DESCRIPTION
Gene expression profile analysis is proposed to risk-stratify individuals with prostate cancer to guide treatment decisions. These tests are intended to be used either on prostate needle-biopsy tissue to guide management regarding active surveillance versus therapeutic intervention, or after radical prostatectomy to guide radiotherapy decisions. Examples of array-based gene expression profiling tests are the Prolaris® Prostate Cancer Prognostic Test (Myriad® Genetics, Inc), the Oncotype Dx® Genomic Prostate Score (Genomic Health, Inc), Decipher® Prostate Genomic Classifier (Veracyte, Inc formerly Decipher Biosciences Inc), and ProMark® Proteomic Prognostic Test (Metamark® Genetics, Inc).
Prolaris® is an mRNA-based assay measuring the expression of 31 cell-cycle progression (CCP) genes and 15 “housekeeping” genes that act as internal controls and normalization standards in each sample. The assay is performed on formalin fixed paraffin-embedded prostate cancer blocks. The assay results are reported as a numerical score (-3 to +3) along with accompanying interpretive information. Higher scores correspond to an increased probability of adverse events following treatment.
The Oncotype DX® Prostate assay includes 5 reference genes and 12 active cancer genes that represent 4 molecular pathways of prostate cancer oncogenesis: androgen receptor, cellular organization, stromal response, and proliferation. The assay results are combined to produce a Genomic Prostate Score (GPS), which ranges from 0 to 100. Higher GPS scores indicate more risk.
Decipher® Prostate is an mRNA microarray gene expression profiling of 22 content genes, utilizing formalin-fixed paraffin-embedded tissue. The assay tests biomarkers associated with prostate cancer aggressiveness after radical prostatectomy and evaluates the risk of metastasis after treatment. A score of 0 to 1 is generated and is measured in increments of 0.1.
The ProMark® assay includes eight biomarkers that predict prostate pathology aggressiveness and lethal outcomes: DERL1, PDSS2, pS6, YBX1, HSPA9, FUS, SMAD4, and CUL2. The assay results are combined using predefined coefficients for each marker from a logistic regression model to calculate a risk score. The test scores range from 1 to 100. Higher scores indicate a greater risk of aggressive disease.
Note: See risk stratification under Additional Information below.
POLICY
Gene expression profile analysis to guide the management of prostate cancer is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Gene expression profile analysis for the evaluation of prostate cancer that does not meet medical appropriateness, including but not limited to individuals with very low risk or very high-risk disease is considered investigational.
MEDICAL APPROPRIATENESS
Gene expression profile analysis to guide the management of prostate cancer is considered medically appropriate if ANY ONE of the following are met:
Individual with low-or favorable intermediate-risk disease with life expectancy of at least 10 years (e.g., Decipher, Oncotype DX Prostate, Prolaris, and ProMark)
Individual with unfavorable intermediate or high-risk disease and life expectancy of at least 10 years (i.e., Decipher or Prolaris tumor-based molecular assays)
Individual with high-risk disease when adverse pathology is found post radical prostatectomy (i.e., Decipher molecular assay).
IMPORTANT REMINDERS
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g., statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan or government program (e.g., TennCare), the express terms of the health plan or government program will govern.
ADDITIONAL INFORMATION
Prostate Cancer Risk Groups / Risk Stratification
Very Low Risk:
ALL of the following: PSA <10 ng/mL, Grade Group 1, T1c, Fewer than 3 prostate biopsy fragments/cores positive with <50% cancer in each fragment/core, PSA density <0.15 ng/mL/g
Low Risk:
ALL of the following: PSA <10 ng/ml, Grade Group 1, T1-T2a
Intermediate (Favorable):
ANY ONE of the following: PSA 10-20 ng/mL or T2b-T2c AND
ALL of the following: <50% biopsy cores positive and Grade group 1 or 2
Intermediate (Unfavorable):
ANY ONE of the following: Grade group 3 or equal to or greater than 50% biopsy cores positive OR
ANY TWO of the following: PSA 10-20 ng/mL, Grade group 2 or 3, T2b-T2c
High Risk:
Has no Very High Risk Features and has ANY ONE of the following: PSA >20 ng/mL, Grade group 4 or 5, T3a
Very High Risk:
ANY ONE of the following Very High Risk features: T3b-T4, Primary Gleason pattern 5, >4 cores with Grade group 4 or 5, OR ANY TWO of the following High Risk features: PSA >20 ng/mL, Grade group 4 or 5, T3a
SOURCES
American Society of Clinical Oncology (ASCO). (2020). Molecular biomarkers in localized prostate cancer: ASCO guidelines. Retrieved January 30, 2021 from https://www.astro.org/.
American Urological Association (AUA)/American Society for Radiation Oncology (ASTRO)/Society of Urological Oncology (SUO). (2022). Clinically localized prostate cancer: AUA/ASTRO/SUA guideline. Retrieved January 23, 2023 from https://www.astro.org/.
BlueCross BlueShield Association. Evidence Positioning System. (12:2023). Gene expression profiling and protein biomarkers for prostate cancer management (2.04.111). Retrieved March 12, 2024 from www.bcbsaoca.com/eps/. (105 articles and/or guidelines reviewed)
CMS.gov. Centers for Medicare & Medicaid Services. Palmetto GBA (2022, February). MolDX: Prostate cancer genomic classifier assay for men with localized disease (L38292). Retrieved January 23, 2023 from https://www.cms.gov.
Cullen, J., Rosner, I., Brand, T., Zhang, N., Tsiatis, A., Moncur, J., et al. (2015). A biopsy-based 17-gene genomic prostate score predicts recurrence after radical prostatectomy and adverse surgical pathology in a racially diverse population of men with clinically low- and intermediate-risk prostate cancer. European Urology, 68 (1), 123-131. (Level 4 evidence)
Cuzick, J., Stone, S., Fisher, G., Yang, Z., North, B., Berney, D., et al. (2015). Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort. British Journal of Cancer, 113, 382-389. (Level 4 evidence)
Eggener, S.E., Rumble, R.B., Armstrong, A.J., Morgan, T., Crispino, T., Cornford, P., et al. (2019). Molecular biomarkers in localized prostate cancer: ASCO Guideline [EPUB ahead of print]. Journal of Clinical Oncology, doi:10.1200/JCO.19.02768
Jairath, N. K., Dal Pra, A., Vince, R., Jr, Dess, R. T., Jackson, W. C., Tosoian, J. J., et al. (2021). A systematic review of the evidence for the decipher genomic classifier in prostate cancer. European Urology, 79(3), 374–383. https://doi.org/10.1016/j.eururo.2020.11.021. [Epub ahead of print] Abstract retrieved December 13, 2021 from PubMed database.
Koch, M., Cho, J., Kaimakliotis, Z., Cheng, L., Sangale, Z., Brawer, M., et al. (2016). Use of the cell cycle progression (CCP) score for predicting systemic disease and response to radiation of biochemical recurrence. Cancer Biomarkers, 17, 83-88. (Level 4 evidence)
Lynch, J., Rothney, M., Salup, R., Ercole, C., Mathur, S., Duchene, D., et al. (2018). Improving risk stratification among veterans diagnosed with prostate cancer: impact of the 17-gene genomic prostate score assay. American Journal of Managed Care, 24 (1 Suppl), S4-S10. (Level 4 evidence)
Moschini, M., Spahn, M., Mattei, A., Cheville, J., & Karnes, J. (2016). Incorporation of tissue-based genomic biomarkers into localized prostate cancer clinics. BMC Medicine, 14, 67. (Level 2 evidence)
National Comprehensive Cancer Network. (2024, March). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Prostate cancer (V.3.2024). Retrieved March 12, 2024 from the National Comprehensive Cancer Network.
National Institute for Health and Clinical Evidence. (NICE). (2019, May; last update search December 2021). Prostate cancer: diagnosis and management. Retrieved March 12, 2024 from http://www.nice.org.uk.
Salmasi, A., Said, J., Shindel, A.W., Khoshnoodi, P, Felker, E.R., Sisk, A.E., et al. (2018). A 17-gene genomic prostate score assay provides independent information on adverse pathology in the setting of combined multiparametric magnetic resonance imaging fusion targeted and systematic prostate biopsy. Journal of Urology, [Epub ahead of print.] Doi: 10.1016/j.juro.2018.03.004. Abstract retrieved July 9, 2018 from PubMed database.
Sommariva, S., Tarricone, R., Lazzeiri, M., Ricciardi, W., & Montorsi, F. (2016). Prognostic value of the cell cycle progression score in patients with prostate cancer: a systematic review and meta-analysis. European Urology, 69 (1), 107-115. Abstract retrieved August 30, 2016 from PubMed database.
Van Den Eeden, S.K., Lu, R., Zhang, N., Quesenberry, C.P., Shan, J, Han, J.S., et al. (2018). A biopsy-based 17-gene genomic prostate score as a predictor of metastases and prostate cancer death in surgically treated men with clinically localized disease. European Urology, 73 (1), 129-138. Abstract retrieved July 9, 2018 from PubMed database.
Vince, R. A., Jr, Jiang, R., Qi, J., Tosoian, J. J., Takele, R., Feng, et al. (2021). Impact of Decipher biopsy testing on clinical outcomes in localized prostate cancer in a prospective statewide collaborative. Prostate Cancer and Prostatic Diseases, https://doi.org/10.1038/s41391-021-00428-y. [Epub ahead of print] Abstract retrieved December 13, 2021 from PubMed database.
ORIGINAL EFFECTIVE DATE: 8/9/2014
MOST RECENT REVIEW DATE: 4/11/2024
ID_BT
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
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