Currentblue cross blue shield - tennesseePolicy N/A

Urinary_Tumor_Markers_For_Bladder_Cancer_G2125_Reimbursement_Policy

Defines coverage and reimbursement policy for urinary tumor marker tests for bladder cancer (BTA, NMP22, UroVysion FISH, ImmunoCyt/uCyt, and other urinary markers/LDTs), specifying covered indications (adjunctive use) and non-covered indications (screening, hematuria evaluation, diagnosis in symptomatic individuals, and other uses). CXbladder is excluded from this policy and managed separately under genetic testing prior authorization.

Policy Summary

Payerblue cross blue shield - tennessee

PolicyUrinary_Tumor_Markers_For_Bladder_Cancer_G2125_Reimbursement_Policy

Policy CodePolicy N/A

Change TypeNo material change

Effective Date

Next Review Date

Key ActionWhen ordering covered urinary biomarkers or ImmunoCyt, document that the test is being used as an adjunct for either diagnostic exclusion in patients with atypical/equivocal cytology or monitoring of high-risk, non-muscle invasive bladder cancer; follow PA process for Cxbladder and validate LDTs per CLIA.

SourceLink

POLICY UPDATE CHANGES

No material changes to clinical coverage criteria or policy provisions.

2Covered indications

MultipleNon-covered indications

5+FDA-approved tests referenced

LDTs regulated (CLIA)Regulatory notes

Coverage Summary

This policy addresses urinary tumor marker tests for bladder cancer including BTA, NMP22, UroVysion FISH, and ImmunoCyt/uCyt+, along with other proprietary assays and laboratory-developed tests (LDTs). It specifies that BTA, NMP22, and UroVysion meet coverage criteria when used as adjuncts either for diagnostic exclusion in patients with atypical or equivocal cytology or for monitoring high‑risk, non‑muscle invasive bladder cancer, and that ImmunoCyt meets criteria when used as an adjunct to cystoscopy or cytology for surveillance. The policy explicitly excludes Cxbladder from this reimbursement policy (it is managed under the Genetic Testing Prior Authorization Program) and takes an overall mixed coverage stance reflecting selective coverage for adjunctive uses while denying screening, hematuria evaluation, diagnostic use in symptomatic individuals, and other non‑specified indications.

Policy-specific thresholds and indication summary

BTA manufacturer-recommended cut-off14 U/mL

NMP22 FDA-approved cut-off10 U/mL

Bladder CARE urine DNA input requirementas little as 5 ng urine DNA from 100 mL urine; limit of detection 0.1%

Covered IndicationsCovered indications: 2 (adjunctive diagnostic exclusion with atypical/equivocal cytology; adjunctive monitoring of high-risk NMIBC)

Non-covered IndicationsNon-covered: screening, hematuria evaluation, diagnostic use in symptomatic individuals, other indications

Medical-Necessity Criteria

Coding

FDA-approved tests and named proprietary assays discussed (informational; no billing codes specified in this part)mixed

BTA stat / BTA TRAK	Bard BTA stat™ Test and BTA TRAK™ Test (FDA approved)
NMP22 / NMP22 BladderChek	MATRITECH NMP22™ Test Kit and NMP22 BladderChek (FDA approved)
UroVysion	UroVysion Bladder Cancer Kit (FISH) (FDA approved)
ImmunoCyt / uCyt+	ImmunoCyt (Diagnocure) (FDA approved for surveillance)
Cxbladder	Cxbladder — not addressed by this reimbursement policy (managed under Genetic Testing PA Program)
Bladder CARE	Pangea Laboratory Bladder CARE (LDT; not FDA approved)
Bladder EpiCheck	Nucleix Bladder EpiCheck (not available in US)
UBC Rapid	UBC® Rapid (ODL Biotech)
URO17	URO17 assay (Protean Biodiagnostics)
Oncuria	Oncuria (Nonagen Bioscience) multiplex immunoassay

Provider Actions

Documentation Required

Adjunctive use documentation

When ordering covered urinary biomarkers (BTA, NMP22, UroVysion) or ImmunoCyt, document that the test is being used as an adjunct for one of the allowed clinical contexts: (a) diagnostic exclusion in patients with atypical or equivocal cytology, or (b) monitoring of high‑risk, non‑muscle invasive bladder cancer (for ImmunoCyt, adjunct to cystoscopy/cytology).

As an adjunct in the diagnostic exclusion of bladder cancer for patients who have an atypical or equivocal cytology
As an adjunct in the monitoring of high‑risk, non‑muscle invasive bladder cancer (ImmunoCyt adjunct to cystoscopy/cytology)

Prior Authorization

CXbladder prior authorization

Cxbladder testing is not covered under this reimbursement policy; Cxbladder is managed under BCBST's Genetic Testing Prior Authorization Program and providers must follow that PA process (managed using eviCore's genetic testing guidelines).

Background and Evidence

Bladder cancer is a common urothelial malignancy in the urinary system with substantial population burden: in 2020–2021 there were roughly 81,000–83,730 new U.S. cases and approximately 17,000–17,900 deaths; it occurs more often in men and typically presents in older adults. The most common presenting symptom is painless hematuria (gross or microscopic), although hematuria has many non‑malignant causes and only a minority of patients with hematuria are found to have bladder cancer. Cystoscopy (white‑light) with urine cytology remains the diagnostic gold standard, though cystoscopy can be uncomfortable and costly and fluorescent cystoscopy can increase sensitivity at the expense of specificity.

Urinary biomarkers have evolved from single protein assays (e.g., BTA, NMP22) to FISH (UroVysion), immunocytology (ImmunoCyt/uCyt+), epigenetic and DNA‑based assays, and multiplex protein panels. FDA has approved BTA, NMP22, UroVysion, and ImmunoCyt with specific intended uses, but many newer assays are LDTs or not FDA‑approved. Although some biomarkers show higher sensitivity than cytology, overall biomarkers generally have lower specificity than cystoscopy/cytology and variable performance across studies; guideline panels (NCCN, AUA, EAU, NACB/AACC) do not support replacing cystoscopy with biomarkers and recommend limited adjunctive use, and LDTs are regulated under CLIA as high‑complexity tests rather than requiring FDA clearance for clinical use.

Evidence	Key findings
Chou et al. meta-analysis
Biomarker sensitivities 0.57–0.82; specificities 0.74–0.88; many false positives and missed cases
Oncuria (Hirasawa et al. 2021)
AUC 0.95; sensitivity 93%; specificity 93%; NPV 99%; PPV 65%
uCAPP-Seq (Dudley et al. 2019)
Detected utDNA pretreatment in 93% (tumor-informed) and 84% (blinded); specificity 96–100%
URO17 (Vasdev et al. 2021)
Sensitivity 100%; specificity 92.6% (PPV 0.957; NPV 1)
FDA approval summary - UroVysion
Detects aneuploidy for chromosomes 3, 7, 17 and loss of 9p21 in urine via FISH
FDA approval summary - ImmunoCyt
Qualitative direct immunofluorescence assay intended as adjunct to cytology for surveillance of previously diagnosed bladder cancer
Regulatory
LDTs regulated by CMS under CLIA as high-complexity tests; FDA clearance/approval not required for clinical use

Definitions

BTABladder tumor antigen

NMP22Nuclear matrix protein 22

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