Prior Authorization Required

Prior authorization is required for multiple services referenced in this policy. Submission of a prior authorization request must include clinical rationale, intended use, and supporting documentation as detailed below. Inclusion of CPT/PLA/GSP codes in this policy does not guarantee coverage — providers must obtain prior authorization when indicated and adhere to plan terms, exclusions, and documentation requirements. Investigational indications and services that do not meet medical necessity criteria may be denied.

• Prior authorization required for evidence-based cfDNA MRD tests (e.g., 0229U, 0306U, 0307U, 0340U, 0422U) when meeting LCD/plan criteria.
• Prior authorization required for HPV-related MRD (0356U) when criteria are met.
• Prior authorization required for red blood cell (RBC) genotyping tests (0001U, 0180U, 0221U) in multiple myeloma when criteria are met.
• Prior authorization required for molecular profiling panels (including tumor-type agnostic panels and newly referenced CPT codes 81457, 81458, 81459, and PLA/unique CPTs such as 0422U).
• Prior authorization expectations: decision-making will follow submitted clinical documentation and adherence to evidence-based guidelines; incomplete documentation may delay or result in denial.

MRD Prior Authorization and Frequency Limits

MRD testing is subject to specific medical necessity criteria and frequency limits consistent with MolDX LCD guidance. For MRD tests that have demonstrated clinical validity and utility in the intended use population, prior authorization will evaluate whether the request meets LCD criteria for intended cancer type, whether identification of recurrence/progression would change management, and whether test performance is adequate relative to existing monitoring modalities. In the absence of clear guideline-directed frequency, the default frequency is once per cancer diagnosis; for patients without known cancer, the default frequency is once every 12 months.

• MRD medical necessity and prior authorization headline reflects MolDX LCD criteria.
• Default single-service limitation: MRD testing may be authorized once per cancer diagnosis unless clinical evidence supports additional testing (e.g., change in tumor genomics).
• Requests for repeat MRD testing must document clinical evidence of change in disease status or treatment implications.
• Investigational solid tumor MRD tests (including NGS-based assays without demonstrated clinical validity for the intended use) may be denied.
• Newly referenced CPT 0422U has been added to MRD code lists and requires use on claims and authorization requests where applicable.

Investigational Indications and Denial Risk

Plan review of requests will consider investigational status and medical necessity. Tests and indications designated investigational in this policy (for example, cancer exome/genome sequencing outside defined criteria, specimen identity testing billed separately, and solid tumor MRD without demonstrated validity) are subject to denial. Coding inclusion is informational only and does not imply coverage — providers must justify clinical need in the prior authorization.

• Investigational services may be denied if not supported by evidence-based guidelines or LCD criteria.
• Solid tumor MRD testing using tissue or assays with insufficient evidence is considered investigational for specified indications and may be denied.
• Specimen identity testing billed separately (e.g., 81265, 81266, 81479 when used for specimen ID) is considered investigational.
• Coding inclusion is not a guarantee of coverage; providers should verify coverage and obtain prior authorization when required.

Required Clinical Documentation

Submit clinical documentation with all prior authorization requests. Documentation must clearly state the clinical rationale, intended use of the test, disease status, prior tests and results, current or planned therapies that would be affected by results, and any guideline references supporting testing. Use of specific panel codes requires documentation that the panel content matches the clinical question.

• Required clinical documentation: diagnosis, stage, treatment history, prior molecular testing and results, and how results will change management.
• Clinical rationale and intended use must be explicit (e.g., therapy selection, monitoring response, confirmation of diagnosis).
• When requesting tumor-type agnostic panels or broad hematologic panels, specify which genes/fusions in the panel are needed and why.
• Coding and documentation updates: use newly referenced CPT codes (e.g., 0422U, 81457-81459) on authorization requests and claims where applicable.

Test-Specific Documentation Requirements

Specific panel and test requests have additional documentation requirements; provide the following when applicable.

• Colorectal panels (81445, 81457): document suspected or proven metastatic colorectal cancer and that panel includes at minimum KRAS, NRAS, and BRAF.
• MPN panels (e.g., 81206, 81207, 81208, 81219, 81270, 81279, 81338, 81339): document suspicion of MPN and that JAK2, CALR, and MPL are included; stepwise testing is acceptable (e.g., JAK2 → CALR/MPL) and may be reflected in authorization requests.
• MLH1 methylation (81288): prior tumor IHC demonstrating loss of MLH1 must be documented before methylation testing.
• HPV-related MRD (0356U): document personal history of HPV-driven oropharyngeal cancer, that detection would change management, absence of concurrent surveillance by other methods, and timing relative to treatment; if using tumor tissue MRD, note investigational status when applicable.
• TMB and RBC genotyping (81479; 0001U, 0180U, 0221U): for TMB, document prior progression and lack of satisfactory options per criteria; for RBC genotyping in multiple myeloma, document planned or ongoing treatment with daratumumab or isatuximab and that testing has not been performed for the current cancer episode or within the prior 12 months.
• HLA typing (81370–81382): document transplant indication (recipient or donor for bone marrow or solid organ) and level of typing required per transplant program.
• MRD documentation requirements: confirm cancer type is within intended use population of the test, provide guideline references showing that molecular detection would lead to definitive change in management, and provide evidence supporting test sensitivity/specificity for the indication.

Coding, Billing, and Precedence

Operational and coding notes to support authorization and claims processing.

• When a multigene panel is performed, appropriate panel codes must be used; newly referenced CPT codes (81457, 81458, 81459 and 0422U) should be used on claims and authorization forms.
• Coding inclusion in this policy is informational and does not imply automatic coverage — providers should obtain prior authorization and ensure documentation aligns with criteria.
• If additional IHC or cytogenetic analyses accompany PLA or GSP codes, these may be billed alongside the panel with documentation supporting medical necessity.

Stepwise Testing for MPN Genes

For MPN gene testing a stepwise testing approach is an acceptable clinical pathway and may be reflected in authorization requests; if initial single-gene testing (e.g., JAK2) is negative, authorization can be requested for subsequent gene testing (CALR, MPL) or a broader NGS panel including all genes. Provide prior test results and rationale for progression to broader testing.

• Stepwise testing option: JAK2 first, followed by CALR and MPL if negative, OR upfront multigene NGS panel including JAK2, CALR, MPL.
• Authorization requests should include prior single-gene test results when applicable to justify stepwise escalation.

Denial Risk for Nonconforming or Emerging Tests

Providers should be aware that some services described in this policy are investigational or have limited evidence. Requests for such services should include strong clinical justification and references to supportive guidelines or technology assessments; absent that, the services may be denied.

• Emerging or limited evidence tests may be denied unless robust evidence or guideline support is provided.
• Changes to MRD or other criteria (e.g., addition of new CPTs) require use of updated codes and documentation consistent with current criteria.