Medical Policy: 02.04.64
Original Effective Date: November 2016
Reviewed: November 2018
Revised: November 2018
Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.
This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.
Numerous genetic mutations are associated with inherited cancer syndromes. Patients may have a personal and/or family history of cancer that suggests that the cancer is syndrome-related. Some patients may meet clinical criteria for 1 or more hereditary cancer syndromes, and it has been proposed that mutation testing using next-generation sequencing technology to analyze multiple genes at 1 time (panel testing) can optimize testing in these patients compared to testing for individual mutations.
For individuals who have a personal and/or family history suggesting an inherited cancer syndrome who receive sequencing panel, the evidence includes mainly reports describing the frequency of detecting mutations in patients referred for panel testing. Relevant outcomes are overall survival, disease-specific survival, test accuracy, and test validity. Published data on analytic validity is lacking, but it has been reported to be high, approaching that of direct sequencing of individual genes. Clinical validity studies have generally reported the results of the frequency with which mutations are identified using large panels, and occasionally have reported the variant of unknown significance rate. Published data on clinical utility is lacking, and it is unknown whether use of these panels improves health outcomes. Many panels include mutations that are considered to be of moderate or low penetrance, and management guidelines are not well-defined in these patients, leading to the potential for harm in identifying one of these non-highly penetrant mutations. The evidence is insufficient to determine the effects of the technology on health outcomes.
Commercially available cancer susceptibility mutation panels can test for multiple mutations associated with a specific type of cancer or can include mutations associated with a wide variety of cancers. Mutations included in these panels are associated with varying levels of risk of developing cancer, and only some mutations included on panels are associated with a high risk of developing a well-defined cancer syndrome for which there are established clinical management guidelines. Clinical management recommendations for the inherited conditions associated with low-to-moderate penetrance are not standardized, and the clinical utility of genetic testing for these mutations is uncertain and could lead to harm. In addition, high rates of variants of uncertain significance have been reported with these panels.
For individuals who have a personal and/or family history suggesting an inherited cancer syndrome who receive testing with a next-generation sequencing panel, the evidence includes mainly reports describing the frequency of detecting mutations in patients referred for panel testing. Relevant outcomes are overall survival, disease-specific survival, test accuracy, and test validity. Published data on analytic validity is lacking, but it has been reported to be high, approaching that of direct sequencing of individual genes. Clinical validity studies have generally reported the results of the frequency with which mutations are identified using large panels, and occasionally have reported the variant of unknown significance rate. Published data on clinical utility is lacking, and it is unknown whether use of these panels improves health outcomes. Many panels include mutations that are considered to be of moderate or low penetrance, and management guidelines are not well-defined, leading to the potential for harm in identifying one of these non-highly penetrant mutations. The evidence is insufficient to determine the effects of the technology on health outcomes.
The U.S. Food and Drug Administration (FDA) currently do not require approval for any expanded genetic panels tests. Because of the large number of mutations contained in expanded panels, it is not possible to determine clinical validity for the panels as a whole. The following list contains some (but not all) examples of expanded genetic panels commercially available at this time:
Although genetic cancer susceptibility panels using next-generation sequencing are considered investigational, there may be individual components of the panel that are medically necessary.
Note: This policy does not apply to the individual markers that have demonstrated efficacy in certain types of cancer.
American Society of Clinical Oncology (ASCO) recognizes that concurrent multigene testing (ie, panel testing) may be efficient in circumstances that require evaluation of multiple high-penetrance genes of established clinical utility as possible explanations for a patient’s personal or family history of cancer. Depending on the specific genes included on the panel employed, panel testing may also identify mutations in genes associated with moderate or low cancer risks and mutations in high-penetrance genes that would not have been evaluated on the basis of the presenting personal or family history. Multigene panel testing will also identify variants of uncertain significance (VUS) in a substantial proportion of patient cases. ASCO affirms that it is sufficient for cancer risk assessment to evaluate genes of established clinical utility that are suggested by the patient’s personal and/or family history.
The U.S. Preventive Services Task Force recommends that primary care providers screen women who have family members with breast, ovarian, tubal, or peritoneal cancer with 1 of several screening tools designed to identify a family history that may be associated with an increased risk for potentially harmful mutations in breast cancer and susceptibility genes (BRCA1 or BRCA2). Women with a positive screening results should receive genetic counseling and, if indicated after counseling, BRCA testing (grade B recommendation, 2013). The use of genetic cancer susceptibility panels is not specifically mentioned.
National Comprehensive Cancer Network (NCCN) guidelines on genetic/familial high-risk assessment for breast and ovarian cancer (v.1.2019) state that, regarding multigene testing:
The Centers for Disease Control and Prevention (CDC) Office of Public Health Genomics helped to establish and support the ACCE Model Project, which has become the standard for evaluating scientific data on new genetic tests. The ACCE Model System* for Collecting, Analyzing and Disseminating Information on Genetic Tests provides an evaluation framework that is applicable to a variety of genetic tests. The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) used the ACCE framework and established this process as a way of evaluating an evidence-based method for assessing genetic tests and other types of genomic technology as it has transitioned from the research arena to the practice arena. The ACCE evaluation framework examines:
Data is lacking for the clinical utility of multigene panels for inherited cancer susceptibility panels. There are management guidelines for syndromes with high penetrance, which have clinical utility in that they inform clinical decision making and result in the prevention of adverse health outcomes. Clinical management recommendations for the inherited conditions associated with low-to-moderate penetrance are not standardized, and the clinical utility of genetic testing for these mutations is uncertain. Variants of uncertain significance are generally not clinically actionable, and most are re-classified as benign.
Genetic cancer susceptibility panels to assess cancer risk using next generation sequencing are considered investigational.
Although multigene genetic cancer susceptibility panels are considered investigational, there may be individual components of the panel that are medically necessary.
The following genes are recommended in the presence of genetic/familial high-risk assessment for breast cancer: (v2.2019)
The following genes are recommended in the presence of genetic/familial high-risk assessment for ovarian cancer (v2.2019)
The following are recommended and considered well-established in the presence of genetic/familial high-risk assessment for colorectal cancer (v1.2018)
The following are recommended and considered well-established in the presence of Lynch Syndrome (Colorectal: Version 1.2018)
The evidence base is insufficient to demonstrate how comprehensive test results from all genes and/or gene mutations included in the panels listed below may be used to manage treatment decisions (i.e., clinical utility) and improve net health outcomes. Panel testing is similar to population testing with minimal value seen in genetic testing for information not effecting treatment. The following below, but not limited to these genetic panels are considered investigational to determine cancer risk.
|Brain Tumor Next||Ambry GeneticsTM|
|BRCA Full Risk Panel||GeneID|
|BRCAplus, BRCA plus expanded||Ambry GeneticsTM|
|Breast Plus Panel||Quest Diagnostics|
|Breast Cancer STAT Panel/Breast Cancer Panel||Invitae|
|Breast and Gyn Cancers Panels||Invitae|
|BreastTrueTM High Risk Panel||Pathway Genomics|
|Breast/Ovarian Cancer Panel||GeneDx|
|Cancer NextGen Sequencing (NGS) Panel||Prevention Genetics|
|Cancer Somatic Mutation Panel||Stanford Hospital and Clinics|
|CancerNext Expanded||Ambry GeneticsTM|
|Colorectal Cancer Panel||GeneDx|
|Colorectal Cancer Panel||Invitae|
|Colorectal Cancer Guidelines Based Panel and add-on gened||Invitae|
|Colorectal and Polyposis Panel||Myriad®|
|ColoSeqTM||University of Washington|
|Combined Mito Genome Plus Mito Nuclear Gene Panel||GeneDx|
|Common Hereditary Cancer Panel||Invitae|
|Comprehensive Cancer Panel||GeneDx|
|Comprehensive Leukemia/Lymphoma Panel||Clarient Diagnostic Services|
|Comprehensive Molecular Genetic Panel||Molecular Testing Lab|
|Comprehensive Panel||Lab Genomics|
|Comprehensive PinPointDNA Panel||PinPoint Clinical, GeneAlign|
|CustomNext Cancer||Ambry GeneticsTM|
|Custom Cancer Panel||GeneDx|
|Counsyl Reliant Cancer Screen||Counsyl|
|Endometrial Cancer Panel||GeneDx|
|Family Prep Screen||Counsyl|
|Gastric Cancer Panel||Invitae|
|GEM Cancer Panel||Ashion Analytics|
|GoodStart Select||GoodStart Genetics|
|GYN plus||Ambry GeneticsTM|
|Hematologic Malignancy Sequencing Panel||Penn Medicine|
|Hereditary Breast Cancer Panel and/or Ovarian Cancer||Invitae|
|Hereditary Cancer Syndromes Panel||Invitae|
|Hereditary Colon Cancer Multi-Gene Panel||Mayo Clinic|
|Hereditary Paraganglioma-Pheochromocytoma Panel|
|High Risk Cancer Panel||Emory Labs|
|High-Moderate Risk Panel||GeneDx|
|HorizonTM Multi-Disease Carrier Screening||Natera, Inc.|
|Invitae Multi-Cancer Panel||Invitae|
|Invitae Melanoma Panel||Invitae|
|Invitae Hereditary Cancer Syndromes Panel||Invitae|
|Inherited Cancer Screen or Comprehensive Panel||Counsyl|
|Lung Cancer Mutation Panel||Quest Diagnostics|
|Lynch/Colorectal High Risk Panel||GeneDx|
|Lynch Syndrome Panel||Invitae|
|Melanoma Next Cancer||Ambry GeneticsTM|
|MSK-IMPACT (Memorial Sloan Kettering)|
|Myeloid Molecular Profile||Genoptix®|
|Myeloid Molecular Profile||Genoptix®|
|myRiskTM Hereditary Cancer Panel||Myriad|
|Next Generation Sequencing Panel for ASXL1, RECQL4, RNU4ATAC, SOX2||Sistemas Genomicos|
|nucSEEKTM||Courtagen Diagnostic Laboratory|
|Pancreatic Cancer Panel||GeneDx|
|Pancreatic Cancer Panel||Invitae|
|Pancreatic Cancer Panel||Myriad®|
|PGL First/ PGL Next||Ambry GeneticsTM|
|PreparentTM Carrier Screening Ashkenazi Jewish Panel||Progenity®|
|PreparentTM Carrier Screening Global Panel||Progenity®|
|PreparentTM Carrier Screening Global+ Panel||Progenity®|
|PreparentTM Carrier Screening Standard Panel||Progenity®|
|PreparentTM Carrier Screening Trio Panel||Progenity®|
|Prostate Cancer Panel||Invitae|
|Renal/Urinary Trtact Cancer Panel||Invitae|
|ResponseDx Lung®||Response Genetics, Inc.|
|Thyroid Cancer Panel||Invitae|
|VistaSeq Hereditary Cancer Panel||LabCorp|
Testing for a large number of genes that have no certain link to risk status or disease development lacks clinical value. Often, abnormal findings in large gene panels are described as variants of uncertain significance. This means that although mutations/variants may be found in these genes, there are no actionable results. Change in clinical treatment or surveillance is not impacted by results.
To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes and / or diagnosis codes.
Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc. They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.
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