Description

Gene expression profiling (GEP) is a type of 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 are also possible. GEP tests are used to determine prognosis, refine risk stratification and/or optimize treatment regimens and have been proposed for prostate cancer. In the setting of prostate cancer, GEP tests may also be referred to as tissue-based molecular assays.

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:

• An epigenetic test analyzes the tissue adjacent to (next to) a nearby cancer focus such as prostate cancer. This tissue can contain DNA molecular changes such as methylation. Cancer cells from a biopsy sample may not be detectable; however, methylation changes associated with the cancer may be identified through a technique referred to as methylation-specific polymerase chain reaction (PCR). The ConfirmMDx assay assesses the DNA methylation status of three genes associated with prostate cancer. The assay has been proposed to assist an individual who may be at high risk for cancer recurrence and are considering a repeat prostate biopsy when the first biopsy result is negative. The test is performed on a formalin-fixed, paraffin-embedded (FFPE) sample. (Refer to Coverage Limitations section)
• Decipher Prostate Biopsy Genomic Classifier is a tumor- (or tissue-) based test that has been proposed to assist in determining prognosis for an individual diagnosed with prostate cancer with a low-, intermediate- or high-risk biopsy result. This test uses oligonucleotide microarrays to analyze 22 RNA expression biomarkers extracted from an FFPE specimen.
• Decipher Prostate RP Genomic Classifier is also a tumor-based test that has been suggested to determine prognosis and treatment options for an individual following radical prostatectomy (RP). (Refer to Coverage Limitations section)
• The ExoDx Prostate Test detects RNA in urine by reverse transcriptase quantitative polymerase chain reaction (RT-PCR) and measure expression levels of three genes associated with prostate cancer. The test has been proposed to determine the aggressiveness of prostate cancer to assist in determining if prostate biopsy can be avoided. ExoDx may be referred to as a liquid biopsy or GEP test. (Refer to Coverage Limitations section)

Gene Expression Profiling for Prostate Cancer

Effective Date: 09/08/2023

Revision Date: 09/08/2023

Review Date: 08/24/2023

Policy Number: HUM-0602-004

Page: 3 of 14

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

• Oncotype DX Genomic Prostate Score (GPS) is another tumor-based genomic test proposed for use for newly diagnosed prostate cancer to predict high grade disease in men under surveillance or as a prognostic following RP. The test utilizes quantitative RT-PCR in which RNA is extracted to measure gene expression from prostate FFPE tissue.
• Prolaris Prostate Cancer (including Prolaris Biopsy Test and Prolaris Post-Prostatecomy Test) is a tumor-based RT-PCR test that evaluates gene expression from FFPE for an individual diagnosed with prostate cancer. A Prolaris Score (also known as cell cycle progression [CCP] score) is then provided and is a measure of cancer aggressiveness.

GEP tests differ from germline genetic tests. Germline genetic testing analyzes an individual's deoxyribonucleic acid (DNA) and can identify genetic variants (mutations) to determine inherited risk of disease. Germline mutations are inherited, are constant throughout an individual's lifetime and identical in all tissue types in the individual. GEP tests evaluate RNA activity in tumor tissue to detect variations that have been acquired over an individual's lifetime. Gene expression is dynamic and responds to cellular environmental signals. Variations are present only in the tissue sampled, are not usually representative of an individual's germline DNA and are not inheritable.

For information regarding genetic testing or liquid biopsy for prostate cancer, please refer to Genetic Testing and Liquid Biopsy for Prostate Cancer Medical Coverage Policy.

For information regarding multianalyte assays with algorithmic analyses (MAAAs) or tumor markers (including prostate specific antigen [PSA]) for prostate cancer, please refer to Laboratory Analysis for Prostate Cancer Medical Coverage Policy.

Coverage Determination

Any state mandates for GEP for prostate cancer take precedence over this medical coverage policy.

Humana members may be eligible under the Plan for Decipher Prostate Biopsy Genomic Classifier (81542), Oncotype DX Genomic Prostate Score (GPS) (0047U) or Prolaris Biopsy Test (81541) when the following criteria are met:

Gene Expression Profiling for Prostate Cancer

Effective Date: 09/08/2023

Revision Date: 09/08/2023

Review Date: 08/24/2023

Policy Number: HUM-0602-004

Page: 4 of 14

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version.

Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

• Life expectancy is at least 10 years; AND
• Post-prostate biopsy; AND
• Prostate cancer risk group of very-low-risk, low-risk, favorable intermediate-risk, unfavorable intermediate-risk or high-risk prostate cancer

Coverage Limitations

Humana members may NOT be eligible under the Plan for GEP for prostate cancer including, but may not be limited to:

• ConfirmMDx for Prostate Cancer (81551)
• Decipher Prostate RP Genomic Classifier
• ExoDx Prostate Test (also known as ExoDx Prostate IntelliScore [EPI]) (0005U)
• Prolaris Post-Prostatectomy Test

These are considered experimental/investigational as they are not identified as widely used and generally accepted for any other proposed use as reported in nationally recognized peer-reviewed medical literature published in the English language.

Additional information about prostate cancer may be found from the following websites:

• American Cancer Society
• National Cancer Institute
• National Library of Medicine

Medical Alternatives

Alternatives to GEP for prostate cancer include, but may not be limited to:

• Management based on traditional clinicopathologic features including, but may not be limited to, life expectancy, PSA level, Gleason score, histologic exam of prostate biopsy

Gene Expression Profiling for Prostate Cancer

Effective Date: 09/08/2023

Revision Date: 09/08/2023

Review Date: 08/24/2023

Policy Number: HUM-0602-004

Page: 5 of 14

Humana's documents are updated regularly online. When printed, the version of this document becomes uncontrolled. Do not rely on printed copies for the most up-to-date version. Refer to Medical and Pharmacy Coverage Policies to verify that this is the current version before utilizing.

Physician consultation is advised to make an informed decision based on an individual’s health needs.

Humana may offer a disease management program for this condition. The member may call the number on his/her identification card to ask about our programs to help manage his/her care.

Any CPT, HCPCS or ICD codes listed on this medical coverage policy are for informational purposes only. Do not rely on the accuracy and inclusion of specific codes. Inclusion of a code does not guarantee coverage and or reimbursement for a service or procedure.