OpenPayer is powered by Trek Health's payer performance platform. Trek continuously ingests, validates, and normalizes Transparency in Coverage data alongside payer policies and other commercial payer data to create a structured payer intelligence foundation. OpenPayer uses this foundation to deliver personalized search results, dynamically generated policy pages, and tailored policy monitoring based on each user's payers, specialties, billing codes, and areas of interest. The same intelligence powers broader payer performance workflows, including reimbursement benchmarking, contract evaluation, payer negotiations, and financial decision-making.

ModifiedCommunity Health Plan WashingtonPolicy N/A

Concert Genetic Oncology: Cytogenetic Testing (Tumor-specific FISH, IHC, PCR, targeted fusion panels)

Customize your policy alerts

Sign up for all Community Health Plan Washington policy alerts

Know when Community Health Plan Washington releases new policies or updates existing guidance.

Monitor payer policy activity

Receive email alerts as soon as relevant payer policies are published or updated.

Defines medical necessity criteria and coding examples for cytogenetic and tumor protein testing (FISH, CISH, IHC, selected NGS fusion panels) for solid tumors and hematologic malignancies; applies to providers and members covered by the payer.

Policy Summary

PayerCommunity Health Plan Washington

PolicyCytogenetic testing for oncology (FISH, CISH, IHC, PCR, targeted panels)

Policy CodePolicy N/A

Change TypeAdded FOLR1 and RET testsstaging language revised to 'Stage IB or higher' and expanded cancer lists

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization when required and document tumor type and disease stage consistent with listed criteria (e.g., Stage IB or higher where specified).

SourceLink

POLICY UPDATE CHANGES

Added Tumor Specific FOLR1 Protein Analysis and related criteria.

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

Replaced 'advanced or metastatic' language with 'Stage IB or higher' (and similar stage wording) across PD-L1 and other tumor-specific criteria.

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

10+Distinct test types

~20Tumor/test pairings

LCD referencedLCD used to change bladder FISH coverage

State-specificApplicable state

FDA-listedFDA-listed PD-L1 companion diagnostics

Medical Necessity Criteria for Tumor and Hematologic Cytogenetic/Protein Testing

ALK gene rearrangement (FISH/PCR)

Somatic ALK rearrangement analysis (88271, 88274) in solid tumors is considered medically necessary when:

ALK testing medical necessity: The member has a diagnosis of or is in the initial work up stage for one of the listed tumor typesany of the listed tumor types

Listed tumor types include 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); and anaplastic thyroid carcinoma.

Bladder cancer diagnostic and surveillance FISH

Bladder cancer diagnostic and recurrence FISH tests (88120, 88121) are considered medically necessary when:

Indications: A. Member has hematuria AND diagnostic studies have failed to identify the etiology AND a bladder cancer diagnostic and recurrence FISH test has not been ordered more than one time in the past 12 months; OR B. Member has been treated for bladder cancer AND the bladder cancer diagnostic and recurrence FISH tests are ordered within the specified frequency limits after diagnosis

Policy Summary

PayerCommunity Health Plan Washington

PolicyCytogenetic testing for oncology (FISH, CISH, IHC, PCR, targeted panels)

Policy CodePolicy N/A

Change TypeAdded FOLR1 and RET testsstaging language revised to 'Stage IB or higher' and expanded cancer lists

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization when required and document tumor type and disease stage consistent with listed criteria (e.g., Stage IB or higher where specified).

SourceLink

On This Page

frequency limits apply

Frequency limits: no more than 4 per year for years 1-2 after diagnosis; no more than 3 per year during year 3; no more than 2 during year 4; and no more than 1 annually for up to 15 years after diagnosis.

CLL/SLL FISH panel

CLL/SLL FISH panel analysis (88271, 88274, 88275, 88291) is medically necessary when:

CLL/SLL panel: A. The panel includes analysis for +12, del(11q), del(13q), and del(17p); AND B. The member is undergoing initial diagnostic workup for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)panel must include specified probes

Specimen: peripheral blood or bone marrow.

ERBB2 (HER2) amplification testing

Somatic ERBB2 (HER2) amplification analysis via ISH (88377) or IHC (88360) is medically necessary when the member has any of the listed tumor types or stages:

ERBB2/HER2 indications: Member has one of the enumerated cancers such as recurrent or newly diagnosed stage I–IV invasive breast cancer; inoperable locally advanced, recurrent or metastatic gastric adenocarcinoma; suspected or proven metastatic colorectal or appendiceal adenocarcinoma; inoperable locally advanced, recurrent or metastatic esophageal/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 adenocarcinomaany listed cancer indication

Multiple tumor types enumerated in the policy and supported by NCCN guidance.

Multiple myeloma FISH panel

Multiple myeloma FISH panel analysis (88237, 88271, 88275, 88291) of bone marrow is medically necessary when:

Multiple myeloma panel: A. The 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 B. The member is undergoing initial diagnostic workup for multiple myelomapanel must include specified abnormalities

Specimen: bone marrow.

NTRK fusion analysis panel

NTRK 1/2/3 fusion analysis panel (81191–81194) via FISH or IHC in solid tumors is medically necessary when:

NTRK indications: A. Member is undergoing initial diagnostic workup for or has advanced, progressive, or metastatic solid tumor, unresectable cancer, or unknown primary; OR B. Member has any of several specific cancers at any stage (for example: cervical sarcoma; anaplastic thyroid carcinoma; acute lymphoblastic leukemia; pediatric diffuse high-grade glioma), or other tumor types listed in NCCN guidance where NTRK testing is recommendedany listed condition

Applies to both initial workup for advanced disease and specific cancer diagnoses per NCCN recommendations.

PD-L1 IHC testing

PD-L1 protein expression analysis via immunohistochemistry (IHC) (88341, 88342, 88360, 88361) is medically necessary when:

PD-L1 indications: Member has a diagnosis of or is in the initial work up stage for one of the listed cancers such as 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 NOS, or locally advanced or metastatic bladder cancer; additional tumor-specific indications are listed in policy and supported by NCCN/FDA guidanceany listed cancer indication

FDA-cleared companion diagnostics are recognized for certain cancer types.

FOLR1 IHC for treatment selection

Tumor-specific FOLR1 IHC (88360) is medically necessary when both criteria are met:

FOLR1 testing: A. Member has recurrent, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer; AND B. Elahere (mirvetuximab soravtansine) is being considered for treatmentboth conditions required

Testing is recommended when prior testing did not include FOLR1 or when therapy selection for mirvetuximab is being considered.

Tumor Specific PD-L1 Protein Analysis

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

PD-L1 IHC criteria: Member has a diagnosis of or is in initial workup for one 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 NOS; locally advanced or metastatic bladder cancer; [additional tumor types referenced elsewhere in document].

Criteria align with NCCN and FDA guidance cited in policy.

Tumor Specific FOLR1 Protein Analysis

FOLR1 IHC is considered medically necessary when ALL of the following apply:

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

From NCCN guidance; perform if prior testing did not include FOLR1.

Tumor Specific PML/RARA Gene Rearrangement

PML/RARA rearrangement analysis via FISH or PCR is considered medically necessary when performed on peripheral blood or bone marrow for specified hematologic and listed solid tumor situations including:

PML/RARA indications: Includes recurrent, progressive, or metastatic cervical cancer; recurrent unresectable or stage IV triple negative breast cancer; locally advanced, recurrent or metastatic esophageal/esophagogastric junction adenocarcinoma; locally advanced, recurrent or metastatic gastric adenocarcinoma; recurrent, unresectable, oligometastatic, or metastatic nasopharyngeal cancer; recurrent, progressive or metastatic squamous cell vulvar cancer; and recurrent or metastatic vaginal cancer.

Also indicated broadly in AML as part of mutation testing per NCCN.

Tumor Specific RET Gene Rearrangement Tests (FISH)

RET gene rearrangement testing via FISH in solid tumors is considered medically necessary when ANY of the following tumor-specific conditions are met (some items include additional requirements):

RET indications list: Recurrent/persistent or metastatic medullary thyroid cancer (if germline RET testing is negative or not 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 NOS; locally advanced or metastatic cervical cancers (squamous, adenocarcinoma, adenosquamous); recurrent unresectable or stage IV breast cancer; suspected or confirmed metastatic colon cancer; resectable/borderline resectable or locally advanced/metastatic pancreatic adenocarcinoma; locally advanced, recurrent or metastatic esophageal/esophagogastric junction cancer; locally advanced, recurrent or metastatic gastric cancer; recurrent or metastatic vaginal cancer; and initial diagnostic workup for AML.

Germline RET testing should be negative or not done for medullary thyroid cancer; RNA-based NGS preferred for fusion detection where noted.

Tumor Specific ROS1 Gene Rearrangement

ROS1 gene rearrangement analysis via FISH is considered medically necessary when ANY of the following tumor-specific conditions are met:

ROS1 indications: Advanced or metastatic lung adenocarcinoma; advanced or metastatic large cell lung carcinoma; advanced or metastatic squamous cell lung carcinoma; advanced or metastatic NSCLC not otherwise specified (NOS); locally advanced or metastatic ampullary adenocarcinoma; resectable/borderline resectable or locally advanced/metastatic pancreatic adenocarcinoma; pediatric diffuse high-grade glioma (diagnosed age 18 years or younger).

Per NCCN recommendations for ROS1 testing and other tumor-specific guidance.

Tumor Specific PD-L1 Protein Analysis

Coverage aligned to NCCN/FDA recommendations for PD-L1 testing in specific tumor types and stages.

PD-L1 testing coverage: PD-L1 testing is recommended during workup for documented or suspected metastatic or Stage IB-IIIA disease in multiple tumor types including gastric, head and neck (nasopharynx), bladder, vulvar, esophageal, cervical, breast (triple negative recurrent unresectable or stage IV), NSCLC (stage IB-IIIA perioperatively and advanced/metastatic), and others as listed by NCCN; FDA-cleared companion diagnostics are recognized for certain cancers.

Reflects NCCN and FDA guidance cited in policy.

Tumor Specific FOLR1 Protein Analysis

Coverage for folate receptor alpha testing in ovarian and related cancers to identify targeted therapy.

FOLR1 testing coverage: FOLR1 testing is recommended for ovarian, fallopian tube, or primary peritoneal cancers, particularly in platinum-resistant recurrent disease, to identify potential benefit from mirvetuximab soravtansine; include testing if prior molecular profiling did not include FOLR1.

Based on NCCN guidelines.

Tumor Specific PML/RARA Gene Rearrangement (Qualitative FISH and PCR)

Coverage for PML-RARA testing in acute myeloid leukemia (AML) and selected tumor contexts.

PML-RARA testing coverage: PML-RARA rearrangement testing (qualitative FISH and PCR) should be performed in all patients with AML as part of mutation testing to guide prognosis and management; additionally, testing is considered for listed recurrent, unresectable, or metastatic solid tumor contexts where indicated.

NCCN AML guideline supports routine testing for PML-RARA.

Tumor Specific RET Gene Rearrangement Tests (FISH)

Coverage for RET gene fusion/rearrangement testing in multiple tumor types when clinically indicated.

RET testing coverage: Somatic RET testing (including FISH) is recommended for recurrent/persistent medullary thyroid carcinoma if germline wild type/unknown; for anaplastic and advanced thyroid cancers not treatable with radioactive iodine; for advanced/metastatic lung adenocarcinoma and other lung subtypes; and for various other metastatic or locally advanced cancers (breast, colon, pancreatic, esophageal, gastric, cervical, vaginal) where RET fusion detection may guide therapy.

RNA-based NGS preferred for fusion detection; tissue or blood may be used for detection in some cancers per NCCN.

Tumor Specific ROS1 Gene Rearrangement

Coverage for ROS1 fusion testing in indicated tumor types.

ROS1 testing coverage: ROS1 rearrangement testing is recommended for advanced/metastatic NSCLC (adenocarcinoma, large cell, NSCLC NOS) and considered for squamous cell carcinoma; also recommended or considered in other cancers (ampullary adenocarcinoma, pancreatic adenocarcinoma, pediatric diffuse high-grade glioma) when profiling for actionable fusions.

Based on NCCN guidance.

Bladder cancer diagnostic and recurrence FISH tests (CPT 88120, 88121) are covered only for the specific indications listed in policy. They are considered medically necessary when: A) the member has hematuria and prior diagnostic studies have failed to identify the etiology and a bladder FISH test has not been ordered more than once in the past 12 months; OR B) the member has been treated for bladder cancer and testing is ordered within the stated frequency limits. Frequency limits are: no more than 4 per year for years 1–2 after diagnosis; 3 per year for year 3; 2 per year for year 4; and 1 per year thereafter for up to 15 years.

Bladder diagnostic/recurrence FISH testing for screening of members with hematuria and for other indications not specified in the policy is considered investigational and not covered. Policy history notes that bladder FISH coverage status was updated to align with an applicable LCD; absence of alignment with the referenced LCD or NCCN guidance could affect coverage.

Bladder tumor marker assays performed by any technology are not covered for screening all patients with hematuria. The CMS Local Coverage Determination for 'Lab: Bladder/Urothelial Tumor Markers' (LCD) specifies that only validated assays (to date, the FDA-cleared UroVysion Bladder Cancer Kit) meet the LCD criteria and includes specific utilization guidelines.

Providers should follow the LCD utilization rules when ordering bladder tumor marker testing: for high-risk patients with persistent hematuria and a negative initial FISH after comprehensive diagnostic workup, one repeat FISH in conjunction with cystoscopy within one year may be reasonable and necessary per the LCD. Prior diagnostic workup is required before ordering bladder FISH for hematuria.

Policy history documents indicate that bladder cancer diagnostic and recurrence FISH tests were previously listed as non-covered but the coverage status was changed to covered in alignment with a CMS LCD. No other prior non-coverage items from these document sections are currently reinstated as not medically necessary in the present policy text.

When state Medicaid coverage provisions conflict with this clinical policy, state Medicaid provisions take precedence for Medicaid members — consult the applicable state Medicaid manual. For Medicare members, review applicable Medicare NCDs and LCDs and Medicare Coverage Articles prior to applying these criteria to ensure consistency with Medicare coverage rules.

The policy was revised to reflect that bladder cancer diagnostic and recurrence FISH testing coverage changed from previously non-covered to covered based on the CMS LCD. Providers should be aware that coverage aligned to the LCD includes the utilization and assay validation requirements described in the LCD and reiterated in this policy.

Tumor- and Disease-specific Covered Indications

Example CPT/Procedure Codes and Groups

ALK gene rearrangement example CPT codesCPT

88271	Cytogenetic analysis; probe
88274	Cytogenetic analysis; FISH

Bladder cancer diagnostic and recurrence FISH CPT codesCPT

88120	FISH, bladder cancer diagnostic kit example
88121	FISH, bladder cancer recurrence example

ERBB2/HER2 IHC and ISH CPT codesCPT

88360	Immunohistochemistry with interpretation
88377	In situ hybridization, each probe

NTRK fusion panel CPT codesCPT

81191	NTRK fusion analysis panel - CPT example
81192	NTRK fusion analysis panel - CPT example
81193	NTRK fusion analysis panel - CPT example
81194	NTRK fusion analysis panel - CPT example

Multiple myeloma FISH panel CPT codesCPT

88237	Multiple myeloma FISH panel - example CPT
88275	Cytogenetic analysis additional code
88291	FISH complex panel probe code

PD-L1 IHC CPT codesCPT

88341	Immunohistochemistry with interpretation, single or multiplex
88342	IHC, additional quantitation/interpretation
88361	IHC, additional complex interpretation

Tumor PD-L1 IHC codesCPTCovered

88341	IHC/related code listed for PD-L1 testing
88342	IHC/related code listed for PD-L1 testing
88360	IHC operating code (noted for PD-L1 and FOLR1)
88361	IHC/related code listed for PD-L1 testing

FISH/PCR codes (PML/RARA, RET, others)CPTCovered

81315	FISH for PML/RARA
81316	FISH for PML/RARA
88271	FISH probe/analysis code used across multiple gene tests
88274	FISH probe/analysis code
88275	FISH probe/analysis code
88291	FISH interpretation/reporting code
88374	FISH related code (listed for RET testing)
88377	FISH related code (listed for RET testing)

ROS1 FISH codesCPTCovered

88271	FISH probe/analysis code (ROS1)
88274	FISH probe/analysis code (ROS1)

Added CPT codesCPT

81315	Added for PML/RARA testing (document references addition)
81316	Added for PML/RARA testing (document references addition)

FISH panel coding changesCPT

88273	Multiple Myeloma FISH Panel Analysis (added)
88274	Multiple Myeloma FISH Panel Analysis (removed from policy)

Prior Authorization, Documentation, and Billing Guidance

Prior Authorization

Prior Authorization Required

Prior authorization (PA) is required for many cytogenetic and tumor‑targeted IHC tests described in this policy. Providers must verify and obtain any plan‑specific PA before ordering testing to avoid claim denials.

Prior authorization applies to listed cytogenetic (FISH) and IHC tests — confirm PA requirements with Community Health Plan Washington prior to testing.
Check PA for newly added or expanded tests/CPT codes before ordering; recent policy updates have added tests (e.g., RET, FOLR1) and CPTs (chunks 43–44).
PA rules follow plan‑level administrative policies and may be governed by applicable Medicare NCDs/LCDs when relevant (chunks 26, 57, 58).
Inclusion of a CPT/ICD code in this policy is informational only; providers should reference current coding guidance and the Concert Platform for registered tests (chunk 3).
Bladder tumor marker (FISH) testing is NOT covered for general screening of all patients with hematuria; covered only when validated assays are used and when criteria are met per LCD (chunks 13, 26).
Bladder FISH frequency limits mirror the CMS LCD: ≤4/year for years 1–2 after diagnosis, ≤3 in year 3, ≤2 in year 4, and ≤1 annually up to 15 years (chunks 13, 26).
Clinical documentation must accompany PA requests and claims: include diagnosis, tumor type, stage, treatment history, and clinical rationale linking the test to management decisions (chunks 12, 21, 24, 36, 40).
Documentation and applicability: this policy provides medical‑necessity guidance only and is subject to contract terms, state Medicaid precedence, and Medicare NCD/LCDs where applicable (chunks 57, 58).
When planning testing for therapy‑directed assays (e.g., FOLR1 IHC when Elahere is considered), include treatment intent and supporting clinical information in the PA request (chunk 19).
For newly added CPTs or expanded indications, always verify whether PA or additional documentation is required by the payer — updates to this policy do not automatically change payer operational requirements (chunks 43, 44, 48).

Documentation Required

Documentation Required to Support Testing

Provide complete clinical information to support medical necessity and PA decisions. Absent adequate documentation, testing may be delayed or denied.

Required documentation: working diagnosis (ICD‑10), tumor type and site, clinical stage, prior therapies and dates, reason test will impact management, and prior related test dates/results.
For tumor staging‑dependent tests (e.g., ALK, PD‑L1, RET), include TNM or stage designation to demonstrate that the ordered test meets guideline‑based indications (chunks 12, 36, 40).
For panel tests (e.g., CLL/SLL FISH), document that the panel includes required probes (e.g., +12, del(11q), del(13q), del(17p)) and that testing is for initial diagnostic evaluation (chunk 14).
For bladder FISH, document prior diagnostic workup for hematuria and prior FISH testing dates to confirm frequency limits are respected (chunks 13, 26).

Billing Rule

Coding Guidance Warning

Coding inclusion in this policy does not guarantee payment. Always verify the most current CPT/ICD guidance and payer coding rules prior to claim submission.

Use current CPT/ICD descriptions and modifiers appropriate to specimen/source and service date.
Confirm laboratory test mapping on the Concert Platform or payer test registry; tests and associated CPTs in this document are examples only (chunk 3).

Note

Alignment with LCD/NCCN and Coverage Limitations

Coverage is aligned with applicable LCDs and NCCN guidance where specified. When conflicts exist between this policy and state Medicaid or Medicare coverage determinations, the higher‑precedence regulation governs.

Bladder FISH coverage changed from non‑covered to covered where LCD criteria are met; assays must be validated (chunk 26).
Providers should review and cite the relevant LCD or NCCN guideline in PA submissions when applicable.
If state Medicaid rules conflict with this policy, state rules prevail; Medicare member/enrollees require review of NCDs/LCDs prior to applying criteria (chunks 57, 58).

Denial Risk

Coverage Limitations and Conflicts

Coverage limitations, conflicts, and the policy's advisory role: this policy is guidance for medical necessity determinations and does not guarantee benefits or payment. Benefit documents and contractual terms control final adjudication.

Denials or coverage exceptions are governed by the member's evidence of coverage, certificate of coverage, and applicable state/federal rules (chunk 57).
The Health Plan may change, amend, or withdraw this policy; operational PA processes may differ and should be confirmed with Community Health Plan Washington prior to ordering tests (chunks 57, 58).

Member and Clinical Eligibility

Eligibility for tumor-specific RET FISH testing requires a documented diagnosis that meets the listed tumor-specific criteria. For medullary thyroid cancer, somatic RET testing is appropriate only when germline RET testing is negative or has not been performed. Orders should include clinical documentation supporting the listed diagnosis and prior testing status where indicated.

Eligibility for bladder cancer diagnostic/recurrence FISH requires either: documented hematuria with a prior diagnostic workup that failed to identify an etiology (and no prior bladder FISH within the past 12 months), or a history of treated bladder cancer with testing requested within the policy-specified frequency limits. For screening-level hematuria without prior workup, testing is investigational and not eligible for coverage.

Eligibility for tumor-specific IHC and FISH testing generally requires that the member have the tumor type and disease stage specified in policy (for example, recurrent platinum-resistant ovarian/fallopian tube/primary peritoneal cancer when FOLR1 is being considered). Documentation should confirm tumor type, disease status (recurrent, metastatic, or stage threshold per NCCN), and any prior testing noted in policy prior testing requirements.

For newly added tumor-specific tests such as FOLR1 IHC, eligibility is restricted to the clinical scenarios described by guideline-based therapeutic intent. Specifically, FOLR1 IHC (CPT 88360) is eligible when the member has recurrent, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer and mirvetuximab (Elahere) is being considered.

Investigational or Not Covered Uses

Bladder cancer diagnostic and recurrence FISH tests (CPT 88120, 88121) are specifically not covered when ordered for screening members with hematuria without prior diagnostic workup; such screening use is considered investigational. Additionally, bladder tumor markers of any technology are not covered for universal hematuria screening — coverage is limited to validated assays per the CMS LCD.

Bladder tumor marker tests (regardless of technology) are not covered for screening all patients with hematuria. The CMS LCD states that only validated assays (for example, the FDA-cleared UroVysion Bladder Cancer Kit) meet coverage criteria and that utilization limits apply to post-diagnosis surveillance testing.

The policy history notes that bladder cancer diagnostic and recurrence FISH tests were previously non-covered and that coverage changed to covered per an LCD. Current policy language reflects that change; no additional previously non-covered bladder FISH items are listed as not medically necessary in the cited sections.

Background and Definitions

Cytogenetic analysis of solid tumors and hematologic malignancies, including testing by FISH, PCR, IHC, and targeted NGS fusion panels, is used to identify somatic driver mutations and chromosomal abnormalities for tumor classification, prognosis, and to guide targeted therapy selection. Tests may be performed on tumor tissue, blood, or bone marrow depending on the tumor type; related policies address circulating tumor DNA/cells.

Driver mutations (somatic oncogenic 'driver' mutations) - definition

DefinitionSomatic oncogenic mutations often called 'driver' mutations that inform targeted therapy selection and prognosis.

Clinical roleIdentify actionable targets for targeted therapies and aid in tumor classification.

Specimen typesTumor tissue; for hematologic malignancies, blood or bone marrow; ctDNA/CTCs addressed in related policies.

Testing modalitiesFISH, PCR, NGS fusion panels, IHC, and other molecular assays as appropriate to detect somatic driver alterations.

Advanced cancer - definition

DefinitionAdvanced cancer: Cancer that is unlikely to be cured or controlled with treatment; may have spread to nearby tissue, lymph nodes, or distant parts of the body.

Treatment intentTreatment may be given to shrink the tumor, slow cancer growth, or relieve symptoms rather than to cure.

Clinical implicationTesting and therapy decisions in policy often reference advanced disease when defining medically necessary indications.

PD-L1 testing (IHC companion diagnostics) - definition

DefinitionImmunohistochemistry (IHC)-based tumor PD-L1 protein analysis used to guide immune checkpoint inhibitor therapy decisions; FDA-cleared companion diagnostics are available for several cancer types.

Common CPT examplesIHC CPT codes referenced: 88341, 88342, 88360, 88361 for PD-L1 testing and interpretation.

Clinical useRecommended during workup for specific tumor types and stages per NCCN (e.g., gastric, head and neck, bladder, cervical, NSCLC, breast, vaginal cancers) to inform PD‑1/PD‑L1 inhibitor use.

FOLR1 (folate receptor alpha) - definition

DefinitionFolate receptor alpha (FOLR1): a tumor expression marker assessed by IHC to identify candidates for mirvetuximab soravtansine (Elahere) in ovarian/fallopian tube/primary peritoneal cancers.

IndicationRecommended for platinum‑resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer when Elahere is being considered.

Testing modalityIHC (CPT example 88360) performed on tumor tissue; include FOLR1 in molecular analysis if prior testing did not include the marker.

Gene rearrangement testing (RET, ROS1, PML/RARA) - definition

DefinitionGene rearrangement testing: molecular assays (FISH, PCR, NGS) to detect gene fusions or rearrangements (e.g., RET, ROS1, PML/RARA) that may inform targeted therapy selection.

Modalities and examplesFISH and PCR are cited for PML/RARA; FISH commonly used for RET and ROS1; RNA‑based NGS preferred for fusion detection where noted.

Clinical contextsRET testing: indicated for recurrent/persistent medullary thyroid cancer (if germline RET wild type/unknown), anaplastic and advanced thyroid cancers, advanced/metastatic lung cancers, and multiple other tumor types per NCCN.

ROS1 contextsROS1 testing recommended in advanced/metastatic NSCLC (adenocarcinoma, large cell, NOS) and considered in other cancers (ampullary, pancreatic, pediatric high‑grade glioma) when profiling for actionable fusions.