9-18-24 MolDX: Definition of Patients With and without Cancer
[Bruce Quinn – Bruce Quinn & Associates] Could MolDX please revisit its definitions of patients with cancer and patients without cancer? For example, a patient has a cancer resection and gets a minimal residual disease plasma series. At what point exactly does he become a patient without cancer and on surveillance testing that is outside NCD 90.2 because he "does not have cancer" anymore. Also, what happens if a patient qualifies for a plasma series, but is positive on the first test? It doesn't seem like further minimal residual disease tests would be of interest after that known early relapse.
Dr. Bien Willner elaborated on the issue: There has been ongoing discussion regarding the definition of patients with cancer versus those without cancer (in remission), particularly in relation to plasma tests under NCD 90.2. The policy applies to patients with cancer, but there are specific criteria that must be met which have some inconsistency in the instructions provided. Novitas has received different guidance than MolDX, apparently Novitas was told the NCD doesn’t apply to liquid biopsy tests. MolDX understands that the NCD does apply to any next-generation sequencing test in cancer.
For a patient to qualify under NCD 90.2, four key criteria must be met:
- The patient must be undergoing treatment or planning for treatment.
- The cancer must be advanced, including metastatic or recurrent.
- The patient must not have been previously tested with that specific test or a test that has the same genetic content.
- Some additional situations and interpretations are described below.
Targeted Therapy: Changes in genetic content can affect the patient's response to targeted therapy. The patient must demonstrate an effective genetic change to qualify for targeted therapy. All other requirements under NCD 90.2 must be met for coverage.
Recurrence: If a patient recurs, meaning there is a genetic change in the cancer, they may qualify for further testing under NCD 90.2. Since they have cancer, they only qualify for one test. However, one test may be priced as "bundles" to reflect comprehensive analysis over time.
Patients in Remission: A patient with no clinical, radiographic, or biological evidence of active disease, considered to be in remission or with a history of cancer, would fall outside of NCD 90.2.
However, these patients still need monitoring, so they may require alternative coverage pathways.
For further clarification, these definitions and criteria are detailed in the MolDX articles for comprehensive genomic profiling (CGP) and minimal residual disease (MRD). There was a discussion about whether it is always clear how a “bundle” duration is described (is it 6, 12, or 18 months), and when rules for “a patient without evidence of cancer” start to apply instead.
9-18-24 MolDX: Minimal Residual Disease (MRD) Technical Assessments (TA)
[Bruce Quinn – Bruce Quinn & Associates] MolDX now lists Z codes specific to indications, as well as specific to tests. There seem to be many lung MRD tests listed in the DEX system, but none of them are covered yet.
Can MolDX generally share what some of the challenges have been for labs submitting MRD TAs in the lung indication?
Also, could you confirm whether or not a company should have a Z code prior to submitting a new TA for the first time?
Dr. Bien-Willner shared the following regarding the challenges with Technology Assessments (TAs). One of the significant issues relates to Minimal Residual Disease (MRD) testing, for which TA applications are still relatively uncommon. He confirmed that for lung cancer, there is currently no approved test available, making it essential to demonstrate clinical validity. Specifically, the test must meet established criteria regarding advancements in radiographic and biological assessment.
There is a greater emphasis on surveillance in lung cancer. The cadence of testing should align with CT imaging to accurately reflect the test's performance. However, the current study design may lead to failure because it compares the test directly with radiological assessments. For example, the MRD test and radiology test are both negative in January, and both positive in June. This data does not document an advantage for the MRD test.
The goal is to ensure the test is superior, more accurate, and faster in identifying cancer. If a patient is determined to be cancer-free, it is permissible to indicate that the test can be performed again for monitoring purposes.
The course of MRD testing does not have a definitive endpoint; according to the policy, if a patient has cancer, they are eligible for testing. This process is structured around a series of defined time points.
[less certainty on this point --]
CMS has clarified that Novitas is not required to apply NCD 90.2 for non-solid tumors, which provides additional flexibility in MRD coverage at that MAC.
