Health First Genetic Cancer Testing Form

Medical Policy Subject: Genetic Testing for Screening, Policy Number: MP-0223 Diagnosis, Monitoring and Treatment of Cancer Individual & Family Plans (IFP) Effective Date: January 2024 Revised: N/A Document Page Length: 17 Applies To: Medicare will follow: NCD 90.2 Next Generation Sequencing NCD 210.1 v2 Prostate Cancer Screening NCD 190.3 Cytogenetic Studies LCD 39367 Genetic testing for Oncology LCD 36499 BRCA1 and BRCA2 Genetic Testing LCD 34912 Genetic Testing for Lynch Syndrome Medical Policy Statement: It is the policy of Health First Health Plans (HFHP) to cover non-experimental genetic cancer testing that is medically necessary. HFHP excludes coverage of technologies determined to be experimental, investigational, or unproven (EIU) for specific diagnoses based on plan documents. Definitions: Actionable Use - A test is considered to have an actionable use when the genotype information may lead to selection of or avoidance of a specific therapy or modification of dosage of a therapy. Biomarker: A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. They are also called molecular markers or signature molecules. Biomarkers are classified into 4 functional types: 1. Diagnostic biomarkers detect or confirm the presence of a disease or condition. 2. Prognostic biomarkers provide information about the likely course of a disease process and potential patient outcomes if left untreated. 3. Predictive biomarkers forecast a patient’s response and/or benefit to a specific treatment. 4. Therapeutic biomarkers identify potential targets for a medical intervention. (e.g., targeted drug therapy) Cancer Screening: An attempt to detect cancer early by routine examination of apparently healthy people. Cancer Staging: Staging describes the spread of cancer within the body. Each type of cancer has specific staging guidelines. In general, cancer staging ranges from 0 to 4. 0 – Abnormal cells are present but have not spread to nearby tissue 1 – Early Stage. Cancer has spread to tissue in a small area 2 – Localized. Tumor is small and localized lymph nodes may be involved 3 – Reginal Spread. Cancer has spread to a wider region 4 – Distant Spread. Cancer has spread to other parts of the body Cancer Surveillance: Closely watching a member's condition but not treating it unless there are changes in test results. Surveillance is also used to find early signs that a disease has come back. During surveillance, certain exams and tests are done on a regular schedule. Experimental, Investigational or Unproven Treatment: Any evaluation, treatment, therapy, or device which involves the application, administration, or use of procedures, techniques, or pharmaceuticals that have not been proven safe and effective for the treatment of the condition in question or where no consensus among practicing physicians that it is safe and effective for the condition in question; or it is not the standard treatment utilized by practicing physicians in treating other patients with the same or similar condition. Genetic Testing: Tests that analyze changes in genes, chromosomes, or proteins. There are several types of genetic tests: • Biochemical Tests: Do not directly analyze DNA but study the amount or activity level of proteins or enzymes that are produced from genes. • Chromosomal Testing: Analyze whole chromosomes or long lengths of DNA. • Gene Expression Testing: Look at which genes are turned on or off (expressed) in different types of cells. Too much activity (overexpression) or too little activity (underexpression) of certain genes suggest particular genetic disorders, such as many types of cancer. • Molecular Tests look for changes in one or more genes. Below are the types of Molecular Tests: o Targeted Single Variant: Single variant tests look for a specific variant in one gene. o Single Gene: Single gene tests look for any genetic changes in one gene. o Gene Panel: Panel tests look for variants in more than one gene. This type of test is used to pinpoint a diagnosis when a person has symptoms that may fit a wide array of conditions, or when the suspected condition can be caused by variants in many genes. o Whole Exome or Whole Genome Sequencing: These tests analyze the bulk of an individual’s DNA to find genetic variations. o Germline Genetic Testing: Germline testing is a type of DNA testing that looks for inherited mutations that are present in every cell of the body and have been present since birth. This is also called genetic testing. Germline genetic testing can be done via cheek swab, spit sample or a blood draw. Immediate – For the purpose of this policy, the term immediate means within 90 days. MCG (formerly Milliman Care Guidelines) - A subscription service purchased by HFHP that provides updated, unbiased clinical guidance that helps healthcare organizations deliver patient-centered care. HFHP uses the most current 27th edition. HFHP relies on MCG criteria to drive Prior Authorization decisions for Commercial Plans. National Comprehensive Cancer Network™ (NCCN Guidelines™): The NCCN definition for Evidence and Consensus (EC) Categories are as follows: • Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate; • Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate; • Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate; • Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate. Neurotrophic tyrosine receptor kinase (NTRK) gene fusions: An actionable biomarker for cancer therapy and can be found in over 25 different types of cancer, regardless of where they are located in the body. These are liquid (blood based) Somatic: A term synonymous with acquired, refers to genetic code alterations that develop after birth. Overview: Genetic testing is the use of medical tests to look for certain mutations (changes) in a person’s genes. Genetic testing is an area of rapid scientific development. Genetic testing can be used to look for gene changes that are linked to cancer. Several types of genetic testing related to cancer screening, diagnosis and monitoring are discussed in this Medical Policy. Genetic testing for screening, diagnosis and monitoring of cancer refers to molecular diagnostic tests whose purposes include identifying the possible presence of cancer in asymptomatic, average risk individuals; confirming the absence or presence of cancer; and monitoring the absence or presence of cancer after a prior diagnosis and treatment. Test results can help determine how advanced a cancer is and the chance of it coming back. Results can also help guide decisions on a treatment and how well the disease may, or is, responding to treatment. I. Clinical Criteria: 1. Prior Authorization is Required A. Prior authorization is required for each genetic testing specific CPT code. B. Testing will be considered only for the number of genes or tests necessary. C. Multiple stacked CPT codes billing from laboratories will not be approved. 2. General Coverage Guidance: Genetic testing for screening, diagnosing, or monitoring cancer may be considered medically necessary when ALL the following conditions are met: A. Actionable Use: The results of the testing will directly impact immediate clinical decision making. B. Treating Physician: Ordered only by the treating physician involved in the management of the member's cancer. C. Technical and clinical validity: The test must be accurate, sensitive and specific, based on sufficient, quality scientific evidence to support the claims of the test. D. Candidate for targeted therapy: The member is a candidate for a targeted therapy associated with a specific tumor biomarker(s) or disease site. E. Repeat testing not permitted: No other tumor biomarker, broad molecular profile panel or gene expression classifier test has been performed on this tumor sample for the same indication. F. Valid and Proven: The testing method is considered to be scientifically valid and proven to have clinical utility based on prospective evidence. G. Performed at a Certified Lab: The genetic cancer tests are performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory 3. Specific Test Criteria: Medical Necessity for cancer related genetic testing in this policy is limited to screening, diagnosing, or monitoring cancer. A. Screening: The goal of cancer screening is to identify the possible presence of cancer before symptoms appear. Screening tests cannot diagnose cancer, but typically determine if there is an increased chance cancer is present, and triages individuals for more invasive, diagnostic testing. Most cancer screening does not include genetic testing, but instead relies on physical exam, radiological exams, or non-genetic laboratory tests. Advances in human genetics, however, have identified several molecular diagnostic tests that may provide clues for early cancer detection. B. Diagnosis: When cancer is suspected because of an abnormal screening test or symptoms, blood tests for tumor markers or molecular testing on tissue samples can aid in confirming a diagnosis of cancer. These tests may contribute information to helping the clinician understand prognosis and treatment options. C. Treatment and Monitoring: During treatment, or after an apparently successful treatment, active monitoring is often recommended to identify if the cancer is responding to treatment or has returned or spread, before any symptoms appear. Monitoring may include increased surveillance or routine blood tests for tumor markers, and increasingly, molecular genetic tests. Note: The Clinical Criteria for Genetic Cancer Testing for treatment and monitoring is for late stage (stage 4) cancer diagnosis. Clinical Criteria Specific to Common Cancer Genetic Tests 1. Ovarian and Breast Cancer testing related hereditary risk factors A. Clinical criteria related to genetic hereditary risk factors for Ovarian and Breast Cancer can be found in the following resources: a. Health First Health Plan Medical Policy 0228 Prophylactic Surgery to Reduce Risk of Breast and Ovarian Cancer b. MCG criteria including: i. ACG: A-0499 (AC) Breast or Ovarian Cancer, Hereditary BRCA1 and BRCA2 Genes; ii. ACG: A-0767 (AC) Breast Cancer (Hereditary) Gene Panel iii. ACG: A-0872 (AC) Ovarian Cancer (Hereditary) Gene and Gene Panel Testing c. Medicare Local Coverage Determination (LCD) L36499 BRCA1 and BRCA2 Genetic Testing d. Medicare Local Coverage Determination (LCD) L34912 Genetic Testing for Lynch Syndrome 2. Breast Cancer Related Testing Criteria A. Gene expression classifier testing (GEC) is considered medically necessary when all the following criteria are met: a. Member is a candidate for chemotherapy b. Adjuvant chemotherapy is being considered and this testing is ordered to assess recurrence risk c. No other GEC has been performed on this tumor sample for the same indication Breast related commonly requested tests and criteria below: 3. Non-small cell lung cancer (proteomic) related testing: Criteria to determine second line treatment is considered medically necessary when ALL the following criteria are met: 4. Prostate Cancer related testing: A. Early Detection of Prostate Cancer The following prostate cancer screening and prognostic genetic tests are considered medically necessary for the early detection of prostate cancer when results will impact medical management and the associated criteria are met: B. Tumor Tissue-Based Molecular and Proteomic Assays for Prostate Cancer The following tumor based molecular assays for detection of prostate cancer are considered medically necessary when the associated criteria are met: 5. Myleoproliferative Neoplasms A. Polycythemia Vera (PV) Genetic Testing for JAK2 common variants (CPT code 81270, 81279), MPL common variants (CPT codes 81338, 81339) and CALR exon 9 common variants (CPT code 81219) is considered medically necessary for the diagnosis of Polycythemia Vera (PV) when BOTH the criteria are met: a. Genetic testing would impact medical management of the individual being tested b. One of the following: i. Hemoglobin >16.5 g/dL in men; >16.0 g/dL in women ii. Hematocrit >49% in men, >48% in women iii. Increased red cell mass (RCM) more than 25% above the mean normal predicted value B. Essential Thrombocythemia Genetic Testing for JAK2 common variants (CPT codes 81270, 81279), MPL common variants (CPT codes 81338, 81339) and CALR exon 9 common variants (CPT code 81219) is considered medically necessary for the diagnosis of Essential Thrombocythemia when BOTH the criteria are met: a. Results will impact medical management b. Either of the following: i. Platelet count >450 x 10^9/L ii. Bone marrow biopsy shows proliferation mainly of megakaryocyte lineage with increased numbers of enlarged, mature megakaryocyte with hyperlobulated nuclei. No significant increase or left shift in neutrophil granulopoiesis or erythropoiesis and very rarely minor (grade 1) increase in reticulin fibers C. Primary Myelofibrosis (PMF) a. Genetic Testing for JAK2 common variants (CPT codes 81270, 81279), MPL common variants (CPT code 81338, 81339) and CALR exon 9 common variants (CPT code 81219) is considered medically necessary for the diagnosis of Primary Myelofibrosis (PMF) when BOTH the criteria are met: i. Results will impact medical management ii. Primary Myelofibrosis is suspected but not confirmed, based on results of conventional testing b. ASXL1, EZH2, TET2, IDH1/IdH2, SRSF2, and SF3B1 (CPT code 81175 and 81176)) testing is considered medically necessary for the diagnosis of Primary Myelofibrosis when ALL the following criteria are met: i. ii. iii. iv. Primary Myelofibrosis confirmed or suspected Based on clinical findings above criteria are met Bone marrow findings of megakaryocytic proliferation and atypia, without reticulin fibrosis >grade1, accompanied by increased age adjusted bone marrow cellularity, granulocytic proliferation and often decreased erythropoiesis Testing will be completed on bone marrow sample v. JAK2, CALR, and MPL mutation analysis was previously completed and was negative D. Chronic Myelogenous Leukemia (CML) and Philadelphia Chromosome Positive (PH+) Acute Lymphoblastic Leukemia (ALL) a. BCR-ABL T31-I mutation testing (CPT codes 81401, 81170) is considered medically necessary in individuals with chronic myelogenous leukemia (CML) or Philadelphia Chromosome Positive (PH+) Acute Lymphoblastic Leukemia (ALL) when ANY of the following are met: Inadequate initial response to tyrosine kinase inhibitor therapy Loss of response to tyrosine kinase inhibitor therapy i. ii. iii. Progression to accelerated or blast phase CML while on tyrosine kinase inhibitor therapy 6. Somatic Pathogenic (or likely) Variant Genetic Testing A. Targeted molecular testing for NTRK fusions is considered medically necessary when the individual has a solid tumor know to respond to treatment with an FDA approved drug targeting NTRK gene fusions. B. Liquid biopsy by cell-free DNA laboratory testing methods is considered medically necessary when tissue testing is not available or contraindicated for EITHER of the following: i. Advanced or metastatic solid tumors ii. Biomarker confirmation is required by an FDA approved or cleared test as described within the section heading "Indications and Usage" of the US FDA approved prescribing label prior to initiating therapy. C. Other testing (e.g. non-high-throughput immunosquencing) for MRD using a validated technology when recommended by the NCCN Guidelines as a category 1, 2A or 2B recommendation. 7. Other Tumor Profile Testing - Is considered experimental, investigational and unproven. NOTE Regarding Panel Testing: If a panel test being presented contains a "U" code the Prior Authorization staff shall review the MCG guidelines. II. Limitations of coverage 1. Genetic testing is not considered medically necessary if healthcare providers cannot use the test results to directly impact medical care for the individual. 2. Genetic testing is not considered medically necessary if testing is considered Investigational/Experimental. 3. Genetic testing is not considered medically necessary for variants of unknown significance. 4. Tests used to determine hereditary cancer risk are not considered medically necessary and are covered separately in the HFHP Genetic Carrier Screening Policy 5. 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, cytologic, and/or flow cytometric examination. 6. Genetic testing of asymptomatic patients for the purposes of screening the patient or their relatives. 7. Repetitions of the same genetic test on the same genetic material CODES: These codes may be covered if medical necessity is established according to the criteria above. Note: This list of CPT codes is NOT all inclusive 81162 81206 81207 81210 81219 81245 81246 81256 81261 81263 BRCA1 (BRCA1, DNA repair associated), BRCA2 (BRCA2, DNA repair associated) (e.g., hereditary breast and ovarian cancer) gene analysis; full sequence analysis and full duplication/deletion analysis (i.e., detection of large gene rearrangements) BCR/ABL1 (t(9;22)) (e.g., chronic myelogenous leukemia) translocation analysis; major breakpoint, qualitative or quantitative BCR/ABL1 (t(9;22)) (e.g., chronic myelogenous leukemia) translocation analysis; minor breakpoint, qualitative or quantitative BRAF (B-Raf proto-oncogene, serine/threonine kinase) (e.g., colon cancer, melanoma), gene analysis, V600 variant(s) CALR (calreticulin) (eg, myeloproliferative disorders), gene analysis, common variants in exon 9 FLT3 (fms-related tyrosine kinase 3) (eg, acute myeloid leukemia), gene analysis; internal tandem duplication (ITD) variants (i.e., exons 14, 15) FLT3 (fms-related tyrosine kinase 3) (eg, acute myeloid leukemia), gene analysis; tyrosine kinase domain (TKD) variants (eg, D835, I836) HFE (hemochromatosis) (eg, hereditary hemochromatosis) gene analysis, common variants (eg, C282Y, H63D) IGH@ (Immunoglobulin heavy chain locus) (eg, leukemias and lymphomas, B- cell), gene rearrangement analysis to detect abnormal clonal population(s); amplified methodology (eg, polymerase chain reaction) IGH@ (Immunoglobulin heavy chain locus) (eg, leukemia and lymphoma, B-cell), variable region somatic mutation analysis 81264 81267 81268 81270 81279 81291 81292 81294 81295 81297 81298 81300 81305 81309 81313 81317 81319 IGK@ (Immunoglobulin kappa light chain locus) (eg, leukemia and lymphoma, B- cell), gene rearrangement analysis, evaluation to detect abnormal clonal population(s) Chimerism (engraftment) analysis, post transplantation specimen (eg, hematopoietic stem cell), includes comparison to previously performed baseline analyses; without cell selection Chimerism (engraftment) analysis, post transplantation specimen (eg, hematopoietic stem cell), includes comparison to previously performed baseline analyses; with cell selection (eg, CD3, CD33), each cell type JAK2 (Janus kinase 2) (eg, myeloproliferative disorder) gene analysis, p.Val617Phe (V617F) variant JAK2 (Janus kinase 2) (eg, myeloproliferative disorder) targeted sequence analysis (eg, exons 12 and 13) MTHFR (5,10-methylenetetrahydrofolate reductase) (eg, hereditary hypercoagulability) gene analysis, common variants (eg, 677T, 1298C) MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) (eg, hereditary non- polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) (eg, hereditary non- polyposis colorectal cancer, Lynch syndrome) gene analysis; duplication/deletion variants MSH2 (mutS homolog 2, colon cancer, nonpolyposis type 1) (eg, hereditary non- polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis MSH2 (mutS homolog 2, colon cancer, nonpolyposis type 1) (eg, hereditary non- polyposis colorectal cancer, Lynch syndrome) gene analysis; duplication/deletion variants MSH6 (mutS homolog 6 [E. coli]) (eg, hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis MSH6 (mutS homolog 6 [E. coli]) (eg, hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; duplication/deletion variants MYD88 (myeloid differentiation primary response 88) (eg, Waldenstrom's macroglobulinemia, lymphoplasmacytic leukemia) gene analysis, p.Leu265Pro (L265P) variant PIK3CA (phosphatidylinositol-4, 5-biphosphate 3-kinase, catalytic subunit alpha) (eg, colorectal and breast cancer) gene analysis, targeted sequence (eg, exons 7, 9, 20) PCA3/KLK3 (prostate cancer antigen 3 [non-protein coding]/ kalikren-related peptidase 3 [prostate specific antigen]) ration (eg, prostate cancer) PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (eg, hereditary non- polyposis colorectal cancer, Lynch syndrome) gene analysis; full sequence analysis PMS2 (postmeiotic segregation increased 2 [S. cerevisiae]) (eg, hereditary non- polyposis colorectal cancer, Lynch syndrome) gene analysis; duplication/deletion variant 81332 81338 81339 81340 81342 81370 81374 81376 81378 81382 81401 81403 81405 81455 81456 81479 81518 SERPINA-1 (serpin peptidase inhibitor, clade A, alpha-1 antiproteinase, antitrypsin, member 1) (eg, alpha-1 antitrypsin deficiency), gene analysis, common variants (eg, *S and *Z) MPL (MPL proto-oncogene, thrombopoietin receptor) (eg, myeloproliferative disorder) gene analysis; common variants (eg, W515A, W515K, W515L, W515R) MPL (MPL proto-oncogene, thrombopoietin receptor) (eg, myeloproliferative disorder) gene analysis; sequence analysis, exon 10 TRB@ (T cell antigen receptor, beta) (eg, leukemia and lymphoma), gene rearrangement analysis to detect abnormal clonal population(s); using amplification methodology (eg, polymerase chain reaction) TRG@ (T cell antigen receptor, gamma) (eg, leukemia and lymphoma), gene rearrangement analysis, evaluation to detect abnormal clonal population(s) HLA Class I and II typing, low resolution (eg, antigen equivalents); HLA-A, -B, -C, - DRB1/3/4/5, and -DQB1 HLA Class I typing, low resolution (eg, antigen equivalents); one antigen equivalent (eg, B*27), each HLA Class II typing, low resolution (eg, antigen equivalents); one locus (eg, HLA- DRB1, -DRB3/4/5, -DQB1, -DQA1, -DPB1, or -DPA1), each HLA Class I and II typing, high resolution (ie, alleles or allele groups), HLA-A, -B, - C, and -DRB1 HLA Class II typing, high resolution (ie, alleles or allele groups); one locus (eg, HLA-DRB1, -DRB3/4/5, -DQB1, -DQA1, -DPB1, or -DPA1), each MOLECULAR PATHOLOGY PROCEDURE LEVEL 2 MOLECULAR PATHOLOGY PROCEDURE LEVEL 4 MOLECULAR PATHOLOGY PROCEDURE LEVEL 6 Targeted genomic sequence analysis panel, solid organ or hematolymphoid neoplasm or disorder, 51 or greater genes (eg, ALK, BRAF, CDKN2A, CEBPA, DNMT3A, EGFR, ERBB2, EZH2, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, MET, MLL, NOTCH1, NPM1, NRAS, PDGFRA, PDGFRB, PGR, PIK3CA, PTEN, RET), interrogation for sequence variants and copy number variants or rearrangements, or isoform expression or mRNA expression levels, if performed; DNA analysis or combined DNA and RNA analysis Targeted genomic sequence analysis panel, solid organ or hematolymphoid neoplasm or disorder, 51 or greater genes (eg, ALK, BRAF, CDKN2A, CEBPA, DNMT3A, EGFR, ERBB2, EZH2, FLT3, IDH1, IDH2, JAK2, KIT, KRAS, MET, MLL, NOTCH1, NPM1, NRAS, PDGFRA, PDGFRB, PGR, PIK3CA, PTEN, RET), interrogation for sequence variants and copy number variants or rearrangements, or isoform expression or MRNA expression levels, if performed, RNA analysis Unlisted molecular pathology procedure Oncology (breast), mRNA, gene expression profiling by real-time RT-PCR of 11 genes (7 content and 4 housekeeping), utilizing formalin-fixed paraffin-embedded tissue, algorithms reported as percentage risk for metastatic recurrence and likelihood of benefit from extended endocrine therapy 81519 81520 81521 81528 81539 81541 81542 81551 Oncology (breast), mRNA, gene expression profiling by real-time RT-PCR of 21 genes, utilizing formalin-fixed paraffin embedded tissue, algorithm reported as recurrence score Oncology (breast), mRNA gene expression profiling by hybrid capture of 58 genes (50 content and 8 housekeeping), utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as a recurrence risk score Oncology (breast), mRNA, microarray gene expression profiling of 70 content genes and 465 housekeeping genes, utilizing fresh frozen or formalin-fixed paraffin-embedded tissue, algorithm reported as index related to risk of distant metastasis Oncology (colorectal) screening, quantitative real-time target and signal amplification of 10 DNA markers (KRAS mutations, promoter methylation of NDRG4 and BMP3) and fecal hemoglobin, utilizing stool, algorithm reported as a positive or negative result (Cologuard) Oncology (high-grade prostate cancer), biochemical assay of four proteins (Total PSA, Free PSA, Intact PSA, and human kallikrein-2 [hK2]), utilizing plasma or serum, prognostic algorithm reported as a probability score Oncology (prostate), mRNA gene expression profiling by real-time RT-PCR of 46 genes (31 content and 15 housekeeping), utilizing formalin-fixed paraffin- embedded tissue, algorithm reported as a disease-specific mortality risk score. Oncology (prostate), mRNA, microarray gene expression profiling of 22 content genes, utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as metastasis risk score. Oncology (prostate), promoter methylation profiling by real-time PCR of 3 genes (GSTP1, APC, RASSF1), utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as a likelihood of prostate cancer detection on repeat biopsy G0452 Molecular pathology procedure; physician interpretation and report