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Currentmedical mutual - ohioPolicy AHS - G2125

Urinary Tumor Markers for Bladder Cancer

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This policy defines coverage stance and limitations for urinary tumor marker tests used to detect or monitor bladder cancer for Medical Mutual - Ohio members, including which specific tests meet or do not meet coverage criteria and applicable use cases.

Policy Summary

Payermedical mutual - ohio

PolicyUrinary Tumor Markers for Bladder Cancer

Policy CodePolicy AHS - G2125

Change TypeCoding reorganization (removed/redirected PLA codes)

Effective DateJun 1, 2026

Last ReviewDec 3, 2025

Next Review Date

Key ActionDocument clinical indication and supporting cytology/cystoscopy results when requesting urinary tumor marker testing for adjunctive use; use specified CPT/HCPCS codes for claims.

SourceLink

POLICY UPDATE CHANGES

Removed CPT codes 0012M, 0013M, 0363U, 0420U, 0452U, 0465U, 0549U (now managed in GTM policy G2054).

Removed CPT code 0613U (mapped to policy during initial 1/1/2026 PLA review but changes to policy required moving 0613U to GTM policy G2054).

83,190US new cases/yr

16,840US deaths/yr

0.71-0.98Cystoscopy sensitivity

0.57–0.82Meta-analysis biomarker sens.

12/03/2025Last revision

Coverage Criteria for Urinary Tumor Markers

Covered indications

The following urinary tumor marker uses meet coverage criteria when applicable:

Adjunct diagnostic use for equivocal cytology: Urinary biomarkers (BTA, NMP22, or UroVysion FISH) as an adjunct in the diagnostic exclusion of bladder cancer for individuals who have an atypical or equivocal cytology.

Supports use when cytology is atypical/equivocal.

Monitoring high-risk NMIBC: Urinary biomarkers (BTA, NMP22, or UroVysion FISH) as an adjunct in the monitoring of high-risk, non-muscle invasive bladder cancer.

Surveillance adjunct for high-risk NMIBC.

ImmunoCyt/uCyt use: Fluorescence immunocytology (ImmunoCyt/uCyt) meets coverage criteria as an adjunct to cystoscopy or cytology in the monitoring of individuals with bladder cancer.

Adjunct for monitoring only.

Policy Summary

Payermedical mutual - ohio

PolicyUrinary Tumor Markers for Bladder Cancer

Policy CodePolicy AHS - G2125

Change TypeCoding reorganization (removed/redirected PLA codes)

Effective DateJun 1, 2026

Last ReviewDec 3, 2025

Next Review Date

Key ActionDocument clinical indication and supporting cytology/cystoscopy results when requesting urinary tumor marker testing for adjunctive use; use specified CPT/HCPCS codes for claims.

SourceLink

On This Page

Not covered indications

The following uses do not meet coverage criteria:

Evaluation of hematuria: Use of urinary biomarkers (BTA, NMP22, UroVysion FISH) for the evaluation of hematuria does not meet coverage criteria.

Hematuria evaluation excluded.

Screening asymptomatic individuals: Use of urinary biomarkers to screen for bladder cancer in asymptomatic individuals does not meet coverage criteria.

Screening excluded.

Diagnosis in symptomatic individuals: Use of urinary biomarkers to diagnose bladder cancer in symptomatic individuals (outside the adjunct indications above) does not meet coverage criteria.

Diagnostic use excluded except as adjunct for equivocal cytology.

ImmunoCyt/uCyt outside adjunct monitoring: Fluorescence immunocytology (ImmunoCyt/uCyt) used outside adjunctive monitoring with cystoscopy/cytology does not meet coverage criteria.

Excluded when not used as adjunct to monitoring.

Other urinary tumor markers: Any other urinary tumor markers for bladder cancer not mentioned above do not meet coverage criteria.

Catch-all exclusion for unlisted tests.

Coverage and clinical-use criteria

Guideline-concordant use and limitations

Surveillance of high-risk NMIBC (guideline-considered): NCCN considers urinary tumor markers during surveillance of high-risk non-muscle-invasive bladder cancer as a category 2B recommendation and advises that testing should not replace cystoscopy; tumor marker testing may be combined with cystoscopy and follow-up tailored to risk and treatment history.

NCCN: consider markers during high-risk NMIBC surveillance; do not replace cystoscopy.

Initial evaluation of microhematuria: AUA/SUFU guidance does not recommend routine use of urine markers (NMP22, BTA-stat, UroVysion) in the initial evaluation of asymptomatic microhematuria and states markers should not replace cystoscopy; cytology may be obtained in select persistent cases with risk factors.

AUA: do not use markers in initial MH evaluation; cytology may be considered in select persistent cases.

Monitoring NMIBC: AUA/SUO (and updated joint guidelines) state urinary biomarkers should not replace cystoscopy for surveillance of NMIBC; biomarkers may be used to assess response to BCG (e.g., UroVysion FISH) or to adjudicate equivocal cytology (UroVysion and ImmunoCyt).

Use biomarkers adjunctively, not as sole surveillance modality.

Performance-based considerations

Performance limitations and appropriate contexts

Tests with variable accuracy: Systematic reviews and meta-analyses report wide sensitivity (eg, 0.57–0.82) and specificity ranges for urinary biomarkers, with lower accuracy for low-stage/low-grade tumors and notable false-positive rates; marker sensitivity tends to increase with higher grade or stage, and single biomarkers generally perform worse than multi-target panels.

Biomarkers perform better for higher-grade/stage disease and multi-target panels outperform single markers.

Promising multi-target assays: Some multi-target assays (for example CxBladder, Bladder EpiCheck, Oncuria, and utDNA methods) have reported high sensitivity and negative predictive value for high-grade disease in select studies and may approach cystoscopy sensitivity in referenced studies, but current evidence is insufficient to support routine replacement of cystoscopy.

EAU notes several promising multi-target tests that might replace or postpone cystoscopy in select low/intermediate NMIBC scenarios; overall not accepted as routine practice.

FDA-labeled adjunctive use

Covered when used as indicated by FDA labeling in conjunction with standard diagnostic procedures:

FDA-approved tests as adjuncts: FDA-approved tests such as BTA stat, BTA TRAK, the Matritech NMP22 Test Kit and NMP22 BladderChek, UroVysion Bladder Cancer Kit, and ImmunoCyt are indicated for use as aids in the management of bladder cancer in conjunction with cystoscopy and/or cytology per their FDA approvals; ImmunoCyt is approved for surveillance adjunctive use with cytology and cystoscopy whereas other listed tests are approved for diagnosis and surveillance as indicated by the FDA.

Approval and intended use statements per FDA labeling.

Coding and Procedure Codes

Applicable CPT/HCPCS procedure codes (section present but codes not listed in this part of the document)mixed

No codes listed

Referenced FDA-approved testsmixed

FDA-approved tests (listed in policy text)

BTA stat, BTA TRAK, NMP22 Test Kit, NMP22 BladderChek, UroVysion Bladder Cancer Kit, ImmunoCyt

Covered CPT CodesCPTCovered

86294	Immunoassay for tumor antigen, qualitative or semiquantitative (eg, bladder tumor antigen).
86316	Immunoassay for tumor antigen, other antigen, quantitative (eg, CA 50, 72-4, 549), each.
86386	Nuclear Matrix Protein 22 (NMP22), qualitative.
88120	Cytopathology, in situ hybridization (eg, FISH), urinary tract specimen with morphometric analysis, 3-5 molecular probes, each specimen; manual.
88121	Cytopathology, in situ hybridization (eg, FISH), urinary tract specimen with morphometric analysis, 3-5 molecular probes, each specimen; using computer-assisted technology.
88346	Immunofluorescence, per specimen; initial single antibody stain procedure.
88350	Immunofluorescence, per specimen; each additional single antibody stain procedure.

Proprietary/PLA HCPCS CodesHCPCSCovered

0365U	Oncology (bladder), analysis of 10 protein biomarkers (A1AT, ANG, APOE, CA9, IL8, MMP9, MMP10, PAI1, SDC1 and VEGFA), by immunoassays, urine, diagnostic algorithm, including patient's age, race and gender, reported as a probability of harboring urothelial bladder cancer; Proprietary test: Oncuria® Detect; Lab/Manufacturer: DiaCarta Clinical Lab.
0366U	Oncology (bladder), analysis of 10 protein biomarkers (A1AT, ANG, APOE, CA9, IL8, MMP9, MMP10, PAI1, SDC1 and VEGFA) by immunoassays, urine, algorithm reported as a probability of recurrent bladder cancer; Proprietary test: Oncuria® Monitor; Lab/Manufacturer: DiaCarta Clinical Lab.
0367U	Oncology (bladder), analysis of 10 protein biomarkers (A1AT, ANG, APOE, CA9, IL8, MMP9, MMP10, PAI1, SDC1 and VEGFA) by immunoassays, urine, diagnostic algorithm reported as a risk score for probability of rapid recurrence of recurrent or persistent cancer following transurethral resection; Proprietary test: Oncuria® Predict; Lab/Manufacturer: DiaCarta Clinical Lab.

Codes removed from this policy (moved to GTM G2054)mixed

0012M	Removed (previously listed PLA/unique code).
0013M	Removed (previously listed PLA/unique code).
0363U	Removed (now managed in GTM policy G2054).
0420U	Removed (now managed in GTM policy G2054).
0452U	Removed (now managed in GTM policy G2054).
0465U	Removed (now managed in GTM policy G2054).
0549U	Removed (now managed in GTM policy G2054).
0613U	Removed (mapped to policy during initial 1/1/2026 PLA review but moved to GTM policy G2054).

BTA manufacturer cut-off

BTA manufacturer cut-off14 U/mL

Assay typesAvailable as quantitative (BTA TRAK) and qualitative (BTA stat) assays

Analyte detectedComplement factor H-related protein (hCFHrp)

NMP22 FDA-approved cut-off

NMP22 FDA-approved cut-off10 U/mL

Assay availabilityAvailable in quantitative (NMP22 Test Kit) and qualitative (NMP22 BladderChek) formats

Indication per FDANMP22 BladderChek indicated as an aid in monitoring bladder cancer patients in conjunction with standard diagnostic procedures

Number of molecular probes for FISH

Reported probe count for urinary FISH (UroVysion)3-5 molecular probes per specimen

CPT descriptorsCodes 88120 and 88121 describe FISH with 3-5 molecular probes (manual or computer-assisted)

Use contextApplied to urinary tract specimens for detection of chromosomal alterations associated with bladder cancer

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior authorization required for non‑covered indications; coverage limited to specified adjunct uses

Coverage for urinary tumor marker testing is limited to the adjunct uses specified in the policy: as an adjunct to diagnostic exclusion when cytology is atypical/equivocal, as an adjunct in monitoring high‑risk non‑muscle invasive bladder cancer (NMIBC), and ImmunoCyt/uCyt only as an adjunct to cystoscopy or cytology in monitoring. Tests requested for indications outside these adjunct uses are not covered and may require prior authorization per the member's benefit specifics.

Covered adjunct indications: atypical/equivocal cytology, monitoring high‑risk NMIBC, ImmunoCyt adjunct to cystoscopy/cytology.
Other indications do not meet coverage criteria and may require prior authorization per benefit rules.

Prior Authorization

Prior authorization may be required for non‑guideline use (replacement of cystoscopy or screening)

Testing intended to replace cystoscopy or for routine screening of asymptomatic individuals is not recommended by major guidelines and may require prior authorization to establish medical necessity when requested outside guideline‑recommended adjunctive uses.

Guidelines (AUA/NCCN) do not support replacing cystoscopy with urine markers.
Prior authorization may be requested to justify biomarker testing used outside recommended scenarios.

Billing Rule

Use specified CPT/HCPCS codes; handle PLA/unique codes per policy

Submit claims using the exact CPT/HCPCS codes listed in the policy for urinary tumor marker procedures; select proprietary/PLA codes where applicable. Note that several PLA/unique codes were removed from this policy and are now managed under GTM policy G2054.

Use listed CPT codes such as 86294, 86316, 86386, 88120, 88121, 88346, 88350 and HCPCS PLA codes 0365U–0367U when appropriate (per coding table).
Codes removed 12/03/2025 (e.g., 0363U, 0613U, 0012M, 0013M, 0420U, 0452U, 0465U, 0549U) are now managed under GTM policy G2054 and should not be billed under this policy.

Denial Risk

Denial risk: non‑covered indications (hematuria evaluation, screening, primary diagnosis)

Requests for urinary tumor marker testing for hematuria evaluation, asymptomatic screening, primary diagnosis in symptomatic patients (outside adjunct situations), or any other non‑specified indication do not meet coverage criteria and may be denied.

Examples of denial triggers: BTA, NMP22, UroVysion FISH, or ImmunoCyt/uCyt ordered for hematuria evaluation or routine screening of asymptomatic individuals.
Tests not listed among the policy’s covered adjunct indications are considered not medically necessary.

Denial Risk

Denial risk: tests billed to replace cystoscopy are not supported

Claims that attempt to substitute urinary biomarkers for cystoscopy (i.e., to replace cystoscopy for diagnosis or surveillance) are not supported by guidelines and may be denied as not medically necessary.

Policy and guidelines state urine markers should not replace cystoscopy; they may be used adjunctively only.
Claims indicating the test is being used to replace cystoscopy are subject to denial.

Note

Coding‑related denial risk for codes moved to GTM G2054

Be aware that CPT/PLA codes removed from this policy on 12/03/2025 were moved to GTM policy G2054; claims using those codes billed under this policy may be administratively denied or redirected.

Removed codes include 0012M, 0013M, 0363U, 0420U, 0452U, 0465U, 0549U and 0613U (moved to GTM G2054).
Billing with these removed codes under this policy risks administrative denial or redirection.

Documentation Required

Clinical documentation required to support coverage

Documentation in the medical record must support the covered adjunct indication (e.g., atypical/equivocal cytology or high‑risk NMIBC surveillance) to substantiate medical necessity for urinary tumor marker testing.

Include cytology and cystoscopy findings demonstrating atypical or equivocal results when testing is ordered as a diagnostic adjunct.
For surveillance indications, document high‑risk NMIBC status and surveillance context.

Documentation Required

Document test type and intended use, including FDA approval status

Document the specific test performed, its FDA approval/indication (when applicable), and whether it is being used as an adjunct to cystoscopy or cytology per the test’s intended use.

Record FDA‑approved test name (e.g., BTA stat, BTA TRAK, NMP22 Test Kit, NMP22 BladderChek, UroVysion, ImmunoCyt) and intended adjunctive use.
For laboratory‑developed tests (LDTs), document that the test is an LDT and any relevant validation information per CLIA if available.

Billing Rule

Coding and documentation: submit claims using the listed CPT/HCPCS codes

When submitting claims, use the CPT/HCPCS codes listed in the policy’s coding section that correspond to the test performed and include supporting documentation tying the code to the covered indication.

Examples of codes to use: 86294, 86316, 86386, 88120, 88121, 88346, 88350 and PLA codes 0365U–0367U as applicable.
Ensure claim documentation shows the clinical indication matches a covered adjunct use.

Denial Risk

Denial triggers: hematuria evaluation, asymptomatic screening, or replacement of cytology/cystoscopy

Tests ordered for hematuria evaluation, routine asymptomatic screening, or to replace cytology/cystoscopy (including claims implying substitution for cystoscopy) are common denial triggers and should be avoided unless clearly supported by a covered adjunct indication.

Do not order urinary biomarkers as first‑line evaluation for hematuria or routine screening of asymptomatic patients under this policy.
If testing is ordered, document the specific adjunct indication to reduce the risk of denial.

Denial Risk

Replacement of cystoscopy with urinary biomarkers is not supported

Claims that seek reimbursement for urinary biomarkers as a substitute for cystoscopy are not supported by the policy or by major guidelines and are subject to denial as not medically necessary.

Policy explicitly states markers should not replace cystoscopy; they are adjuncts only.
Claims describing the test as a replacement for cystoscopy are likely to be denied.

Note

Coding‑related denial risk: codes moved to GTM G2054 may be denied or redirected

Administrative coding changes effective 12/03/2025 removed specific PLA/unique CPT codes from this policy and reassigned them to GTM policy G2054; billing with these moved codes to this policy may be administratively denied or redirected.

Removed codes include 0012M, 0013M, 0363U, 0420U, 0452U, 0465U, 0549U and 0613U (now managed under GTM G2054).
Verify appropriate policy (G2054) for billing those codes to avoid administrative denials.

Background and Context

Background: Bladder cancer most commonly arises from the urothelium and frequently presents with hematuria. Cystoscopy (white light) with urine cytology remains the diagnostic gold standard and the primary surveillance modality, although it is invasive and resource‑intensive. Urinary tumor markers — including protein, DNA, methylation and mRNA assays — have been developed to augment detection and surveillance. Some markers show promising sensitivity for higher‑grade disease or in multi‑target panels, but none have sufficient evidence to replace cystoscopy for initial diagnosis or routine surveillance across general populations.

Definitions

FISH (UroVysion) — definition and target chromosomal alterations

DefinitionFluorescence in situ hybridization (FISH; UroVysion) is a DNA-probe–based assay that detects chromosomal alterations associated with bladder cancer

Target alterationsAneuploidies of chromosomes 3, 7, and 17 and loss of the 9p21 locus

FDA approvalUroVysion Bladder Cancer Kit approved by FDA to detect these chromosomal alterations in urine specimens

NMP22 — definition and FDA-approved cut-off

DefinitionNuclear matrix protein 22 (NMP22) is a urinary biomarker released from cancer cells and measured by quantitative or qualitative assays

FDA-approved cut-off10 U/mL

Assay examplesMatritech NMP22 Test Kit (quantitative) and NMP22 BladderChek (qualitative)

BTA — definition and manufacturer cut-off

DefinitionBladder tumor antigen (BTA) tests detect complement factor H-related protein (hCFHrp) in urine and are available in qualitative and quantitative forms

Manufacturer-recommended cut-off14 U/mL

Assay examplesBTA stat (qualitative) and BTA TRAK (quantitative)

FDA-approved urinary tumor marker tests — list

FDA-approved urinary tumor marker testsBTA stat, BTA TRAK, NMP22 Test Kit, NMP22 BladderChek, UroVysion, ImmunoCyt

Regulatory noteThese tests are FDA-approved for use as aids in management of bladder cancer in conjunction with cystoscopy and/or cytology (ImmunoCyt only approved for surveillance)

Assay modalitiesIncludes immunoassays (BTA, NMP22), FISH (UroVysion), and immunofluorescence (ImmunoCyt)

Laboratory-developed test (LDT) — definition and regulatory context

DefinitionLaboratory-developed test (LDT): an in-house assay developed and validated by a clinical laboratory and regulated under CLIA as a high-complexity test

FDA statusLDTs are not FDA-approved or cleared; FDA clearance is not currently required for clinical use

Regulatory oversightRegulated by CMS under CLIA '88 as high-complexity laboratory tests

LDT — alternate entry

Alternate LDT entryLDT: in-house assays performed after laboratory validation and regulated under CLIA; not FDA-approved

Clinical useMay be used clinically after laboratory validation despite lack of FDA approval

OversightSubject to CMS/CLIA requirements for high-complexity testing

FDA-approved urine tumor markers — examples list

Examples of FDA-approved urine tumor markersBTA stat, BTA TRAK, NMP22 Test Kit, NMP22 BladderChek, UroVysion, ImmunoCyt

Intended useThese assays are indicated as aids in management of bladder cancer when used with cystoscopy and/or cytology

Modality mixIncludes protein-based immunoassays, DNA FISH assays, and immunofluorescence tests

References and Revision History

References: A comprehensive bibliography supporting this policy is provided (items 1–69), including guideline documents (NCCN, AUA, EAU), systematic reviews and meta‑analyses, FDA summaries for approved assays, and primary diagnostic and surveillance studies. Key sources include NCCN Guidelines (item 4), AUA/SUFU microhematuria guidance (items 48–49), USPSTF and NCI screening statements (items 30, 32), and FDA approvals and summaries for individual tests (items 63–69).

2025-12-03coding updateLatest

Off-cycle coding modification: removed CPT/PLA codes 0012M, 0013M, 0363U, 0420U, 0452U, 0465U, 0549U, and 0613U and moved management of these codes to GTM policy G2054.