LCD Reference Article Response To Comments Article

Response to Comments: MolDX: APC and MUTYH Gene

A55452

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Article ID
A55452
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Article Title
Response to Comments: MolDX: APC and MUTYH Gene
Article Type
Response to Comments
Original Effective Date
03/13/2017
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The comment period for the MolDX: APC and MUTYH Gene Testing (LCD) DL36910 began on 11/16/2016 and ended on 01/03/2017. Comments were received from
the provider community. The notice period begins on 01/26/2017 and ends 03/12/2017 . The LCD becomes final on 03/13/2017 .

The following also includes comments received by Noridian Healthcare Solutions, LLC JE-DL36882, JF -DL36884 and Palmetto DL36827.

Response To Comments

Number Comment Response
1 We thank you for your decision to cover APC and MUTYH gene testing for individuals suspected of having Familial Adenomatous Polyposis (FAP), Attenuated FAP (AFAP) or MYH-associated polyposis (MAP). The coverage parameters outlined in this draft policy are well supported by the evidence and published guidelines, as well as by recent peer reviewed literature. However, it is important to note that approximately 5% of individuals with AFAP or MAP may present with 10-19 polyps, and language should be incorporated in the LCD that covers testing when indicated in these cases. dLCD Statement: This policy provides Medicare coverage for APC and MUTYH gene testing for individuals suspected to have Familial Adenomatous Polyposis (FAP), Attenuated FAP (AFAP) or MYH-associated polyposis (MAP) who have a personal history of =20 adenomas over a lifetime. We request that contractor revise its policy to include the following language: “Coverage may be reasonable and necessary for individuals who have less than 20 polyps, when supported by family history or clinical presentation, as documented in the medical record." A summary of submitted literature follows: A. Hegde M, et al. Genet Med. 2014 Jan;16(1):101-16. doi: 10.1038/gim.2013.166.
  1. AFAP testing: 10-100 adenomatous polyps with dominant inheritance
  2. MAP testing: 10-100 adenomatous polyps with family history suggestive of recessive inheritance
B. Stoffel EM, et al. J Oncol Pract. 2015 May;11 (3):e437-41. doi: 10.1200/JOP.2015.003665.
  1. Patients with multiple colorectal adenomas (>10), should be considered for germline genetic testing of APC and/or MUTYH.
C. Syngal S, et al. Am J Gastroenterol. 2015 Feb;110 (2):223-62; quiz 263. doi: 10.1038/ajg.2014.435. Epub 2015 Feb 3. Review.
  1. Individuals who have a personal history of >10 cumulative colorectal adenomas, a family history of one of the adenomatous polyposis syndromes, or a history of adenomas and FAP-type extracolonic manifestations (duodenal/ampullary adenomas, desmoid tumors (abdominal>peripheral), papillary thyroid cancer, congenital hypertrophy of the retinal pigment epithelium, epidermal cysts, osteomas) should undergo assessment for the adenomatous polyposis syndromes.
D. NCCN ® Clinical Practice Guidelines in Oncology, Genetic/Familial High-Risk Assessment: Colorectal. Version 2.2016. Available at www.nccn.org.
  1. Personal history of =20 adenomas
  2. Consider testing if a personal history of a desmoid tumor, hepatoblastoma, cribriformmorular variant of papillary thyroid cancer, or multifocal/bilateral CHRPE, or between 10-20 adenomas Age of onset, family history, and/or presence of other features may influence whether genetic testing is offered in these situations.
Four other publications were submitted and reviewed: E. F Grover S, et al. Prevalence and phenotypes of APC and MUTYH mutations in patients with multiple colorectal adenomas. JAMA. 2012 Aug 1;308(5):485-92. doi: 10.1001/jama.2012.8780. PubMed PMID: 22851115.
  1. Among 970 individuals with 10-19 colon adenomas, 5% had an APC mutation and 4% had biallelic MUTYH mutations
F. Neklason DW, et al. American founder mutation for attenuated familial adenomatous polyposis. Clin Gastroenterol Hepatol. 2008 Jan;6(1):46-52. Epub 2007 Dec 11. PubMed PMID: 18063416.
  1. Currently, the American Gastroenterological Association recommends genetic testing for AFAP in those with = 20 adenomas but no known family history 33. However, the AGA technical review of this subject details that “no clear standard exists concerning the number of colorectal adenomas needed to suspect this diagnosis in the index case” . Based on our observation of mutation carriers developing colon cancer, regardless of polyp number, this guideline may be insensitive. More recently, we and others have suggested that genetic testing should be considered when 10 or more colonic adenomatous polyps have been found in a patient at one examination or over time.”
G. Nielsen M, et al. Germline mutations in APC and MUTYH are responsible for the majority of families with attenuated familial adenomatous polyposis. Clin Genet. 2007 May;71(5):427-33. PubMed PMID: 17489848.
  1. Polyp number among families in a polyposis registry were stratified into categories of 1-9, 10-100, and >100
  2. 61% and 52% of APC and biallelic MUTYH carriers, respectively, had between 10-100 adenomas
H. Burt RW, et al. Genetic testing and phenotype in a large kindred with attenuated familial adenomatous polyposis. Gastroenterology. 2004 Aug;127(2):444-51. PubMed PMID: 15300576
  1. 10% of individuals with an APC mutation had between 11-19 adenomas
Comment 1 Summary: National guidelines do NOT support universal APC/MUTYH testing for patients with =10 adenomas in a lifetime. For each reference, words are highlighted that bring attention to the additional information that can and/or should be considered in addition to the numerical count of adenomas. While coverage may be reasonable and necessary for individuals who have fewer than 20 polyps, when supported by additional criteria, the policy will not be changed to cover =10 adenomas. Denied claims for patients with =10 adenomas can be appealed with the appropriate supporting documentation of medical necessity.
2 We suggest adding the following ICD-10 codes to the list of “Group 1 Codes” in the LCD, as they are applicable to beneficiaries who meet the coverage indications. D12.0 Benign neoplasm of cecum D12.1 Benign neoplasm of appendix D12.2 Benign neoplasm of ascending colon D12.3 Benign neoplasm of transverse colon D12.4 Benign neoplasm of descending colon D12.5 Benign neoplasm of sigmoid colon D12.7 Benign neoplasm of rectosigmoid junction D12.8 Benign neoplasm of rectum Z85.048 Personal history of other malignant neoplasm of rectum, rectosigmoid junction, and anus ICD D12.0-D12.8 has been added to the policy. ICD Z85.048 is to non-specific and will not be added.
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