Sunflower Health Plan Concert Genetic Oncology: Algorithmic Testing (PDF) Form

Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 CONCERT GENETICS ONCOLOGY: ALGORITHMIC TESTING See Important Reminder at the end of this policy for important regulatory and legal information. OVERVIEW Oncology prognostic and algorithmic tests are developed to aid in determining the likelihood that an individual has cancer, the prognosis for a patient diagnosed with cancer, and/or surveillance for recurrence. These tests may be used to guide clinical decision making for an individual diagnosed with cancer. The testing methodologies include Gene Expression Profiling (GEP), which analyzes messenger RNA (mRNA) typically of multiple genes simultaneously, multimarker serum analysis, single-nucleotide variant testing, plasma-based proteomic analysis, and incorporation of other clinical data into test outputs. In addition to the tests previously mentioned, proteogenomic testing is an emerging area. Proteogenomic testing combines the analysis of DNA with RNA and/or protein analysis. The current focus of proteogenomics is primarily on diagnostic and prognostic analyses in various cancers. Results also seek to provide potential treatment options, and to which treatments the cancer may be resistant. Polygenic Risk Score (PRS) tests are another emerging area. These tests combine information from population SNP analysis with clinical and family history and aim to give additional insight into an individual's lifetime risk to develop a specific cancer. Results of prognostic and algorithmic tests are often reported as a recurrence score, probability of distant disease recurrence, malignant potential, probable site of origin, or cancer risk score. Additionally, the output of these prognostic and algorithmic tests may be useful to assist in surgical and management decision-making and to identify individuals who may benefit from adjuvant therapy. 1 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 POLICY REFERENCE TABLE Below is a list of higher volume tests and the associated laboratories for each coverage criteria section. This list is not all inclusive. Coding Implications This clinical policy references Current Procedural Terminology (CPT®). CPT® is a registered trademark of the American Medical Association. All CPT codes and descriptions are copyrighted 2022, American Medical Association. All rights reserved. CPT codes and CPT descriptions are from the current manuals and those included herein are not intended to be all-inclusive and are included for informational purposes only. Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to the submission of claims for reimbursement of covered services. Coverage Criteria Sections Breast Cancer Breast Cancer Treatment and Prognostic Algorithmic Tests Breast Cancer Prognostic Algorithmic Tests Gene Expression Profiling Breast Cancer Subtyping Tests Example Tests, Labs Common CPT Codes Common ICD Codes Ref Oncotype Dx Breast Recurrence Score (Exact Sciences) 81519, S3854 C50.011 through C50.92, Z17.0 1 Breast Cancer Index Prognostic (bioTheranostics) 81518, S3854 EndoPredict (Myriad) 81522, S3854 C50, Z17.0, Z17.1 1 MammaPrint (Agendia, Inc.) 81521, 81523 S3854 Prosigna Assay (NeoGenomics) 81520 BluePrint (Agendia, Inc.) 81599, S3854 Insight TNBCtype™ (Insight Molecular Labs) 0153U C50 through C50.929 Breast DCIS Prognostic Algorithmic Tests Oncotype DX Breast DCIS Score (Exact Sciences) 0045U D05.1 Colorectal Cancer Colorectal Cancer Prognostic Algorithmic Oncotype DX Colon Recurrence Score (Exact Sciences) 81525 C18.0 through C18.9 1 1 2 2 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 Tests miR-31now (GoPath Laboratories) 0069U Prostate Cancer Prostate Cancer Treatment and Prognostic Algorithmic Tests Oncotype DX Genomic Prostate Score (MDxHealth) Decipher Prostate Biopsy Genomic Classified Classifier (Veracyte) Decipher Prostate RP Genomic Classifier (Veracyte) 0047U C61 3, 19 81542 Prostate Cancer Risk Assessment Algorithmic Tests Prolaris (Myriad Genetics) 81541 4K Prostate Score (Serum) (BioReference Laboratories) 81539 C61, Z12.5 4, 27, 29 Prostate Health Index (ARUP Laboratories) 84153, 84154, 86316 Prostate Cancer Diagnostic Algorithmic Tests Thyroid Cancer Thyroid Cancer Diagnostic Algorithmic Tests SelectMDx for Prostate Cancer (MDx Health) ExoDx Prostate Test (ExosomeDx) IsoPSA® (Cleveland Diagnostics, Inc) ConfirmMDx for Prostate Cancer (MDxHealth) 0339U 0005U 0359U 81551 C61, Z12.5 5, 29 MyProstateScore (MPS) (University of Michigan MLabs) 0113U ThyroSeq Genomic Classifier (CBLPath) ThyGeNEXT (Interpace Diagnostics) ThyraMIR (Interpace Diagnostics) Afirma Genomic Sequencing Classifier (Veracyte) 0026U C73, D44.0, E04.1 6, 7, 8 0245U 0018U 81546 3 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 Afirma Xpression Atlas (Veracyte) 0204U DecisionDX-UM (Castle Bioscience, Inc.) 81552 C69 9 Uveal Melanoma Uveal Melanoma Prognostic Algorithmic Tests Cutaneous Melanoma Cutaneous Melanoma Prognostic Algorithmic Tests Cutaneous Melanoma Diagnostic Algorithmic Tests Cutaneous Melanoma Risk Assessment Algorithmic Tests Ovarian Cancer Ovarian Cancer Treatment Algorithmic Tests Gynecologic Cancer Gynecologic Cancer Treatment Algorithmic Tests Lung Cancer DecisionDX-Melanoma (Castle Biosciences, Inc.) 81529 myPath Melanoma (Castle Biosciences Inc) Pigmented Lesion Assay (DermTech) C43, D03.0 through D03.9, Z12.83 D22.0 through D22.9, D48.5, D49.2, Z12.83 10, 11 10, 11, 26 D22 through D23, Z12.83 23 12 D27.0, D27.1, D27.9, D39.10 through D39.12, D39.9, D49.59, D49.9 0090U 0089U 81503 0003U 81500 0375U 0172U C48, C56, C57.0 12, 20 Ovarian Cancer Diagnostic Algorithmic Tests OVA1 (Aspira) Overa (Aspira) Ovarian Malignancy Risk (ROMA) (LabCorp) OvaWatch (Aspira Women’s Health) myChoice CDx (Myriad Genetics) ChemoFx (Helomics Corporation) ChemoFx - Additional Drug (Helomics Corporation) 81535 81536 C51 through C57 12, 17, 18 Lung Cancer Diagnostic Nodify XL2 (Biodesix) 0080U R91.1 25 4 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 Algorithmic Tests REVEAL Lung Nodule Characterization (MagArray) Percepta Bronchial Genomic Classifier (Veracyte) Lung Cancer Treatment Algorithmic Tests VeriStrat (Biodesix) DetermaRx (Oncocyte) Bladder and Urinary Tract Cancer 0092U 81599 81538 0288U C34, D38.1, D38.6 24 Bladder Cancer Diagnostic and Recurrence Algorithmic Tests Urinary Tract Cancer Recurrence Algorithmic Tests Pancreatic Cancer Pancreatic Cyst Risk Assessment Algorithmic Tests Cxbladder Triage (Pacific Edge) 0363U Cxbladder Detect (Pacific Edge) 0012M C67, D09.0, D49.4, R31.9, Z85.51 13, 14 Cxbladder Monitor (Pacific Edge) Oncuria Detect (DiaCarta Clinical Lab) Oncuria Monitor (DiaCarta Clinical Lab) Oncuria Predict (DiaCarta Clinical Lab) Alere NMP22® (Alere) Alere NMP22® BladderChek® (Alere) PancraGEN (Interpace Diagnostics) Pancreatic Cyst Fluid NGS Analysis-PancreaSeq (Univ of Pittsburgh Medical Center) 0013M 0365U 0366U 0367U 86386 86386 81479 0313U C67 D09.0, D49.4, R31.9, Z85.51 D49, K86.2 21, 22 Cancer of Unknown Primary Cancer of Unknown Primary Gene Expression Profiling Tests CancerTYPE ID (Biotheranostics) 81540 C79.9, C80.0, C80.1 16 Polygenic Risk Score Tests 5 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 Breast Cancer Polygenic Risk Score Tests BrevaGenplus (Pathogen Sciences Laboratories) 81599 Z13.71, Z13.79 Z80.3 15 Multiple Myeloma Polygenic Risk Score Tests Myeloma Prognostic Risk Signature (MyPRS) (Cleveland Clinic Laboratories) 81599 Oncology: Test-Specific Not Covered Algorithmic Tests C90.00 through C90.02 15, 28 Oncology: Test-Specific Not Covered Algorithmic Tests Onco4D (Animated Dynamics, Inc.) BBDRisk Dx (Silbiotech) PreciseDx Breast Cancer Test (PreciseDx) Lymph3Cx Lymphoma Molecular Subtyping Assay (Mayo Clinic Laboratories) 0083U 0067U 0220U 0120U LC-MS/MS Targeted Proteomic Assay (OncoOmicDx laboratory) 0174U OTHER RELATED POLICIES This policy document provides coverage criteria for tests that determine the risk for or the prognosis for cancer. For other oncology related testing, please refer to: ● ● ● ● Oncology: Molecular Analysis of Solid Tumors and Hematologic Malignancies for criteria related to DNA testing of a solid tumor or a blood cancer. Genetic Testing: Hereditary Cancer Susceptibility Syndromes for criteria related to genetic testing to determine if an individual has an inherited cancer susceptibility syndrome. Oncology: Cancer Screening for criteria related to the use of non-invasive fecal, urine or blood tests for screening for cancer. Oncology: Circulating Tumor DNA and Circulating Tumor Cells (Liquid Biopsy) for criteria related to circulating tumor DNA (ctDNA) or circulating tumor cell testing performed on peripheral blood for cancer diagnosis, management and surveillance. 6 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 ● Genetic Testing: General Approach to Genetic Testing for coverage criteria related to algorithmic testing in oncology that is not specifically discussed in this or another non- general policy. back to top CRITERIA It is the policy of health plans affiliated with Centene Corporation® that the specific genetic testing noted below is medically necessary when meeting the related criteria: BREAST CANCER Breast Cancer Treatment and Prognostic Algorithmic Tests I. The use of the breast cancer treatment and prognostic algorithmic test Oncotype DX Breast Recurrence Score (81519, S3854) is considered medically necessary in all patients, regardless of gender, when: A. The member/enrollee has primary breast cancer that is ductal/NST, lobular, mixed or micropapillary, AND B. The member’s/enrollee’s tumor is hormone receptor-positive (estrogen receptor- positive or progesterone receptor-positive), AND C. The member’s/enrollee’s tumor is human epidermal growth factor receptor 2 (HER2)-negative, AND D. The member/enrollee is considering treatment with adjuvant therapy (for example, tamoxifen, aromatase inhibitors, immunotherapy), AND E. The member/enrollee meets one of the following (regardless of menopausal status): 1. Tumor is greater than 0.5 cm and node negative (pN0), OR 2. Lymph nodes are pN1mi (2mm or smaller axillary node metastases), OR 7 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 3. Lymph nodes are pN1 (1 to 3 positive nodes), OR II. The use of the breast cancer treatment and prognostic algorithmic test Breast Cancer Index (BCI) (S3854, 81518) is considered medically necessary when: A. The member/enrollee is female, AND B. The member/enrollee has primary breast cancer that is ductal/NST, lobular, mixed or micropapillary, AND C. The member’s/enrollee’s tumor is hormone receptor-positive (estrogen receptor- positive or progesterone receptor-positive), AND D. The member’s/enrollee’s tumor is human epidermal growth factor receptor 2 (HER2)-negative, AND E. The member/enrollee is considering treatment with adjuvant therapy (for example, tamoxifen, aromatase inhibitors, immunotherapy), AND 1. The member/enrollee meets one of the following based on menopausal status: a) The member/enrollee is premenopausal and meets one of the following: (1) Tumor is greater than 0.5 cm and node negative (pN0), OR (2) Lymph nodes are pN1mi (2mm or smaller axillary node metastases), OR (3) Lymph nodes are pN1 (1 to 3 positive nodes), OR b) The member/enrollee is postmenopausal and meets one of the following: (1) Tumor is greater than 0.5 cm, OR (2) Lymph nodes are pN1mi (2mm or smaller axillary node metastasis), OR (3) Lymph nodes are pN1 (1 to 3 positive nodes). 8 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 III. The use of the breast cancer treatment and prognostic algorithmic test Breast Cancer Index (BCI) (81518, S3854) in men with breast cancer is considered investigational. IV. The use of a breast cancer treatment and prognostic algorithmic test (i.e., Oncotype DX, Breast Recurrence Score, or Breast Cancer Index) (81518, 81519, S3854) is considered investigational for all other indications. back to top Breast Cancer Prognostic Algorithmic Tests I. The use of a breast cancer prognostic algorithmic test (i.e., Endopredict, Prosigna, Mammaprint) (S3854, 81520, 81521, 81522, 81523) is considered medically necessary when: A. The member/enrollee is female, AND B. The member/enrollee has primary breast cancer that is ductal/NST, lobular, mixed or micropapillary, AND C. The member’s/enrollee’s tumor is hormone receptor-positive (estrogen receptor- positive or progesterone receptor-positive), AND D. The member’s/enrollee’s tumor is human epidermal growth factor receptor 2 (HER2)-negative, AND E. The member/enrollee is considering treatment with adjuvant therapy (for example, tamoxifen, aromatase inhibitors, immunotherapy), AND F. The member/enrollee meets one of the following based on menopausal status: 1. The member/enrollee is premenopausal and meets one of the following: a) Tumor is greater than 0.5 cm and node negative (pN0), OR b) Lymph nodes are pN1mi (2mm or smaller axillary node metastases), OR c) Lymph nodes are pN1 (1 to 3 positive nodes), OR 2. The member/enrollee is postmenopausal and meets one of the following: 9 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 a) Tumor is greater than 0.5 cm, OR b) Lymph nodes are pN1mi (2mm or smaller axillary node metastasis), OR c) Lymph nodes are pN1 (1 to 3 positive nodes). II. The use of a breast cancer prognostic algorithmic test (i.e., Endopredict, Prosigna, Mammaprint) (S3854, 81520, 81521, 81522, 81523) in men with breast cancer is considered investigational. III. The use of a breast cancer prognostic algorithmic test (i.e., Endopredict, Prosigna, Mammaprint ) (S3854, 81520, 81521, 81522, 81523) is considered investigational for all other indications. back to top Gene Expression Profiling Breast Cancer Subtyping Tests I. Gene expression profiling breast cancer subtyping tests (e.g., BluePrint) (81599, S3854, 0153U) are considered investigational. back to top Breast DCIS Prognostic Algorithmic Tests I. Breast DCIS prognostic algorithmic tests (0045U) are considered investigational. COLORECTAL CANCER Colorectal Cancer Prognostic Algorithmic Tests I. Colorectal cancer prognostic algorithmic tests (81525, 0069U) are considered investigational. back to top 10 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 back to top PROSTATE CANCER Prostate Cancer Treatment and Prognostic Algorithmic Tests I. The use of a prostate cancer treatment and prognostic algorithmic test (i.e., Oncotype DX Prostate (0047U), Prolaris (81541)) is considered medically necessary when: A. The member/enrollee has a life expectancy of 10 years or more, AND B. The member/enrollee has any of the following: 1. Low-risk prostate cancer, OR 2. Favorable intermediate prostate cancer, OR 3. Unfavorable intermediate prostate cancer, OR 4. High-risk prostate cancer. II. The use of the prostate cancer treatment and prognostic algorithmic test Decipher assay (81542) is considered medically necessary when: A. The member/enrollee meets the following: 1. The member/enrollee has a life expectancy of 10 years or more, AND 2. The member/enrollee has any of the following: a) Low-risk prostate cancer, OR b) Favorable intermediate prostate cancer, OR c) Unfavorable intermediate prostate cancer, OR d) High-risk prostate cancer, OR B. The member/enrollee meets the following: 1. The test is being used to inform adjuvant treatment and counseling for risk stratification, AND 11 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 2. Adverse features were found post-radical prostatectomy, including but not limited to PSA resistance/recurrence. III. The use of a prostate cancer treatment and prognostic algorithmic test (0047U, 81541, 81542) is considered investigational for all other indications. back to top Prostate Cancer Risk Assessment Algorithmic Tests I. Prostate cancer risk assessment algorithmic tests (81539, 84153, 84154, 86316, 0339U, 0005U, 0359U) are considered investigational. Prostate Cancer Diagnostic Algorithmic Tests I. Prostate cancer diagnostic algorithmic tests (81551, 0113U) are considered investigational. back to top back to top THYROID CANCER Thyroid Cancer Diagnostic Algorithmic Tests I. The use of a thyroid cancer diagnostic algorithmic test (0026U, 0018U, 0204U, 0245U, 81546) in fine needle aspirates of thyroid nodules is considered medically necessary when: A. The fine needle aspirate showed indeterminate cytologic findings, AND B. Clinical and/or radiologic findings of the thyroid nodules are indeterminate of malignancy, AND C. The result of the test would affect surgical decision making. 12 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 II. The use of a thyroid cancer diagnostic algorithmic test (0026U, 0018U, 0204U, 0245U, 81546) in fine needle aspirates of thyroid nodules is considered investigational for all other indications. back to top UVEAL MELANOMA Uveal Melanoma Prognostic Algorithmic Tests I. The use of a uveal melanoma prognostic algorithmic test (81552) is considered medically necessary when: A. The member/enrollee has primary, localized uveal melanoma. II. The use of a uveal melanoma prognostic algorithmic test (81552) is considered investigational for all other indications. CUTANEOUS MELANOMA Cutaneous Melanoma Prognostic Algorithmic Tests I. Cutaneous melanoma prognostic algorithmic tests (81529) are considered investigational. back to top back to top Cutaneous Melanoma Diagnostic Algorithmic Tests I. Cutaneous melanoma diagnostic algorithmic tests (0090U) are considered medically necessary when: A. The member/enrollee has a melanocytic neoplasm that is diagnostically uncertain or equivocal after histopathology. 13 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 II. Cutaneous melanoma diagnostic algorithmic tests (0090U) are considered investigational for all other indications, including: A. A melanocytic neoplasm that has pathology definitive for melanoma, desmoplastic melanoma, or sclerosing nevus. Cutaneous Melanoma Risk Assessment Algorithmic Tests I. Cutaneous melanoma risk assessment algorithmic tests (0089U) are considered investigational. back to top back to top OVARIAN CANCER Ovarian Cancer Diagnostic Algorithmic Tests I. Ovarian cancer diagnostic algorithmic tests (i.e., OVA1, Overa, ROMA, and OvaWatch) (0003U, 81500, 81503, 0375U) are considered investigational for all indications, including but not limited to: A. Preoperative evaluation of adnexal masses to triage for malignancy B. Screening for ovarian cancer C. Selecting patients for surgery for an adnexal mass D. Evaluation of patients with clinical or radiologic evidence of malignancy E. Evaluation of patients with nonspecific signs or symptoms suggesting possible malignancy F. Postoperative testing and monitoring to assess surgical outcome and/or to detect recurrent malignant disease following treatment back to top 14 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 Ovarian Cancer Treatment Algorithmic Tests I. Ovarian cancer treatment algorithmic tests (0172U) are considered medically necessary when: A. The member/enrollee has a diagnosis of ovarian cancer, AND B. The member/enrollee is being considered for PARP inhibitor therapy. II. Ovarian cancer treatment algorithmic tests (0172U) are considered investigational for all other indications. back to top GYNECOLOGIC CANCER Gynecologic Cancer Treatment Algorithmic Tests I. Gynecologic cancer treatment algorithmic tests (81535, 81536) in the assessment of gynecological cancers are considered investigational. back to top LUNG CANCER Lung Cancer Diagnostic Algorithmic Tests I. Lung cancer diagnostic algorithmic tests (0080U, 0092U, 81599) are considered investigational, including for members/enrollees with undiagnosed pulmonary nodules. back to top Lung Cancer Treatment Algorithmic Tests I. Lung cancer treatment algorithmic tests (81538, 0288U) are considered investigational. back to top 15 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 BLADDER AND URINARY TRACT CANCER Bladder Cancer Diagnostic and Recurrence Algorithmic Tests I. Bladder cancer diagnostic and recurrence algorithmic tests (0012M, 0013M, 0363U,, 0375U, 0376U, 0377U), which are performed on urine, are considered investigational. back to top Urinary Tract Cancer Recurrence Algorithmic Tests I. Urinary tract cancer recurrence algorithmic tests (86386) which are typically performed on urine are considered investigational. PANCREATIC CANCER Pancreatic Cyst Risk Assessment Algorithmic Tests I. Pancreatic cyst risk assessment algorithmic tests (0313U, 81479) are considered investigational. back to top back to top CANCER OF UNKNOWN PRIMARY Cancer of Unknown Primary Gene Expression Profiling Tests I. The use of a cancer of unknown primary gene expression profiling test (81540) to evaluate the site of origin of a tumor of unknown primary, or to distinguish a primary from a metastatic tumor is considered investigational. back to top 16 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 POLYGENIC RISK SCORE TESTS Breast Cancer Polygenic Risk Score Tests I. The use of a breast cancer polygenic risk score test (81599) is considered investigational. Multiple Myeloma Polygenic Risk Score Tests I. The use of a multiple myeloma polygenic risk score test (81599) is considered investigational. back to top back to top ONCOLOGY: TEST-SPECIFIC NOT COVERED ALGORITHMIC TESTS I. The use of these specific oncology algorithmic tests are considered investigational: A. BBDRisk Dx (0067U) B. Onco4D (0083U) C. Lymph3Cx Lymphoma Molecular Subtyping Assay (0120U) D. PreciseDxTM Breast Cancer Test (0220U) E. LC-MS/MS Targeted Proteomic Assay (OncoOmicDx laboratory) (0174U) back to top CLINICAL CONSIDERATIONS The Oncotype DX, EndoPredict, Breast Cancer Index, MammaPrint, and Prosigna assays should only be ordered on a tissue specimen obtained during surgical removal of the tumor and after 17 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 subsequent pathology examination of the tumor has been completed and determined to meet the above criteria (ie, the test should not be ordered on a preliminary core biopsy). The test should be ordered in the context of a physician-patient discussion regarding risk preferences when the test result will aid in making decisions regarding chemotherapy. For patients who otherwise meet the criteria for gene expression profiling for breast cancer but who have multiple ipsilateral primary tumors, a specimen from the tumor with the most aggressive histologic characteristics should be submitted for testing. It is not necessary to test each tumor; treatment is based on the most aggressive lesion. back to top DEFINITIONS 1. Ductal/NST breast cancer is ductal cancer that is no special type (NST), meaning the cancer cells have no features that class them as a special type of breast cancer when examined by microscope. 2. Thyroid nodules with indeterminate findings include Bethesda diagnostic category III (atypia/follicular lesion of undetermined significance) or Bethesda diagnostic category IV (follicular neoplasm/suspicion for a follicular neoplasm) 3. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other diseases. 4. Adjuvant therapy refers to medication (such as chemotherapy or endocrine therapy) given after the surgical removal of a cancerous tumor. 5. Prostate cancer pathology risk stratification is described in detail in the NCCN Prostate Cancer 1.2023 guidelines (p. PROS-2). BACKGROUND AND RATIONALE BREAST CANCER back to top 18 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 National Comprehensive Cancer Network (NCCN) NCCN Guidelines for Breast Cancer (2.2023) makes recommendations for gene expression testing when considering adjuvant systemic therapy based on characteristics of the patient and the breast cancer. These characteristics include the patient’s sex, menopause status, the TNM staging of the tumor, the expression of hormone receptors, HER2 status, and how the test will be used (i.e., prognosis alone,or prognosis and treatment decisions). Breast Cancer Treatment and Prognostic Algorithmic Tests Oncotype DX Oncotype DX for breast cancer is a 21-gene expression assay. NCCN guidelines for Breast Cancer (2.2023) strongly recommends consideration of the 21-gene expression assay for both prognosis and treatment decisions in the following patients: ● ● ● ● Patients of either sex (p. BINV-J 1 of 2) Evidence level 1: Postmenopausal patients with a ductal/NST, lobular, mixed, or micropapillary tumor that is pT1–3, and at least 0.5cm, with pN1mi (2 mm or smaller axillary node metastases) or pN1 (1 to 3 positive nodes). Tumor must be HR positive, HER2 negative. (p. BINV-6, BINV-N 1 of 5, BINV-N 2 of 5) Evidence level 1: Premenopausal patient with a ductal/NST, lobular, mixed, or micropapillary tumor that is at least 0.5cm and pN0. Tumor must be HR positive, HER2 negative. (p. BINV-7, BINV-N 1 of 5, BINV-N 2 of 5) Evidence level 2A: Premenopausal patient with a ductal/NST, lobular, mixed, or micropapillary tumor that is at least 0.5cm and pN1mi (2 mm or smaller axillary node metastasis) or pN1 (1 to 3 positive nodes). Tumor must be HR positive, HER2 negative. (p. BINV-8, BINV-N 1 of 5, BINV-N 2 of 5) Breast Cancer Index (BCI) The BCI is recommended by NCCN (Breast Cancer, 2.2023) for both indications of prognosis as well as predicting treatment for extended adjuvant endocrine therapy. Appropriate patients for this test are: ● ● Patients who are female (p. BINV-J 1 of 2) Evidence level 2A: Postmenopausal patients with a ductal/NST, lobular, mixed, or micropapillary tumor that is pT1–3, and 0.5cm or larger, with pN1mi (2 mm or smaller 19 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 ● ● axillary node metastases) or pN1 (1 to 3 positive nodes). Tumor must be HR positive, HER2 negative. (p. BINV-6, BINV-N 1 of 5, BINV-N 4 of 5) Evidence level 2A: Premenopausal patients with a ductal/NST, lobular, mixed, or micropapillary tumor that is at least 0.5cm and pN0. Tumor must be HR positive, HER2 negative. (p. BINV-7, BINV-N 1 of 5, BINV-N 4 of 5) Evidence level 2A: Premenopausal patients with a ductal/NST, lobular, mixed, or micropapillary tumor that is at least 0.5cm and pN1mi (2 mm or smaller axillary node metastasis) or pN1 (1 to 3 positive nodes). Tumor must be HR positive, HER2 negative. (p. BINV-8, BINV-N 1 of 5, BINV-N 4 of 5) Breast Cancer Prognostic Algorithmic Tests While Oncotype DX for Breast Recurrence Score is preferred by NCCN (Breast Cancer, 2.2023), other tests may be considered for prognosis/recurrence risk without treatment guidelines for patients who have hormone receptor-positive breast cancer. These tests include Endopredict and Prosignia (evidence level category 2A) and Mammaprint (evidence level category 1),which are appropriate for the following patients: ● ● ● ● Patients who are female (p. BINV-J 1 of 2) Evidence level 2A: Postmenopausal patients with a ductal/NST, lobular, mixed, or micropapillary tumor that is pT1–3, and 0.5cm or larger, with pN1mi (2 mm or smaller axillary node metastases) or pN1 (1 to 3 positive nodes). Tumor must be HR positive, HER2 negative. (p. BINV-6, BINV-N 1 of 5, BINV-N 3 of 5) Evidence level 2A: Premenopausal patients with a ductal/NST, lobular, mixed, or micropapillary tumor that is at least 0.5cm and pN0. Tumor must be HR positive, HER2 negative. (p. BINV-7, BINV-N 1 of 5, BINV-N 3 of 5) Evidence level 2A: Premenopausal patients with a ductal/NST, lobular, mixed, or micropapillary tumor that is at least 0.5cm and pN1mi (2 mm or smaller axillary node metastasis) or pN1 (1 to 3 positive nodes). Tumor must be HR positive, HER2 negative. (p. BINV-8, BINV-N 1 of 5, BINV-N 3 of 5) Gene Expression Profiling Breast Cancer Subtyping Tests National Comprehensive Cancer Network (NCCN) 20 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 NCCN Breast Cancer guidelines (2.2023) do not reference gene expression profiling tests ( i.e., Blueprint) for the purpose of subtyping breast cancer to provide information for clinical decision-making. Breast DCIS Prognostic Algorithmic Tests National Comprehensive Cancer Network (NCCN) NCCN Breast Cancer guidelines (2.2023) do not reference DCIS prognostic algorithmic tests as part of the clinical work-up for DCIS. COLORECTAL CANCER Colorectal Cancer Prognostic Algorithmic Tests National Comprehensive Cancer Network (NCCN) NCCN guidelines for Colon Cancer (3.2022) state that there is currently insufficient data to recommend multigene panels to assist in making clinical decisions about adjuvant therapy (p. COL-3). PROSTATE CANCER Prostate Cancer Treatment and Prognostic Algorithmic Tests National Comprehensive Cancer Network (NCCN) Current NCCN guidelines for Prostate Cancer (1.2023) support the consideration of gene expression profiling (specifically Decipher, Oncotype DX Prostate, and Prolaris) for prognosis and management in men with low, favorable intermediate, unfavorable intermediate, or high-risk disease, and if the patient is expected to live 10 years or longer. (p. PROS-D 2 of 4) American Society of Clinical Oncology (ASCO) ASCO (2020) issued a guideline for the use of molecular biomarkers in localized prostate cancer that included the following summary of recommendations: 21 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 “Tissue-based molecular biomarkers (evaluating the sample with the highest volume of the highest Gleason pattern) may improve risk stratification when added to standard clinical parameters, but the Expert Panel endorses their use only in situations in which the assay results, when considered as a whole with routine clinical factors, are likely to affect a clinical decision. These assays are not recommended for routine use as they have not been prospectively tested or shown to improve long-term outcomes—for example, quality of life, need for treatment, or survival.” (p. 1474) Prostate Cancer Risk Assessment Algorithm Tests American Urological Association The American Urological Association (Carter et al, 2013; confirmed 2018) published guidelines on the early detection of prostate cancer and concluded that the literature supporting the use of genetic and protein biomarkers for prostate cancer screening and risk assessment provides little evidence for routine use at this time (p. 5). However, the guidelines did recognize that multiple approaches subsequent to a PSA test (e.g., urinary and serum biomarkers, imaging, risk calculators) are available for identifying men more likely to harbor prostate cancer and/or one with an aggressive phenotype. The use of such tools can be considered in men with a suspicious PSA level to inform prostate biopsy decisions (p. 17). American Urological Association and Society of Abdominal Radiology The American Urological Association and the Society of Abdominal Radiology (Rosenkrantz et al, 2016) published joint guidelines on prostate magnetic resonance imaging and magnetic resonance imaging-targeted biopsy. The associations commented that there may be value in using genetic and protein biomarkers for prostate cancer risk in patients warranting repeat biopsy; however, further research is needed to fully assess the utility (p. 2) National Comprehensive Cancer Network (NCCN) NCCN guidelines for Prostate Cancer early detection (1.2023) state that biomarkers meant to improve the specificity of detection of prostate cancer are not yet mandated as a first-line screening test in conjunction with serum prostate-specific antigen (PSA) (p. PROSD-3). Prostate Cancer Diagnostic Algorithmic Tests 22 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 American Urological Association, American Society for Radiation Oncology, and Society of Urological Oncology The American Urological Association, American Society for Radiation Oncology, and the Society of Urologic Oncology (Sanda et al, Part 1 2017, Part 2 2018) published joint guidelines on the management of clinically localized prostate cancer which state that among most low-risk localized prostate cancer patients, genomic biomarkers have not demonstrated a clear role in the selection of active surveillance (Part 1, p. 686) or in the follow-up of patients on active surveillance. (Part 2, p. 991) National Comprehensive Cancer Network (NCCN) NCCN guidelines for Prostate Cancer early detection (1.2023) state that biomarkers meant to improve the specificity of detection of prostate cancer are not yet mandated as a first-line screening test in conjunction with serum prostate-specific antigen (PSA) (page PROSD-3). THYROID CANCER Thyroid Cancer Diagnostic Algorithmic Tests American Thyroid Association The American Thyroid Association (2016) updated its guidelines on the management of thyroid nodules and differentiated thyroid cancer in adults. These guidelines made the following statements on molecular diagnostics in thyroid nodules: “For nodules with AUS/FLUS [atypia of undetermined significance/follicular lesion of undetermined significance]... molecular testing may be used to supplement malignancy risk assessment in lieu or proceeding directly with either surveillance or diagnostic surgery.” (p. 21) National Comprehensive Cancer Network (NCCN) Current NCCN Guidelines for Thyroid Carcinoma (3.2022) state that clinicians can consider molecular diagnostics on fine needle aspirate (FNA) results of thyroid nodules which are classified as Bethesda III or Bethesda IV if there is not high clinical and/or radiographic suspicion of malignancy. (p. THRY-1) American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazone Medici Endocrinologi 23 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 The American Association of Clinical Endocrinologists, American College of Endocrinology, and Associazone Medici Endocrinologi (2016) updated their joint guidelines on molecular testing for cytologically indeterminate thyroid nodules and endorsed the following: ● ● ● TERT mutational analysis may improve the diagnostic sensitivity of molecular testing on cytologic samples. (p. 32) There is insufficient evidence to recommend either in favor of or against the use of gene expression classifiers for cytologically indeterminate nodules. (p. 10) With the exception of mutations such as BRAF V600E, there is insufficient evidence to recommend in favor of or against the use of mutation testing to determine the extent of surgery. (p. 10) UVEAL MELANOMA Uveal Melanoma Prognostic Algorithmic Tests National Comprehensive Cancer Network (NCCN) NCCN guidelines for Uveal Melanoma (2.2022) support gene expression profiling and chromosome analysis in all patients with uveal melanoma and further state that molecular testing for prognostication is preferred over cytology alone. (p. MS-6) CUTANEOUS MELANOMA Cutaneous Melanoma Prognostic Algorithmic Tests National Comprehensive Cancer Network (NCCN) NCCN guidelines for Cutaneous Melanoma (1.2023) recognize that the use of gene expression profiling as an emerging technology to differentiate melanomas at low versus high risk for metastasis, to clarify indeterminate melanocytic neoplasms following histopathology, and to classify cutaneous melanoma into separate categories based on metastasis; however, currently there is insufficient data to recommend the use of gene expression profiling for cutaneous melanoma as the impact of these tests has not been established. (p. ME-C 1 of 8) American Academy of Dermatology 24 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 The American Academy of Dermatology (2019) published guidelines of care for the management of primary cutaneous melanoma. The guidelines state the following regarding GEP tests: ● ● There is insufficient evidence of benefit to recommend routine use of currently available prognostic molecular tests, including GEP, for prognosis of CM. (page 219) Routine molecular testing, including GEP, for prognostication is discouraged until better use criteria are defined. The application of molecular information for clinical management is not recommended. (p. 219) Cutaneous Melanoma Diagnostic Algorithmic Tests National Comprehensive Cancer Network (NCCN) NCCN guidelines for Cutaneous Melanoma (1.2023) indicate that gene expression profiling is an acceptable test for diagnosing indeterminate melanocytic neoplasms by histopathology, along with immunohistochemistry (IHC), comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), single-nucleotide polymorphism (SNP) array, and next-generation sequencing (NGS). These tests may lead to a definitive diagnosis and guide therapy in cases that are diagnostically uncertain or controversial by histopathology. (p. ME-C 1 of 8). American Academy of Dermatology The American Academy of Dermatology (Swetter, 2019) published guidelines of care for the management of primary cutaneous melanoma. The guidelines state the following regarding GEP tests: ● Diagnostic molecular techniques are still largely investigative and may be appropriate as ancillary tests in equivocal melanocytic neoplasms, but they are not recommended for routine diagnostic use in CM. These include comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), gene expression profiling (GEP), and (potentially) next-generation sequencing. (page 219) ● Ancillary diagnostic molecular techniques (eg, CGH, FISH, GEP) may be used for equivocal melanocytic neoplasms. (p. 219) American Society of Dermatopathology The American Academy of Dermatopathology (AUC Committee Members, 2022) published conditions where a 23 gene qRT-PCR test (MyPath Melanoma) was determined by a review of 25 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 published evidence to be “majority usually appropriate.” These include the differential diagnosis of nevus versus melanoma in fully sampled histopathologically ambiguous tumors, partially sampled nevus versus melanoma in adults, nevus versus nevoid melanoma, and nevus versus melanoma in cosmetically sensitive sites and special sites in pediatric patients. These recommendations specifically exclude scenarios where pathology is definitive for melanoma or for distinction between incompletely sampled sclerosing (desmoplastic) nevus versus desmoplastic melanoma. (p. 237-8) Cutaneous Melanoma Risk Assessment Algorithmic Tests Concert Genetics This review focused on peer-reviewed, published evidence of the clinical utility of DermTech PLA through May, 2022. PubMed and ECRI Guidelines Trust searches were performed. Search terms included pigmented lesion assay, DermTech, 0089U, PRAME, LINC00518, cutaneous melanoma risk. References were also identified from the performing laboratory’s website. A total of 110 abstracts from these sources were reviewed, and 30 full text publications were evaluated. At the present time, the DermTech Pigmented Lesion Assay has not been adequately shown in peer-reviewed publications to effectively result in improved health outcomes compared to the current standard of care. OVARIAN CANCER Ovarian Cancer Diagnostic Algorithmic Tests National Comprehensive Cancer Network (NCCN) NCCN guidelines for Ovarian Cancer, Fallopian Tube Cancer, and Primary Peritoneal Cancer (1.2023) recognize the use of biomarker analysis for risk assessment for ovarian cancer in women with a pelvic mass as an emerging technology; however, the NCCN panel of experts currently does not recommend these biomarker tests for clinical use. (p. MS-10 and p. MS-11) Ovarian Cancer Treatment Algorithmic Tests National Comprehensive Cancer Network (NCCN) NCCN guidelines for Ovarian Cancer, Fallopian Tube Cancer, and Primary Peritoneal Cancer (1.2023) recommend genetic risk evaluation, and germline and somatic testing if not previously 26 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 done, including BRCA1/2 to inform maintenance therapy for patients with ovarian, fallopian tube, or primary peritoneal cancer. If a patient does not have a germline BRCA1/2 mutation, homologous recombination status may inform on the benefit of PARP inhibitor therapy. (p. OV- 1) American Society of Clinical Oncology (ASCO) ASCO (2020) issued a guideline for the use of PARP inhibitors in the management of ovarian cancer, which included the following summary of recommendations: “The guideline pertains to patients who are PARPi naïve. All patients with newly diagnosed, stage III-IV EOC (epithelial ovarian, tubal, or primary peritoneal cancer), whose disease is in complete or partial response to first-line, platinum-based chemotherapy with high-grade serous or endometrioid EOC should be offered PARPi maintenance therapy with niraparib. For patients with germline or somatic pathogenic or likely pathogenic variants in BRCA1 (g/sBRCA1) or BRCA2 (g/sBRCA2) genes, should be treated with olaparib. The addition of olaparib to bevacizumab may be offered to patients with stage III-IV EOC with g/sBRCA1/2 and/or genomic instability and a partial or complete response to chemotherapy plus bevacizumab combination. Maintenance therapy (second line or more) with single-agent PARPi may be offered for patients with EOC who have not received a PARPi and have responded to platinum-based therapy regardless of BRCA mutation status. Treatment with a PARPi should be offered to patients with recurrent EOC that has not recurred within 6 months of platinum-based therapy, who have not received a PARPi and have a g/sBRCA1/2, or whose tumor demonstrates genomic instability. PARPis are not recommended for use in combination with chemotherapy, other targeted agents, or immune-oncology agents in the recurrent setting outside the context of a clinical trial. Recommendations for managing specific adverse events are presented. Data to support reuse of PARPis in any setting are needed.” (p. 3) GYNECOLOGIC CANCER Gynecologic Cancer Treatment Algorithmic Tests National Comprehensive Cancer Network (NCCN) NCCN guidelines for Ovarian c=Cancer, Fallopian Tube Cancer, and Primary Peritoneal Cancer (1.2023) state that chemosensitivity or chemoresistance assays, or other biomarker assays, are 27 Concert Oncology: Algorithmic Testing V2.2023 Date of Last Revision: 3/1/2023 being used at some institutions, but the current level of evidence is not sufficient to replace the current standard of care of chemotherapy (p. OV-C). NCCN guidelines for Cervical Cancer (1.2023) do not mention chemosensitivity or chemoresistance assays as part of clinical care. NCCN guidelines for Uterine Neoplasms (1.2023) do not mention chemosensitivity or chemoresistance assays as part of clinical care. LUNG CANCER Lung Cancer Treatment Algorithmic Tests Concert Genetics This review focused on peer-reviewed, published evidence of the clinical utility of VeriStrat® through June 2022. PubMed and ECRI Guidelines Trust searches were performed. Search terms included VeriStrat®, proteomic non-small cell lung cancer, prognosis, and survival. References were also identified from the performing laboratory’s website. At the present time, the VeriStrat® test has not been adequately shown in peer-reviewed publications to effectively result in improved health outcomes compared to the current standard of care. Lung Cancer Diagnostic Algorithmic Tests Concert Genetics This review focused on peer-reviewed, published evidence of the clinical utility of NodifyXL2, Percepta Bronchial Genomic Classifier, and Reveal Lung Nodule Characterization through June 2022. PubMed and ECRI Guidelines Trust searches were performed. Search terms included Nodify, Percepta, lung nodule, plasma-protein and multiplex.