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05-82000-31

Original Effective Date: 10/15/01

Reviewed: 05/26/16

Revised: 06/15/16

Subject: Genetic Testing for Lynch Syndrome and Other Inherited Colon Cancer Syndromes

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Position Statement Billing/Coding Reimbursement Program Exceptions Definitions Related Guidelines
           
Other References Updates    
           

DESCRIPTION:

There are currently 2 well-defined types of hereditary colorectal cancer (CRC), familial adenomatous polyposis (FAP) and Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer or HNPCC).

Familial Adenomatous Polyposis (FAP) and Associated Variants

FAP typically develops by age 16 years and can be identified by the appearance of hundreds to thousands of characteristic, pre-cancerous colon polyps. If left untreated, all affected individuals will go on to develop colorectal cancer. The mean age of colon cancer diagnosis in untreated individuals is 39 years. FAP accounts for about 1% of colorectal cancer.

Germline mutations in the adenomatous polyposis coli (APC) gene, located on chromosome 5, are responsible for FAP and are inherited in an autosomal dominant manner. Mutations in the APC gene result in altered protein length in about 80% to 85% of cases of FAP.

A subset of FAP patients may have attenuated FAP (AFAP), characterized by 10-99 cumulative colorectal adenomas occurring later in life than in classical FAP, CRC occurring at an average age of 50-55, but a high lifetime risk of CRC of about 70% by age 80. Only 30% or fewer of AFAP patients have APC mutations; some of these patients instead have mutations in the MUTYH (formerly MYH) gene and are then diagnosed with MYH-associated polyposis (MAP). MAP occurs with a frequency approximately equal to FAP. While clinical features of MAP are similar to FAP or AFAP, a strong multigenerational family history of polyposis is absent.

Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer or HNPCC)

Patients with Lynch syndrome have a predisposition to CRC and certain other malignancies as a result of an inherited mutation in a DNA mismatch repair (MMR) gene. Lynch syndrome includes those with an existing cancer and those who have not yet developed cancer. The term HNPCC originated prior to the discovery of explanatory MMR mutations for many of these patients, and now includes some who are negative for MMR mutations and likely have mutations in as yet unidentified genes.

Lynch syndrome is estimated to account for 3% to 5% of all colorectal cancer and is also associated with an increased risk of other cancers such as endometrial, ovarian, urinary tract, and biliary tract cancer.

POSITION STATEMENT:

NOTE: Coverage for genetic testing, screening, and counseling are applicable only under those contracts that include benefits for genetic testing, preventative health services, screening services, and medical counseling.

APC

Genetic testing for APC gene mutations meets the definition of medical necessity for one of the following:

1. At-risk relatives (eg. first-degree relatives; or in the case of a small family pedigree when extended family members may need to be included in the testing strategy) of members with familial adenomatous polyposis (FAP) and/or a known APC mutation.

2. Members with a differential diagnosis of attenuated FAP versus MUTYH-associated polyposis versus Lynch syndrome.

Genetic testing for APC gene mutations does not meet the definition of medical necessity for members with colorectal cancer with classical FAP for confirmation of the FAP diagnosis. The testing is not needed to make the diagnosis of FAP in these members and testing for the APC mutation has no role (no purpose) in the evaluation, diagnosis, or treatment of these members where the diagnosis and treatment are based on the clinical presentation.

MUTYH

Genetic testing for MUTYH gene mutations meets the definition of medical necessity in members with a differential diagnosis of attenuated FAP versus MUTYH-associated polyposis versus Lynch syndrome and a negative result for APC gene mutations. Family history of no parents or children with FAP is consistent with MUTYH-associated polyposis (autosomal recessive).

MMR

Genetic testing for MMR gene mutations meets the definition of medical necessity for one of the following:

1. Members with colorectal cancer, for the diagnosis of Lynch syndrome.

2. Members with endometrial cancer and 1 first-degree relative diagnosed with a Lynch-associated cancer, for the diagnosis of Lynch syndrome.

3. At-risk relatives (eg. first-degree relatives; or in the case of a small family pedigree when extended family members may need to be included in the testing strategy) of members with Lynch syndrome with a known MMR mutation.

4. Members with a differential diagnosis of attenuated FAP versus MUTYH-associated polyposis versus Lynch syndrome.

5. Members without colorectal cancer but with a family history meeting the Amsterdam or Revised Bethesda criteria*, when no affected family members have been tested for MMR mutations.

EPCAM

Genetic testing for EPCAM mutations meets the definition of medical necessity for one of the following:

1. Members with colorectal cancer, for the diagnosis of Lynch syndrome when:

­ Tumor tissue shows lack of MSH2 expression by immunohistochemistry and member is negative for a germline mutation in MSH2; OR

­ Tumor tissue shows a high level of microsatellite instability and member is negative for a germline mutation in MSH2, MLH1, PMS2, and MSH6.

2. At-risk relatives (eg. first-degree relatives; or in the case of a small family pedigree when extended family members may need to be included in the testing strategy) of members with Lynch syndrome with a known EPCAM mutation; OR

3. Members without colorectal cancer but with a family history meeting the Amsterdam or Revised Bethesda criteria*, when no affected family members have been tested for MMR mutations, and when sequencing for MMR mutations is negative.

BRAF V600E or MLH1 Promoter Methylation

Genetic testing for BRAF V600E or MLH1 promoter methylation meets the definition of medical necessity to exclude a diagnosis of Lynch syndrome when MLH1 protein is not expressed in a colorectal cancer on immunohistochemical (IHC) analysis.

Genetic testing for all other indications and for all other gene mutations for Lynch syndrome or colorectal cancer is considered experimental or investigational. The evidence is insufficient to permit conclusions on efficacy and net health outcomes.

Pre- and post test genetic counseling meets the definition of medical necessity as an adjunct to the genetic testing itself.

* Amsterdam II Criteria

Three or more relatives with a cancer associated with Lynch syndrome (cancers include colorectal, endometrial, stomach, ovarian, duodenal or small bowel, sebaceous adenomas or sebaceous carcinoma, ureteral or renal pelvis, brain tumors (particulary glioblastomas), hepatobiliary or pancreas ) and ALL of the following:

• One must be a first-degree relative of the other two; AND

• Two or more successive generations must be affected; AND

• One or more relatives with cancer associated with Lynch syndrome should be diagnosed before age 50 years; AND

• Familial adenomatous polyposis (FAP) should be excluded in the colorectal cancer (CRC) cases; AND

• Tumors should be verified by pathologic examination.

Modifications: Either very small families, which cannot be further expanded, can be considered to have hereditary nonpolyposis colorectal cancer (HNPCC) with only 2 colorectal cancers in first-degree relatives if at least 2 generations have the cancer and at least 1 case of colorectal cancer was diagnosed by the age of 55 years; OR in families with 2 first-degree relatives affected by colorectal cancer, the presence of a third relative with an unusual early-onset neoplasm or endometrial cancer is sufficient.

*Revised Bethesda Guidelines:

Member must have a cancer associated with Lynch syndrome (cancers include colorectal, endometrial, stomach, ovarian, duodenal or small bowel, sebaceous adenomas or sebaceous carcinoma, ureteral or renal pelvis, brain tumors (particulary glioblastomas), hepatobiliary or pancreas) and ANY one of the following;

• Colorectal cancer (CRC) diagnosed in an individual younger than 50 year; OR

• Presence of synchronous (at the same time) or metachronous (at another time, ie, a recurrence of) CRC or other Lynch syndrome‒associated tumors, regardless of age; OR

• CRC with the MSI-H histology diagnosed before 60 years; OR

• CRC diagnosed in an individual with at least one first-degree relative with a Lynch syndrome-associated tumor, with one of the cancers being diagnosed at younger than 50 years of age; OR

• CRC diagnosed in a in an individual with two or more first- or second-degree relatives with Lynch syndrome-related cancers (cancers include colorectal, endometrial, stomach, ovarian, duodenal or small bowel, sebaceous adenomas or sebaceous carcinoma, ureteral or renal pelvis, brain tumors (particulary glioblastomas), hepatobiliary or pancreas), regardless of age.

(First-degree relatives: Parents, full-siblings or children; Second-degree relatives: Aunts, uncles, grandparents, grandchildren, nieces, nephews or half-siblings; Third-degree relatives: Great-grandparents, great-aunts, great-uncles or first cousins)

BILLING/CODING INFORMATION:

CPT Coding:

81201

APC (adenomatous polyposis coli) (eg, familial adenomatosis polyposis [FAP], attenuated FAP) gene analysis; full gene sequence

81202

APC (adenomatous polyposis coli) (eg, familial adenomatosis polyposis [FAP], attenuated FAP) gene analysis; known familial variants

81203

APC (adenomatous polyposis coli) (eg, familial adenomatosis polyposis [FAP], attenuated FAP) gene analysis; duplication/deletion variants

81210

BRAF (B-Raf proto-oncogene, serine/threonine kinase) (eg, colon cancer, melanoma), gene analysis, V600 variant(s)

81288

MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) (eg, hereditary non-­‐polyposis colorectal cancer, Lynch syndrome) gene analysis; promoter methylation analysis

81292

MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) (e.g. hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis

81293

MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) (e.g. hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; known familial variants

81294

MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) (e.g. hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; duplication/deletion variants

81295

MSH2 (mutS homolog 2, colon cancer, nonpolyposis type 1) (e.g. hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis

81296

MSH2 (mutS homolog 2, colon cancer, nonpolyposis type 1) (e.g. hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; known familial variants

81297

MSH2 (mutS homolog 2, colon cancer, nonpolyposis type 1) (e.g. hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; duplication/deletion variants

81298

MSH6 (mutS homolog 6 [E. coli]) (e.g. hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis

81299

MSH6 (mutS homolog 6 [E. coli]) (e.g. hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; known familial variants

81300

MSH6 (mutS homolog 6 [E. coli]) (e.g. hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; duplication/deletion variants

81301

Microsatellite instability analysis (e.g. hereditary non-polyposis colorectal cancer, Lynch syndrome) of markers for mismatch repair deficiency (e.g.BAT25, BAT26), includes comparison of neoplastic and normal tissue, if performed

81317

PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (e.g. hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis

81318

PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (e.g. hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; known familial variants

81319

PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (e.g. hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; duplication/deletion variants

REIMBURSEMENT INFORMATION:

Services may be subject to medical review. The following information is required documentation to support medical necessity: reason for test(s), previous lab results, how the results of the test will be utilized, how the results of the test will contribute to improved health outcomes, or alters patient’s treatment and or management.

LOINC Codes:

Documentation Table

LOINC Codes

LOINC
Time Frame
Modifier Code

LOINC Time Frame Modifier Codes Narrative

Physician history and physical

28626-0

18805-2

Include all data of the selected type that represents observations made six months or fewer before starting date of service for the claim

Attending physician visit note

18733-6

18805-2

Include all data of the selected type that represents observations made six months or fewer before starting date of service for the claim.

Attending physician progress note

18741-9

18805-2

Include all data of the selected type that represents observations made six months or fewer before starting date of service for the claim.

Plan of treatment

18776-5

18805-2

Include all data of the selected type that represents observations made six months or fewer before starting date of service for the claim.

Laboratory studies

26436-6

18805-2

Include all data of the selected type that represents observations made six months or fewer before starting date of service for the claim

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Advantage products:

The following Local Coverage Determination (LCD) was reviewed on the last guideline reviewed date: Genetic Testing for Lynch Syndrome (L34912) located at fcso.com.

DEFINITIONS:

None applicable.

RELATED GUIDELINES:

Genetic Testing, 05-82000-28
Genetic Testing for Hereditary Breast or Ovarian Cancer, 05-82000-30

OTHER:

Note: The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Colaris®

Colaris® AP

ColarisPLUS®

REFERENCES:

  1. American Gastroenterological Association, Medical Position Statement: Hereditary Colorectal Cancer and Genetic Testing, 07/01.
  2. American Society of Colon & Rectal Surgeons, Practice Parameters for the Identification and Testing of Patients at Risk for Dominantly Inherited Colorectal Cancer, October 2001.
  3. Blue Cross Blue Shield Association Medical Policy Genetic Testing for Lynch Syndrome and Other Inherited Colon Cancer Syndromes (2.04.08), 02/16.
  4. Blue Cross Blue Shield Association Technology Evaluation Center “Genetic Testing for Inherited Susceptibility to Colorectal Cancer: Part I Adenomatous Polyposis Coli Gene Mutations” Vol 13, No 10, June 1998.
  5. Blue Cross Blue Shield Association Technology Evaluation Center “Genetic Testing for Inherited Susceptibility to Colorectal Cancer: Part II Hereditary Nonpolyposis Colorectal Cancer” Vol 13, No 11, June 1998.
  6. Bonis PA, Trikalinos TA, Chung M, et al, Hereditary Nonpolyposis Colorectal Cancer: Diagnostic Strategies and Their Implications, Evid Rep Technol Assess, 2007 May; (150): 1-180.
  7. ClinicalTrials.gov, Cost Effectiveness of Two Different Implementation Procedures to Change Clinicians Practice Roles in the Detection of Hereditary Colorectal Cancer, sponsored by Radboud University & ZonMw: The Netherlands Organization for Health Research, accessed 05/07/08.
  8. ClinicalTrials.gov, Establishing Effective Screening Methods for Diagnosing Hereditary Nonpolypoisis Colorectal Cancer, sponsored by Samsung Medical Center, accessed 05/07/08.
  9. ClinicalTrials.gov, Genetics Education: Preparing Physicians for the Future, sponsored by University of Toronto, accessed 05/17/10.
  10. ClinicalTrials.gov, Implementation of a New Strategy to Identify HNPCC Patients, sponsored by Radboud University, accessed 05/17/10;
  11. ClinicalTrials.gov, Multimedia Intervention in Patients with Familial Adenomatous Polyposis (FAP), sponsored by M.D. Anderson Cancer Center, accessed 05/17/10.
  12. ClinicalTrials.gov, Natural History of Familial Carcinoid Tumor, sponsored by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), accessed 05/17/10.
  13. ClinicalTrials.gov, Outcomes in Education and counseling for HNPCC Testing, sponsored by National Human Genome Research Institute (NHGRI) & national Cancer Institute (NCI), accessed 05/07/08.
  14. ClinicalTrials.gov, Study of the Results of Education and Counseling for Persons Undergoing Genetic Testing for Hereditary Nonpolyposis Colon Cancer, sponsored by National Human Genome Research Institute (NHGRI), accessed 05/17/10.
  15. Collins VR, Meiser B, Ukoumunne OC, Gaff C, et al, The Impact of Predictive Genetic Testing for Hereditary Nonpolyposis Colorectal Cancer: Three Years After Testing, Genet Med. 2007 May; 9(5): 290-7.
  16. ECRI Custom Hotline Response “Guidelines for Genetic Testing to Identify Persons at Risk for Colorectal Cancer”, 03/06.
  17. ECRI Institute, Custom Hotline Response: Genetic Testing for Hereditary Nonpolyposis Colorectal Cancer Syndrome, updated 02/05/08.
  18. ECRI Windows on Medical Technology “Microsatellite Instability Testing for Hereditary Nonpolyposis Colorectal Cancer” Issue 64, 01/02.
  19. Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Recommendations From the EGAPP Working Group: Genetic Testing Strategies in Newly Diagnosed Individuals with Colorectal Cancer Aimed At Reducing Morbidity and Mortality From Lynch Syndrome in Relatives, Genetics in Medicine;11(1): 35-41.
  20. First Coast Service Options, Inc, LCD for Genetic Testing for Lynch Syndrome (L34912), 03/16.
  21. Gryfe R, Inherited Colorectal Cancer Syndromes, Clinics in Colon and Rectal Surgery, 2009; 22(4): 198-208.
  22. Hayes Medical Technology Directory “Genetic Testing for Susceptibility to Hereditary Nonpolyposis Colorectal Cancer” (12/05), updated 02/08.
  23. Hayes Medical Technology Directory “Genetic Testing for Susceptibility to Familial Adenomatous Polyposis”, (01/03) update 02/06.
  24. Kim KH, Kim JY, OH SI, et al, A Novel Germline Mutation of hMLH1 in a Korean Hereditary Non-Polyposis Colorectal Cancer Family, Int J Oncol. 2009 May; 34: 1313-8.
  25. Martellucci J, Civitelli S, Dhamo A, Tanzini G, Familial Colorectal Cancer: A Concept Revisited, Colorectal Dis. 2009 Feb; 11: 133-7.
  26. Meyer LA, Broaddus RR, Lu KH, Endometrial Cancer and Lynch Syndrome: Clinical and Pathologic Considerations, Cancer Control. 2009 Jan; 16: 14-22.
  27. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Colorectal Cancer Screening, Version 1.2014.
  28. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Genetic/Familial High-Risk Assessment: Colorectal Version 2.2015.
  29. Palomaki GE, McClain MR, Melillo S, et al. EGAPP supplementary evidence review: DNA testing strategies aimed at reducing morbidity and mortality from Lynch syndrome. Genet Med. Jan 2009;11(1):42-65.
  30. Ramsoekh D, Van Leerdam ME, Wagner A, Kuipers EJ, Detection and Management of Hereditary Non-Polyposis Colorectal Cancer (lynch Syndrome), Aliment Pharmacol Ther. 2007 Dec.
  31. Robson ME, Storm CD, et al. American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility, Journal of Clinical Oncology, 01/11/10.
  32. Schmeler KM, Lu KH, Gynecologic Cancers Associated with Lynch Syndrome/HNPCC, Clin Transl Oncol. 2008 Jun; 10:313-7.
  33. Stoffel EM, Turgeon DK, Stockwell DH, et al, Missed Adenomas During Colonoscopic Surveillance in Individuals with Lynch Syndrome, Cancer Prev Res (Phila Pa). 2008 Nov; 1:470-5.
  34. Vasen HF, Watson P, Mecklin JP, et al. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology. Jun 1999;116(6):1453-1456.
  35. Wakefield CE, Meiser B, Homewood J, Ward R, et al, Randomized Trial of A Decision Aid For Individuals Considering Genetic Testing fro Hereditary Nonpolyposis Colorectal Cancer Risk, Cancer. 2008 Sep 1: 956-65.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Medical Policy & Coverage Committee on 05/26/16.

GUIDELINE UPDATE INFORMATION:

11/15/03

Medical Coverage Guideline Annual review. Developed separate policy for Genetic Testing for Inherited Susceptibility to Colon Cancer Including Microsatellite Instability.

11/15/04

Revised description section. Revised coverage criteria based on the Amsterdam II criteria. Update references.

07/01/05

HCPCS update. Added S0265.

01/01/06

Annual HCPCS coding update: added 83900, 83907, 83908, 83909, and 83914. Revised 83898.

06/15/06

Revision to include new codes into limitation section.

10/15/06

Biennial review; investigational statement deleted; HNPCC coverage edited; coding information revised; categorized as NLR.

01/01/07

Annual HCPCS coding update: added 96040, deleted 99401, 99402, 99403, 99404.

08/15/07

Review, coverage statements maintained, guideline reformatted, references updated.

01/01/08

Annual HCPCS coding update: revised 83898, 83900, and 83908.

07/15/08

Annual review: position statements maintained, references updated.

01/01/09

Annual HCPCS coding update: descriptor updated for codes 83890, 83892, 83894, 83896, 83897, 83900, 83903, 83907, 83909, and 83914.

08/15/09

Annual review: position statements revised, description section and references updated.

10/15/09

Reimbursement section updated.

07/15/10

Annual review: position statements maintained and references updated.

10/01/11

Revision; formatting changes

01/01/12

Annual HCPCS update. Added codes 81292-81301, 81317-81319; revised Billing/Coding and Reimbursement Information sections.

04/01/12

Quarterly HCPCS update. Deleted codes S3828-S3831.

01/01/13

Annual HCPCS update. Added codes 81201-81203.

01/01/14

Annual HCPCS update. Deleted codes S3833-S3834. Program Exceptions section updated.

01/01/15

Annual HCPCS/CPT update. Added code 81288.

02/15/15

Review; description section, position statements, Medicare program exception, coding, and references updated; formatting changes.

01/01/16

Annual HCPCS/CPT update; code 81210 revised.

06/15/16

Review; guideline title, position statement section, Medicare program exception and references updated; formatting changes.

Date Printed: June 23, 2017: 11:43 AM