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CurrentProvidence Health PlanPolicy 111

Minimal Residual Disease (MRD) Testing

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Medicare medical coverage criteria and guidance for MRD testing (solid tumor and selected hematologic indications) for Providence Health Plan Medicare products, describing test-specific and general MolDX/LCD-based requirements that affect ordering and reimbursement.

Policy Summary

PayerProvidence Health Plan

PolicyMinimal Residual Disease (MRD) Testing

Policy CodePolicy 111

Change TypeNo material changes

Effective DateJul 1, 2026

Last ReviewJul 1, 2026

Next Review DateJun 1, 2027

Key ActionObtain MolDX technical assessment (TA) completion or prior authorization when billing unlisted/complex MRD tests to avoid denial.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

MedicareProduct applicability

MultipleNamed assays with criteria

<=1/30dFrequency ceiling

MultipleTests listed not covered

MolDX LCDsMedicare references

Coverage Criteria and Test-Specific Rules

Signatera (0340U) coverage — Initial and Repeat testing

Covered when specified language-based conditions from MolDX LCD L38814/LCA A58454 are met

Initial testing WITH active cancer: Testing may be considered medically necessary for individuals WITH active cancer when A and B are met: A. Testing is for the type and staging within the intended use of Signatera and those intended uses have met Medicare's clinical validity criteria (e.g., diagnosis of disease progression/recurrence for specified advanced cancers such as colorectal (stages II–IV), muscle-invasive bladder (stages II–III), ovarian (stages II–IV), or breast (stages IIb–IV), or monitoring response to immune checkpoint inhibitor [ICI] therapy). B. Member intends to pursue treatment for the cancer undergoing MRD testing.

based on LCD L38814 and LCA A58454

Repeat testing WITH active cancer: Repeat testing may be considered medically necessary when the member meets both of the following: A. Member meets applicable monitoring or disease-diagnosis criteria (e.g., monitoring response to ICI or diagnosis of progression/recurrence for listed cancers). B. Member intends to pursue treatment; repeat testing may also be allowed when there is clinical evidence of an a priori change in genetic content (e.g., acquired resistance).

based on LCD L38814 and LCA A58454

Policy Summary

PayerProvidence Health Plan

PolicyMinimal Residual Disease (MRD) Testing

Policy CodePolicy 111

Change TypeNo material changes

Effective DateJul 1, 2026

Last ReviewJul 1, 2026

Next Review DateJun 1, 2027

Key ActionObtain MolDX technical assessment (TA) completion or prior authorization when billing unlisted/complex MRD tests to avoid denial.

SourceLink

On This Page

NavDx (0356U) coverage and limits

NavDx coverage is limited to HPV-driven cancers and subject to timeframe and frequency restrictions

Covered indication: NavDx may be considered medically necessary when used to monitor for recurrence of HPV-driven (HPV-positive/HPV-associated) oropharyngeal cancers and anal squamous cell cancers when testing is performed within appropriate timeframes for the applicable cancer type (see Table 2).

based on Palmetto GBA LCD L38779 and LCA A58376

Not covered indications: NavDx is considered not medically necessary for other cancer types and is not covered when testing frequencies specified by the LCD/LCA are exceeded; NavDx does not have established clinical utility for non‑HPV indications.

based on LCA A58454 and LCD L38779

RaDaR (NeoGenomics) coverage

RaDaR may be considered medically necessary for specific active and non-active cancer scenarios

Active cancer indications: RaDaR may be considered medically necessary for individuals WITH active cancer when one of the following applies: active HPV‑negative head and neck squamous cell carcinoma (HNSCC) OR advanced breast cancer (stages II, III, or IV).

based on LCD L38814 and LCA A58454

Without active cancer indications: RaDaR may be considered medically necessary for individuals WITHOUT active cancer when all of the following are met: A. Testing is performed within appropriate timeframes (see Table 2); B. Personal history of cancer with no evidence of active disease; and C. One of: 1) personal history of HR+ HER2– advanced (stage II or III) breast cancer; or 2) personal history of locally advanced HPV‑negative HNSCC.

based on LCD L38814 and LCA A58454

Oncodetect (Exact Sciences) coverage

Oncodetect bundle and bespoke assays have defined indications for CRC and surveillance

Initial Oncodetect WITH active cancer: Oncodetect testing bundle may be considered medically necessary for initial testing of individuals WITH active advanced colorectal cancer to aid in diagnosis of disease progression, recurrence, or relapse.

based on LCD L38814 and LCA A58454

Repeat Oncodetect WITH active cancer: Repeat Oncodetect testing for individuals WITH active cancer may be considered medically necessary when the member meets both specified criteria consistent with LCD L38814/LCA A58454.

based on LCD L38814 and LCA A58454

Initial Oncodetect WITHOUT active cancer: Initial Oncodetect bespoke assay plus single plasma test may be considered medically necessary for individuals WITHOUT active advanced colorectal cancer (stages II–IV) to aid diagnosis of progression/recurrence when timing and other criteria are met.

based on LCD L38814 and LCA A58454

Oncodetect / NeXT Personal / Pathlight — Initial and Repeat Testing

Initial and repeat MRD testing coverage logic (separate branches for WITH active cancer and WITHOUT active cancer)

Initial testing - WITH active cancer: Oncodetect, NeXT Personal, or Pathlight initial testing may be considered medically necessary for individuals WITH active advanced cancer to aid diagnosis of progression, recurrence, or relapse consistent with LCD L38814/L38779 and companion LCAs.

Active cancer defined by LCD L38814

Repeat testing - WITH active cancer: Repeat testing for individuals WITH active cancer may be considered medically necessary when the member meets LCD/LCA‑specified criteria (documented active disease and other test‑specific conditions).

See LCD and companion LCA

Initial/Repeat testing - WITHOUT active cancer: Initial or repeat MRD testing (e.g., Oncodetect bespoke, Pathlight, NeXT Personal) for individuals WITHOUT active cancer may be considered medically necessary for diagnosis of progression/recurrence when the member has a personal history of the applicable cancer type (stages II–IV) and testing is performed within appropriate timeframes per Table 2.

Based on LCDs L38814/L38779 and companion LCAs

Repeat testing WITHOUT active cancer (NeXT/Pathlight): Repeat MRD testing with NeXT Personal MRD or Pathlight Recurrence Monitoring for individuals WITHOUT active cancer may be considered medically necessary when: A. Member has a personal history of advanced breast cancer (stages II–IV) or NSCLC; and B. Testing is performed within the MRD timeframes (Table 2).

Based on LCDs L38814 and L38779 and LCAs A58454 and A58376

ClonoSEQ — Hematologic MRD testing

ClonoSEQ (hematologic cancers) — Covered when ALL criteria met

ClonoSEQ WITH active cancer: ClonoSEQ testing for individuals WITH active cancer may be considered medically necessary when all of the following are met: A. Patient has a diagnosis such as ALL, MM, CLL, DLBCL, or mantle cell lymphoma; B. Patient intends to be treated or is being treated; and C. Either the patient has not been previously tested with the same test or there is clinical evidence of an a priori change in genetic content.

Based on LCD L38814 and LCA A58996

ClonoSEQ WITHOUT active cancer: ClonoSEQ testing for individuals WITHOUT active cancer may be considered medically necessary when the patient has a personal history of one of the listed hematologic malignancies and meets other LCA‑specified conditions.

Based on LCD L38814 and LCA A58996

Medicare LCD/LCA-based MRD coverage logic

Coverage considerations derived from Medicare LCD/LCA guidance and Plan supplemental criteria

MRD testing when patient known to have cancer: When the patient is known to have cancer, MRD testing is considered a series of assays: tumor diagnostic material establishes a baseline signature followed by serial plasma assays; this series comprises a single test for billing and coverage determinations.billing: single-test-per-series

Supported by LCD/LCA text

MRD testing when patient not known to have cancer: When the patient is not known to have cancer (no clinical, radiographical, or biological evidence of tumor post‑treatment), a single plasma timepoint may constitute a single test; testing schedules should follow national or society guidelines and the Plan's testing schedules.follow national/society guidelines

Supported by LCD/LCA text

Frequency limits: Testing frequency should not exceed once in a 30‑day period per Medicare guidance; the Plan supplements with cancer‑type‑specific schedules described in the policy.<=1 per 30 days

Plan uses additional criteria for scheduling

Indications and Clinical Scenarios Where MRD Testing May Be Covered

MRD testing for specified tumor types and scenarios

MRD testing for specific tumor types and scenarios (coverage requires meeting MolDX LCD/LCA criteria and timing schedules)

Colorectal cancer: MRD testing may be considered for colorectal cancer (stages II, III, IV) in the adjuvant setting and for post‑surgical CRC monitoring per Guardant Reveal bundle criteria.follow Table 2 timeframes

based on LCD L38814/LCA A58454

Bladder cancer: MRD testing may be considered for muscle‑invasive bladder cancer (stages II–III) for diagnosis of progression/recurrence when LCD criteria are met.follow Table 2 timeframes

based on LCD L38814 and references

Ovarian cancer: MRD testing may be considered for ovarian/fallopian tube/primary peritoneal cancers (stages II–IV) in the adjuvant setting when timeframes and criteria are met.follow Table 2 timeframes

based on LCD L38814

Breast cancer: MRD testing may be considered for selected breast cancer scenarios (e.g., stages IIb–IV and HR+ HER2‑ advanced disease for RaDaR) per assay‑specific criteria.follow Table 2 timeframes

based on LCD L38814 and LCA A58454

NSCLC: MRD testing may be considered for non‑small cell lung cancer for certain surveillance and monitoring indications when criteria and timing are met.follow Table 2 timeframes

based on LCD L38814

HPV‑driven cancers (NavDx): NavDx is limited to HPV‑driven oropharyngeal and anal squamous cell cancers per its MolDX LCD/LCA guidance.follow Table 2 timeframes

based on LCD L38779 and LCA A58376

Diagnosis and monitoring for specified advanced cancers

Diagnosis of disease progression, recurrence, or relapse and monitoring in individuals with a personal history of specified advanced cancers

Advanced colorectal cancer: MRD testing may be considered to diagnose progression, recurrence, or relapse in individuals with advanced colorectal cancer (stages II–IV) when performed per LCD/LCA criteria and timing.follow Table 2 timeframes

based on LCD L38814 and companion LCA

Advanced breast cancer: MRD testing may be considered for diagnosis or monitoring in advanced breast cancer (stages II–IV) per assay‑specific criteria (e.g., RaDaR, NeXT Personal) and timing requirements.follow Table 2 timeframes

based on LCD L38814 and LCA A58454

NSCLC: MRD testing may be considered for diagnosis or surveillance in NSCLC per applicable LCD/LCA criteria and schedules.

Surveillance, recurrence detection, and therapy response monitoring

Surveillance or monitoring (MRD) in patients previously diagnosed with cancer who presently do not have evidence of active disease; monitoring response to therapy in patients with known cancer.

Tumor‑informed personalized assays: Personalized two‑part assays (tumor tissue baseline followed by periodic plasma testing), such as Signatera and RaDaR, may be used for surveillance/monitoring when baseline and timing criteria are met.baseline required before monitoring

based on Signatera and RaDaR test descriptions in DEX registry

Monitoring response to therapy: MRD testing may be used to monitor response to therapies, including immune checkpoint inhibitors, when test‑specific timing windows and LCD criteria are satisfied.ICI monitoring: ICI within prior 90 days; timing per assay

based on LCD L38814/LCA A58454

MRD testing for hematologic and selected solid tumors

MRD testing for hematolymphoid neoplasms and various solid tumors as described by specific assay codes and LCD/LCA context

Hematologic MRD assays (ClonoSEQ): ClonoSEQ has defined two‑part workflows (ID baseline and Tracking MRD reports); ClonoSEQ B‑Cell Set (combined service) is FDA approved and may be covered when criteria are met; the single timepoint/Tracking assessments have their own coverage determinations per DEX registry.

based on MolDX communications and LCA A58996

Solid tumor MRD assays: Multiple solid tumor MRD assays (tumor‑informed and tumor‑agnostic) are addressed with specific U‑codes (e.g., Guardant Reveal, Haystack MRD, PredicineBEACON, Plasma Detect) and coverage depends on meeting LCD/LCA criteria and DEX registry determinations.

based on policy coding and DEX registry entries

Surveillance, recurrence detection, and monitoring of MRD/ctDNA

Surveillance, recurrence detection, and monitoring of minimal residual disease (MRD) and circulating tumor DNA (ctDNA) in oncology patients

Tumor‑informed baseline and monitoring: Policy includes tumor‑informed personalized MRD panels (baseline design and subsequent monitoring comparisons) and tumor‑agnostic assays (e.g., methylation, viral DNA) which are evaluated under the LCD/LCA framework.baseline and monitoring distinguished

based on policy assay listings and descriptions

CPT/HCPCS Codes, Billing Units, and Frequency Rules

Examples of MRD test HCPCS/CPT codes mentionedCPT

0356U

NavDx (Naveris Inc.)

Covered/considered MRD assay codesCPTCovered

0340U	Signatera (Natera)
0422U	Guardant360 Response (Guardant Health)
0569U	Guardant Reveal (Guardant Health) CRC Post-Surgery MRD Bundle

Additional tests referenced (some without numeric codes in excerpt)mixed

0569U	Guardant Reveal single plasma test / CRC Post-Surgery MRD bundle (Guardant Health)
Oncodetect	Oncodetect (Exact Sciences) - bundle / bespoke assay (no numeric CPT shown in excerpt)

Covered/Referenced CPT CodesCPTCovered

81479

ClonoSeq Assay B-Cell Set

Not Covered / Not Medically Necessary Codes (examples)CPTNot Covered

0560U	Haystack MRD ™ Baseline
0561U	Haystack MRD ™ Monitoring
0306U	Invitae PCM Tissue Profiling and MRD Baseline Assay
0307U	Invitae PCM MRD Monitoring
0467U	UroAmp MRD
0641U	PredicineBEACON Baseline
0642U	PredicineBEACON MRD
0646U	Plasma Detect Genome MRD - Baseline
0647U	Plasma Detect Genome MRD - Monitoring

Not Covered / Not Medically Necessary Codes (hematologic examples)CPTNot Covered

0049U	NPM1 MRD Assay by NGS
0171U	MyMRD® NGS Panel test
0644U	FusionMRD ™ Baseline
0645U	FusionMRD ™ Monitoring

Frequency thresholdmixed

No codes listed

MRD-related CPT/HCPCS U-codes mentionedCPT/HCPCS

0049U	Oncology MRD - NPM1 (listed in document)
0171U	MyMRD® NGS Panel test
0306U	Invitae PCM Tissue Profiling and MRD Baseline Assay (initial baseline)
0307U	Invitae PCM MRD Monitoring (subsequent assessment)
0340U	Signatera - oncology pan-cancer, personalized plasma MRD
0356U	NavDx - evaluation of 17 DNA biomarkers using ddPCR (HPV)
0364U	ClonoSeq B-Cell Single Assay (adaptive)
0422U	ClonoSEQ/related hematolymphoid MRD assay (listed)
0467U	Guardant360 Response - cfDNA response assay
0470U	HPV-SEQ / urine NGS MRD (referenced)

1–10 of 12

1/2

Covered/Referenced CPT/HCPCS examplesCPT

0560U	Haystack MRD ™ Baseline
0561U	Haystack MRD ™ Monitoring
0470U	HPV-SEQ Test (referenced)
0569U	Guardant Reveal (associated entry)
0641U	PredicineBEACON Baseline
0642U	PredicineBEACON MRD
0644U	FusionMRD Baseline
0645U	FusionMRD Monitoring
0644U	FusionMRD (appears associated with leukemia MRD entry)
81479	Unlisted molecular pathology procedure

Unlisted codesHCPCS

HCPCS Unlisted molecular pathology procedure

Unlisted molecular pathology procedure — submitted as needed for tests without specific CPT

Immunotherapy response monitoring window — Testing initiated between 4 - 10 weeks after treatment initiation with immunotherapy

Immunotherapy response monitoring windowTesting should be initiated between 4 - 10 weeks after immunotherapy (ICI) treatment initiation.

Applicable scenarioUsed when monitoring response to immune checkpoint inhibitor (ICI) therapy for colorectal cancer patients who received an ICI within the prior 90 days.

Source guidanceTiming derived from MolDX LCD/LCA guidance as adopted in Plan policy for Guardant360 Response and related assays.

Maximum MRD testing frequency — No more than once in a 30-day period

Maximum frequencyNo more than once in a 30-day (monthly) period.

Medicare basisFrequency ceiling follows Medicare MRD LCAs which state testing should not exceed once per month and Plan supplements schedules accordingly.

Plan enforcementPlan uses supplemental criteria and Table 2 schedules to operationalize frequency limits for specific cancer types.

Unit of service for MRD testing — 1 (the testing series billed at the start of the episode)

Unit of service1 — the entire MRD testing series (bundle) is the unit of service and is billed at the start of the episode.

Implication for timepointsIndividual plasma timepoint assays are considered part of the series and are not separately billable when patient is known to have cancer.

Medicare referenceBased on MRD LCAs and Medicare billing guidance cited in the policy.

Reporting format — Some assays reported as presence/absence of ctDNA, tumor fraction, or percent ctDNA

Common reporting formatsAssays may report presence/absence of ctDNA, tumor fraction, or percent ctDNA depending on platform and methodology.

Examples by assay typeGuardant Reveal reports presence/absence with tumor fraction; Plasma Detect reports negative or percent ctDNA; other assays use tumor-informed trend reporting.

Implication for interpretationReporting format varies by test and should be considered when comparing baseline and serial monitoring results.

Provider Requirements, Prior Authorization, and Billing Practices

Prior Authorization

MolDX technical assessment required

Specific MRD tests require successful completion of the MolDX technical assessment (TA) by the Medicare MolDX contractor before they can be considered medically reasonable and necessary for Medicare coverage under LCDs L38814/L38779.

Prior Authorization

MolDX TA and DEX registry required for coverage

Genetic and molecular tests performed in MolDX service areas must undergo MolDX TA review and have their coverage outcome recorded in the DEX registry; coverage is allowed only when applicable NCD/LCD/LCA criteria are met and the member has relevant signs/symptoms.

Tests listed as 'covered' in DEX have completed TA but still require meeting applicable LCD/LCA criteria and member signs/symptoms.
Tests not yet TA-reviewed are by default considered not medically reasonable or necessary.

Prior Authorization

Authorize baseline + serial MRD series as single service

Prior authorization workflows should account for MRD testing commonly being a baseline tumor assay followed by serial plasma tests that are treated as a single testing series for billing and coverage; testing frequency should not exceed once per 30 days unless LCD/LCA or plan schedule allows.

Baseline tumor diagnostic material establishes the personalized assay, followed by serial plasma assays that comprise one service when the patient has cancer.
Medicare guidance: testing frequency not to exceed once in a 30-day period.

Billing Rule

Follow Medicare/MolDX series billing cadence

Prior authorization or claims may be reviewed or denied if billing does not follow Medicare/MolDX guidance that the MRD service (for patients with cancer) is billed as a single unit of service at the start of the testing episode.

Individual timepoint tests that are part of a testing series may be clinically performed but are not separately reimbursable if included in the episode billing.
Plan may deny separate reimbursement for tests billed outside the series billing cadence.

Prior Authorization

Recommend PA for unlisted/complex molecular codes

When submitting services using unlisted molecular pathology codes (e.g., 81479) or other unlisted codes for potentially covered MRD services, prior authorization is recommended to avoid post-service denial; unlisted submissions for services explicitly non-covered will be denied.

All unlisted codes are reviewed at the claim level for medical necessity, correct coding, and pricing.
Prior authorization recommended for unlisted codes tied to potentially covered services to prevent post-service denial.

Step Therapy

Step therapy not specified

No step therapy requirements are specified in this policy excerpt.

Prior Authorization

Ensure baseline established before repeat testing

Initial versus repeat MRD testing is distinguished by whether the patient has active cancer; repeat testing for personalized assays generally requires an established tumor tissue baseline and adherence to the plan's timing criteria.

Part 1 (tumor tissue baseline) is required before Part 2 (periodic plasma monitoring) for tumor-informed assays.
Repeat testing without an established baseline may not meet coverage criteria.

Billing Rule

Bill serial-assay MRD testing as single episode

When MRD testing is ordered for patients known to have cancer as part of a serial assay series, ordering and billing should follow the single-test-per-episode convention described in Medicare LCD/LCA guidance.

The series (baseline plus subsequent timepoints) is considered one unit of service and should be billed at the start of the episode.
Individual timepoints are part of that series and not separately reimbursable.

Note

Documentation Required

Document analytical/clinical validity and TA outcome

Coverage determinations rely on LCD/LCA guidance and require documentation demonstrating analytical and clinical validity and clinical utility; MolDX TA outcomes and supporting evidence should be included in the record.

Tests must meet analytical and clinical validity standards and demonstrate clinical utility to be 'reasonable and necessary'.
MolDX TA completion and DEX registry status inform coverage decisions.

Documentation Required

Document linkage between baseline tumor and serial plasma tests

For two-part MRD assays, documentation should include linkage between the tumor tissue baseline (personalized tumor signature) and subsequent periodic plasma tests to support that the plasma tests are part of the same personalized MRD series.

Record the specimen type and tumor diagnostic material used to create the baseline fingerprint.
Include reports showing the initial baseline plasma result and subsequent plasma comparisons.

Documentation Required

Support tumor-baseline and serial assay linkage in records

Documentation must support that a tumor tissue baseline (personalized tumor signature) was established when required (e.g., tumor diagnostic material or CGP) and that subsequent plasma assays are linked as serial MRD testing per Medicare/LCD guidance.

If the service is a bundled personalized assay, note that baseline assay development and included plasma tests cannot be billed separately.
Include DEX registry identifiers or MolDX TA documentation when available.

Billing Rule

Report correct CPT and bill series at episode start

Providers must report MRD services with the appropriate CPT/HCPCS code and follow Medicare billing guidelines; for patients with cancer the unit of service is the testing series and billing should occur at the start of the episode per MRD LCAs.

Follow LCD/LCA instructions that the testing series is 1 unit of service billed at episode start.
Ensure correct CPT or unlisted code submission and obtain PA for unlisted codes when appropriate.

Denial Risk

Unlisted code claims undergo review; non-covered unlisted submissions denied

All unlisted codes submitted are reviewed for medical necessity, correct coding, and pricing; submission of an unlisted code for services explicitly non-covered in this policy will be denied as not covered.

To avoid post-service denial, prior authorization is recommended when using unlisted codes for potentially covered services.
Provider contracts, member benefits, and eligibility can affect coverage despite coding.

Denial Risk

Ensure tests meet validity and clinical utility requirements

Tests must meet analytical validity, clinical validity, and demonstrate clinical utility to be considered medically necessary; tests that lack these may be denied.

MolDX TA completion is the mechanism used to evaluate CU/AV for many MRD assays.
Tests without proven validity/utility pose patient risks and may be considered not medically necessary.

Denial Risk

NavDx limited to HPV-driven oropharyngeal and anal cancers

NavDx is considered not medically necessary for cancer types other than HPV-driven oropharyngeal and anal squamous cell cancers and will be non-covered if testing frequencies are exceeded.

Use NavDx only for HPV-driven oropharyngeal or anal squamous cell cancers within the plan's timeframe limits.
Exceeding frequency limits can render NavDx not medically necessary.

Denial Risk

Risk of NMN if LCD/LCA or TA criteria not met

Several named MRD assays (Signatera, NavDx, Guardant360 Response, Guardant Reveal, RaDaR) will be considered not medically necessary when applicable LCD/LCA coverage criteria are not met or when the tests have not completed MolDX TA review.

Confirm LCD/LCA criteria are satisfied and MolDX TA status before ordering these assays.
Tests lacking TA completion or LCD/LCA support are treated as not medically necessary.

Denial Risk

CU/AV evidence required in non-MolDX areas

In service areas that have not adopted MolDX guidelines, tests must demonstrate established clinical utility and analytical validity (CU/AV) to be eligible for Medicare coverage; absence of CU/AV may lead to denial.

The Plan applies an objective, evidence-based process in non-MolDX areas to assess tests not called out in an LCD.
Orderers should include CU/AV evidence when requesting coverage in non-MolDX areas.

Denial Risk

Denial risk when timepoints billed outside series

Claims or prior authorization requests may be denied when an individual timepoint test is billed separately but is considered part of an overall MRD testing series that should have been billed at the start of the episode.

Even if clinically appropriate, separately billed timepoints that belong to a billed series may be denied administratively.
Confirm series billing conventions with the laboratory and include documentation linking the timepoint to the baseline episode.

Denial Risk

Unlisted code submissions for non-covered services will be denied

Submission of an unlisted code for services that are explicitly non-covered in this policy will be denied as not covered; use prior authorization for unlisted codes tied to potentially covered services to reduce post-service denial risk.

All unlisted codes are subject to claim-level review for necessity, coding, and pricing.
Provider should obtain PA for unlisted molecular pathology procedures when coverage is uncertain.

Documentation Required

Document tumor baseline and subsequent plasma linkage

Many personalized MRD assays use a two-part process (tumor tissue baseline plus periodic plasma testing); documentation should include the tumor baseline identification and evidence linking subsequent plasma tests to that baseline.

Document the CGP/tumor diagnostic material used to create the personalized panel.
Retain records of the baseline plasma test and each subsequent plasma result with comparisons.

Documentation Required

Support specimen type and baseline establishment in documentation

Documentation must show specimen type and that the tumor tissue baseline (personalized tumor signature) was established when required, and that subsequent plasma assays are linked as serial MRD testing in accordance with Medicare/LCD guidance.

For bundled personalized assays, note that baseline development and included plasma tests cannot be billed separately.
Include MolDX DEX identifiers or TA documentation where available.

Tests and Uses Deemed Not Medically Necessary

The policy declares that tests which have not completed MolDX technical assessment, lack analytic/clinical validity or clinical utility, or are being used for unsupported indications are not covered. Numerous specific MRD assays and associated CPT/HCPCS codes are listed as not covered when those conditions apply. Additionally, submission of unlisted codes for services explicitly non‑covered will result in denial, and all unlisted codes are reviewed for medical necessity and correct coding at claim adjudication.

The document provides an explicit list of MRD assays and CPT/HCPCS entries that are considered not medically necessary / not covered when they lack FDA approval/clearance or MolDX TA completion. Examples in the list include Guardant Reveal Advanced Cancer Therapy Monitoring Bundle; Haystack MRD Baseline/Monitoring (0560U/0561U); Invitae PCM Baseline/Monitoring (0306U/0307U); UroAmp MRD (0467U); PredicineBEACON Baseline/MRD (0641U/0642U); Plasma Detect Genome MRD Baseline/Monitoring (0646U/0647U); NPM1 MRD by NGS (0049U); MyMRD® (0171U); and FusionMRD Baseline/Monitoring entries.

National guideline bodies (NCCN, ASCO) do not currently recommend routine ctDNA/circulating biomarker testing for surveillance in many cancer types; consequently, in indications where guideline support is lacking or evidence is insufficient, MRD testing is often treated as not medically necessary unless Medicare LCD/LCA criteria and MolDX TA status support coverage.

The policy does not declare a single blanket exclusion of named tests across all contexts, but it does note that some assays (for example, Signatera and Guardant Reveal as of April 2023) had not received FDA companion diagnostic approvals and that many lab‑developed tests require MolDX TA completion for coverage. Coverage determinations are therefore test‑ and context‑specific rather than universally applied.

Services submitted with unlisted molecular pathology codes are reviewed at claim level for medical necessity, coding accuracy, and pricing. If an unlisted code corresponds to a service that is explicitly non‑covered under this policy, the claim will be denied as not covered. Prior authorization is recommended for unlisted codes associated with potentially covered services to reduce the risk of post‑service denial.

Key Definitions

Active cancer / Without active cancer — Per LCD L38814: 'without active cancer' means there is no clinical, radiographical, or other biological evidence that tumor cells remain ...

Definition (without active cancer)Per LCD L38814, 'without active cancer' means there is no clinical, radiographical, or other biological evidence that tumor cells remain post treatment and the patient is no longer being subjected to therapeutic interventions for cancer.

Contrast (active cancer)Active cancer is the converse: clinical, radiographical, or other biological evidence that tumor cells remain and the patient is subjected to therapeutic interventions.

Policy useThis definition is used to distinguish billing and coverage rules for baseline/series testing versus single timepoint testing.

Without active cancer — An individual is considered 'without active cancer' when there is no clinical, radiographical, or other biological evidence that tumor ce...

Operational definitionAn individual is considered 'without active cancer' when there is no clinical, radiographical, or other biological evidence that tumor cells remain post treatment and the patient is no longer being subjected to therapeutic interventions for cancer.

Coverage implicationWhen 'without active cancer', a single plasma timepoint may constitute a single test and testing schedules follow national/society guidelines or Plan Table 2.

Reference LCDDefinition sourced from MolDX LCD L38814 as cited in the policy.

Two-part MRD test — A test with Part 1 identifying tumor-specific DNA changes via tissue (baseline) and Part 2 consisting of periodic plasma tests to monitor...

Two-part structurePart 1: tumor tissue testing to identify tumor-specific DNA changes (baseline); Part 2: periodic plasma tests to monitor those tumor-specific changes over time.

Billing linkageWhen performed as part of a serial service for a patient known to have cancer, the two parts are considered a single testing series for billing.

Typical use-casesUsed by personalized assays (e.g., Signatera, ClonoSEQ) that require a baseline tumor fingerprint followed by serial plasma MRD monitoring.

Personalized MRD assay — A two-component service where tumor tissue is profiled to create an individualized tumor DNA fingerprint (baseline) followed by plasma-ba...

Personalized assay componentsComponent 1: tumor tissue profiling to create an individualized tumor DNA fingerprint (baseline). Component 2: plasma-based assays run periodically to detect recurrence or monitor tumor changes.

ExamplesSignatera and RaDaR are described as personalized MRD assays using this two-component approach.

Documentation requirementBaseline tumor tissue CGP and linkage to subsequent plasma assays should be documented to meet coverage criteria.

Laboratory-developed test (LDT) — A test developed and validated within a laboratory and regulated under CLIA '88 as a high-complexity test; not FDA-cleared/approved but a...

Regulatory statusLaboratory-developed test (LDT) is developed and validated within a laboratory and is regulated under CLIA '88 as a high-complexity test; FDA clearance/approval is not required for clinical use.

Implication for coverageLDTs may be used clinically but coverage depends on MolDX/MAC technical assessments and demonstrated analytical/clinical validity and utility.

ExamplesSeveral MRD assays in the policy are performed as LDTs and are discussed with respect to MolDX TA and FDA status.

Unit of service (MRD testing series) — Per MRD LCAs, the unit of service for cancer MRD testing is the entire testing series (typically billed at the start of the episode), not...

Unit of service definitionPer MRD LCAs, the unit of service for cancer MRD testing is the entire testing series (typically billed at the start of the episode), not each individual timepoint.

Billing consequenceIndividual timepoint assays ordered during the episode are considered part of the billed series and are not separately reimbursable when patient is known to have cancer.

Plan practiceThe Plan follows Medicare MolDX billing guidance and may deny separate reimbursement for timepoint billing inconsistent with series billing.

MRD / molecular residual disease — Detection of tumor-derived DNA (ctDNA) or rearrangements in blood or bone marrow to identify minimal residual disease following treatment...

MRD / molecular residual disease definitionDetection of tumor-derived DNA (ctDNA) or rearrangements in blood or bone marrow to identify minimal residual disease following treatment.

Assay approachesIncludes tumor-informed (personalized baseline + monitoring) and tumor-agnostic methods (methylation, viral DNA) as referenced in policy examples.

Clinical purposeUsed for surveillance, recurrence detection, and monitoring response to therapy in oncology patients.

Policy Revision History

2026-07-01policy_effectiveLatest

Policy effective date; annual review updated coverage for NeXT Personal MRD tests.

2026-06-01next_review

Next scheduled annual review date set for 2027-06-01.

2026-06-01last_review

Last review completed (June 2026) aligning document metadata with effective date.

2026-02-14interim_update

Interim update replaced multiple MolDX LCDs and LCAs due to Noridian JF consolidation with JE LCD policies and clarified Signatera and NavDx criteria.

2025-08-01regulatory_update

FDA Breakthrough Device designation granted for Quest Haystack MRD (August 2025) noted in regulatory section; related code listings updated earlier in Q3 2025.

2025-07-01code_update

Interim update (July 2025) changed Guardant Reveal single plasma test status to 'covered' and included Q3 2025 code updates.

2024-07-01annual_review

Annual review (July 2024) updated coverage for ClonoSEQ tests per MolDX/Medicare determinations; no changes to clinical criteria.

2023-07-27coverage_notice

NeoGenomics announced Medicare coverage for RaDaR assay (July 27, 2023) referenced in the policy.

2023-04-01code_update

Q2 2023 code updates added 0364U to the policy.

2022-10-01code_update

Q4 2022 code updates and conversion to new format completed in early 2023.

Minimal Residual Disease (MRD) Testing

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Coverage Criteria and Test-Specific Rules

Indications and Clinical Scenarios Where MRD Testing May Be Covered

CPT/HCPCS Codes, Billing Units, and Frequency Rules

Provider Requirements, Prior Authorization, and Billing Practices

Tests and Uses Deemed Not Medically Necessary

Key Definitions

Background and Context

Policy Revision History