LCD L38835: MolDX: Minimal Residual Disease Testing for Cancer

This Medicare contractor will provide limited coverage for minimally invasive molecular deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) tests that detect minimal residual disease (MRD) in patients with a personal history of cancer.

This Contractor provides limited coverage for MRD testing in cancer when ALL of the following are true:

• If Next-Generation Sequencing (NGS) methodology is used in testing, the conditions set by NCD 90.2 are fulfilled (summarized: 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) or are not applicable (the patient does not have cancer as defined below);

• 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;

• To be reasonable and necessary, it must also be medically acceptable that 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;

• If the test is to be used for monitoring a specific therapeutic response, it must demonstrate the clinical validity of its results in published literature for the explicit management or therapy indication (allowing for the use of different drugs within the same therapeutic class, so long as they are considered ‘equivalent and interchangeable’ for the purpose of MRD testing , as determined by national or society guidelines);

• Clinical validity (CV) of any analytes (or expression profiles) measured must be established through a study published in the peer-reviewed literature for the intended use of the test in the intended population;

• The test is being used (a) in a patient who is part of the population in which the test was analytically validated and (b) according to the intended use of the test;

• The MRD test [(unless it is a Food and Drug Administration (FDA)-approved and established standard-of-care single-gene polymerase chain reaction (PCR)] satisfactorily completes a technical assessment (TA) that will evaluate and confirm that the analytical validity, clinical validity, and clinical utility criteria set in this policy are met to establish the test as Reasonable and Necessary;

• Tests utilizing a similar methodology or evaluating a similar molecular analyte to a test for which there is a generally accepted testing standard or for which existing coverage exists must demonstrate equivalent or superior test performance (i.e., sensitivity and/or specificity) when used for the same indication in the same intended-use population;

MRD testing often requires 2 types of assays to be performed as part of the service. First, a sample is taken from a tumor diagnostic material to establish a baseline (solid and/or liquid) tumor signature as defined by the test methodology. This is followed by a series of assays run on a minimally invasive specimen (i.e., liquid biopsy or bone marrow aspirate) to detect the presence or recurrence of a tumor based on the measured biomarkers, expression, or other analytes over various timepoints. Other approaches are also acceptable, based on the validity established for the individual test comprising the service. This series of assays comprises a single test when the patient is known to have cancer.

When the patient is NOT known to have cancer (specifically when there is no clinical, radiographical, or other biological evidence that tumor cells remain post treatment and subsequently the patient is no longer being subjected to therapeutic interventions for cancer), a second kind of test may exist wherein a single timepoint may constitute a single test. In such patients, the frequency of MRD testing is in accordance with national or society guidelines or recommendations.

For patients with or without cancer (as defined above), established standard-of-care MRD tests using single-gene PCR (i.e., BCR-ABL1) are covered under this policy according to testing schedules outlined in national (i.e., NCCN) or society guidelines.

MRD testing in accordance with this policy can be performed using PCR and/or sequencing-based technologies and is not restricted to a single type of biological material or defined number of genes.

Background

MRD testing for cancer is rapidly becoming a sensitive and specific method for monitoring the relative amounts of tumor-derived genetic material circulating in the blood of cancer patients. These tests leverage new genomic technologies that allow detection of extremely dilute tumor material, yielding an extremely sensitive method for determining the continued presence of tumor material or, by serially testing the same individual, tracking the relative increase or decrease of tumor material being deposited in the blood. Although it is a relatively new application of novel genomic technologies, it has rapidly demonstrated its ability to impact patient care in several ways in cancer diagnosis and treatment. MRD testing can be used to:

• Diagnose cancer progression, recurrence, or relapse before there is clinical, biological, or radiographical evidence of progression, recurrence, or relapse.

• Detect tumor response to therapy by measuring the proportional changes in the amount of available tumor DNA.