Minimal Residual Disease (MRD) Testing for Cancer - Coverage Criteria
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Defines medical coverage criteria, coding, and prior authorization expectations for MRD testing (including clonoSEQ, Guardant Reveal, and Guardant Response) for Medicare Advantage and Commercial products; affects ordering physicians, laboratories, and covered members.
No material clinical or coverage changes in this revision.
Coverage Criteria for MRD Testing
General MRD medical necessity criteria and clonoSEQ-specific coverage
Medicare Advantage Plans and Commercial Products: The following tests may be considered medically necessary to detect MRD when ALL of the following criteria are met
Applies to Guardant Response and Guardant Reveal as named; clonoSEQ noted separately for specific hematologic malignancies.
See coding section for clonoSEQ CPT 0364U.
Clinical utility and coding-linked coverage statements
Policy notes on clinical utility and contexts where MRD testing is supported
Supports medical utility in hematologic malignancies; see clonoSEQ code 0364U
Enables risk-adapted therapy and potential pre-emptive interventions; implementation details remain evolving
Important for interpretation and clinical decision-making
Links clinical criteria to CPT coding and prior authorization requirements
Some commercial groups subject to a self-funded contract exclusion under the state Biomarker Testing Mandate (R.I.G.L. §27-19-81) may have specific gene/genetic testing services excluded from coverage. For members whose employer plan has such an exclusion, coverage status for MRD and other genetic tests (covered with prior authorization, not medically necessary, or not covered) is determined by that group's Benefit Booklet and the applicable Related Policies (for example, Genetic Testing Services or Proprietary Laboratory Analyses). Providers should consult the member’s Benefit Booklet or contact the plan for group-specific determinations before ordering testing.
ctDNA-based MRD assays are tumor-specific and therefore cannot be used to detect a second primary tumor (even if the second primary is in the same organ). These assays also require a sufficient number of ctDNA molecules in the tested compartment (e.g., plasma), which limits utility in smaller or less aggressive tumors where ctDNA shedding may be minimal. Finally, MRD assays used for surveillance must achieve high analytical sensitivity with limits of detection substantially lower than typical diagnostic NGS tests to be clinically useful for early molecular recurrence detection.
Interpretation of blood-based liquid biopsy and ctDNA results can be confounded by clonal hematopoiesis of indeterminate potential (CHIP). CHIP-associated variants may appear in circulating cell-free DNA and mimic tumor-derived alterations; published evidence describes age-related prevalence and specific gene associations that can interfere with plasma-based testing. When CHIP is possible, paired white blood cell controls or bioinformatic filtering are important to avoid misclassification of results and to inform clinical decision-making.
Benefits and coverage for MRD and other genetic tests vary by product, employer group, and contract. Providers should refer to the member’s Benefit Booklet, Evidence of Coverage, or Subscriber Agreement to confirm whether a requested test is a covered benefit and whether prior authorization or other requirements apply.
This policy is informational and does not guarantee payment; the member’s subscriber or employer agreements govern benefits and eligibility and supersede policy statements. For member-specific coverage questions contact the provider call center.
Services determined to be not medically necessary, or services that are medically necessary but are non-covered by a member’s specific benefit plan, may be denied. Providers may not bill or collect payment from the member for services that are denied as not medically necessary unless the provider has obtained the member’s informed written agreement in advance to accept financial responsibility. Refer to your participation agreement for additional billing restrictions.
Coding and Diagnosis Codes
| Unlisted CPT | Unlisted genetic testing CPT codes for services without specific CPT coding |
| 0364U | Oncology (hematolymphoid neoplasm), genomic sequence analysis using multiplex (PCR) and next-generation sequencing with algorithm, quantification of dominant clonal sequence(s), reported as presence or absence of minimal residual disease (MRD) with quantitation of disease burden, when appropriate |
| 0422U | Oncology (pan-solid tumor), analysis of DNA biomarker response to anti-cancer therapy using cell-free circulating DNA, biomarker comparison to a previous baseline pre-treatment cell-free circulating DNA analysis using next-generation sequencing, algorithm reported as a quantitative change from baseline, including specific alterations, if appropriate |
| 0569U | Oncology (solid tumor) next-generation sequencing analysis of tumor methylation markers (>20,000 differentially methylated regions) present in cell-free circulating tumor DNA (ctDNA), whole blood, algorithm reported as presence or absence of ctDNA with tumor fraction, if appropriate |
| 81479 | Unlisted molecular pathology procedure |
| C83.10 | Non-Hodgkin lymphoma, unspecified site (example range listed) |
| C83.1A | (Listed range example) |
| C83.30 | (Listed range example) |
| C83.3A | (Listed range example) |
| C90.00 | Multiple myeloma unspecified |
| C90.02 | (Listed range example) |
| C91.00 | Acute lymphoblastic leukemia, unspecified |
| C91.02 | (Listed range example) |
| C91.10 | Chronic lymphocytic leukemia of specified type |
| C91.12 | (Listed range example) |
Provider Actions, Prior Authorization, and Billing Guidance
Prior Authorization Required
Prior authorization is required for all Unlisted genetic testing CPT codes (including 81479 Unlisted molecular pathology procedure) to determine what service is being rendered and whether the service is covered or medically necessary. Prior authorization is required for Medicare Advantage Plans and recommended for Commercial Products. Prior authorization for participating providers must be obtained via the online tool. Laboratories must not obtain authorization on behalf of the ordering physician; if a laboratory or third party participates in the authorization process, BCBSRI may deem the action a violation and take severe action up to termination from the provider network. Services provided without required authorization may be denied and the financial liability may fall to the laboratory or provider and may not be billed to the member.
- All Unlisted genetic testing CPT codes require prior authorization to determine the service and medical necessity.
- 81479 (Unlisted molecular pathology procedure) requires prior authorization when used for tests referenced in this policy that lack a specific CPT code.
- Prior authorization required for Medicare Advantage; recommended for Commercial Products.
- Prior authorization for participating providers is obtained via the online tool.
Required Diagnosis Coding on Claims
When filing claims for named MRD tests, include an appropriate ICD-10 diagnosis code from the list specified in this policy. Claims for clonoSEQ should be filed with CPT 0364U and one of the applicable diagnosis codes. Claims for Guardant Response (0422U) and Guardant Reveal (0569U) should also include an appropriate diagnosis from the ICD-10 list. Failure to include an applicable diagnosis code may result in claim denial or processing delays.
- Use CPT 0364U for clonoSEQ with one of the listed ICD-10 codes.
- Use CPT 0422U for Guardant Response with an appropriate ICD-10 diagnosis.
- Use CPT 0569U for Guardant Reveal with an appropriate ICD-10 diagnosis (for dates of service prior to 7/1/2025 file 81479).
- List of applicable ICD-10 codes includes: C83.10-C83.1A, C83.30-C83.3A, C90.00-C90.02, C91.00-C91.02, C91.10-C91.12, Z85.6, Z85.72, Z85.79.
Verify Member Benefits
Verify member benefits and eligibility prior to ordering testing. Benefits and eligibility are determined by the member's subscriber agreement or employer contract and supersede this policy. For member-specific benefit information, contact the provider call center. If a service is determined to be not medically necessary or a non-covered benefit, do not bill the member unless the member has been informed and provided written agreement to accept financial responsibility.
- Benefits and eligibility are determined by the member's subscriber agreement or employer agreement and supersede policy provisions.
- For member-specific benefits call the provider call center.
- Do not charge the member for services determined not medically necessary unless the member provided written agreement in advance.
Laboratory Participation Restriction and Denial Risk
Laboratories are prohibited from obtaining prior authorization or participating in the authorization process on behalf of the ordering physician. If a laboratory obtains authorization or otherwise participates in the process, BCBSRI may consider the authorization invalid and deny the service, and may pursue sanctions against the laboratory up to termination from the network. If an unauthorized laboratory service is provided, the service may be denied and the participating laboratory may be financially liable and may not bill the member.
- Only the ordering physician shall be involved in authorization, appeals, and related administrative processes.
- Use of a laboratory representative or third party to obtain authorization on behalf of the ordering physician is prohibited and may lead to denial and sanctions.
- If a laboratory provides a service that has not been authorized, the service will be denied and may not be billed to the member.
Prior Authorization and Documentation for Unlisted Genetic Testing
For tests referenced in this policy that do not have a specific CPT code, use Unlisted molecular pathology procedure (CPT 81479) and obtain prior authorization. Prior authorization and supporting documentation must clearly describe the test performed, its intended use, and how it meets the medical criteria in this policy. Authorization is required to determine coverage and medical necessity.
- When filing for tests without a specific CPT code, use 81479 and include documentation describing the test and clinical rationale.
- All Unlisted genetic testing CPT codes require prior authorization.
- Prior authorization is required for Medicare Advantage and recommended for Commercial Products.
Background and Scope
Minimal Residual Disease (MRD) testing detects very low levels of tumor-derived genetic material—such as rearranged immunoglobulin sequences or circulating tumor DNA—using sensitive molecular methods like PCR or next-generation sequencing. MRD assays can identify molecular recurrence or residual disease earlier than clinical, radiographic, or standard biologic assessments and are used to monitor response to therapy, risk-stratify patients, and guide management in both hematologic malignancies and some solid tumors.
Definitions and Test Descriptions
Line of Therapy Contexts
mixed
Applies across lines where surveillance or therapeutic decision-making depends on MRD status.
salvage
Serial monitoring frequently required; positive molecular recurrence should be interpreted in context of guidelines that recommend altering patient management.
Biomarker Sensitivity and Reporting Requirements
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