ModifiedCentenePolicy N/A

CONCERT GENETIC ONCOLOGY: CYTOGENETIC TESTING

Defines medical necessity and coding guidance for cytogenetic and related protein analyses (FISH, CISH, IHC, PCR, selected NGS fusion panels) for solid tumors and hematologic malignancies for Centene-affiliated health plans.

Policy Summary

PayerCentene

PolicyCONCERT GENETIC ONCOLOGY: CYTOGENETIC TESTING

Policy CodePolicy N/A

Change TypeMaterial additions and revisions (RET, FOLR1, stage-based language, added tumor types)

Effective DateN/A

Next Review DateN/A

Key ActionObtain and document prior authorization when required and ensure clinical documentation supports the tumor-specific indication and stage for the requested test.

SourceLink

POLICY UPDATE CHANGES

Added Tumor Specific FOLR1 Protein Analysis and related criteria.

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

Replaced language 'advanced or metastatic' with stage-based language (e.g., 'Stage IB or higher' or specific stage ranges) for multiple biomarker criteria including PD-L1 and ALK.

Added cancer types for coverage (e.g., recurrent or metastatic vaginal cancer) based on updated NCCN guidance.

Clarified ovarian cancer pathology in FOLR1 Protein Analysis guidance.

PD-L1, FOLR1, RET, ROS1, ALK, ERBB2, NTRKTumor markers addressed

NCCNGuideline citations

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.

RET & FOLR1 addedRevisions in this update

CMS LCD/AExternal references

Coverage Criteria and Medical Necessity

inv-01: ALK rearrangement - Medical necessity

Tumor Specific ALK Gene Rearrangement (Qualitative FISH and PCR) Tests are considered medically necessary when ALL of the following apply:

ALK medical necessity: Somatic ALK rearrangement analysis (CPT examples 88271, 88274) in solid tumors is considered medically necessary when the member/enrollee has a diagnosis of or is in the initial work up stage for any of: Stage IB or higher lung adenocarcinoma; Stage IB or higher large cell lung carcinoma; Stage IB or higher squamous cell lung carcinoma; Stage IB or higher non-small cell lung cancer (NSCLC) not otherwise specified (NOS); or anaplastic thyroid carcinoma.

Supports targeted therapy selection

inv-02: Bladder cancer diagnostic and recurrence FISH - Medical necessity and frequency limits

Bladder Cancer Diagnostic and Recurrence FISH Tests are considered medically necessary when:

Bladder FISH: A. Member/enrollee has hematuria AND diagnostic studies have failed to identify the etiology AND a bladder cancer diagnostic and recurrence FISH test (CPT examples 88120, 88121) has not been ordered more than once in the past 12 months; OR B. Member/enrollee has been treated for bladder cancer AND the bladder cancer diagnostic and recurrence FISH tests are ordered within the following frequency limits by post-diagnosis year: no more than 4 per year for years 1-2 after diagnosis; no more than 3 in year 3 after diagnosis; no more than 2 in year 4 after diagnosis; and no more than 1 annually for up to 15 years after diagnosis.frequency limits as specified

Screening with bladder FISH for hematuria is investigational; other indications outside those listed are investigational

inv-03: CLL/SLL FISH panel - Medical necessity

CLL/SLL FISH Panel Analysis is considered medically necessary when ALL of the following are met:

CLL/SLL FISH panel: Panel includes analysis for +12, del(11q), del(13q), and del(17p), AND the member/enrollee is undergoing initial diagnostic workup for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Specifies required panel components

inv-04: ERBB2 (HER2) ISH/IHC - Medical necessity

ERBB2 (HER2) amplification analysis via ISH or IHC is medically necessary when ANY of the listed tumor types/stages apply:

ERBB2 (HER2) ISH/IHC: Member/enrollee has any of: recurrent or newly diagnosed stage I–IV invasive breast cancer; inoperable locally advanced, recurrent or metastatic gastric cancer; suspected or proven metastatic colorectal cancer or appendiceal adenocarcinoma; inoperable locally advanced, recurrent or metastatic esophageal and/or esophagogastric junction adenocarcinoma; recurrent, unresectable or metastatic salivary gland tumors; recurrent, advanced or metastatic cervical carcinoma; serous endometrial carcinoma; endometrial carcinosarcoma; p53 abnormal endometrial carcinoma; resectable, borderline resectable or locally advanced/metastatic pancreatic adenocarcinoma; recurrent ovarian/fallopian tube/primary peritoneal cancer; recurrent or metastatic vaginal cancer; Stage IIIB or higher muscle invasive bladder cancer; or metastatic small bowel adenocarcinoma.

Covers tumor types where HER2 testing is indicated per NCCN

inv-05: Multiple myeloma FISH panel - Medical necessity

Multiple myeloma FISH panel analysis of bone marrow is medically necessary when ALL of the following apply:

Multiple myeloma FISH panel: Panel includes analysis for del(13), del(17p13), t(4;14), t(11;14), t(14;16), t(14;20), 1q21 gain/amplification, and del(1p), AND the member/enrollee is undergoing initial diagnostic workup for multiple myeloma.

Specifies required panel components for prognostic and treatment planning

inv-06: NTRK fusion analysis - Medical necessity

NTRK 1/2/3 fusion analysis panel (FISH or IHC) is medically necessary when ANY of the following apply:

NTRK fusion panel: A. Member/enrollee is undergoing initial diagnostic workup for or has a diagnosis of an advanced, progressive, or metastatic solid tumor; cancer for which surgical resection is not possible; or an unknown primary cancer; OR B. Member/enrollee has a diagnosis of any stage of cervical sarcoma, anaplastic thyroid carcinoma, acute lymphoblastic leukemia (ALL), or pediatric (diagnosed age ≤18 years) diffuse high-grade glioma.

Includes both broad advanced/unknown primary indications and specific tumor types supported by NCCN

inv-07: PD-L1 protein expression analysis - Medical necessity

PD-L1 protein expression analysis via IHC is medically necessary when ALL of the following apply:

PD-L1 IHC: Member/enrollee has a diagnosis of or is in the initial work up stage for any of: Stage IB or higher lung adenocarcinoma; Stage IB or higher large cell lung carcinoma; Stage IB or higher squamous cell lung carcinoma; Stage IB or higher non-small cell lung cancer (NSCLC) not otherwise specified (NOS); or locally advanced or metastatic bladder cancer.

Used to guide immunotherapy decisions; NCCN and FDA companion diagnostic guidance referenced

inv-08: FOLR1 protein expression analysis - Medical necessity

FOLR1 protein expression analysis via IHC is medically necessary when ALL of the following apply:

FOLR1 IHC: Member/enrollee has recurrent, platinum‑resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, AND mirvetuximab soravtansine (Elahere) is being considered for treatment.

Companion diagnostic use per NCCN ovarian cancer guidance; include if prior testing did not assess FOLR1

inv-09: Tumor-specific PD-L1 protein analysis (IHC)

PD-L1 IHC in solid tumors is considered medically necessary when:

Indications: Member/enrollee has a diagnosis of or is in the initial workup for any of: Stage IB or higher lung adenocarcinoma; Stage IB or higher large cell lung carcinoma; Stage IB or higher squamous cell lung carcinoma; Stage IB or higher NSCLC not otherwise specified (NOS); locally advanced or metastatic bladder cancer; or other tumor-specific indications supported by NCCN and FDA companion diagnostic approvals.

See PD-L1 section and NCCN references for tumor-specific guidance

inv-10: Tumor-specific FOLR1 protein analysis (IHC 88360)

FOLR1 IHC (CPT example 88360) is considered medically necessary when ALL of the following are met:

FOLR1 criteria: (A) Member/enrollee has recurrent, platinum‑resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer; AND (B) mirvetuximab soravtansine (Elahere) is being considered as a treatment option.

Include testing if prior molecular analysis did not assess FOLR1

inv-11: PML/RARA rearrangement analysis (FISH/PCR)

PML/RARA rearrangement analysis via FISH or PCR in peripheral blood or bone marrow is considered medically necessary when any of the listed hematologic or tumor contexts apply:

PML-RARA indications: Indications include contexts where PML‑RARA is part of AML mutation testing and selected solid tumor contexts as listed (examples in policy include recurrent/progressive/metastatic cervical cancer; recurrent unresectable or stage IV triple negative breast cancer; locally advanced/recurrent/metastatic esophageal/esophagogastric junction adenocarcinoma; locally advanced/recurrent/metastatic gastric adenocarcinoma; recurrent/unresectable/oligometastatic/metastatic nasopharyngeal cancer; recurrent/progressive/metastatic squamous cell vulvar cancer; recurrent or metastatic vaginal cancer).

PML‑RARA is included among genetic markers for AML and is listed for selected solid tumor contexts in the policy

inv-12: RET gene rearrangement testing (FISH)

RET FISH testing in solid tumors is considered medically necessary when the member/enrollee has any of the listed diagnoses (for medullary thyroid cancer, germline context is considered):

RET indications: Member/enrollee has any of: recurrent or persistent locoregional or metastatic medullary thyroid cancer (and germline RET testing is negative or has not been done); anaplastic thyroid carcinoma; locally recurrent/advanced/metastatic papillary, follicular, or oncocytic (Hurthle cell) thyroid carcinoma; advanced or metastatic adenocarcinoma of the lung, large cell lung cancer, or NSCLC not otherwise specified; locally advanced or metastatic squamous cell, adenocarcinoma, or adenosquamous carcinoma of the cervix; initial diagnostic workup for acute myeloid leukemia; recurrent unresectable or stage IV breast cancer; suspected or confirmed metastatic colon cancer; resectable/borderline resectable/locally advanced or metastatic pancreatic adenocarcinoma; locally advanced/recurrent/metastatic esophageal or esophagogastric junction cancer; locally advanced/recurrent/metastatic gastric cancer; or recurrent or metastatic vaginal cancer. RNA‑based NGS is preferred over DNA‑based NGS for fusion detection per guideline rationale.

Includes tumor types where RET fusion testing is recommended/considered per NCCN; germline testing context specified for medullary thyroid cancer

inv-13: ROS1 gene rearrangement testing (FISH)

ROS1 FISH testing is considered medically necessary when the member/enrollee has any of the following diagnoses:

ROS1 indications: Member/enrollee has advanced or metastatic lung adenocarcinoma; advanced or metastatic large cell lung carcinoma; advanced or metastatic squamous cell lung carcinoma; advanced or metastatic non‑small cell lung cancer (NSCLC) not otherwise specified (NOS); locally advanced or metastatic ampullary adenocarcinoma; resectable/borderline resectable/locally advanced or metastatic pancreatic adenocarcinoma; or pediatric (diagnosed age ≤18 years) diffuse high‑grade glioma.

ROS1 fusion testing supported by NCCN for NSCLC and considered in specified non‑lung tumors

inv-14: Tumor-specific biomarker coverage rationale

Coverage is supported when testing aligns with tumor-specific indications in current NCCN guidelines and FDA companion diagnostic approvals.

PD-L1 testing indications: PD‑L1 testing is recommended during workup or for documented/suspected metastatic or stage‑based disease for multiple tumor types (including gastric, head & neck, bladder, vulvar, esophageal, cervical, NSCLC, breast triple‑negative, and vaginal cancers) per NCCN; FDA lists PD‑L1 IHC companion diagnostics for selected cancer types.

NCCN and FDA companion diagnostic support referenced

FOLR1 testing indication: FOLR1 (folate receptor alpha) testing is recommended for recurrent, platinum‑resistant ovarian/fallopian tube/primary peritoneal cancer to determine suitability for mirvetuximab soravtansine (Elahere); include if prior testing did not assess FOLR1.

NCCN ovarian cancer guideline reference

PML-RARA testing indication: PML‑RARA gene rearrangement is included among genetic markers that should be tested in all patients with acute myeloid leukemia to guide prognosis and therapy.

NCCN AML guideline reference

Bladder cancer diagnostic and recurrence FISH tests (CPT 88120, 88121) are considered investigational for screening of members with hematuria. The policy specifies that FISH for hematuria is only medically necessary when diagnostic studies have failed to identify the etiology and the test has not been ordered more than once in the prior 12 months; otherwise, screening use is investigational.

Bladder cancer diagnostic and recurrence FISH tests (CPT 88120, 88121) are considered investigational for indications not specifically listed in the criteria. The policy language states these FISH tests are investigational when used for diagnosing or monitoring outside the enumerated, medically necessary indications.

The policy excludes bladder tumor marker testing by any technology from coverage when used to screen all patients with hematuria. The CMS LCD cited in the policy notes that bladder tumor markers (immunoassay, molecular, or FISH) are not covered for screening all patients with hematuria and references validated assays (e.g., UroVysion) for specific covered uses.

The excerpt does not contain a comprehensive list of explicit exclusions. It documents that prior policy versions removed certain procedure codes and adjusted coverage statuses (for example, changes involving bladder cancer FISH tests), indicating code and coverage updates were made in revisions rather than presented as a new, standalone exclusion table in this excerpt.

When state Medicaid coverage provisions conflict with this clinical policy, state Medicaid coverage provisions take precedence. Providers should consult the applicable state Medicaid manual for any differing coverage rules.

Within the provided excerpt there are no explicit statements labeling services as 'not medically necessary'. The policy text instead identifies investigational and not-covered situations and documents prior revisions; it does not include separate not‑medically‑necessary declarations in this selection.

Covered Indications by Tumor / Test Group

inv-55: Tumor- and hematologic-specific molecular/cytogenetic testing when listed diagnostic/stage/therapy-related criteria are met (see ALK, bladder FISH, CLL/SLL panel, ERBB2/HER2, multiple myeloma panel, NTRK, PD-L1, FOLR1).

Tumor- and hematologic-specific molecular/cytogenetic testing is covered when the diagnostic, stage, or therapy‑related criteria listed for each specific test are met (see individual test sections: ALK, bladder FISH, CLL/SLL panel, ERBB2/HER2, multiple myeloma panel, NTRK, PD‑L1, FOLR1).

Covered tumor/hematologic tests: Coverage applies when the member meets the detailed diagnostic/stage/therapy‑related criteria specified for each named test group (e.g., ALK, bladder diagnostic/recurrence FISH, CLL/SLL FISH panel, ERBB2/HER2 ISH or IHC, multiple myeloma FISH panel, NTRK fusion panel, PD‑L1 IHC, FOLR1 IHC).

See individual test criteria for component and staging requirements

inv-56: NTRK fusion analysis

NTRK fusion testing is recommended by NCCN across many tumor types; testing is medically necessary in the contexts specified in the NTRK section.

NTRK guideline support: NCCN recommends consideration of NTRK fusion analysis for a range of tumor types (thyroid, colon, NSCLC, cervical sarcoma, vulvar, uterine sarcoma, breast recurrent/metastatic, gastric, esophageal, pancreatic, pediatric CNS, GIST, neuroendocrine/adrenal, head & neck, hepatic, ovarian) particularly in advanced, recurrent, metastatic, or when targeted NTRK inhibitors are being considered.

Coding and CPT/HCPCS References

Tumor Specific ALK Gene Rearrangement - Common CPT CodesCPT

88271	FISH analysis (example: ALK)
88274	FISH analysis (example: ALK)

Bladder Cancer Diagnostic and Recurrence FISH - Common CPT CodesCPT

88120	FISH, bladder cancer diagnostic/recurrence
88121	FISH, bladder cancer diagnostic/recurrence

CLL/SLL and Multiple Myeloma FISH Panel - Common CPT CodesCPT

88275	FISH panel component (CLL/MM examples)
88291	FISH panel analysis (CLL/MM examples)
88237	Cytogenetic analysis (multiple myeloma example)

ERBB2 (HER2) and Protein IHC/ISH - Common CPT CodesCPT

88360	IHC, protein analysis (ERBB2/HER2, FOLR1 examples)
88377	In situ hybridization (ISH) (ERBB2/HER2)

NTRK Fusion Analysis Panel - Common CPT CodesCPT

81191	NTRK fusion analysis (NGS) - panel
81192	NTRK fusion analysis (NGS) - panel
81193	NTRK fusion analysis (NGS) - panel
81194	NTRK fusion analysis (NGS) - panel

PD-L1 Protein Analysis - Common CPT CodesCPT

88341	PD-L1 IHC with interpretation
88342	PD-L1 IHC with interpretation
88361	Protein IHC (additional reporting code)

PD-L1 / IHC related CPT codesCPTCovered

88341	IHC (listed in PD-L1 section)
88342	IHC (listed in PD-L1 section)
88360	IHC (immunohistochemistry) — general (also used for FOLR1)
88361	IHC (listed in PD-L1 section)

FISH / gene rearrangement CPT codesCPTCovered

81315	PML/RARA testing (qualitative)
81316	PML/RARA testing (qualitative)
88271	FISH — probe specific, each probe
88274	FISH — multi-probe
88275	FISH — multi-probe variations
88291	Interpretation and report (cytogenetic)
88374	FISH technical/procedural code (listed under RET)
88377	FISH technical/procedural code (listed under RET)

ROS1 FISH codesCPTCovered

88271	FISH — probe specific, each probe (ROS1)
88274	FISH — multi-probe (ROS1)

Examples of added molecular CPT codesCPT

81315	PML-RARA gene rearrangement (added)
81316	PML-RARA gene rearrangement (added)

Referenced LCDmixed

L33420

CMS LCD: MolDX: Lab: Bladder/Urothelial Tumor Markers

Referenced CMS Articlemixed

A53095

CMS Billing and Coding Article: MolDX: Billing and Coding: Lab: Bladder/Urothelial Tumor Markers

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Verify Prior Authorization with Health Plan

Prior authorization may be required for certain tumor-specific immunohistochemistry and molecular tests. Providers should verify plan-specific prior authorization requirements with the Health Plan before ordering tests.

Verify prior authorization requirements with the member's Health Plan prior to test order/submission.

Prior Authorization

Prior Authorization Required for FOLR1 IHC

Tumor-specific FOLR1 protein expression analysis by IHC (CPT 88360) requires prior authorization when ordered to evaluate recurrent, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer and when mirvetuximab soravtansine (Elahere) is being considered as a treatment option.

Prior authorization required for FOLR1 IHC (88360) in recurrent, platinum-resistant epithelial ovarian/fallopian tube/primary peritoneal cancer when Elahere is being considered.

Not Covered / Investigational

Bladder cancer FISH tests (88120, 88121) for screening of hematuria and for other indications not listed in the criteria are designated NOT COVERED / investigational. The policy cites CMS LCD utilization guidance and specifies frequency limits for surveillance when test use is medically necessary after diagnosis.

Bladder tumor marker testing by any technology (immunoassay, molecular, or FISH) is NOT COVERED for screening all patients with hematuria. The CMS guidance referenced in the policy also notes that only validated FISH assays (for example, the FDA‑cleared UroVysion kit) are recognized for specific uses.

The excerpt documents that coverage status and procedure-code lists were revised between versions (for example, bladder cancer diagnostic and recurrence FISH tests changed status in prior revisions). These changes are noted in the revision history rather than as new exclusion language in the excerpt.

Definitions and Key Terms

driver mutations

DefinitionSomatic oncogenic mutations (driver mutations)

Clinical relevanceDriver mutations help select targeted therapies and inform prognosis and treatment response in cancers

Specimen typesDetected in tumor tissue; may also be identified via blood-based assays in some contexts (see ctDNA/CTCs)

ctDNA/CTCs

DefinitionCirculating tumor DNA (ctDNA) or circulating tumor cells (CTCs) used for non-tissue molecular analysis

Use caseAlternative to tumor tissue testing for molecular analysis of solid tumors

Related policy note

Eligibility Requirements

Eligibility requirement details are not present in the provided excerpt.

Background and Rationale

Cytogenetic analysis of solid tumors and hematologic malignancies is used to classify tumors and to identify somatic driver mutations that inform diagnosis, prognosis, and selection of targeted therapies. Testing may be performed on tumor tissue or, for some solid tumors, via circulating tumor DNA or circulating tumor cells.

Policy Summary

PayerCentene

PolicyCONCERT GENETIC ONCOLOGY: CYTOGENETIC TESTING

Policy CodePolicy N/A

Change TypeMaterial additions and revisions (RET, FOLR1, stage-based language, added tumor types)

Effective DateN/A

Next Review DateN/A

Key ActionObtain and document prior authorization when required and ensure clinical documentation supports the tumor-specific indication and stage for the requested test.

SourceLink

On This Page

RET gene rearrangement testing indications: Somatic RET testing is recommended or considered across multiple tumor types including medullary and anaplastic thyroid cancers (when germline wild type/unknown), advanced/metastatic lung adenocarcinoma, and other metastatic/recurrent tumors per NCCN; RNA‑based NGS is preferable for fusion detection.

Multiple NCCN guideline citations

ROS1 gene rearrangement testing indications: ROS1 rearrangement testing is recommended in advanced/metastatic NSCLC (adenocarcinoma, large cell, NSCLC NOS) and considered for other tumor types (ampullary, pancreatic, pediatric CNS high‑grade gliomas) when broad molecular profiling is indicated.

NCCN guideline citations

See NTRK Fusion Analysis Panel section and NCCN citations

inv-57: ERBB2/HER2 testing (IHC, FISH, CISH)

NCCN guideline support for ERBB2/HER2 testing across multiple tumor types is summarized below.

ERBB2/HER2 guideline support: NCCN recommends HER2 testing (IHC with reflex to ISH/FISH/CISH) for tumor types including esophageal and esophagogastric junction adenocarcinoma, gastric cancer when trastuzumab is being considered, salivary gland tumors, metastatic colorectal/appendiceal adenocarcinoma, all new primary or metastatic breast cancers, recurrent/metastatic cervical carcinoma, uterine serous/carcinosarcoma and p53 abnormal endometrial tumors, pancreatic adenocarcinoma in certain settings, recurrent ovarian disease, bladder stage IIIB+, and small bowel metastatic disease when HER2‑directed therapy is a consideration.

NCCN guideline references provided in ERBB2 section

inv-58: FISH panels for hematologic malignancies (CLL/SLL and multiple myeloma)

FISH panels for hematologic malignancies are supported by guideline recommendations when performed as part of initial diagnostic workup.

Hematologic FISH panels: NCCN recommends FISH testing during initial workup for CLL/SLL (for +12, del(11q), del(13q), del(17p)) and for multiple myeloma (del(13), del(17p13), t(4;14), t(11;14), t(14;16), t(14;20), 1q21 gain/amplification, del(1p)) for prognostic and treatment planning purposes.

See CLL/SLL and Multiple Myeloma sections for specific panel components

inv-59: PD-L1 testing during workup for documented or suspected metastatic or stage-based disease in multiple cancers (gastric, head & neck, bladder, vulvar, esophageal, cervical, NSCLC, breast TNBC, vaginal).

PD-L1 testing is recommended during workup for documented or suspected metastatic or stage‑based disease in multiple cancers per NCCN.

PD-L1 guideline support: NCCN recommends PD‑L1 testing during the workup for documented or suspected metastatic disease or stage‑based indications in gastric, head & neck, bladder, vulvar, esophageal, cervical, NSCLC, breast (triple negative) and vaginal cancers; FDA‑cleared PD‑L1 IHC companion diagnostics exist for selected cancer types.

Guideline and FDA companion diagnostic support

inv-60: FOLR1 testing for platinum-resistant recurrent ovarian/fallopian tube/primary peritoneal cancer to determine suitability for mirvetuximab soravtansine.

FOLR1 testing is indicated in ovarian/fallopian tube/primary peritoneal cancer for selection of mirvetuximab soravtansine in platinum‑resistant recurrent disease.

FOLR1 guideline support: NCCN recommends including folate receptor alpha (FOLR1) testing in tumor molecular analysis for recurrent, platinum‑resistant epithelial ovarian/fallopian tube/primary peritoneal cancer to identify potential benefit from mirvetuximab soravtansine; perform if prior testing did not assess FOLR1.

Companion diagnostic rationale per NCCN

inv-61: PML-RARA gene rearrangement testing in all patients with acute myeloid leukemia as part of mutation panel to guide prognosis and therapy.

PML‑RARA gene rearrangement testing is part of recommended mutation panels in AML.

PML-RARA in AML: NCCN recommends that all patients with acute myeloid leukemia be tested for a range of mutations that guide prognosis and therapy; PML‑RARA is included among these markers.

Guideline‑based recommendation for AML workup

inv-62: RET gene rearrangement testing for multiple tumor types including medullary and anaplastic thyroid cancers (when germline wild type/unknown), advanced/metastatic lung adenocarcinoma, and other metastatic/recurrent tumors per NCCN.

RET gene rearrangement testing is recommended or considered across multiple tumor types per NCCN; RNA‑based NGS is preferred for fusion detection.

RET guideline support: NCCN recommends somatic RET testing for recurrent/persistent medullary thyroid carcinoma when germline is wild type or unknown, and for anaplastic and other thyroid cancers not amenable to radioactive iodine; recommends RET testing in advanced/metastatic lung adenocarcinoma and considers RET testing for other tumor types including cervical, breast, colon, pancreatic, esophageal, gastric, and vaginal cancers. RNA‑based NGS is preferable to DNA‑based NGS for fusion detection.

Multiple NCCN citations

inv-63: ROS1 rearrangement testing in advanced/metastatic NSCLC (adenocarcinoma, large cell, NSCLC NOS) and considered in other tumor types when broad molecular profiling is indicated.

ROS1 rearrangement testing is recommended in advanced/metastatic NSCLC and considered in other tumor types when broad molecular profiling is indicated.

ROS1 guideline support: NCCN recommends ROS1 rearrangement testing in advanced/metastatic NSCLC (adenocarcinoma, large cell, NSCLC NOS) and considers ROS1 testing for squamous histology and other tumor types (ampullary, pancreatic, pediatric CNS high‑grade gliomas) when comprehensive molecular profiling is performed to inform systemic therapy options.

NCCN guideline references

Billing Rule

Prior Authorization and Coding Updates

Recent policy revisions added or updated CPT codes for molecular and other tumor-specific tests. Inclusion or removal of a CPT code in this policy does not guarantee coverage; providers must consult current coding guidance and plan requirements prior to claim submission.

Policy revisions include addition of CPT codes such as 81315 and 81316 and other molecular test codes — check the Concert Platform or plan for the authoritative code list.
Inclusion or exclusion of any codes in this document does not guarantee coverage.

Documentation Required

Required Clinical Indication and Supporting Documentation

Medical necessity determinations require clear clinical documentation demonstrating that the member meets the specific diagnostic, staging, and treatment-context indications listed for each test. Documentation must support the cancer diagnosis, disease stage (when specified), prior therapies, and the clinical context (e.g., recurrent, metastatic, platinum-resistant) that justify the requested testing.

Required: documentation of tumor type and relevant staging where specified.
Required: documentation of prior relevant tests and therapies (e.g., prior molecular testing results, prior lines of therapy, platinum-resistance status).
Documentation should explicitly reference the indication from the policy (e.g., recurrent, platinum-resistant ovarian cancer when ordering FOLR1 IHC).

Step Therapy

Bladder Tumor Marker Frequency Limits and Step Therapy

Bladder tumor marker (FISH) testing is subject to frequency limits and step/coverage constraints. There are no explicit step therapy requirements stated for other tests in this excerpt.

Frequency limits for bladder tumor marker studies when used for surveillance after bladder cancer diagnosis: maximum of 4 per year for years 1–2 after diagnosis; maximum of 3 per year for year 3; maximum of 2 for year 4; and maximum of 1 per year for up to 15 years thereafter.
Bladder tumor marker FISH testing is not covered for general screening of all patients with hematuria; only validated assays (e.g., UroVysion) are considered where specified.
Step therapy: No explicit step therapy requirements are stated in this policy excerpt for molecular/IHC tests.

Note

Provider Judgment and Coverage Caveats

Providers must apply professional medical judgment. Coverage determinations in this policy are guides to medical necessity and are not guarantees of payment. Always confirm coding and authorization requirements prior to claim submission.

Inclusion or exclusion of codes is informational only; always reference up-to-date coding guidance and plan-specific rules.
Coverage is contingent on alignment of the requested test with the listed clinical criteria (e.g., NCCN or companion diagnostic guidance).
Coverage decisions are subject to Health Plan benefit documents, exclusions, limitations, and applicable state/federal rules.

Policy addresses tissue-based testing here; ctDNA/CTC testing is referenced under Other Related Policies

Advanced cancer

DefinitionCancer unlikely to be cured or controlled with treatment; may have spread locally, to lymph nodes, or distantly

Treatment goalsTreatment may be given to shrink the tumor, slow cancer growth, or relieve symptoms

Context in policyUsed to frame indications for testing when advanced-stage disease is specified in tumor-specific criteria

RET/ROS1 gene rearrangement

DefinitionFusion or gene rearrangement testing to detect RET or ROS1 gene fusions/rearrangements

Testing methodsCommonly performed by FISH or NGS-based fusion panels; RNA-based NGS is preferable for fusion detection

Clinical rationaleDetection guides targeted therapy selection in multiple tumor types per NCCN guidance

PD-L1 protein analysis (IHC)

DefinitionProtein expression testing by immunohistochemistry (IHC) used as a companion diagnostic to guide therapy selection based on PD-L1 status

Regulatory contextFDA has cleared/approved PD-L1 IHC companion diagnostic devices for selected cancer types (e.g., head and neck, urothelial carcinoma, TNBC)

Clinical useNCCN recommends PD-L1 testing during workup for multiple tumor types (gastric, head & neck, bladder, vulvar, esophageal, cervical, NSCLC, breast TNBC, vaginal)

'Health Plan' definition

Definition'Health Plan' means a health plan that has adopted this clinical policy and that is operated or administered, in whole or in part, by Centene Management Company, LLC, or any of such health plan's affiliates.

Policy roleThis clinical policy is adopted and applied by the Health Plan as described; it is a guide to medical necessity, not a guarantee of payment

Legal noteCoverage determinations are subject to terms, exclusions, limitations of coverage documents and to state and federal requirements