Description

Laboratory analysis for prostate cancer may be used to screen and manage 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 men and in certain circumstances, biopsy may be avoidable. To assist with clinical decision making regarding initial or repeat prostate biopsies, laboratory tests beyond standard PSA testing have been developed and include different types of PSA tests, multianalyte assays with algorithmic analyses (MAAAs) and tumor marker testing.

Standard PSA test also referred to as total PSA (tPSA) is a laboratory method that measures the amount of PSA (also known as KLK3) in blood. Other types of PSA tests may be performed when standard PSA levels are abnormal. These may assist in differentiating prostate cancer from other noncancerous prostate conditions also associated with elevated PSA, such as benign prostatic hyperplasia and may prevent unnecessary prostate biopsies. Common PSA tests include, but are not limited to:

• Complexed PSA (cPSA)
• Free PSA (fPSA)
• Free-to-total PSA (fPSA/tPSA)
• Intact PSA (iPSA) (Refer to Coverage Limitations section)
• IsoPSA (Refer to Coverage Limitations section)
• Percent-free PSA (%fPSA)
• PSA density (PSAD)
• PSA doubling time (PSADT)
• PSA slope (Refer to Coverage Limitations section)
• PSA velocity (PSAV)

MAAAs are laboratory measurements that use a mathematic formula to analyze multiple markers that may be associated with a particular disease state and are designed to evaluate disease activity or an individual’s risk for disease. The laboratory performs an algorithmic analysis using the results of the assays and sometimes other individual information, such as gender and age and converts the information into a numeric score, which is conveyed on a laboratory report. Generally, MAAAs are exclusive (proprietary) to a single laboratory which owns the algorithm. Examples of MAAAs for prostate cancer include, but may not be limited to:

• 4Kscore measures the blood plasma levels of four proteins (total PSA, free PSA, intact PSA and human kallikrein2 [hK2]) and uses an algorithm to combine the results with age, digital rectal exam (DRE) and prior prostate biopsy results. The result purports to identify an individual’s specific probability for finding a high- grade prostate cancer upon biopsy. (Refer to Coverage Limitations section)
• ArteraAI Prostate Test is a multimodal artificial intelligence (MMAI) prognostic biomarker that has been developed to identify an individual with high-risk prostate cancer who may benefit from therapy personalization. The test utilizes a proprietary algorithm that assesses digital images from an individual’s prostate biopsy and learns from the individual’s clinical data. The AI combines this information to determine if an individual may benefit from hormone therapy as well as estimate prognosis.

• EpiSwitch Prostate Screening Test (PSE) is a blood test that is used in combination with an individual’s PSA score and measures 5 epigenetic biomarkers to determine the likelihood of prostate cancer. (Refer to Coverage Limitations section)
• MyProstateScore 2.0 (MPS2) (formerly Mi-Prostate Score [MiPS]) is the next-generation of the MyProstateScore test. It is a noninvasive urine assay that analyzes gene transcripts and a proprietary algorithm purportedly to predict cancer in an individual with an elevated PSA results and a negative biopsy. (Refer to Coverage Limitations section)
• PanGIA Prostate is a multianalyte molecular profiling urine test that uses a proprietary machine learning algorithm purported to assist with prostate biopsy decisions. (Refer to Coverage Limitations section)
• ProMark Proteomic Prognostic Test is a protein-based prognostic test that analyzes 8 biomarkers (DERL1, CUL2, SMAD4, PDSS2, HSPA9, FUS, pS6, YBOX1), quantitative immunofluorescence and digitalized quantitative measurements to evaluate for prostate cancer.
• Prostate Health Index (PHI) (also referred to as proPSA) utilizes a calculation that combines the results of three quantitative blood serum immunoassays (PSA, free PSA, and p2PSA) into a single numerical result known as a PHI score. This score has been suggested to determine the probability of finding prostate cancer with a biopsy.

A tumor marker is a substance such as a protein, antibody, antigen, or hormone in the body that may indicate the presence of cancer. Generally, these markers are specific to certain types of cancer and can be detected in blood, bodily fluids, stool, tissue, and urine samples. The body may produce the marker in response to cancer or the tumor itself may produce the marker. The detection of tumor markers may be used to determine a diagnosis, as an indicator of cancer progression, or analysis of clinical response to treatment. Prostate cancer tumor markers include, but may not be limited to:

Laboratory Analysis for Prostate Cancer

Effective Date: 12/14/2023
Revision Date: 12/14/2023
Review Date: 07/27/2023
Policy Number: HUM-0594-010
Page: 4 of 22

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.

• Cancer antigen tests have been proposed for the management of prostate cancer. These tests measure the blood level of a specific cancer antigen present on the surface of a cancer cell and released into the blood stream. Examples of prostate cancer-related cancer antigen tests include, but may not be limited to, CA 50, CA 549, CA 72-4. (Refer to Coverage Limitations section)
• Human kalikrein2 (hK2) is a prostate-specific kallikrein, a type of protease (an enzyme that breaks down proteins and peptides). hK2 has been suggested as a prostate cancer tumor marker to be used with PSA. (Refer to Coverage Limitations section)
• Ki-67 is a protein and has been proposed as a biomarker to help determine prognosis for an individual diagnosed with prostate cancer. (Refer to Coverage Limitations section)
• Prostate cancer antigen 3 (PCA3) is an in vitro nucleic acid amplification test that measures the concentration of PCA3 and PSA in post-digital rectal exam (DRE) first-catch urine specimens. Progensa PCA3 is an example of a US Food & Drug Administration (FDA)-approved PCA3 test.

(Refer to Coverage Limitations section)

For information regarding genetic testing for the following, please refer to Genetic Testing Medical Coverage Policy:

• DNA banking or preservation
• General population screening
• Individual 17 years of age or younger for adult-onset conditions
• Interpretation and reporting for molecular pathology procedure
• Polygenic risk score (PRS) and single nucleotide polymorphisms (SNPs)

Laboratory Analysis for Prostate Cancer

Effective Date: 12/14/2023
Revision Date: 12/14/2023
Review Date: 07/27/2023
Policy Number: HUM-0594-010
Page: 5 of 22

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.

Repeat germline or somatic genetic testing • Retrieved archival tissue

Humana recognizes that the field of genetic testing is rapidly changing and that other tests may become available.

Coverage Determination

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

Genetic testing may be excluded by certificate. Please consult the member's individual certificate regarding Plan coverage.

Apply General Criteria for Genetic and Pharmacogenomics Tests when disease- or gene-specific criteria are not available on a medical coverage policy. For information regarding general criteria for genetic tests, please refer to Genetic Testing Medical Coverage Policy.

Prostate-Specific Antigen Testing

Humana members may be eligible under the Plan for prostate-specific antigen (PSA) testing* when the following indications are met:

• Annual prostate cancer screening (G0103) in an asymptomatic individual when the following criteria are met:
  1. 45 years of age or older; OR
  2. 40 years of age or older when any of the following are present:
     • African American; OR
     • Personal history of pathogenic or likely pathogenic variant in ATM, BRCA1, BRCA2, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, PALB2, PMS2 or TP53 gene; OR

Laboratory Analysis for Prostate Cancer

Effective Date: 12/14/2023
Revision Date: 12/14/2023
Review Date: 07/27/2023
Policy Number: HUM-0594-010
Page: 6 of 22

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.

• First- second- or third-degree relative with pathogenic or likely pathogenic variant in ATM, BRCA1, BRCA2, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, PALB2, PMS2 or TP53 genes; OR
• First- or second-degree relative diagnosed with any of the following:
  • Breast cancer in a relative assigned female at birth diagnosed at 45 years of age or younger; OR
  • Breast cancer in a relative assigned male at birth; OR
  • Colorectal or endometrial cancer at 50 years of age or younger; OR
  • Ovarian cancer; OR
  • Pancreatic cancer; OR
  • Prostate cancer, metastatic; OR
  • Two or more first-or second-degree relatives (on the same side of the family) diagnosed at any age with breast, colorectal, endometrial or prostate cancer (not clinically localized Grade Group 1); OR
• Evaluation of suspected prostate cancer (PSA may be repeated following an elevated PSA test as determined by laboratory reference range); OR
• Management (eg, determination of biopsy necessity, monitoring, prognosis, recurrence detection) for an individual diagnosed with prostate cancer

PSA testing includes:

• Complexed PSA (cPSA) (84152)
• Free PSA (fPSA) (84154)
• Free-to-total PSA (fPSA/tPSA)
• Percent-free PSA (%fPSA)
• PSA density (PSAD)
• PSA doubling time (PSADT)
• PSA velocity (PSAV)
• Total PSA (tPSA) (84153)

Laboratory Analysis for Prostate Cancer

Effective Date: 12/14/2023
Revision Date: 12/14/2023
Review Date: 07/27/2023
Policy Number: HUM-0594-010
Page: 7 of 22

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.

ProMark Proteomic Prognostic Test

Humana members may be eligible under the Plan for ProMark Proteomic Prognostic Test when the following criteria are met:

• Life expectancy is at least 10 years; AND
• Post-biopsy; AND
• Very-low-risk, low-risk or favorable intermediate-risk prostate cancer

Prostate Health Index

Humana members may be eligible under the Plan for Prostate Health Index (PHI) (86316) when criteria are met:

• 45 years of age or older and repeat PSA serum level is greater than 3 ng/mL; OR
• Biopsy results indicate any of the following:
  • Atypia, suspicious for cancer; OR
  • Benign; OR
  • High-grade prostate neoplasia

Note: The criteria for PSA testing are not consistent with the Medicare National Coverage Policy and therefore may not be applicable to Medicare members. Refer to the CMS website for additional information.

Coverage Limitations

Humana members may NOT be eligible under the Plan for laboratory analysis for prostate cancer for any tests other than those listed above including, but may not be limited:

• MAAAs for prostate cancer including, but may not be limited:
  • 4Kscore Test (81539)
  • ArteraAI Prostate Test (0376U)

Laboratory Analysis for Prostate Cancer

Effective Date: 12/14/2023
Revision Date: 12/14/2023
Review Date: 07/27/2023
Policy Number: HUM-0594-010
Page: 8 of 22

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.

• EpiSwitch Prostate Screening Test (PSE) (0433U)
• MyProstateScore 2.0 (MPS2) (0403U) (formerly MyProstateScore and Mi- Prostate Score [MiPS]) (0113U)
• PanGIA Prostate (0228U)

PSA derivative testing including, but may not be limited to:

• iPSA
• IsoPSA Assay (0359U)
• PSA slope

Tumor marker tests for prostate cancer including, but may not be limited to:

• CA 50 (86316)
• CA 549 (86316)
• CA 72-4 (86316)
• hK2
• Ki-67
• PCA3 (eg, Progensa PCA3 Assay) (81313) alone or in combination with TMPRSS2:ERG gene fusion

These are considered experimental/investigational as they are not identified as widely used and generally accepted for the proposed uses 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:

Background

• American Cancer Society

Laboratory Analysis for Prostate Cancer

Effective Date: 12/14/2023
Revision Date: 12/14/2023
Review Date: 07/27/2023
Policy Number: HUM-0594-010
Page: 9 of 22

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.

• National Cancer Institute
• National Library of Medicine

Medical Alternatives

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.