CurrentPremera BluecrossPolicy 2.04.520

MEDICAL POLICY - Laboratory Testing Investigational Services

Defines Premera's policy that numerous laboratory genetic, molecular, proteomic, and other diagnostic/prognostic/risk assessment tests not covered by separate policies are considered investigational due to insufficient evidence of clinical utility. Lists many specific CPT/HCPCS (mostly PLA/Category III U-codes and unlisted) test codes considered investigational.

Policy Summary

PayerPremera Bluecross

PolicyMEDICAL POLICY - Laboratory Testing Investigational Services

Policy CodePolicy 2.04.520

Change TypeCoding updates and additions; literature review

Effective DateJan 1, 2026

Next Review Date

Key ActionProvider must confirm that the requested laboratory test is not covered by a separate policy; if a separate policy exists, it supersedes this policy.

POLICY UPDATE CHANGES

Policy statement unchanged during 01/01/26 Annual Review; literature review through September 06, 2025; references deleted.

Numerous CPT coding updates were made across multiple dates (codes added, removed, relocated to other policies).

Original policy created and approved 08/08/23; all tests listed considered investigational.

100+Listed Investigational Tests (codes)

150+CPT codes referenced/managed

1Policy Statement (All tests investigational)

Coverage Summary

Background: This policy applies to laboratory diagnostic, prognostic, and risk assessment tests that are not addressed by separate policies. Tests included here are considered investigational because they are in a developmental phase and lack sufficient evidence of clinical validity or clinical utility to demonstrate an improvement in net health outcomes. If a separate policy exists for a specific test, that separate policy supersedes this policy.

Policy statement / coverage stance: All tests listed in this policy are investigational and not covered (insufficient evidence that testing improves net health outcomes).

Policy Overview

policy_number2.04.520

subjectLaboratory testing investigational services (tests not addressed in separate policies)

effective date2026-01-01

last_review2026-02-13

statusCURRENT

Investigational Tests

All tests listed in this policy are considered investigational as there is insufficient evidence to determine that the technology results in an improvement in the net health outcome.

Test listed: Test is listed in this policy and is not addressed by a separate policy that supersedes this one.
Insufficient evidence: There is insufficient evidence of clinical validity and/or clinical utility for the listed test.

Medical Necessity / Coverage Criteria

Investigational Tests Coverage Statement (referenced in history)

All tests listed in this policy are considered investigational.

Coverage statement (history referenced): Tests listed in this policy are considered investigational (not medically necessary/covered).

Guideline Positions Referenced

Guideline recommendations summarized in policy body:

Guideline positions

AUA PCR/NGS UTI position: AUA guideline: More evidence needed before PCR/NGS for bacterial identification in lower urinary tract symptoms; concern about antibiotic overtreatment.

Coding

Investigational - Listed CodesmixedNot Covered

0002U	Oncology (colorectal), quantitative assessment of three urine metabolites... (PolypDX)
0016M	Oncology (bladder), mRNA microarray gene expression profiling of 209 genes (Decipher Bladder TURBT+G54)
0019M	Cardiovascular disease, plasma, aptamer-based microarray protein biomarkers, reported as 4-year likelihood of coronary event
0112U	Infectious agent detection targeted sequence analysis (16S and 18S rRNA) with drug-resistance gene (MicroGenDx)
0163U	Oncology (colorectal) screening, ELISA of 3 plasma proteins with demographic data (BeScreened-CRC test)
0174U	Oncology (solid tumor), mass spectrometric 30 protein targets, prognostic/predictive algorithm (LC-MS/MS Target Proteomic Assay)
0176U	CdtB and vinculin IgG antibodies by immunoassay (IBScheck)
0180U	Red cell antigen (ABO) genotyping, Sanger sequencing (Navigator ABO Sequencing)
0181U	Red cell antigen (Colton) genotyping (Navigator CO Sequencing)
0182U	Red cell antigen (Cromer) genotyping (Navigator CROM Sequencing)

1–10 of 126

1/13

Investigational / All tests listed in policyCPTNot Covered

0112U
0002U
0016M
0019M
0163U
0174U
0176U
0180U
0181U
0182U

1–10 of 128

1/13

Provider coding note: Report the laboratory tests using the specific U-codes listed in the policy or the unlisted chemistry procedure code 84999 where applicable. CPT and HCPCS code descriptions are copyrighted by the American Medical Association (AMA) and Centers for Medicare & Medicaid Services (CMS).

Billing/coding update note: Many CPT/PLA/U-codes have been added, removed, or moved to other policies on effective dates called out in the policy history; follow current coding updates because claims and billing may be affected if incorrect codes are billed.

Provider Actions / Billing Impact

Prior Authorization

Prior authorization may be required per plan

Because the tests listed in this policy are considered investigational and not covered, providers should expect denials or may need to obtain prior authorization according to the member's plan rules before ordering these tests.

Documentation Required

Confirm absence of separate policy

Confirm that the requested laboratory test is not covered by a separate policy; if a separate policy exists, that policy supersedes this one.

Background & Evidence Summary

This policy addresses laboratory services considered investigational when there is not a separate policy that outlines specific criteria for testing. These tests are often available clinically before an adequate evidence base establishes clinical validity and utility. Because many tests are proprietary, independent evaluation data may be limited. The tests listed are currently in a developmental phase with limited evidence that they improve diagnosis, prognosis, or risk assessment decision-making.

Scope: Applies to numerous genetic, molecular, proteomic, and other laboratory diagnostic/prognostic/risk tests not covered by separate policies. When a separate policy exists for a test, that policy supersedes this one.

Investigational (definition): Tests with insufficient evidence to determine that the technology results in an improvement in the net health outcome.

Laboratory-developed test (LDT) (definition): A test developed and validated in-house by a clinical laboratory and offered as a laboratory service; such tests must meet CLIA high-complexity standards.

Summary of Evidence: No formal evidence review was conducted; for the tests addressed in this policy the evidence on clinical utility is insufficient or non-evaluable and does not demonstrate improved net health outcomes.

Guideline/evidence positions: The American Urological Association (AUA) states more evidence is needed before PCR/NGS technologies for bacterial identification in lower urinary tract symptoms are incorporated into practice due to concern for antibiotic overtreatment; the AUA/SUO NMIBC guideline recommends do not replace cystoscopy with urinary biomarkers and allows limited use of biomarkers in specific scenarios (BCG response, adjudicating equivocal cytology).

NCCN positions: NCCN bladder cancer (v.4.2024) indicates urinary urothelial tumor markers may be considered during surveillance of high-risk NMIBC (category 2B) but notes it is unclear whether they add useful information for detection/management; NCCN colon cancer (v.5.2024) states molecular markers (other than MSI-H/dMMR) are not established for treatment determination or prognosis. Medicare national coverage: no National Coverage Determination (NCD) exists for these tests.

Medicare Determinations

Name	Number	Effective
National Coverage Determination		none — No NCD exists

Revision History

08/08/23added

Original policy created and approved; initial coding added early CPT codes including 0112U and 0365U-0367U; all tests listed considered investigational.

01/01/26clarified

Annual review: policy statement unchanged; coding changes noted (added multiple CPT codes effective January 1, 2026); literature review through September 06, 2025; references deleted.

04/01/25revised

Coding update: added multiple new CPT codes effective 04/01/25 (e.g., 0531U, 0535U, 0541U, 0542U, 0545U, 0546U, 0548U, 0550U).

Policy Summary

PayerPremera Bluecross

PolicyMEDICAL POLICY - Laboratory Testing Investigational Services

Policy CodePolicy 2.04.520

Change TypeCoding updates and additions; literature review

Effective DateJan 1, 2026

Next Review Date

Key ActionProvider must confirm that the requested laboratory test is not covered by a separate policy; if a separate policy exists, it supersedes this policy.

On This Page

AUA/SUO NMIBC guidance:

AUA/SUO guideline on NMIBC: Do not use urinary biomarkers in place of cystoscopic evaluation; may use biomarkers to assess response to intravesical BCG (UroVysion FISH) and adjudicate equivocal cytology (UroVysion FISH and ImmunoCyt).

NCCN bladder cancer v.4.2024: Urinary urothelial tumor markers may be considered during surveillance of high-risk NMIBC (category 2B); unclear if they add useful information for detection/management.

NCCN colon cancer v.5.2024: Molecular markers (other than MSI-H/dMMR) not established for treatment determination and prognosis.

Medicare NCD: Medicare: No national coverage determination exists for these tests.

Billing Rule

Use specified HCPCS/PLA/U-codes

Report these laboratory tests using the specific HCPCS/PLA (Category III U‑codes) or the unlisted chemistry code (84999) as listed in the policy.

0002U
0016M
0019M
0112U
0163U
0174U
0176U
0180U
0181U
0182U
0183U
0184U
0185U
0186U
0187U
0188U
0189U
0190U
0191U
0192U
0193U
0194U
0195U
0196U
0197U
0198U
0199U
0200U
0201U
0210U
0219U
0220U
0221U
0222U
0295U
0337U
0338U
0342U
0344U
0357U
0365U
0366U
0367U
0371U
0372U
0373U
0374U
0375U
0376U
0377U
0384U
0385U
0390U
0395U
0404U
0406U
0415U
0418U
0421U
0430U
0435U
0436U
0441U
0442U
0450U
0451U
0457U
0458U
0462U
0463U
0468U
0470U
0472U
0490U
0491U
0492U
0495U
0501U
0510U
0511U
0512U
0513U
0521U
0522U
0525U
0528U
0531U
0535U
0541U
0542U
0545U
0546U
0548U
0550U
0556U
0558U
0559U
0563U
0564U
0570U
0571U
0572U
0573U
0574U
0577U
0579U
0580U
0581U
0584U
0587U
0588U
0589U
0590U
0593U
0594U
0595U
0598U
0599U
0600U
0601U
0602U
0606U
0607U
0608U
0609U
84999

Documentation Required

Investigational status requires documentation

Document the clinical rationale when ordering tests listed in this policy and consult the member benefit booklet for the coverage determination; the policy states these tests are investigational and lack sufficient evidence of clinical utility.

Billing Rule

CPT coding updates must be followed

Follow current CPT/HCPCS coding as updated in the policy. Numerous CPT/Category III U‑codes have been added, removed, or moved to other policies on specified effective dates (examples: codes 0531U, 0535U, 0541U, 0542U added effective 04/01/25; 0558U–0574U added 07/01/25; many codes added effective 10/01/25; codes 0600U–0609U added effective 01/01/26; code 81515 removed 06/06/25). Claims may be affected if incorrect or outdated codes are billed.

06/06/25revised

Coding update: removed CPT code 81515.

07/01/25revised

Coding update: added multiple CPT codes effective 07/01/25 (e.g., 0558U, 0559U, 0563U, 0564U, 0570U, 0571U, 0572U, 0573U, 0574U).

02/13/26revisedLatest

Coding update: removed CPT code 0505U and updated related policies and related policy references; numerous CPT coding updates across multiple dates (codes added, removed, relocated to other policies).