusion testing or where an FDA-approved targeted therapy requires companion diagnostic confirmation.
- HER2 (ERBB2) amplification/protein testing by ISH or IHC in tumor types and stages listed in the Tumor Specific ERBB2 (HER2) criteria group (e.g., recurrent or newly diagnosed invasive breast cancer, selected gastric/upper GI and other tumors as enumerated).
Broad molecular profiling (including RNA-based fusion detection or NGS) is acceptable when NCCN guidelines or FDA companion diagnostic language indicate higher sensitivity or preferred methodology for the actionable alteration.
When multiple methods exist, prefer the method recommended by NCCN or the FDA for the specific alteration (e.g., RNA-based NGS for fusion detection when noted).
Testing not aligned with NCCN guideline recommendations or FDA-specified tumor types/stages may be denied as not medically necessary.
Operational: prior authorization and clinical documentation supporting the indication and intended therapeutic decision are recommended.

Tumor- and Hematologic Malignancy–Specific Indications

inv-52: Tumor- or hematologic malignancy–specific indications as detailed per test section (ALK, HER2, NTRK, PD-L1, FOLR1, PML-RARA, CLL/SLL, multiple myeloma, bladder FISH).

Tumor- or hematologic malignancy–specific indications as detailed per test section (examples shown):

ALK (88271, 88274): See ALK indications: Stage IB+ lung cancers and specified thyroid, pancreatic, pediatric CNS, and histiocytic/neoplastic disorders where ALK rearrangement testing is indicated.

HER2 (88360, 88377): See ERBB2 indications: breast, gastric, colorectal/appendiceal, esophageal/EGJ, salivary gland, cervical, endometrial (serous/carcinosarcoma/p53 abnormal), pancreatic, ovarian/fallopian tube/primary peritoneal, bladder (stage IIIB+), and small bowel as specified in HER2 criteria.

NTRK (81191-81194): NTRK fusion testing recommended for multiple tumor types when advanced, unresectable, metastatic, unknown primary, or specific tumor histologies (e.g., cervical sarcoma, anaplastic thyroid, ALL, pediatric diffuse high‑grade glioma).

CPT/HCPCS and Related Codes

Tumor Specific ALK Gene Rearrangement (example CPTs)CPT

88271	FISH, probe specific
88274	FISH, probe specific (additional?)

Bladder Cancer Diagnostic and Recurrence FISH TestsCPTCovered

88120	Bladder cancer diagnostic FISH
88121	Bladder cancer recurrence FISH

ERBB2 (HER2) and Protein/IHC/ISH testingCPT

88360	IHC with interpretation
88377	In situ hybridization (e.g., FISH/CISH)

NTRK Fusion Analysis Panel CPT CodesCPT

81191	NTRK fusion analysis
81192	NTRK fusion analysis
81193	NTRK fusion analysis
81194	NTRK fusion analysis

Additional FISH/Chromosomal / Molecular Codes referencedCPT

81315	PML-RARA rearrangement testing (molecular)
81316	PML-RARA rearrangement testing (molecular)
88237	FISH analysis (multiple myeloma panel example)
88275	FISH, multiple probes
88291	FISH panel analysis

PD-L1 Protein Analysis CPT CodesCPT

88341	PD-L1 IHC with interpretation
88342	PD-L1 IHC with interpretation (alternate?)
88361	IHC microarray/other interpretation

Tumor-specific IHCCPTCovered

88360

IHC analysis (FOLR1 protein expression)

PML/RARA FISH/PCRmixedCovered

81315	PML/RARA rearrangement
81316	PML/RARA rearrangement
88271	FISH analysis
88274	FISH analysis
88275	FISH analysis
88291	FISH analysis

RET FISHmixedCovered

88374	FISH testing (RET rearrangement)
88377	FISH testing (RET rearrangement)
88271	FISH analysis
88275	FISH analysis
88291	FISH analysis

ROS1 FISHCPTCovered

88271	FISH analysis (ROS1)
88274	FISH analysis (ROS1)

Added procedure codes (PML-RARA)CPTCovered

81315	PML-RARA testing (as added in criteria)
81316	PML-RARA testing (as added in criteria)

Bladder tumor marker frequency limits

Frequency limits summaryNo more than 4 bladder tumor marker studies per year for years 1–2 after diagnosis; no more than 3 per year in year 3; no more than 2 per year in year 4; and no more than 1 per year annually for up to 15 years after diagnosis.

Hematuria diagnostic constraintAllowed when member has hematuria and diagnostic studies have failed to identify the etiology.

Prior-year ordering limitBladder FISH test must not have been ordered more than 1 time in the past 12 months unless member has been treated for bladder cancer and ordering respects frequency limits.

Investigational useBladder cancer diagnostic and recurrence FISH tests (88120, 88121) for screening of members with hematuria are considered investigational.

Provider Requirements, Prior Authorization, and Documentation

Prior Authorization

Check Concert Platform / payer for PA

Providers must check the Concert Platform or payer-specific resources for prior authorization (PA) requirements and the most up-to-date coding guidance before ordering molecular, FISH, IHC, or other tumor-specific tests. Inclusion or exclusion of codes in this policy does not guarantee coverage.

Verify plan-specific PA rules and submission portals on the Concert Platform before ordering.
Reference current CPT coding and payer guidance when submitting claims.

Prior Authorization

Prior authorization for tumor-specific assays

Prior authorization is required for tumor-specific assays when indicated by this policy or the member's plan. PA submissions must include documentation of the tumor diagnosis, stage, and the clinical context supporting use of the assay (e.g., recurrent/metastatic disease, consideration of a targeted therapy).

Document tumor histology, stage, and clinical rationale in the PA request.
Include imaging, pathology, and treatment history as applicable to demonstrate medical necessity.

Investigational and Not-Covered Uses

Bladder cancer diagnostic and recurrence FISH testing (CPT 88120, 88121) for screening asymptomatic members or as a routine hematuria screen is considered investigational and not covered by this policy unless the specific diagnostic or surveillance criteria are met.

Bladder tumor marker testing for general hematuria screening is explicitly not covered. In addition, assays that are not validated (the CMS LCD names UroVysion as the only FDA‑approved assay for this purpose) may be excluded from coverage.

Some CPT codes referenced in earlier policy versions were removed from the policy reference table; the provided excerpt does not contain a complete, explicit list of codes that are not covered. Providers must consult the payer’s current coding resources for the definitive not‑covered code list.

Definitions and Test Types

Cytogenetic analysis — FISH/CISH/karyotype definitions and purpose

DefinitionCytogenetic analysis (e.g., FISH, CISH, karyotype) identifies chromosomal rearrangements, amplifications, and deletions in tumors to classify cancer type and detect somatic driver mutations.

PurposeUsed to classify tumors and detect somatic oncogenic mutations that inform diagnosis, prognosis, and targeted therapy selection.

Specimen typesPerformed on solid tumor tissue and on blood or bone marrow for hematologic malignancies.

Common methodsIncludes FISH and CISH for localization of chromosomal changes and karyotype for broader chromosomal alterations.

Molecular analysis of solid tumors — tumor tissue/cfDNA testing definition

DefinitionMolecular analysis of solid tumors: testing of tumor tissue (or circulating tumor DNA/cells) to detect mutations and other molecular alterations relevant to diagnosis and targeted treatment selection.

Member Eligibility and Operational Eligibility Notes

Eligibility criteria for tumor‑ and hematologic malignancy testing are defined within each tumor‑specific section of the policy. Requirements commonly include documentation of the tumor diagnosis and clinical context (e.g., initial diagnostic workup, recurrent or metastatic disease, or consideration of a targeted therapy) and adherence to any test‑specific preconditions such as prior diagnostic studies for bladder FISH. Refer to the individual test criteria for exact eligibility conditions.

For bladder FISH testing: the member must have hematuria and prior diagnostic studies must have failed to identify an etiology before FISH is considered medically necessary for diagnostic evaluation; alternatively, FISH may be used for surveillance in members previously treated for bladder cancer when ordered within the policy’s specified frequency limits.

For tumor‑specific tests that guide targeted therapy (for example, FOLR1 testing in recurrent, platinum‑resistant ovarian/fallopian tube cancer), eligibility includes the presence of the specified clinical state (e.g., recurrent, platinum‑resistant disease) and that the targeted therapy is being considered, or prior testing did not include the relevant marker.

For somatic RET rearrangement testing, eligibility may depend on the tumor type and prior germline testing status (for medullary thyroid carcinoma, somatic RET testing is indicated when germline RET is wild type or unknown), and on guideline‑recommended disease stages or recurrent/metastatic status as specified in the RET criteria.

Background and Rationale

Cytogenetic and molecular analyses (e.g., FISH, CISH, karyotype, PCR, IHC, and NGS fusion panels) are used to classify tumors, identify somatic driver alterations that can inform prognosis, and select targeted therapies. These tests may be performed on tumor tissue, blood or bone marrow (for hematologic malignancies), or on circulating tumor DNA/cells for selected solid tumor indications.

Policy Updates and Changes

03/23revisionLatest

Inserted Tumor Specific RET gene rearrangement (FISH) criteria and added related content across the policy (coding, reference table, background and criteria).

03/23revision

Added Tumor Specific FOLR1 protein analysis and related criteria, including clarification of ovarian cancer pathology and linkage to mirvetuximab consideration.

03/23revision

Policy Summary

PayerCentene

PolicyCONCERT GENETIC ONCOLOGY: CYTOGENETIC TESTING

Policy CodePolicy N/A

Change TypeCriteria additions and coverage expansions (added RET, FOLR1, PML‑RARA codesstage-language revisions)

Effective DateN/A

Next Review DateN/A

Key ActionCheck the Concert Platform and payer-specific prior authorization processes before ordering tumor-specific IHC or FISH assays and document the tumor type and treatment rationale.

SourceLink

On This Page

inv-53: NTRK fusion testing — recommended across many tumor types when metastatic, unresectable, or advanced

NTRK fusion analysis is recommended in multiple tumor types when metastatic, unresectable, advanced, or when testing could identify eligibility for NTRK‑targeted therapies (entrectinib, larotrectinib, repotrectinib).

NTRK recommended contexts: Consider NTRK fusion testing for patients with metastatic, unresectable, advanced, or unknown primary tumors and for specific histologies including anaplastic thyroid carcinoma, cervical sarcoma, pediatric diffuse high‑grade glioma, and others as outlined in NCCN guidance; positive results can direct entrectinib, larotrectinib, or repotrectinib therapy.

inv-54: HER2 (ERBB2) testing — recommended for multiple cancers when trastuzumab or other HER2-directed therapy is considered

ERBB2 (HER2) testing by IHC with reflex to ISH/ISH is recommended when HER2‑directed therapy (e.g., trastuzumab) is being considered in the following tumor types:

HER2 recommended contexts: Breast (newly diagnosed or metastatic), gastric, esophageal/EGJ, pancreatic, colorectal/appendiceal metastatic disease, salivary gland, cervical, endometrial serous/carcinosarcoma/p53‑abnormal tumors, ovarian/fallopian tube/primary peritoneal recurrent disease, stage IIIB+ muscle‑invasive bladder cancer, and metastatic small bowel adenocarcinoma per NCCN recommendations when HER2‑directed therapy is contemplated.

inv-55: PD-L1 protein (IHC) testing — Recommended for various cancers to guide immunotherapy decisions

PD‑L1 protein immunohistochemistry testing is recommended where PD‑L1 status influences immunotherapy decisions per NCCN and FDA companion diagnostic indications.

PD-L1 recommended contexts: PD‑L1 IHC is recommended for cancers including gastric, head and neck (including nasopharynx), bladder/urothelial carcinoma, vulvar, esophageal/EGJ, cervical, NSCLC (stage IB+ or as specified), triple‑negative breast cancer, and vaginal cancer when PD‑1/PD‑L1 inhibitor therapy is being considered and where FDA‑cleared companion diagnostics apply.

inv-56: PD-L1 IHC and protein markers — Covered where PD-L1 status influences therapy

PD‑L1 IHC and related protein markers are covered where PD‑L1 status informs therapy selection per NCCN/FDA guidance.

PD-L1 coverage contexts: Covered for tumor types where PD‑L1 expression guides therapy (examples include triple‑negative breast cancer, head and neck cancers, urothelial carcinoma) and when FDA‑cleared companion IHC assays are indicated.

inv-57: FOLR1 IHC — Covered for ovarian cancer contexts predicting benefit from mirvetuximab soravtansine

FOLR1 immunohistochemistry is covered in ovarian cancer contexts predicting benefit from mirvetuximab soravtansine when prior testing did not include FOLR1.

FOLR1 recommendation: In recurrent, platinum‑resistant epithelial ovarian/fallopian tube/primary peritoneal cancer, perform FOLR1 IHC to determine eligibility for mirvetuximab soravtansine if prior testing did not include this marker.

inv-59: RET/ROS1/ALK/NTRK fusion testing — Covered across multiple tumor types per updated NCCN guidance

RET, ROS1, ALK and NTRK fusion/rearrangement testing are covered across multiple tumor types per updated NCCN guidance when molecular profiling is indicated.

RET/ROS1/ALK/NTRK coverage: Covered for tumor types including NSCLC, thyroid, cervical, colorectal, pancreatic, gastric, esophageal/EGJ, ampullary, pediatric CNS tumors, breast, and others when NCCN recommends molecular profiling for advanced, recurrent, locally advanced, or specific staged disease or when targeted therapies are available.

Prior Authorization

Prior authorization for added codes

Certain newly added or specific molecular test codes may be subject to PA. Providers should confirm whether recently added CPT codes (e.g., those referenced in policy updates) require prior authorization.

Confirm PA requirements for newly added codes such as recently listed PML-RARA CPT codes or other additions.
If uncertain, submit a PA inquiry via the Concert Platform before testing.

Denial Risk

Bladder FISH validation and use

Only validated bladder FISH assays should be used. Frequency limits per guideline and LCD (e.g., UroVysion) apply; non-validated assays may not be covered and repeat testing beyond specified intervals risks denial.

Use validated assays (for example, UroVysion) for bladder FISH testing.
Adhere to frequency limits (e.g., maximum tests per year by year since diagnosis as specified in policy and CMS LCD).
Do not use bladder FISH testing for general hematuria screening unless criteria are met.

Denial Risk

Mismatch with guideline-specified indications

Requests that fall outside NCCN- or guideline-specified tumor types, or lack documentation to support the indicated tumor type or clinical scenario, may be denied. Ensure the requested test aligns with guideline-based indications.

Provide guideline citations or rationale when ordering tests for less common tumor types.
If the tumor type is not an NCCN-specified indication, include detailed clinical justification in the PA.

Documentation Required

Clinical indication documentation

Documentation submitted with orders and PA requests must support the clinical indication for testing, including tumor diagnosis, stage, prior treatments, and whether disease is recurrent or metastatic.

Include pathology reports confirming tumor type and biomarker status when available.
Indicate disease stage and whether testing is for initial workup, recurrence, or metastatic disease.

Documentation Required

Clinical indication and prior testing documentation

Include documentation of prior molecular or biomarker testing to avoid redundant testing. If prior testing was incomplete or negative for the marker(s) of interest, state this clearly in the PA.

Attach prior test reports or state dates and results of prior molecular testing.
Explain why repeat or additional testing is needed (e.g., new therapy consideration, prior panel did not include marker).

Documentation Required

Testing to enable targeted therapy

When testing is performed to determine eligibility for targeted therapy (for example, FOLR1 expression testing prior to mirvetuximab), document the intended therapy and any sequencing of prior tests that support the current request.

Specify the targeted therapy being considered (e.g., mirvetuximab) in the PA or order.
Indicate whether prior biomarker testing included the relevant marker and if not, why additional testing is necessary.

Advanced cancer — definition

DefinitionAdvanced cancer: cancer that is unlikely to be cured or controlled with treatment; it may have spread from the primary site to nearby tissue, lymph nodes, or distant parts of the body, and treatment may be palliative to shrink tumor, slow growth, or relieve symptoms.

Clinical implicationAdvanced cancer often indicates need for molecular profiling to guide palliative or targeted therapy decisions.

Use in policyTerm used to define coverage contexts for certain tumor-specific molecular tests (e.g., fusion testing, PD-L1) where guideline-specified disease stage affects medical necessity.

PD-L1 analysis — definition and clinical role

DefinitionPD-L1 analysis: immunohistochemistry (IHC) assay to assess tumor PD-L1 protein expression used to guide immunotherapy treatment decisions.

Clinical rolePD-L1 IHC informs use of PD-1/PD-L1 inhibitors and is recommended where PD-L1 status affects therapy per NCCN and where FDA companion diagnostics exist.

Assay examplesFDA-cleared/approved companion diagnostic IHC assays are listed for select cancers (e.g., head and neck, urothelial carcinoma, triple negative breast cancer).

Gene rearrangement testing — definition for fusion detection (RET, ROS1, ALK, NTRK)

DefinitionGene rearrangement (fusion) testing detects actionable fusions (e.g., RET, ROS1, ALK, NTRK) using FISH, PCR, or NGS to identify candidates for targeted therapies.

Detection methodsIncludes FISH for locus-specific rearrangements, PCR for specific fusions, and RNA-based NGS (preferred for fusion detection) for comprehensive profiling.

Clinical purposeIdentifies tumor-specific driver fusions to guide selection of FDA-approved or guideline-recommended targeted agents across multiple tumor types.