Humana Gene Expression Profiling for Cancer Indications - Medicare Advantage Form

Please refer to CMS website for the most current applicable CMS Online Manual System (IOMs)/National Coverage Determination (NCD)/ Local Coverage Determination (LCD)/Local Coverage Article (LCA)/ Transmittals. Type Title ID Number Jurisdiction Medicare Administrative Contractors (MACs) Applicable States/Territories Gene Expression Profiling for Cancer Indications Page: 2 of 58 J5, J8 - Wisconsin Physicians Service Insurance Corporation IA, IN, KS, MI, MO, NE NCD Next Generation Sequencing (NGS) MolDX: Breast Cancer Assay: Prosigna® 90.2 L36811 Billing and Coding: MolDX: Breast Cancer Assay: Prosigna® A57560 MolDX: Breast Cancer Index® (BCI) Gene Expression Test Billing and Coding: MolDX: Breast Cancer Index® (BCI) Gene Expression Test MolDX: EndoPredict® Breast Cancer Gene Expression Test LCD LCA Billing and Coding: MolDX: EndoPredict® Breast Cancer Gene Expression Test Billing and Coding: MolDX: MammaPrint® Billing and Coding: MolDX: Oncotype DX® Breast Cancer Assay MolDX: Oncotype DX® Breast Cancer for DCIS (Genomic Health™) Billing and Coding: MolDX: Oncotype DX® Breast Cancer for DCIS (Genomic Health™) L37913 A56335 L37663 A57567 A55175 A55230 L37199 A57583 MolDX: DecisionDx-UM (Uveal Melanoma) L37210 MolDX: Melanoma Risk Stratification Molecular Testing L38018 Gene Expression Profiling for Cancer Indications Page: 3 of 58 Billing and Coding: MolDX: Melanoma Risk Stratification Molecular Testing A56636 Response to Comments: MolDX: Melanoma Risk Stratification Molecular Testing A59117 MolDX: Pigmented Lesion Assay Billing and Coding: MolDX: Pigmented Lesion Assay L38178 A57983 Response to Comments: MolDX: Pigmented Lesion Assay A57979 MolDX: Molecular Biomarkers to Risk-Stratify Patients at Increased Risk for Prostate Cancer L39042 MolDX: Prostate Cancer Genomic Classifier Assay for Men with Localized Disease MolDX: Percepta® Bronchial Genomic Classifier Billing and Coding: MolDX: Percepta© Bronchial Genomic Classifier L38433 L37195 A57584 MolDX: Predictive Classifiers for Early Stage Non-Small Cell Lung Cancer L38443 MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer L38684 Billing and Coding: MolDX: Oncotype DX® Colon Cancer Assay Update A55231 Gene Expression Profiling for Cancer Indications Page: 4 of 58 J6, JK - National Government Services, Inc. CT, IL, ME, MA, MN, NH, NY, RI, VT, WI J15 - CGS Administrators, LLC KY, OH LCD LCD LCA MolDX: Molecular Diagnostic Tests (MDT) Billing and Coding: MolDX: Molecular Diagnostic Tests (MDT) Biomarker Testing for Prostate Cancer Diagnosis L36807 A57772 L37733 Molecular Pathology Procedures L35000 Billing and Coding: Molecular Pathology Procedures MolDX: Breast Cancer Assay: Prosigna® A56199 L36425 Billing and Coding: MolDX: Breast Cancer Assay: Prosigna® A56989 MolDX: Breast Cancer Index® (BCI) Gene Expression Test L37832 Billing and Coding: MolDX: Breast Cancer Index™ (BCI) Gene Expression Test A56884 MolDX: EndoPredict Breast Cancer Gene Expression Test L37356 Billing and Coding: MolDX: EndoPredict Breast Cancer Gene Expression Test A56997 MolDX: Oncotype DX® Breast Cancer for DCIS (Genomic Health™) Billing and Coding: MolDX: MammaPrint Billing and Coding: MolDX: Oncotype DX® Breast Cancer Assay L36951 A54194 A54195 Gene Expression Profiling for Cancer Indications Page: 5 of 58 MolDX: DecisionDx-UM (Uveal Melanoma) L37130 MolDX: Melanoma Risk Stratification Molecular Testing L38016 Billing and Coding: MolDX: Melanoma Risk Stratification Molecular Testing A57165 Response to Comments: MolDX: Melanoma Risk Stratification Molecular Testing A59084 MolDX: Pigmented Lesion Assay Billing and Coding: MolDX: Pigmented Lesion Assay L38111 A57915 Response to Comments: MolDX: Pigmented Lesion Assay A57916 MolDX: ConfirmMDx Epigenetic Molecular Assay L36006 MolDX: Molecular Biomarkers to Risk-Stratify Patients at Increased Risk for Prostate Cancer L38997 MolDX: Prostate Cancer Genomic Classifier Assay for Men with Localized Disease MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer MolDX: Percepta® Bronchial Genomic Classifier Billing and Coding: MolDX: Percepta® Bronchial Genomic Classifier L38303 L38586 L36908 A56972 Gene Expression Profiling for Cancer Indications Page: 6 of 58 JE - Noridian Healthcare Solutions, LLC CA, HI, NV, American Samoa, Guam, Northern Mariana Islands MolDX: Predictive Classifiers for Early Stage Non-small Cell Lung Cancer L38284 Billing and Coding: MolDX: Oncotype DX® Colon Cancer Assay Update MolDX: Molecular Diagnostic Tests (MDT) Billing and Coding: MolDX: Molecular Diagnostic Tests (MDT) Gene Expression Test MolDX: Breast Cancer Assay: Prosigna® A54196 L36021 A56973 L37822 Billing and Coding: MolDX: Breast Cancer Assay: Prosigna® A57773 MolDX: Breast Cancer Index® (BCI) Gene Expression Test L36380 Billing and Coding: MolDX: Breast Cancer Index® (BCI) Gene Expression Test A57363 MolDX: EndoPredict® Breast Cancer Gene Expression Test L37295 Billing and Coding: MolDX: EndoPredict® Breast Cancer MolDX: Oncotype DX® Breast Cancer for DCIS (Genomic Health™) Billing and Coding: MolDX: MammaPrint Billing and Coding: MolDX: BluePrint® Test A57607 L36941 A54445 A55115 A54480 LCD LCA Gene Expression Profiling for Cancer Indications Page: 7 of 58 Billing and Coding: MolDX: Oncotype DX® Breast Cancer Assay MolDX: DecisionDx-UM (Uveal Melanoma) MolDX: Melanoma Risk Stratification Molecular Testing Billing and Coding: MolDX: Melanoma Risk Stratification Molecular Testing Response to Comments: MolDX: Melanoma Risk Stratification Molecular Testing MolDX: Pigmented Lesion Assay Billing and Coding: MolDX: Pigmented Lesion Assay Response to Comments: MolDX Pigmented Lesion Assay MolDX: Molecular Biomarkers to Risk-Stratify Patients at Increased Risk for Prostate Cancer MolDX: Prostate Cancer Genomic Classifier Assay for Men with Localized Disease MolDX: Percepta© Bronchial Genomic Classifier Billing and Coding: MolDX: Percepta© Bronchial Genomic Classifier MolDX: Predictive Classifiers for Early Stage Non-Small Cell Lung Cancer L37070 L37750 A57268 A59134 L38151 A58052 A58072 L39005 L38339 L36886 A57502 L38327 L38647 Gene Expression Profiling for Cancer Indications Page: 8 of 58 JF - Noridian Healthcare Solutions, LLC AK, AZ, ID, MT, ND, OR, SD, UT, WA, WY MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer Billing and Coding: MolDX: Oncotype DX® Colon Cancer MolDX: Molecular Diagnostic Tests (MDT) Billing and Coding: MolDX: Molecular Diagnostic Tests (MDT) MolDX: Breast Cancer Assay: Prosigna® Billing and Coding: MolDX: Breast Cancer Assay: Prosigna® A54484 L35160 A57526 L36386 A57364 MolDX: Breast Cancer Index® (BCI) Gene Expression Test L37824 Billing and Coding: MolDX: Breast Cancer Index™ (BCI) Gene Expression Test A57774 MolDX: EndoPredict® Breast Cancer Gene Expression Test LCD LCA Billing and Coding: MolDX: EndoPredict® Breast Cancer Gene Expression Test Billing and Coding: MolDX: MammaPrint Billing and Coding: MolDX: Oncotype DX® Breast Cancer Assay MolDX: Oncotype DX® Breast Cancer for DCIS (Genomic Health™) L37311 A57608 A54447 A54482 L36947 Gene Expression Profiling for Cancer Indications Page: 9 of 58 Billing and Coding: MolDX: Oncotype DX® Breast Cancer for DCIS (Genomic Health™) MolDX: DecisionDx-UM (Uveal Melanoma) MolDX: Melanoma Risk Stratification Molecular Testing Billing and Coding: MolDX: Melanoma Risk Stratification Molecular Testing Response to Comments: MolDX: Melanoma Risk Stratification Molecular Testing MolDX: Molecular Assays for the Diagnosis of Cutaneous Melanoma MolDX: Pigmented Lesion Assay Billing and Coding: MolDX: Pigmented Lesion Assay A57620 L37072 L37748 A57290 A59135 L39375 L38153 A58053 Response to Comments: MolDX Pigmented Lesion Assay A58073 MolDX: Molecular Biomarkers to Risk-Stratify Patients at Increased Risk for Prostate Cancer L39007 Billing and Coding: MolDX: Oncotype DX® Genomic Prostate Score A56372 MolDX: Prostate Cancer Genomic Classifier Assay for Men with Localized Disease L38341 Gene Expression Profiling for Cancer Indications Page: 10 of 58 JH, JL - Novitas Solutions, Inc. AR, CO, DE, LA, MD, MS, NJ, NM, OK, PA, TX, D.C. JJ, JM - Palmetto GBA AL, GA, NC, SC, TN, VA, WV MolDX: Percepta© Bronchial Genomic Classifier L36891 MolDX: Predictive classifiers for early stage non-small cell lung cancer L38329 MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer L38649 Billing and Coding: MolDX: Oncotype DX® Colon Cancer MolDX: Molecular Diagnostic Tests (MDT) Billing and Coding: MolDX: Molecular Diagnostic Tests (MDT) Biomarkers for Oncology Billing and Coding: Biomarkers for Oncology MolDX: Breast Cancer Assay: Prosigna® Billing and Coding: MolDX: Breast Cancer Assay: Prosigna® MolDX: Breast Cancer Index® (BCI) Gene Expression Test Billing and Coding: MolDX: Breast Cancer Index™ (BCI) Gene Expression Test MolDX: EndoPredict® Breast Cancer Gene Expression Test Billing and Coding: MolDX: EndoPredict® Breast Cancer Gene Expression Test A54486 L36256 A57527 L35396 A52986 L36125 A56949 L37794 A56875 L37264 A56963 A53104 LCD LCA LCD LCA Gene Expression Profiling for Cancer Indications Page: 11 of 58 Billing and Coding: MolDX: MammaPrint Billing and Coding: MolDX: Oncotype DX® Breast Cancer Assay MolDX: Oncotype DX® Breast Cancer for DCIS (Genomic Health™) Billing and Coding: MolDX: Oncotype DX® Breast Cancer for DCIS (Genomic Health™) A53105 L36912 A56870 MolDX: DecisionDx-UM (Uveal Melanoma) L37033 MolDX: Melanoma Risk Stratification Molecular Testing L37725 Billing and Coding: MolDX: Melanoma Risk Stratification Molecular Testing Response to Comments: MolDX: Melanoma Risk Stratification Molecular Testing MolDX: Pigmented Lesion Assay Billing and Coding: MolDX: Pigmented Lesion Assay A56961 A59070 L38051 A57868 Response to Comments: MolDX Pigmented Lesion Assay A57869 MolDX: Molecular Biomarkers to Risk-Stratify Patients at Increased Risk for Prostate Cancer L38985 A56372 Gene Expression Profiling for Cancer Indications Page: 12 of 58 Billing and Coding: MolDX: Oncotype DX® Genomic Prostate Score L38292 MolDX: Prostate Cancer Genomic Classifier Assay for Men with Localized Disease MolDX: Percepta© Bronchial Genomic Classifier MolDX: Predictive classifiers for early stage non-small cell lung cancer L36854 L38238 L38576 MolDX: Prognostic and Predictive Molecular Classifiers for Bladder Cancer A53106 Billing and Coding: MolDX: Oncotype DX® Colon Cancer L35025 MolDX: Molecular Diagnostic Tests (MDT) A56853 Billing and Coding: MolDX: Molecular Diagnostic Tests (MDT) LCD Molecular Pathology Procedures L34519 JN - First Coast Service Options, Inc. FL, PR, U.S. VI Description Gene expression profiling (GEP) is a laboratory test that measures the activity, or expression, of ribonucleic acid (RNA) of hundreds to thousands of genes at one time to give an overall picture of gene activity. GEP tests are typically performed on tumor tissue but may also be performed on other specimens such as blood. These tests often use microarray technology though other methodologies, such as next generation sequencing (NGS), whole transcriptome sequencing and reverse transcription polymerase chain reaction (RT-PCR), are also used. GEP tests are currently offered primarily for the management of cancer, most notably breast. Other cancer indications include bladder, colon, cancer of unknown primary (CUP), cutaneous (skin) melanoma, Gene Expression Profiling for Cancer Indications Page: 13 of 58 cutaneous squamous cell cancer (SCC), hematologic malignancies, lung cancer, oral cancer, pancreatic cancer, prostate cancer and uveal melanoma. Breast cancer – Indicated to estimate risk of distant recurrence (metastasis) and predict likelihood of benefit from chemotherapy or extended use of endocrine (hormone) therapy for an individual diagnosed with early-stage invasive node negative (no cancer cells detected in lymph glands) or node positive (cancer cells detected in lymph glands) breast cancer. Several tests are commercially available, each analyzing the expression of different numbers of genes and are typically combined with a proprietary algorithm to produce test scores. A low-risk test result may indicate that an individual can safely forgo chemotherapy while a high-risk test score suggests that chemotherapy in addition to endocrine therapy may be necessary. Examples include, but may not be limited to: • Breast Cancer Index (BCI) • EndoPredict Prognosis Breast Cancer • MammaPrint • Oncotype DX Breast Recurrence Score • Prosigna Breast Cancer Prognostic Gene Signature Assay (PAM50) Molecular subtyping has been developed to predict response to chemotherapy as well as risk of distant recurrence. Tumors are grouped into distinct categories based on the gene expression pattern of the tumor. Subtypes appear to be associated with different prognoses and responses to treatment options. Examples include, but may not be limited to, BluePrint (offered in conjunction with MammaPrint) and Insight TNBCtype. GEP has also been established to predict likelihood of breast cancer for an individual diagnosed with precancerous lesions such as ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), usual ductal hyperplasia (UDH), papilloma and sclerosing adenosis. BBDRisk Dx is an example of this type of test. Ductal in situ carcinoma (DCIS) of the breast - To estimate risk of local recurrence and predict likelihood of benefit from radiation therapy. An example is Oncotype DX Breast DCIS Score. Bladder cancer – Used for the diagnosis, monitoring and molecular subtyping for urothelial cancer. Examples include, but may not be limited to, Bladder EpiCheck, Cxbladder Detect, Cxbladder Monitor, Cxbladder Triage, Decipher Bladder Genomic Classifier, Decipher Bladder TURBT, Xpert Bladder Cancer Detection and Xpert Bladder Cancer Monitor. Colon cancer – A method to determine risk of relapse for node positive or node negative stage II colon cancer and for metastatic colon cancer to assist in treatment decisions. Oncotype DX Colon Cancer Recurrence Score Test is an example of this type of test. CUP (also referred to tumor of unknown origin or tissue of origin [TOO])- For the identification of the site of origin for an uncertain cancer diagnosis. CancerTYPE ID is an example of this type of test. NeoTYPE Cancer Profile, a molecular profiling test for cancer, is available for use in conjunction with CancerTYPE ID. Gene Expression Profiling for Cancer Indications Page: 14 of 58 Cutaneous melanoma – Several tests are offered for the management of melanoma including, but may not be limited to: • DecisionDx-Melanoma – To aid in determining risk of recurrence or metastasis and likelihood of sentinel lymph node (SLN) positivity in an individual diagnosed with melanoma. • DecisionDx DiffDx-Melanoma and myPath Melanoma – To differentiate benign nevi (a birthmark or mole) from malignant melanoma in an individual with melanocytic lesions. • Merlin Test – To predict risk of metastasis in an individual with diagnosed with melanoma. • Pigmented Lesion Assay – To assist in ruling out melanoma and need for a surgical biopsy for an individual with atypical pigmented lesions. Cutaneous SCC – Developed for squamous cell cancer, a type of skin cancer, to identify metastatic risk and assist in treatment decisions. DecisionDx-SCC is an example of this type of testing. Hematologic malignancies – Used for the classification of hematologic cancers to assist in treatment decisions for leukemia, lymphoma, multiple myeloma, myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs). Lymph2Cx (also referred to as Lymphoma Subtyping Test) and Lymph3Cx are examples of assays proposed to subclassify lymphoma. Lung cancer – For use in an individual diagnosed or at risk for lung cancer. Examples include, but may not be limited to: • DetermaRx has been proposed to determine risk of recurrence and chemotherapy treatment decisions in an individual diagnosed with stage I or stage IIA nonsquamous non-small cell lung cancer (NSCLC). • Percepta Bronchial Genomic Sequencing Classifier to purportedly assess risk and stratify an individual who is a current or former smoker when results of bronchoscopy are indeterminate. Oropharyngeal/oral cancer – For the diagnosis of oral and/or oropharyngeal cancer. CancerDetect is an example of this type of testing. Pancreatic cancer – A method to evaluate pancreatic cyst fluid for the early detection of pancreatic cancer. An example is PancreaSeq Genomic Classifier. Prostate cancer - While prostate-specific antigen (PSA) testing is considered the gold standard for prostate cancer screening and management, only biopsy of the prostate gland can establish a prostate cancer diagnosis. However, studies indicate that biopsies fail to identify prostate cancer in some individuals and in certain circumstances, biopsy may be avoidable. To assist with clinical decision making regarding initial or repeat prostate biopsies, laboratory tests such as GEP have been suggested for cancer management. Examples of GEP assays for prostate cancer include, but may not be limited to, ConfirmMDx for Prostate Cancer, Decipher Prostate Biopsy Genomic Classifier, Decipher Prostate RP Genomic Classifier, ExoDx Gene Expression Profiling for Cancer Indications Page: 15 of 58 Prostate Test, Oncotype DX Genomic Prostate Score (GPS), Prolaris Biopsy Test and Prolaris Post- Prostatecomy Test. Uveal melanoma – Utilized to predict risk of metastasis for uveal melanoma. Examples include, but may not be limited to, DecisionDx-PRAME, DecisionDx-UM, DecisionDx-UMSeq. GEP tests differ from germline genetic tests. GEP tests analyze RNA which is dynamic, responds to cellular environmental signals, are not usually representative of an individual’s germline DNA and are not inheritable. Germline genetic testing analyzes an individual’s deoxyribonucleic acid (DNA) to detect genetic variants (mutations). Germline mutations are inherited, are constant throughout an individual’s lifetime and are identical in every cell of the body. Coverage Determination Humana follows the CMS requirements that only allows coverage and payment for services that are reasonable and necessary for the diagnosis and treatment of illness or injury or to improve the functioning of a malformed body member except as specifically allowed by Medicare. Genetic tests must demonstrate clinical utility, analytical and clinical validity and fulfill the CMS “reasonable and necessary” criteria. Analytic validity (test accurately identifies the gene variant), clinical validity (test identifies or predicts the clinically defined disorder) and clinical utility (test measurably improves clinical outcomes) of the genetic test is supported by generally accepted standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, specialty society recommendations, and views of physicians practicing in relevant clinical areas. The test must be ordered by a physician who is treating the beneficiary and the results will be used in the management of a beneficiary’s specific medical problem. For jurisdictions with no Medicare guidance for a particular test, Humana will utilize the MolDX program and Technical Assessments for molecular assays as the standard to evaluate clinical utility, analytical and clinical validity in conjunction with adhering to Medicare’s reasonable and necessary requirement.  In interpreting or supplementing the criteria above and in order to determine medical necessity consistently, Humana may consider the following criteria: GENERAL CRITERIA FOR GENE EXPRESSION PROFILING FOR CANCER INDICATIONS Apply General Criteria for Gene Expression Profiling for Cancer Indications when test specific criteria are not available on this medical coverage policy. Gene expression profiling for cancer will be considered medically reasonable and necessary when the following requirements are met: • Individual to be tested is under active management or being evaluated for cancer; AND Gene Expression Profiling for Cancer Indications Page: 16 of 58 • Individual is within the population and has the indication for the test’s intended use; AND • Results of testing must directly impact treatment or management of the Medicare beneficiary; AND • Analytic validity, clinical validity and clinical utility of the genetic test is supported by the MolDX program; AND • Test is ordered by a physician who is treating the individual CRITERIA FOR SPECIFIC TESTS Breast Cancer Breast Cancer Index (BCI) (81518) will be considered medically reasonable and necessary when the following requirements are met:50,51,52,53,54 • Individual is a postmenopausal female diagnosed with early-stage invasive disease (tumor, node, metastasis [TNM] stage T1-3, pN0-N1, M0) that is estrogen receptor (ER) positive and/or progesterone receptor (PR) positive and human epidermal growth factor receptor (HER2) negative; AND • Individual has no evidence of distant breast cancer metastasis (nonrelapsed); AND • Test results will be used to determine treatment with chemotherapy and/or endocrine therapy NOTE: BCI is tested once per patient lifetime on formalin-fixed, paraffin-embedded (FFPE) tissue from the primary tumor specimen obtained prior to adjuvant treatment.49,50,51,52,53 EndoPredict Prognosis Breast Cancer Test (81522) will be considered medically reasonable and necessary when the following requirements are met:61,62,63,64,65 • Individual is a postmenopausal female diagnosed with early-stage disease (TNM stage T103, N0-1) that is ER positive and HER2 negative; AND • Lymph node negative or 1-3 positive nodes; AND • No evidence of distant metastasis; AND • Treatment with adjuvant endocrine therapy (eg, tamoxifen or aromatase inhibitors) is under consideration MammaPrint (81521, 81523) will be considered medically reasonable and necessary when the following requirements are met:25,26,27,28,29 Gene Expression Profiling for Cancer Indications Page: 17 of 58 • Individual diagnosed with early stage (I or II) breast cancer; AND • Tumor size less than 5.0 cm; AND • Lymph node negative or 1-3 positive lymph nodes NOTE: MammaPrint may be performed one time on a given date of service for a given individual. This test may be performed upon occasion twice per individual lifetime for bilateral disease.25,26,27,28,29 Oncotype DX Breast Recurrence Score (81519) will be considered medically reasonable and necessary when the following indications:30,31,32,33,34,111 • ER positive, lymph node-negative carcinoma of the breast; OR • ER positive micrometastases of carcinoma of the breast; OR • ER positive, lymph node-positive (1-3 nodes) Prosigna Breast Cancer Prognostic Gene Signature Assay (81520) will be considered medically reasonable and necessary for a postmenopausal female for the following indications:45,46,47,48,49,111 • ER positive, lymph node-negative, stage I or II breast cancer; OR • ER positive, lymph node-positive (1-3), stage II breast cancer Oncotype DX DCIS Breast Cancer Test (0045U) will be considered medically reasonable and necessary when the following requirements are met:82,83,84,85 • Individual diagnosed with ductal carcinoma in situ (DCIS) of the breast; AND • Tissue specimen is at least 0.5 mm in length; AND • Individual is a candidate for breast conserving surgery and is considering the addition of radiation therapy and testing will help inform the choice between surgery alone versus surgery with radiation therapy; AND • Has not undergone or is not planning a mastectomy Cancer of Unknown Primary CancerTYPE ID (81540) will be considered medically reasonable and necessary in the pathologic diagnosis of cancer of unknown primary (CUP) when a conventional surgical pathology/imaging work-up has not identified a primary neoplastic site. Other applications of this technology are considered not medically reasonable and necessary. (CancerTYPE ID is covered once per lifetime).43 Gene Expression Profiling for Cancer Indications Page: 18 of 58 Colon Cancer Oncotype DX Colon Recurrence Score Test (81525) will be considered medically reasonable and necessary for the management of stage II colon cancer.35,36,37,38,41 Cutaneous Melanoma Melanoma risk stratification molecular testing (eg, DecisionDx-Melanoma [81529], DecisionDx DiffDx- Melanoma [0314U], Merlin Test, myPath Melanoma [0090U]) will be considered medically reasonable and necessary when the following requirements are met:66,67,68,69,70 • The individual to be tested has a personal history of melanoma; AND o Has stage T1b or above disease; OR o Has stage T1a disease with documented concern about adequacy of microstaging; AND • Is undergoing workup or being evaluated for treatment; AND • Does not have metastatic disease; AND • Presumed risk of 5% or greater for a positive sentinel lymph node biopsy (SLNB) based on clinical, histological or other information; AND • Has a disease stage, grade and Breslow thickness (or other qualifying conditions) within the intended use of the test; AND • Analytic validity, clinical validity and clinical utility of the genetic test is supported by the MolDX program Pigmented Lesion Assay (0089U) will be considered medically reasonable and necessary when the following requirements are met:91,92,93,94,95 • For the evaluation of pigmented skin lesions (suspicious areas of the skin) for which a diagnosis of melanoma (skin cancer) is being considered; AND • Test ordered by clinicians who evaluate pigmented skin lesions and perform biopsies; AND • The lesion must meet one or more ABCDE (asymmetry, border, color, diameter, evolving) criteria for skin cancer; AND • Pigmented skin lesions between 5mm and 19mm in size; AND • Lesions where the skin is intact (non-ulcerated, non-bleeding); AND Gene Expression Profiling for Cancer Indications Page: 19 of 58 • Lesions that do not contain a scar or were previously biopsied; AND • Lesions not located in areas of skin conditions (eg, eczema or psoriasis); AND • Lesions not clinically diagnosed as melanoma or clinical suspicion is sufficiently high that the treating clinician believes melanoma is a more likely diagnosis than not; AND • Lesions are not on the palms of the hands, soles of the feet, under the nails, in the mucous membranes (eg, inside of the mouth) or hair-covered areas that cannot be trimmed; AND • For skin lesions already under consideration for biopsy; AND • Only one test may be used per individual per clinical encounter. In the rare instance that a second test may be indicated for the same clinical encounter, submit an appeal with supporting documentation Lung Cancer DetermaRx (0288U) will be considered medically reasonable and necessary when the following requirements are met:96,97,98,99,100 • Individual to be tested diagnosed with non-squamous non-small cell lung cancer (NSCLC); AND • Tumor size is less than 5cm; AND • No positive lymph nodes (stages I and IIa); AND • Individual is sufficiently healthy to tolerate chemotherapy; AND • Adjuvant platinum-containing chemotherapy is being considered; AND • Test will help inform the decision to pursue adjuvant chemotherapy Percepta Genomic Sequencing Classifier will be considered medically reasonable and necessary for the evaluation of potentially cancerous lung nodules when the following requirements are met:86,87,88,89,90 • Individual to be tested is a current or former smoker; AND • Physician-assessed low or intermediate pretest risk of malignancy based upon the following clinical characteristic stratification: o Low pretest risk of malignancy (lung nodules are smaller than 10 mm and individual has less than a 10 pack per year smoking history); OR o Intermediate pretest risk of malignancy (lung nodules measure between 10 and 30 mm and/or the individual has a 10 to 60 pack per year smoking history; AND Gene Expression Profiling for Cancer Indications Page: 20 of 58 • Bronchoscopy is nondiagnostic; AND • Test results will be utilized to determine whether computed tomography (CT) surveillance is appropriate in lieu of further invasive biopsies or surgical procedures; AND • Ordering physician is certified in Percepta Certification and Training Registry (CTR); AND • Individual monitored for malignancy (suggested monitoring includes serial CT scans at 3 to 6, 9 to 12 and 18 to 24 months, using thin sections and noncontrast, low-dose techniques) Prostate Cancer NOTE: For prostate cancer, only one molecular biomarker may be performed unless a second test, meeting criteria for a specific test, is medically reasonable and necessary as an adjunct to the first test.72,73,74,75,76 ConfirmMDx for Prostate Cancer (81551) will be considered medically reasonable and necessary for an individual without an established diagnosis of prostate cancer when the following requirements are met:72,73,74,75,76 • 75 years of age or younger with a prostate specific antigen (PSA) (or adjusted PSA for an individual receiving 5-alpha-reductase inhibitors) of greater than 3 but less than 10 ng/mL and/or digital rectal exam (DRE) findings are suspicious for cancer; OR • Less than 75 years of age with a PSA (or adjusted PSA for an individual receiving 5-alpha-reductase inhibitors) of greater than or equal to 4 but less than 10 ng/mL and/or DRE findings are suspicious for cancer; AND o Is a candidate for an initial prostate biopsy; OR o Is a candidate for repeat prostate biopsy (following repeat PSA and/or DRE) and previous prostate biopsy was negative or benign but with abnormal histopathology (ie, atypical small acinar proliferation [ASAP] or high-grade prostatic intraepithelial neoplasia [HGPIN]); OR o Is a candidate for repeat biopsy (following repeat PSA and/or DRE) and PSA is greater than 10 ng/mL and multiparametric magnetic resonance imaging (mpMRI) is negative, if performed Decipher Prostate Biopsy Genomic Classifier (81542) will be considered medically reasonable and necessary when the following requirements are met:106,107,108,109,110 • Diagnosed with localized prostate cancer or biochemically recurrent adenocarcinoma of the prostate; AND Gene Expression Profiling for Cancer Indications Page: 21 of 58 • No clinical evidence of metastasis; AND • Life expectancy of at least 10 years; AND • Candidate for active surveillance based on National Comprehensive Cancer Network (NCCN) guidelines (category 1 or 2A recommendation); AND • Assay is performed on formalin-fixed paraffin embedded (FFPE) prostate biopsy tissue with at least 0.5 mm of linear tumor diameter or FFPE tissue from a prostate resection specimen; AND • Has not received pelvic radiation or androgen deprivation therapy (ADT) prior to the biopsy or prostate resection specimen; AND • Is being monitored for disease progression; AND • Is considering the following: o Conservative management and is eligible for definitive therapy such as radical prostatectomy (RP), radiation or brachytherapy; OR o Radiation therapy and is eligible for the addition of a brachytherapy boost; OR o Radiation therapy and is eligible for the addition of short-term ADT; OR o Radiation therapy with short-term ADT and is eligible for the use of long-term ADT; OR o Radiation with standard ADT and is eligible for systemic therapy intensification using next generation androgen signaling inhibitors or chemotherapy; OR o Observation post-prostatectomy and is eligible for the addition of postoperative adjuvant radiotherapy; OR o Salvage radiotherapy post-prostatectomy and is eligible for the addition of ADT ExoDx Prostate Test (also known as ExoDx Prostate IntelliScore [EPI]) (0005U) will be considered medically reasonable and necessary when the following requirements are met:42 • Testing is performed prior to initial prostate biopsy and individual to be tested is at least 50 years of age with PSA* greater than 4 ng/mL; AND o No other relative indication for prostate biopsy including any of the following: ▪ DRE suspicious for cancer (eg, nodules, induration or asymmetry); OR Gene Expression Profiling for Cancer Indications Page: 22 of 58 ▪ Positive multiparametric MRI (Prostate Imaging Reporting and Data System [PI-RADS] greater than or equal to 3), if available; OR ▪ Positive prior biopsy (cancer Histologic Grade Group greater than or equal to 1, intraductal carcinoma [IDC], atypical intraductal proliferation [AIP]); AND o No other relative contraindication for prostate biopsy including any of the following: ▪ Less than 10 year life expectancy or is otherwise not a candidate for prostate cancer treatment; OR ▪ Invasive treatment for benign prostatic disease or taking medications that influence serum PSA levels within 6 months; OR ▪ Active prostatitis on antibiotics; OR • Testing is performed prior to repeat biopsy in an individual who is at higher risk despite a negative prior prostate biopsy and has a confirmed moderately elevated PSA* (greater than 3ng/mL and less than 10 ng/mL for an individual 75 years of age or younger or PSA greater than 4 ng/mL and less than 10 ng/mL for an individual greater than 75 years of age); AND o No other relative indication for prostate biopsy including any of the following: ▪ DRE suspicious for cancer (eg, nodules, induration or asymmetry); OR ▪ Positive multiparametric MRI (Prostate Imaging Reporting and Data System [PI-RADS] greater than or equal to 3), if available; OR ▪ Positive prior biopsy (cancer Histologic Grade Group greater than or equal to 1, intraductal carcinoma [IDC], atypical intraductal proliferation [AIP]); OR ▪ Other major risk factor for prostate cancer including any of the following: ❖ Ethnicity at higher risk for prostate cancer (eg, Ashkenazi Jewish ancestry); OR ❖ First-degree relative with prostate cancer; OR ❖ High-penetrance prostate cancer risk gene(s) (those most linked to prostate cancer such as BRCA1, BRCA2, ATM, CHEK2 and HOXB13) per NCCN (category 1 or 2A recommendation), if known; AND o No other relative contraindication for prostate biopsy including any of the following: ▪ Less than 10 year life expectancy or is otherwise not a candidate for prostate cancer treatment; OR Gene Expression Profiling for Cancer Indications Page: 23 of 58 ▪ Invasive treatment for benign prostatic disease or taking medications that influence serum PSA levels within 6 months; OR ▪ Active prostatitis on antibiotics Oncotype DX Genomic Prostate Score (GPS) (0047U) will be considered medically reasonable and necessary for Prostate Cancer Risk Group very-low-risk, low-risk, and favorable-intermediate risk prostate cancer.39 Prolaris Biopsy Test (81541) will be considered medically reasonable and necessary for Prostate Cancer Risk Group low, favorable-intermediate, unfavorable-intermediate or high-risk prostate cancer with a life expectancy of at least 10 years.206 SelectMDx (0339U) will be considered medically reasonable and necessary when the following requirements are met:42 • Testing is performed prior to initial prostate biopsy and individual to be tested is at least 50 years of age with PSA* greater than 4 ng/mL; AND • No other relative indication for prostate biopsy including any of the following: o DRE suspicious for cancer (eg, nodules, induration or asymmetry) o Positive multiparametric MRI (Prostate Imaging Reporting and Data System [PI-RADS] greater than or equal to 3), if available o Positive prior biopsy (cancer Grade Group greater than or equal to 1, intraductal carcinoma [IDC], atypical intraductal proliferation [AIP]); AND o Other major risk factor for prostate cancer including any of the following: ▪ Ethnicity at higher risk for prostate cancer (eg, Ashkenazi Jewish ancestry); OR ▪ First-degree relative with prostate cancer; OR ▪ High-penetrance prostate cancer risk gene(s) (those most linked to prostate cancer such as BRCA1, BRCA2, ATM, CHEK2 and HOXB13) per NCCN (category 1 or 2A recommendation), if known • No other relative contraindication for prostate biopsy including any of the following: o Less than 10 year life expectancy or is otherwise not a candidate for prostate cancer treatment o Invasive treatment for benign prostatic disease or taking medications that influence serum PSA levels Gene Expression Profiling for Cancer Indications Page: 24 of 58 within 6 months o Active prostatitis on antibiotics *PSA elevation should be confirmed after a few weeks under standardized conditions (ie, no ejaculation, manipulations and urinary tract infections) in the same laboratory before considering a biopsy.41 Uveal Melanoma DecisionDx-UM (81552) will be considered medically reasonable and necessary when the following requirements are met:56,57,58,59,60 • Individual to be tested is newly diagnosed with uveal melanoma; AND • No evidence of metastatic disease The use of the criteria in this Medicare Advantage Medical Coverage Policy provides clinical benefits highly likely to outweigh any clinical harms. Services that do not meet the criteria above are not medically necessary and thus do not provide a clinical benefit. Medically unnecessary services carry risks of adverse outcomes and may interfere with the pursuit of other treatments which have demonstrated efficacy. Coverage Limitations US Government Publishing Office. Electronic code of federal regulations: part 411 – 42 CFR § 411.15 - Particular services excluded from coverage The following tests may not be considered a benefit (statutory exclusion): • BluePrint Test;24 OR • Tests considered screening in the absence of clinical signs and symptoms of disease that are not specifically identified by the law;218 OR • Tests that confirm a diagnosis or known information;218 OR • Tests to determine risk for developing a disease or condition;218 OR • Tests performed to measure the quality of a process;218 OR • Tests without diagnosis specific indications;218 OR Gene Expression Profiling for Cancer Indications Page: 25 of 58 • Tests identified as investigational by available literature and/or the literature supplied by the developer and are not a part of a clinical trial218 These treatments and services fall within the Medicare program’s statutory exclusion that prohibits payment for items and services that have not been demonstrated to be reasonable and necessary for the diagnosis and treatment of illness or injury (§1862(a)(1) of the Act). Other services/items fall within the Medicare program’s statutory exclusion at 1862(a)(12), which prohibits payment. The following items will not be considered medically reasonable and necessary: • Genetic tests that have not demonstrated clinical utility, analytical and clinical validity via the MolDX Program A review of the current medical literature shows that the evidence is insufficient to determine that these services are standard medical treatments. There remains an absence of randomized, blinded clinical studies examining benefit and long-term clinical outcomes establishing the value of these services in clinical management. The following items will not be considered medically reasonable and necessary: • Pigmented Lesion Assay when used for screening for an individual without melanocytic skin lesions91,92,93,94,95 A review of the current medical literature shows that there is no evidence to determine that this service is standard medical treatment for these indications. There is an absence of randomized, blinded clinical studies examining benefit and long-term clinical outcomes establishing the value of this service in clinical management for these indications.