Local Coverage Article Response to Comments

Response to Comments: MolDX: Plasma-Based Genomic Profiling in Solid Tumors


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Response to Comments: MolDX: Plasma-Based Genomic Profiling in Solid Tumors
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Response to Comments
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The comment period for the MolDX: Plasma-Based Genomic Profiling in Solid Tumors DL39232 Local Coverage Determination (LCD) began on 01/20/2022 and ended on 03/05/2022. The comments below were received from the provider community. The notice period for L39232 begins on 11/10/2022 and will become effective on 12/26/2022.

Noridian received comments from 6 different commenters.

Introduction to Responses

Noridian appreciates the comments received from stakeholders during the open comment period on the proposed MolDX: Plasma-Based Genomic Profiling Local Coverage Determination (LCD). We reviewed the comments in their entirety. Submitted comments that cite published, peer-reviewed literature provide suitable evidence that may inform policy, while less rigorous comments (e.g., anecdotal, unpublished information not subject to peer review) are much less influential to policy determinations.

NOTE: Noridian reviews all submitted comments; however, MACs may choose to consolidate similar thematic comments, redact, or withhold certain submissions (or portions thereof) such as those containing private or proprietary information, or inappropriate language. This may result in discrepancies between the number of comments in the article and the actual number of comments received.

Response To Comments


Several commenters wrote in support of the LCD DL39230 coverage criteria, with the exception of the requirement that prior to liquid biopsy, tissue testing/biopsy should be infeasible or incomplete. One wrote, “As you know, neither blood-based nor tissue-based NGS has 100% sensitivity, but blood-based testing has advantages for underserved/community practitioners and patients as a faster, less-invasive method to genotype with comparable sensitivity and concordance in CRC (References submitted).

Tissue-based NGS has inherent limitations in CRC, including failure to capture clonal evolution, intratumor heterogeneity (References submitted) and low adoption in community oncology practices (References submitted). By requiring providers to attempt or document infeasibility of tissue-based testing, MolDx policy limits the patient-provider decision making and introduces unnecessary delays and documentation challenges.” All commenters requested for this criterion to be removed.

Noridian appreciates the commenter’s advocacy on behalf of Medicare beneficiaries. However, no literature was submitted to support the claim that documentation requirements limit the appropriate use or adoption of plasma-based genomic testing for solid tumors. We believe that the proposed LCD uses an evidenced-based, patient-oriented approach, and focuses the documentation requirements to those that support medical necessity for testing which is statutorily required by Medicare.


On commenter requested, “…coverage should be provided on all FDA-approved testing methods. We believe that clinicians and their patients should determine the most appropriate choices for the diagnosis, therapy, and post-therapy management of colorectal cancer, and that these choices are not determined or influenced by financial considerations based on coverage. This is particularly important in that blood-based testing may have advantages for underserved patients as it provides a faster, less-invasive method to genotype. As a patient advocacy organization, we do not opine on specific elements of an LCD but support a positive coverage determination so that physicians have access to this testing method without restriction.”

Thank you for the comment.


One commenter wrote that, “…considerable evidence demonstrates that first-line use of liquid biopsy is often appropriate based on the emerging literature, precedent set by Medicare coverage and FDA approval, and updated clinical guidelines supportive of plasma-based biopsy. When considered holistically, liquid biopsy overcomes the significant issues of delay, assay incompletion, and heterogeneity that limit the benefits patients may derive from tissue-based testing. When liquid is deployed as the first-line CGP methodology, it is able to uncover an equivalent number of biomarkers much more rapidly than tissue CGP. As a result, we respectfully request the removal of the tissue insufficiency prerequisite.”

Thank you for the comment; however, this is outside the scope of this LCD reconsideration.


Two societies jointly wrote, “…we are concerned that as drafted the policy sets difficult criteria and unclear process for non-Guardant360 plasma-based genomic profiling tests. Historically, tests are regulated and validated under the Clinical Laboratory Improvement Amendments (CLIA) program. AMP and CAP are concerned that the proposed coverage criteria may unintentionally exclude tests with a long history of being utilized successfully in CLIA-certified laboratories. Regulatory requirements stipulated in CLIA already provide strict validation requirements that must be followed before an assay can be offered to patients. Additionally, the use of these tests are often supported by well-established clinical guidelines that have been developed and endorsed by leading scientists, subject matter experts, and National Comprehensive Cancer Network and professional society guidelines, including those from AMP and CAP. Rather than requiring other liquid biopsies to mirror the performance standards of Guardant360®, we recommend Noridian provide coverage for other plasma-based genomic profiling tests when the test is performed in a CLIA-certified laboratory. If a laboratory test is properly validated, meeting certain criteria and standards set forth by regulatory programs, like CLIA, the laboratory test should be covered. No references were submitted.

Thank you for the comments; however, we respectfully disagree. Evidenced-based patient-oriented public policy requires that the clinical validity and utility of diagnostic testing be proven based on data that is published in peer-reviewed literature with a high degree of certainty in addition to the analytic validity upon which CLIA certification typically focuses.


Another comment submitted by specialty societies asks for clarification of coverage of other tests whose analytic performance is not explicitly published in the policy but may perform similarly in their intended use applications.

This interpretation is correct; other next-generation sequencing assays will be covered for the same indications if they display similar performance statistics published in this LCD and meet all the conditions stated in the policy for coverage.


Another comment recommended guidelines be added to this policy to ensure that tests meet the necessary requirements for coverage. They added, “we recommend that specific instructions, including parameter or criteria requirements, be outlined clearly for compliance purposes. Laboratories are already complying with certain standards and all coverage criteria should be clearly articulated. …What if any specific documentation of tissue insufficiency or invasive biopsy contraindication does Noridian envision, that tissue-based sampling of a tumor is “infeasible”?

Thank you for the comment; however, this is outside the scope of this LCD reconsideration. We will take these comments under advisement for clarifying guidance in the accompanying billing and coding article.


AMP and CAP recognize that Guardant360® identifies mutations in over 70 genes. As such, we believe their assay would be consistent with CPT code 81455. As such, we recommend the inclusion of CPT 81455 to the policy

Thank you for the comment; however, this is outside the scope of this LCD reconsideration.

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