CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

Medical Coverage Policy | Minimal Residual Disease Testing for Cancer

Defines medical necessity criteria, covered tests, coding, prior authorization requirements, and intended-use populations for MRD testing (clonoSEQ, Guardant Reveal, Guardant Response) for Medicare Advantage and commercial products. Describes clinical contexts (hematologic malignancies and solid tumors) where MRD testing may be used and limitations of ctDNA-based MRD.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyMedical Coverage Policy | Minimal Residual Disease Testing for Cancer

Policy CodePolicy N/A

Change TypeNo material change

Effective Date08/01/2024

Next Review Date

Key ActionObtain prior authorization for Medicare Advantage Plans (required) and for Commercial Products (recommended) via the online tool; all unlisted genetic testing CPT codes require prior authorization to determine service and medical necessity.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes — has_material_change=false.

4Hematologic malignancies listed for clonoSEQ

3Guardant tests listed

2Prior authorization required/recommended

1Unlisted CPT (81479) requires authorization

93+Referenced publications

Coverage Summary

This policy provides coverage criteria for Minimal Residual Disease (MRD) testing in cancer, defining intended-use populations, test-specific coverage, coding, and prior authorization requirements for Medicare Advantage Plans and Commercial Products. The policy stance is mixed: certain MRD tests and uses are covered when medical necessity criteria are met, while other services may require an unlisted CPT with prior authorization or be subject to benefit limitations. Covered tests addressed include clonoSEQ (CPT 0364U), Guardant Reveal (unlisted 81479), and Guardant Response (CPT 0422U), with established single-gene PCR MRD tests (e.g., BCR-ABL1) covered per guideline schedules.

Effective date: 08/01/2024. Policy last reviewed: 04/03/2024.

High-level Key Values (stats & thresholds)

Hematologic malignancies explicitly listed (clonoSEQ)4 (ALL, MM, CLL, DLBCL)

Guardant tests listedGuardant Reveal; Guardant Response (Response duplicated) — 3 entries

Prior authorizationRequired for Medicare Advantage; recommended for Commercial Products

Unlisted CPT requirement81479 Unlisted molecular pathology — requires prior authorization

Referenced Publications countReferences: 93+

BCR-ABL1 thresholdqPCR sensitivity of at least BCR-ABL1 IS ≤0.0032% (MR4.5) with time to results < 2 weeks

Medical-Necessity Criteria

Medicare Advantage Plans and Commercial Products - General Medical Necessity for MRD testing

The following tests may be considered medically necessary to detect MRD in patients when the criteria below are met:

ALL of the following

Test-specific covered tests
- Guardant Response (Guardant Health)
- Guardant Response (Guardant Health)
Either 1 OR 2 above must apply
- The patient has advanced cancer; plans on being treated for said cancer, and has not been previously tested with the same test for the same genetic content

Coding

Covered CPT - clonoSEQCPTCovered

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

Covered CPT - Guardant ResponseCPTCovered

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 (New code effective 1/01/2024)

Unlisted molecular pathology (requires prior authorization)CPT

81479

Unlisted molecular pathology procedure — requires prior authorization for Medicare Advantage Plans and Commercial Products; can be used for any test in this policy without a specific CPT

ICD-10 Diagnosis Codes applicable for clonoSEQICD-10

C83.30
C83.3A
C90.00
C90.02
C91.00
C91.02
C91.10
C91.12
Z85.6
Z85.79

Provider Actions

Prior Authorization

Prior authorization required / recommended

Prior authorization is required for Medicare Advantage Plans and recommended for Commercial Products for the following CPT codes: 81479, 0364U, 0422U. Participating providers obtain prior authorization via the insurer's online tool. All Unlisted molecular pathology CPT codes require prior authorization to determine the service rendered and medical necessity.

Affected codes: 81479 (Unlisted molecular pathology), 0364U (clonoSEQ), 0422U (Guardant Response)
PA required for Medicare Advantage; recommended for Commercial Products
PA obtained via online tool for participating providers

Documentation Required

Ordering physician must obtain authorization

The ordering (treating) physician is responsible for obtaining prior authorization; laboratories are not permitted to obtain clinical authorization or otherwise participate in the authorization process on behalf of the ordering physician.

Background & Evidence

MRD testing (PCR- or sequencing-based) detects tumor-derived genetic material at high sensitivity to monitor recurrence, progression, or response to therapy across hematologic and solid tumors. Methods described include single-gene RT-qPCR (for established targets such as BCR-ABL1), multiplex PCR, and next-generation sequencing (NGS) assays applied to tumor tissue or minimally invasive specimens (e.g., plasma ctDNA or bone marrow aspirate) to establish a baseline tumor signature and then perform serial monitoring.

Some MRD assays require initial tumor baseline sampling followed by serial minimally invasive assays to track quantitative changes over time; however, when a patient has no known active cancer (no clinical, radiographical, or biological evidence of tumor), a single timepoint assay may constitute a single test per guideline-recommended frequency. Established single-gene PCR MRD tests (for example, BCR-ABL1 qPCR) are covered according to national or specialty society testing schedules.

Limitations of ctDNA-based MRD include discordance between tissue and ctDNA due to tumor heterogeneity, clonal evolution, and timing of sampling; requirement for sufficient tumor-derived DNA in the tested compartment (which may be problematic for small or less aggressive tumors); and confounding by clonal hematopoiesis of indeterminate potential (CHIP), which can produce somatic variants in blood cells that mimic tumor-derived mutations and lead to misclassification unless mitigated (for example, by paired white blood cell controls or algorithmic filtering).

Evidence Highlights

Sensitivity / Specificity summarySensitivity 88-100%; Specificity 98-100% (approx. 400 unique patients across studies)

Definitions

term	definition
MRD (Measurable / Minimal Residual Disease)	Testing to detect residual tumor-derived genetic material in blood or other specimens to monitor recurrence, progression, or response to therapy.
ctDNA	Circulating tumor DNA — cell-free tumor-derived DNA detected in plasma.
CHIP	Clonal hematopoiesis of indeterminate potential — somatic variants in blood cells that can confound ctDNA results.

Medicare Determinations

type	name	number
LCD	MolDX: Minimal Residual Disease Testing for Cancer	L38816
Article	MolDX: Minimal Residual Disease Testing for Hematologic Cancers - Billing and Coding	A58997
LCD	MolDX: Minimal Residual Disease Testing for Cancer	L38814
Article	MolDX: Minimal Residual Disease Testing for Solid Tumor Cancers - Billing and Coding	A58454

Revision History

2024-08-01Policy effectiveLatest

Policy effective date for Minimal Residual Disease Testing for Cancer

2024-04-03Last review

Policy last reviewed

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyMedical Coverage Policy | Minimal Residual Disease Testing for Cancer

Policy CodePolicy N/A

Change TypeNo material change

Effective Date08/01/2024

Next Review Date

SourceLink

On This Page

The patient has a personal history of cancer, the type and staging of which is within the intended use of the MRD test

The identification of recurrence or progression of disease within the intended use population of the test is identified in the National Comprehensive Cancer Network (NCCN) or other established guidelines as a condition that requires a definitive change in patient management

The test is demonstrated to identify molecular recurrence or progression before there is clinical, biological, or radiographical evidence of recurrence or progression AND demonstrates sensitivity and specificity of subsequent recurrence or progression comparable with or superior to radiographical or other evidence (as per the standard-of-care for monitoring a given cancer type) of recurrence or progression

The test being utilized precludes other surveillance or monitoring tests intended to provide the same or similar information, unless they either: a. are required to follow-up or confirm the findings of this test or b. are medically required for further assessment and management of the patient

Tests considered medically necessary for specific hematologic malignancies

The following test may be considered medically necessary for the listed hematologic indications when medical criteria are met:

clonoSEQ may be considered medically necessary for Acute lymphoblastic leukemia (ALL), Multiple myeloma (MM), Chronic lymphocytic leukemia (CLL), and Diffuse Large B-Cell Lymphoma (DLBCL)

Guardant REVEAL / Guardant Response

These tests may be considered medically necessary when the medical criteria above are met:

ANY of the following

Guardant REVEAL
Guardant Response

Unlisted tests

When no specific CPT exists for a service referenced in this policy:

An Unlisted CPT code (81479) should be used and requires prior authorization to determine what service is being rendered and if it is covered or not medically necessary

Prior authorization is required for Medicare Advantage Plans and recommended for Commercial Products.

Billing Rule

Unauthorized lab services denied to laboratory

If a laboratory provides a laboratory service that has not been authorized, the service will be denied and the financial liability will be that of the participating laboratory. Such unauthorized services may not be billed to the member.

Unauthorized lab services are denied to the laboratory
Laboratory assumes financial liability and may not bill the member for unauthorized services

Documentation Required

Use policy and member-specific benefit verification

Providers must verify benefits and eligibility using the member's subscriber agreement, member certificate, or employer agreement. This policy is provided for informational purposes only and is not a guarantee of payment; benefits and eligibility are determined by the member's plan documents which supersede the medical policy.

Check subscriber agreement, evidence of coverage, or employer agreement for member-specific benefits
Policy informational only — not a guarantee of payment

Denial Risk

Potential member liability for non-covered services

If services are determined to be not medically necessary or are non-covered benefits, providers may not charge the member unless the member was informed in advance and provided written agreement to pay at their own expense.

Providers may not bill members for non-covered services unless prior written member agreement exists

Lead time (TRACERx, NSCLC)Median 70 days (range 10–346 days); some >6 months

Sensitivity/specificity evidence contextMRD ctDNA studies across multiple solid tumors showing lead time over imaging and high diagnostic performance

Bibliography entriesMultiple peer‑reviewed studies and guideline references (items 48–93)

Bibliography range detailReferences list includes items 48 through 93 covering hematologic MRD and ctDNA research