Proposed LCD - Genetic Testing for Oncology (DL39367)

CMS National Coverage PolicyThis LCD supplements but does not replace, modify or supersede existing Medicare applicable National Coverage Determinations (NCDs) or payment policy rules and regulations for genetic testing for oncology. Federal statute and subsequent Medicare regulations regarding provision and payment for medical services are lengthy. They are not repeated in this LCD. Neither Medicare payment policy rules nor this LCD replace, modify or supersede applicable state statutes regarding medical practice or other health practice professions acts, definitions and/or scopes of practice. All providers who report services for Medicare payment must fully understand and follow all existing laws, regulations and rules for Medicare payment for genetic testing for oncology and must properly submit only valid claims for them. Please review and understand them and apply the medical necessity provisions in the policy within the context of the manual rules. Relevant CMS manual instructions and policies may be found in the following Internet-Only Manuals (IOMs) published on the CMS Web site:IOM Citations:CMS IOM Publication 100-02,Medicare Benefit Policy Manual,Chapter 15, Section 50.4.5 Off Label Use of Anti-Cancer Drugs and Biologicals, Section 80.1 Clinical Laboratory Services and Section 280 Preventive and Screening ServicesCMS IOM Publication 100-03,Medicare National Coverage Determinations (NCD) Manual,Chapter 1, Part 2, Section 90.2 Next-Generation Sequencing for Patients with Advanced CancerChapter 1, Part 4, Section 210.3 Colorectal Cancer Screening TestsCMS IOM Publication 100-08,Medicare Program Integrity Manual,Chapter 13, Section 13.5.4 Reasonable and Necessary Provisions in an LCDSocial Security Act (Title XVIII) Standard References:Title XVIII of the Social Security Act, Section 1862(a)(1)(A) states that no Medicare payment may be made for items or services which are not reasonable and necessary for the diagnosis or treatment of illness or injury.Code of Federal Regulations (CFR) References:CFR, Title 42, Volume 2, Chapter IV, Part 410.32(d)(3) Diagnostic x-ray tests, diagnostic laboratory tests, and other diagnostic tests: ConditionsCoverage Indications, Limitations, and/or Medical NecessityCompliance with the provisions in this LCD may be monitored and addressed through post payment data analysis and subsequent medical review audits.History/Background and/or General InformationWith advancement in science and technology comes the ability to incorporate genetic testing for oncology biomarkers into clinical care, with the goal of improved patient outcomes. The scope of this LCD is DNA and RNA genetic testing in the practice of oncology in the Medicare population.As defined by the Food and Drug Administration (FDA) and National Institutes of Health (NIH) Biomarker Working Group, a biomarker is A defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, orbiological responses to an exposure or intervention, including therapeutic interventions, and may include molecular, histologic, radiographic, or physiologic characteristics.1 (p.45)Cancer is a disease caused by changes or alterations to a persons genome. Some genetic changes or alterations can be inherited (also known as germline mutations). About 5-10% of all cancer diagnoses result from germline mutations, and over 50 hereditary cancer syndromes are known. Other cancer-causing (oncogenic) genetic changes or alterations result from acquired genetic damage (also known as somatic mutations). Somatic mutations can arise in numerous scenarios, including exposure to chemicals that alter DNA (carcinogens) or ultraviolet (UV) radiation from the sun.2Biomarker testing is a part of personalized laboratory medicine (also known as precision medicine). Precision medicine is a tailored approach to medical care and treatment. Because each patient has a unique combination of genetic changes, and therefore, a unique pattern of biomarkers, precision medicine for oncology involves the use of biomarker testing to pinpoint the disease management needs of individual patients (and avoid the use of treatments which are unlikely to be successful).3Much of this testing involves direct evaluation of the genetics of the malignancy through various testing methodologies. These methodologies can include high level genetic evaluations such as karyotyping (analysis of chromosomes) to more detailed evaluations such as identifying specific pathogenic point variations (analysis of specific nucleotide changes).Additionally, testing may be used to check for a single biomarker or multiple biomarkers at the same time via a multigene test or panel.3As a result, the growing compendium of products described as biomarkers requires careful evaluation to determine what testing configurations are medically reasonable and necessary under Medicare.Biomarkers for oncology can be generally classified into four functional types4:Diagnosticbiomarkers detect or confirm the presence of a disease or conditionPrognosticbiomarkers provide information about the likely course of a disease process and potential patient outcomes if left untreatedPredictivebiomarkers forecast a patients response and/or benefit to a specific treatmentTherapeuticbiomarkers identify potential targets for a medical intervention (e.g., targeted drug therapy)In certain circumstances, genetic testing for oncology biomarkers in patients with the corresponding appropriate medical condition could have the potential to assist patient management in the Medicare population. However, given the complexity and rapidly expanding knowledge in this topic area, there is also a potential for testing that does not help the patient or leads to confusion. In order for services to be considered medically reasonable and necessary, they must impact the management of the patient. Specialized clinical expertise in oncology in addition to advanced knowledge in both genetic variation and effect on gene function is required to facilitate optimal outcomes for patients.DefinitionsActionable usedescribes a scenario when the genotype information identified via genetic testing may lead to selection of or avoidance of a specific intervention.Analytical validationis a process intended to determine if a test, tool, or instrument has acceptable technical performance (sensitivity, specificity, accuracy, precision, etc.). Analytical validation is an assessment of the tests technical performance (that it measures what it was intended to measure), not its usefulness or clinical significance.1Clinical validityis defined as the ability of a test to classify a patients specific circumstance into a diagnostic, prognostic, or predictive functional category. It should be noted that clinical validity is not a fixed value.5Clinical utilitycan be defined as the ability of a test to provide information related to the patients care and management, and thus, its ability to inform treatment decisions.5Covered IndicationsThree evidence-based databases and/or knowledge bases have been identified as valid and reliable sources. Note that a specific genetic test may be listed in one database or knowledge base, but not others; therefore, providers may choose to utilize guidelines from any of the three databases/knowledge bases. However,for services to be considered medically reasonable and necessary, #1 below is required regardless of which guidelines are utilized.Genetic testing for oncology will be considered medically reasonable and necessary if:The provider has either established a diagnosis of cancer or found significant evidence to create suspicion for cancer in their patient via a clinical evaluation and abnormal results (cancer or suspicious for cancer) from histologic and/or cytologic examination. If then, as a next step in the clinical management of the patient, genetic testing would directly impact the management of the patients condition, the testing would be indicated.AND ONE OF THE FOLLOWING:The evidence for the gene-disease association is evaluated by the evidence-based, transparent, peer-reviewed process of the National Institutes of Health (NIH) sponsored Clinical Genome Resource (ClinGen)6and is determined to demonstrate actionability in clinical decision making,meeting the criteria for all 5 categories below.At leastoneof the items listed under each of the categories (severity, likelihood of disease, effectiveness, nature of the intervention, and validity) must be satisfied:Disease severity equal to:Sudden death (Level 3), orPossible death or major morbidity (Level 2), orModest morbidity (Level 1)Likelihood of disease equal to:Substantial evidence of a >40% chance (Level 3A), orModerate evidence of a >40% chance (Level 3B)Effectiveness equal to:Substantial evidence of a highly effective intervention (Level 3A), orModerate evidence of a highly effective intervention (Level 3B), orSubstantial evidence of a moderately effective intervention (Level 2A), orModerate evidence of a moderately effective intervention (Level 2B)Nature of the intervention is equal to:Low risk/medically acceptable/low intensity (Level 3), orModerately acceptable/risk/intensive (Level 2)Validity of the gene-disease relationship equal to:Definitive, orStrong, orModerateORThe evidence for the intervention is evaluated by the National Comprehensive Cancer Network (NCCN)7and is determined to demonstrate actionability in clinical decision making, meeting the following metric:Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate (Category 1), orBased upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate (Category 2A)ORThe evidence for the intervention is evaluated by the Memorial Sloan Kettering Cancer Center-sponsored Oncology Knowledge Base (OncoKB)8and is determined to demonstrate actionability in clinical decision making, meeting one of the following metrics:For therapeutic use cases:The intervention is an FDA-recognized biomarker predictive of response to an FDA-approved drug in this indication (Level 1)ORThe intervention is a standard care biomarker recommended by the NCCN or other professional guidelines predictive of response to an FDA-approved drug in this indication (Level 2)ORThe intervention is a standard care biomarker predictive of resistance to an FDA-approved drug in this indication (Level R1)For diagnostic use cases:The intervention is an FDA and/or professional guideline-recognized biomarker required for diagnosis in this indication (Level Dx1)ORThe intervention is an FDA and/or professional guideline-recognized biomarker that supports diagnosis in this indication (Level Dx2)For prognostic use cases:The intervention is an FDA and/or professional guideline-recognized biomarker prognostic in this indication based on a well-powered study (or studies) (Level Px1)ORThe intervention is an FDA and/or professional guideline-recognized biomarker prognostic in this indication based on a single study or multiple small studies (Level Px2)LimitationsThe following are considered not medically reasonable and necessary:A genetic test where either analytical validity, clinical validity, or clinical utility has not been established.Interventions with levels of evidence not identified by either ClinGen, NCCN, or OncoKB as demonstrating actionability in clinical decision making as noted in Covered Indications.Genetic testing in patients who do not have either an established diagnosis of cancer or substantiated suspicion of cancer as determined by a clinical evaluation and abnormal results (cancer or suspicious for cancer) from histologic and/or cytologic examination.Genetic testing of asymptomatic patients for the purposes of screening the patient or their relatives.Repetitions of the same genetic test on the same genetic material.Genetic tests for hereditary cancer syndromes, which are considered germline testing, may only be performed once per beneficiarys lifecycle.Provider QualificationsThe following provider qualification requirements must be met for the service to be considered medically reasonable and necessary.The ordering provider of a genetic test for a patient with an established diagnosis of cancer or substantiated suspicion of cancer:Must be the treating clinician who is responsible for the management of the patients cancer; and,Understands how the test result will impact the patients condition; and,Has presented this information to the patient eliciting patient understanding.Notice:Services performed for any given diagnosis must meet all of the indications and limitations stated in this LCD, the general requirements for medical necessity as stated in CMS payment policy manuals, any and all existing CMS national coverage determinations, and all Medicare payment rules.General InformationAssociated InformationPlease refer to the related Draft Local Coverage Article: Billing and Coding: Genetic Testing for Oncology (DA59123) for documentation requirements, utilization parameters and all coding information as applicable.Sources of InformationContractor Medical DirectorsPrivate Insurer PoliciesOther Contractor PoliciesBibliographyThis bibliography presents those sources that were obtained during the development of this policy. The Contractor is not responsible for the continuing viability of Website addresses listed below.FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource [Internet]. Silver Spring (MD): Food and Drug Administration (US); 2016-. Co-published by National Institutes of Health (US), Bethesda (MD).The Genetics of Cancer. National Cancer Institute website. https://www.cancer.gov/about-cancer/causes-prevention/genetics. Published October 12, 2017. Accessed January 5, 2022 to April 7, 2022.Biomarker Testing for Cancer Treatment. National Cancer Institute website. https://www.cancer.gov/about-cancer/treatment/types/biomarker-testing-cancer-treatment. Published October 5, 2017. Accessed January 5, 2022 to April 7, 2022.Califf RM. Biomarker definitions and their applications.Exp Biol Med (Maywood).2018;243(3):213-221. doi:10.1177/1535370217750088Joseph L, Cankovic M, Caughron S, et al. The Spectrum of Clinical Utilities in Molecular Pathology Testing Procedures for Inherited Conditions and Cancer: A Report of the Association for Molecular Pathology.J Mol Diagn. 2016;18(5):605-619. doi:10.1016/j.jmoldx.2016.05.007