CurrentBlue Cross Blue Shield - MassachusettsPolicy N/A

Investigational genetic and molecular laboratory tests

This policy governs coverage for a list of proprietary genetic and molecular diagnostic, prognostic, and risk-assessment laboratory tests for Blue Cross Blue Shield - Massachusetts members, indicating these tests are considered investigational and not supported by sufficient evidence; it applies to commercial and Medicare products described in the policy.

Policy Summary

PayerBlue Cross Blue Shield - Massachusetts

PolicyInvestigational genetic and molecular laboratory tests

Policy CodePolicy N/A

Change TypeNo material change

Effective DateN/A

Next Review DateN/A

Key ActionObtain precertification/prior authorization when these tests are performed inpatient; some tests require prior authorization through Carelon.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

All tests listedconsidered investigational

Prior auth (inpatient)precertification noted

Multiple PLA/CPTspecific codes enumerated

Insufficientevidence summary

Coverage Criteria

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Investigational / Not Medically Necessary

Covered when ALL of the following are met

Investigational tests: All tests listed in this policy are considered investigational due to insufficient evidence of clinical utility or improvement in net health outcome.

If a separate evidence review exists for a particular test, that review supersedes this policy.

If a specific test has its own evidence review that defines medical necessity criteria, that review takes precedence. Tests with separate evidence reviews are excluded from this policy and are governed by their respective policy.

All tests listed in this policy are considered investigational because there is insufficient evidence to determine that use of the technology improves net health outcome. As noted, these proprietary genetic and molecular diagnostic, prognostic, and risk‑assessment tests are often available clinically before adequate evidence of clinical validity and utility has been established, and therefore are not medically necessary.

COVERED INDICATIONS

No covered indications: No indications are supported as medically necessary in this policy; tests are considered investigational across their intended diagnostic, prognostic, therapeutic, or risk‑assessment uses.

If a separate evidence review exists for a specific test, the criteria in that review supersede this policy.

Coding and Billing Codes

Investigational CPT/PLA CodesCPTExperimental

0112U	Infectious agent detection and identification, targeted sequence analysis (16S and 18S rRNA genes) with drug-resistance gene
0365U	Oncology (bladder), 10 protein biomarkers by immunoassays, urine, diagnostic algorithm including patients age, race, and gender; reported as a probability of harboring urothelial cancer
0366U	Oncology (bladder), analysis of 10 protein biomarkers by immunoassays, urine, algorithm reported probability of recurrent bladder cancer
0367U	Oncology (bladder), analysis of 10 protein biomarkers by immunoassays, urine, diagnostic algorithm reported as a risk score for probability of rapid recurrence following transurethral resection
0376U	Oncology (prostate), image analysis of ≥128 histologic features and clinical factors, prognostic algorithm for risk of distant metastases and prostate cancer-specific mortality; includes predictive algorithm for androgen-deprivation therapy response if appropriate
0377U	(Included per completeness review)
0384U	Nephrology (chronic kidney disease), carboxymethyllysine, methylglyoxal hydroimidazolone, and carboxyethyl lysine by LC-MS/MS with HbA1c and eGFR; risk score for progression to high-stage kidney disease
0385U	Nephrology (chronic kidney disease), apolipoprotein A4, CD5 antigen-like, and IGFBP3 by ELISA; algorithm combining results with HDL, eGFR, and clinical data reported as a risk score
0386U	Gastroenterology (Barrett's esophagus), P16, RUNX3, HPP1 and FBN1 methylation analysis; prognostic and predictive algorithm reported as a risk score for progression to high-grade dysplasia or esophageal cancer
0406U	Oncology (lung), flow cytometry, sputum, 5 markers with algorithm reported as likelihood of lung cancer

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Evidence Sufficiency

Evidence sufficiency summaryThere are no established decision thresholds and the clinical utility of the tests listed is not demonstrated. Evidence is insufficient because data are limited or absent, the clinical pathway role is unclear (replacement, triage, add-on), how results would change management is not defined, decision thresholds have not been established, and test results have not been shown to produce clinically meaningful improvement in health outcomes.

Tests with Insufficient Evidence

Definition — Insufficient Evidence/InvestigationalTests listed in this section are considered investigational when evidence is insufficient to demonstrate clinical utility or an improvement in net health outcome. This includes tests with limited or no published data, unclear placement in clinical care pathways, undefined impact on management decisions, and absence of established decision thresholds. If a separate evidence review exists for a specific test, that review supersedes the guidance here.

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for inpatient services described in this policy. For some tests performed outpatient, prior authorization may also be required depending on the product and managed testing program. Prior authorization requirements may be managed through Carelon Genetic Testing program for specific codes/tests — providers should confirm program routing and obtain authorization before performing the service.

Precertification/prior authorization IS REQUIRED for all products if the procedure is performed inpatient.
Some outpatient services may require prior authorization; check product-specific rules and managed-program routing (for example, tests managed by the Carelon Genetic Testing program require prior authorization through Carelon).

Billing Rule

Coding and Evidence Review Guidance

Providers should report all services using the most up-to-date industry-standard procedure, revenue, and diagnosis codes, including modifiers where applicable. Inclusion of a code in policy does not guarantee coverage or reimbursement; always refer to the member's contract benefits in effect at the time of service to determine coverage. The policy's coding lists are informational and not exhaustive.

Report services with current CPT/HCPCS/ICD-10 and relevant modifiers.
Refer to member contract to determine coverage or non-coverage.
Coding included in the policy is for informational purposes only and does not imply coverage.

Denial Risk

Investigational Tests — Noncoverage Risk

All tests listed in this policy are considered investigational due to insufficient evidence of clinical utility and therefore are subject to non‑coverage. When services are investigational or not supported by sufficient evidence, claims are at risk for denial. Providers should document medical necessity and be aware that a separate evidence review (if present) supersedes the general guidance in this policy.

Tests in this policy are investigational — insufficient evidence to demonstrate improvement in net health outcome.
Investigational status may lead to claim denial; supportive documentation does not guarantee coverage.
If a separate evidence review exists for a specific test, that review takes precedence.

Documentation Required

Provider Action: Documentation & Submission

When prior authorization is required, include the clinical rationale and documentation that supports medical necessity and any relevant test-specific information. Follow managed-program submission instructions where applicable (for example, Carelon Genetic Testing program managed tests). If you are unsure whether a test is managed or requires authorization, contact the payer or managed-program for guidance before testing.

Submit clinical documentation supporting the requested test when seeking prior authorization.
Follow the managed-program (Carelon) submission process for tests it manages.
Contact payer or managed program to confirm authorization requirements prior to testing.

Ordering Requirements

Step Therapy

Ordering requirements — precertification/prior authorization and Carelon-managed tests

Precertification/prior authorization is required for procedures performed inpatient; tests managed by the Carelon Genetic Testing program require prior authorization through Carelon as noted in the policy.

Precertification/prior authorization IS REQUIRED for all products if the procedure is performed inpatient.
Certain codes/tests are managed by the Carelon Genetic Testing program and require prior authorization through Carelon (Policy History).

Frequency Limits

FREQUENCY LIMITS and related constraints

Preauthorization for inpatientPrecertification/prior authorization IS REQUIRED for services described in this policy if the procedure is performed inpatient.

Outpatient prior authSome products may require prior authorization if the procedure is performed outpatient — refer to product-specific guidance.

Frequency limits presentNo specific numeric frequency limits are listed in this policy for the tests; inventory flagged frequency as important but provided no explicit limits.

Not Covered

The tests enumerated in this policy are designated investigational and are not covered because available evidence is limited or unclear regarding clinical validity, clinical utility, and whether testing changes management to improve outcomes.

Background

Proprietary genetic and molecular diagnostic tests are frequently introduced into clinical practice before an adequate evidence base for clinical validity and utility exists. Many of these tests are in a developmental phase and may lack independent evaluation; consequently, evidence is insufficient to conclude that they improve net health outcomes. This policy addresses such laboratory services and explains that, unless a separate evidence review specifies otherwise, these tests are considered investigational.

Definitions

Definitions — investigational tests

Investigational — definitionTests for which evidence is insufficient to demonstrate clinical utility or improvement in net health outcome are designated investigational.

Policy stanceAll tests listed in this policy are considered investigational and therefore not medically necessary due to insufficient evidence.

Evidence basisDesignation is based on limited published data, unclear clinical pathway placement, lack of decision thresholds, or absence of demonstrated outcome benefit.