LCD Reference Article Response To Comments Article

Response to Comments: MolDX: Genetic Testing for Lynch Syndrome

A54965

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A54965
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Article Title
Response to Comments: MolDX: Genetic Testing for Lynch Syndrome
Article Type
Response to Comments
Original Effective Date
06/01/2016
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Noridian’s Response to Provider Recommendations (for comment period ending 12/7/2015):

Response To Comments

Number Comment Response
1 Include new content in LCD to define patients at-risk for hereditary CRC who are eligible for multi-gene panel tests which have the ability to increase diagnostic yield for clinical actionable mutations. The commenter notes that there is growing use of multi-gene panel tests as first-line approach for some patients. The commenter submitted a power-point presentation noting that for 279 less than 50 years patients, all of whom underwent tumor screening for LS, (all negative for mismatch repair deficiency), their 25-gene hereditary cancer panel detected a variety of other CRC-related mutations. The commenter also cited a study by Yurgelum et al. in which 1260 patients suspected of having LS received NGS panel testing. One hundred eight two of these patients carried 1 or more pathogenic mutation including 114 patients with a LS mutation and 71 with non-LS mutations. Of the 71 non-LS mutations, 24 were in high-penetrance genes, 20 were moderate-penetrance cancer susceptibility genes and 27 monoallelic MUTYH mutation carriers (significance debatable). A total of 682 VUS were detected in 479 individuals predominately in ATM, APC NBN and BRIP1 genes. The PowerPoint presentation does not provide the level of supporting detail needed to be considered for a Medicare coverage determination. The Yurgelum et al. demonstrate that large cancer panels can identify high-penetrance mutations and a significant number of mutations (38% of individuals) of uninformative and potentially anxiety producing results. At the current time, NGS hereditary cancer risk panels are not an alternative strategy for LS testing and will not be added to the policy. Limited disease specific NGS panels may be considered via MolDX after comprehensive review, and may be covered on an individual test basis.
2 In section III of the LCD, under “IHC and/or MSI testing”, ensure indications for LS testing are consistent with the language in the current NCCN guidelines. The commenter suggest slight changes to the revised Bethesda criteria and the addition of a statement clarifying the cancer sites that are considered to be LS related cancers to be consistent with NCCN. Select editorial changes and the cancer sites associated with LS-related cancer will be added. Permission to reproduce the revised Bethesda criteria was not obtained by this contractor, thus the non-substantive changes in the LCD.
3 In section III of the LCD, under “MMR Germline Mutation Testing Exception”, clarify how the listed exceptions apply to patients with endometrial cancer. The commenter requests testing exceptions apply to patients with endometrial cancer also. Agree to include patients with endometrial cancer in testing exceptions.
4 In section III of the LCD, under “MMR Germline Mutation Testing Exception”, allow MLH1, MSH2 and MSH6 testing, and if negative, follow by PMS2 testing. The commenter indicated that when targeted gene testing is not possible, the draft LCD requires that MLH1 and MSH2 testing be performed first, followed by MSH6 and then PMS2. The commenter states that the 3-step gene sequence will result in substantial turn-around of 2-4 weeks, and requests a two-step process in which MLH1, MSH2 and MSH6 are performed together first, and if negative, followed by PMS2. Many labs are using NGS testing so the 4-gene results are available concurrently. Labs using non-NGS methodology can perform all 4 genes concurrently, as a business decision to shorten turn-around time, but a business decision does not constitute a medical decision. If a lab chooses based on a business decision to test all 4 genes concurrently, it can only bill for testing based on the 3-step process because it is not reasonable and necessary to perform all genes if MLH1 or MSH2 are identified in the 1 step, or if MSH6 is identified in the 2nd step.
5 In section III of the LCD, under “MMR Germline Mutation Testing Exception” add language to provide coverage for genetic testing for patients diagnosed with a LS-associated cancer other than CRC or endometrial cancer based on specific criteria. At present, patients diagnosed with other LS-associated cancers (ovarian, gastric, small bowel, ureter and renal pelvis, pancreas, hepatobiliary tract, glioblastoma, and sebaceous carcinomas) should be considered under the “MMR Germline Gene Mutation Testing Exception” if they meet specified clinical criteria. Patients diagnosed with these cancers who have a family history suggestive of LS do not have coverage for diagnostic testing. The commenter suggests a threshold of 5% for the patient’s estimated likelihood to test positive for a Lynch mutation, as calculated by one of several available risk models that take personal and family history of Lynch cancers into account. The commenter suggests an alternative approach by applying the revised Bethesda guidelines to these patients. The patient would need to have the necessary number of 1st and/or 2nd degree relatives with CRC or other Lynch-associated cancer at specified ages of diagnosis, so that the pattern of diagnoses of cancer in the family would meet one of the criteria. The commenter is correct that Medicare coverage cannot be based on family history.
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Associated Documents

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Medicare BPM Ch 15.50.2
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Keywords

  • Genetic
  • testing
  • Lynch
  • Syndrome