Genetic Molecular Testing for Oncologic Indications*

Medical Policy: 02.04.07 
Original Effective Date: May 2005 
Reviewed: August 2008 
Revised:  

This policy applies to all products unless specific contract limitations, exclusions or exceptions apply. Please refer to the member's coverage manual for benefit availability. Managed care guidelines related to referral authorization, and precertification of inpatient hospitalization, home health, home infusion and hospice services apply.

Description: 

Genetic molecular testing involves the analysis of human DNA, RNA, chromosomes, certain metabolites and proteins to detect heritable disease-related genotypes, mutations, phenotypes, or karyotypes for clinical  purposes.  Certain genetic molecular tests have been demonstrated to be of significant value in providing information with regard to diagnosis and treatment of a given condition.  However, clinical usefulness of any genetic molecular test is dependent on the availability of specific, effective interventions to reduce risk or treat disease.  When the results of conventional test are inconclusive, the use of genetic molecular testing may add an additional measure of certainty to diagnosis, permitting refinement of clinical therapy.

Commercial availability in and of itself does not ensure that a genetic molecular test is indicated for clinical application.  Genetic molecular testing is a rapidly evolving science in which the significance of detecting specific germ-line mutations has yet to be clarified, especially in individuals with no known family history of a given disease.

Prior approval is recommended for genetic testing.  Submit a prior approval now   

Policy: 

Certain genetic molecular tests may be considered medically necessary, if provided under the following conditions to a patient with personal or family history features suggestive of a genetic cancer susceptibility condition, and if the results will assist in diagnosis or influence medical or surgical management.

  • The genetic molecular testing is conducted in a laboratory certified, at a minimum, under the Clinical Laboratory Improvement Amendments of 1988 (CLIA).
  • The genetic molecular testing is accompanied by pre-and post-test genetic counseling, which discusses the possible risks and benefits of early detection and prevention modalities.

I.  Hereditary Breast and Ovarian Cancer Syndrome (BRCA1 and BRCA2)

Genetic molecular testing for the BRCA1 and BRCA2 genes may be considered medically necessary when the above-mentioned conditions have been satisfied and the person being tested meets any of the following:

  • Women with three or more affected first degree (e.g., mother, sister, daughter) or second degree (e. g., grandmother, niece) blood relatives on the same side of the family irrespective of age at diagnosis
  • Women with multiple primary or bilateral breast cancers
  • Women with one or more first or second degree relatives with multiple or bilateral breast cancers
  • Women with one or more first or second degree relatives who have a BRCA1 or BRCA2 mutation
  • Women with one or more cases of ovarian cancer and one or more first or second degree relatives on the same side of the family with breast cancer
  • Women with one or more male blood relative with breast cancer
  • Men with breast cancer
  • Women who are at increased risk for specific mutations due to ethnic background (e.g., Ashkenazi Jewish descent) and who have one or more first or second degree blood relatives with breast or ovarian cancer irrespective of age at diagnosis
  • Women who are under the age of 50 or premenopausal at the time of breast cancer diagnosis, including diagnosis of ductal carcinoma in situ

Assays for rearrangement detection, such as the BRACAnalysis® Rearrangement Test (BART), are considered an integral component of genetic molecular testing for BRCA1 and BRCA2.

II.  Hereditary colorectal and endometrial cancer (MLH1, MSH2, MSH6, APC)

Currently there are two well-defined types of hereditary colorectal cancer.  They are: Hereditary nonpolyposis colorectal cancer (HNPCC) and Familial adenomatous polyposis (FAP).

     A.  Hereditary nonpolyposis colorectal cancer (HNPCC) 

  • Genetic molecular testing to determine carrier status of the HNPCC gene in patients who have a first or second degree relative with known HNPCC mutation may be considered medically necessary.
  • Genome testing for HNPCC may be considered medically necessary when the person being tested meets all of the following Amsterdam II or any of the following Bethesda criteria:

1.  Amsterdam II criteria (person being tested must meet all of the following):

  • There should be at least 3 relatives with HNPCC-associated cancer (colorectal, cancer of the endometrium, small bowel, ureter, or renal pelvis)
  • One should be a first degree relative of the other 2
  • At least 2 successive generations should be affected
  • At least 1 should be diagnosed before the age of 50
  • Familial adenomatous polyposis should be excluded in the colorectal cancer case(s), if any
  • Tumors should be verified by a pathological exam

OR

2.  Bethesda criteria (person being tested may meet any of the following): 

  • Individuals with 2 HNPCC-related cancers, including synchronous and metachronous colorectal cancers or associated extracolonic cancers
  • Individuals with colorectal cancer and a first-degree relative with colorectal cancer and/or HNPCC-related extracolonic cancer and/or colorectal adenoma:  one of the cancers diagnosed at age less than 45 years, and the adenoma diagnosed at age less than 40 years.
  • Individuals with colorectal cancer or endometrial cancer diagnosed at age less than 45 years
  • Individuals with right-sided colorectal cancer with an undifferentiated pattern on histopathology diagnosed at age less than 45 years
  • Individuals with signet ring cell type colorectal cancer diagnosed at age less than 45 years
  • Individuals with adenomas diagnosed at age less than 40 years.

Microsatellite Instability (MSI) testing

(MSI) testing of an affected patient's tumor may be considered medically necessary to determine whether further genetic molecular testing for HNPCC mutation is indicated IF the person being tested meets one of the following:

2004 Revised Bethesda Guidelines for Testing Colorectal Tumors for Microsatellite Instability

  • Colorectal cancer diagnosed in a patient who is less than 50 years of age
  • Presence of synchronous, metachronous colorectal or other HNPCC-associated tumors, regardless of age
  • Colorectal cancer with the MSI-H histology diagnosed in a patient who is less then 60 years of age
  • Colorectal cancer diagnosed in one ore more first-degree relatives with an HNPCC-related tumor, with one of the cancers being diagnosed under the age of 50 years
  • Colorectal cancer diagnosed in two or more first-or second-degree relatives with HNPCC-related tumors, regardless of age

B.  Familial Adenomatous Polyposis (FAP)

Determination of carrier status of the Adenosis Polyposis Coli (APC) gene may be considered medically necessary for patients meeting one of the following:

  • Patients with greater than 20 adenomatous colonic polyps during their lifetime
  • First degree relatives of patients diagnosed with Familial Adenomatous Polyposis (FAP)

III.  Multiple Endocrine Neoplasia Type 2 and Medullary Thyroid Cancer

Multiple endocrine neoplasia type 2 (MEN 2) is classified into 3 subtypes:  MEN 2A, FMTC (familial medullary thyroid carcinoma) and MEN 2B.  All carry a high risk for  development of medullary carcinoma of the thyroid; MEN 2A and MEN 2B carry an increased risk of pheochromocytoma; MEN 2A carries an increased risk for parathyroid adenoma or hyperplasia; and, MEN 2B is associated with onset of FMTC in early childhood and with characteristic facial features, mucosal neuromas of the lips and tongue, and ganglioneuromatosis of the gastrointestinal tract.  Genetic molecular testing for RET proto-oncogene point mutations may be considered medically necessary for any of the following:

  • Patients has no symptoms, but has a family member with defined RET gene mutations
  • Patient has a family member known to be affected by inherited medullary thyroid cancer, but not previously evaluated for RET mutations
  • Patients has sporadic medullary thyroid cancer

Genetic molecular testing is considered not medically necessary when performed despite high clinical evidence of a disease and when the treatment plan will not be altered based on the genetic testing result.

Genetic testing performed for determination of occupation-associated risk is considered not medically necessary.

Genetic molecular testing focused on personal reproductive decision-making rather than clinical management of a genetic disease is considered not medically necessary.

Genetic molecular testing for HNPCC of asymptomatic individuals in the general population who do not meet the criteria for HNPCC testing, or of individuals with a personal or family history of colorectal cancer or polyps who do not fit the criteria for HNPCC families is considered not medically necessary.

Genetic molecular tests conducted solely for knowledge when the knowledge will not alter medical management of the patient is considered not medically necessary.


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Procedure Codes and Billing Guidelines: 

  • To report provider services, use appropriate CPT** codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or ICD-9-CM diagnostic codes.
  • These HCPCS codes may be used to report genetic testing:
  • S3818 Complete gene sequence analysis; BRCA 1 gene
  • S3819 Complete gene sequence analysis; BRCA 2 gene
  • S3820 Complete BRCA 1 and BRCA 2 gene sequence analysis for susceptibility to breast and ovarian cancer
  • S3822 Single mutation analysis (in individual with a known BRCA 1 or BRCA 2 mutation in the family) for susceptibility to breast and ovarian cancer
  • S3823 Three-mutation BRCA 1 & BRCA 2 analysis for susceptibility to breast & ovarian cancer in Ashkenazi individuals.
  • S3828 Complete gene sequence analysis; MLH 1 gene
  • S3829 Complete gene sequence analysis; MLH 2 gene
  • S3830 Complete MLH 1 & MLH 2 gene sequence analysis for hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing
  • S3831 Single-mutation analysis (in individual with a know MLH 1 & MLH 2 mutation in the family) for hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing
  • S3833 Complete APC gene sequence analysis for susceptibility to familial adenomatous polyposis (FAP) and attenuated FAP.
  • S3834 Single-mutation analysis (in individual with a known APC mutation in the family) for susceptibility to familial adenomatous polyposis (FAP) and attenuated FAP.
  • S3840 DNA analysis for germline mutations for the RET proto-oncogene for susceptibility to multiple endocrine neoplasia type 2.
  • S3841 Genetic testing for retinoblastoma 

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Selected References: 

  • McConnell LM, Koenig BA, Greely HT et al. Genetic testing and Alzheimer's disease: has the time come? Alzheimer Disease Working Group of the Stanford Program in Genomics, Ethics & Society. Nat Med 1998; 4(7):7579.
  • Aaltonen LA, Salovaara R, Kristo P et al. Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. N Engl J Med 1998; 338(21):1481-7.
  • Vasen HF, Watson P, Mecklin JP et al. New clinical criteria for hereditary nonpolyposis colorectal cancer: database and results of a collaborative study. The International Collaborative Group on Hereditary Nonpolyposis Colorectal Caner. Gastroenterology 1999 Jun; 116(6):1453-6.
  • Rodriguez-Bigas MA, Boland CR, Hamilton SR, et al. A National Cancer Institute Workshop on Hereditary Nonpolyposis Colorectal Cancer Syndrome: meeting highlights and Bethesda guidelines. J Natl Cancer Inst 1998; 90(12):939-40.
  • Umar A, Boland CR, Terdiman JP et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004; 96(4):261-8.
  • Cawkwell L, Gray S, Murgatroyd H et al. Choice of management strategy for colorectal cancer based on a diagnostic immunohistochemical test for defective mismatch repair. Gut 1999; 45(3):409-15.
  • Calistri D, Presciuttini S, Buonsanti G et al. Microsatellite instability in colorectal cancer patients with suspected genetic predisposition. Int J Cancer 2000; 89(1):87-91.
  • Paraf F, Gilquin M, Longy M et al. MLH1 and MSH2 protein immunohistochemistry is useful for detection of hereditary non-polyposis colorectal cancer in young patients. Histopathology 2001; 39(3):250-8.
  • Krainer M, Silva-Arrieta S, FitzGerald MG, Shimada A, Ishoika C, Kanamaru R, MacDonald DJ, Unsal H, Finkelstein DM, Bowcock A, Isselbacher KJ, Harber DA. Differential contributions of BRCA1 and BRCA2 to early-onset breast cancer. N Engl J Med 1997 May; 336(20): 1416-21.
  • Clark BA. Cancer genetics for the clinician: recommendations on screening for BRCA1 and BRCA2 mutations. Cleveland Clinics Journal of Medicine, June 2000; 67(6):408-15.
  • Bansal A, Critchfield GC, Frank TS, Reid JE, Thomas A, Deffenbaugh AM, Neuhausen SL. The predictive value of BRCA1 and BRCA2 mutation testing. Genetic Testing 2000, 4(1): 45-8.
  • Antoniou A, Pharoah PDP, Narod S, et al. Average Risks of Breast and Ovarian Cancer Associated with BRCA1 and BRCA2 Mutations Detected in Case Series Unselected for Family History: A Combined Analysis of 22 Studies. Am J Hum Genet. 2003 May; 72(5):1117-30. Epub 2003 Apr 03.
  • Scheuer L, Kauff N, Robson M. Outcome of Preventative Surgery and Screening for Breast and Ovarian cancer in BRAC Mutation Carriers. J Clin Oncol. 2002 Mar 1; 20(5):1260-8.
  • Lawrence WF, Peshkin BN, Liang W, Isaacs C, Mandelbatt JS. Cost of genetic counseling and testing for BRCA1 and BRCA2 breast cancer susceptibility mutations. Cancer Epidermiol Biomarkers Prev. 2001 May; 10(5):475-81.
  • Mincey BA, Genetics and the management of women at high risk for breast cancer. Oncologist. 2003; 8(5):466-73.
  • Burke W. Genetic testing. N Engl J Med; 2002 Dec; 347(23): 1867-75.
  • American Society of Clinical Oncology. Statement Update: Genetic Testing for Cancer Susceptibility. J Clin Oncol; 21(12) 2003.
  • Claus EB, Petruzella S, Matloff E, Carter D. Prevalence of BRCA1 and BRCA2 Mutations in Women Diagnosed With Ductal Carcinoma In Situ. JAMA 2005; 293:964-69.
  • GeneTests-GeneReviews web site; http/www.geneclinics.org
  • Mathew C. Postgenomic technologies: hunting the genes for common disorders. BMJ 2001; 322:1031-4.
  • ECRI. Microsatellite Instability Testing for Hereditary Nonpolyposis Colorectal Cancer. Plymouth Meeting (PA): ECRI Health Technology Assessment Information Service; 2002 Jan. 28p. (Windows on medical technology no. 64).
  • Agency for Healthcare Research and Quality. Genetic Tests for Cancer. Technology Assessment Program. January 2006.
  • Machado PM, Brandao RD, Cavaco BM et al. Screening for a BRCA2 rearrangement in high-risk breast/ovarian cancer families: evidence foe a founder effect and analysis of the associated phenotypes. J Clin Oncolo. 2007 May 20;25(15):2027-34.
  • Hogervorst FB, Nederlof PM, Gille JJ et al. Large genomic deletions and duplications in the BRCA1 gene identified by a novel quantitative method. Cancer Res 2003 Apr 1 (637):1449-53. 

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New information or technology that would be relevant for Wellmark to consider when this policy is next reviewed may be submitted to:

Wellmark Blue Cross and Blue Shield
Medical Policy Analyst
Station 304
636 Grand Ave
Des Moines, Iowa 50309

*Prior approval is recommended for this policy.

**Current Procedural Terminology © 2008 American Medical Association. All Rights Reserved.

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