Concert Genetic Oncology: Cancer Screening Form

Concert Genetic Oncology: Cancer Screening
V1.2025
Date of Last Revision: 11/2024
CENTENE Corporation

Revision log
Coding Implications

CONCERT GENETIC ONCOLOGY: CANCER SCREENING

See Important Reminder at the end of this policy for important regulatory and legal
information.

OVERVIEW
This policy relates to genetic and biomarker tests that aim to screen for specific cancers in
individuals who are at risk to develop them. These screening tests can be designed for
asymptomatic individuals that are at an average risk level for cancer, or for individuals that are
known to be at a higher risk to develop a specific cancer. Genetic and biomarker cancer screening
tests aim to identify the presence of cancer before symptoms appear and when treatment is often
most effective. These tests are not currently diagnostic for cancer, but typically determine if an
individual has an increased chance that cancer is present.

Screening tests for colorectal cancer may be performed by analyzing specific DNA present in fecal
matter or peripheral blood. Cancer screening tests may also be performed on urine samples to
screen for bladder cancer and colon polyps. These methods offer a noninvasive alternative to
currently available screening approaches such as colonoscopy.

Screening tests for lung cancer are potentially useful adjuncts to the low-dose computed
tomography (LDCT), a recommended lung cancer screening tool in high-risk populations.
Biomarkers such as autoantibodies, metabolites, proteins, and microRNA may be sampled from
many different bodily sources, including whole blood, serum, plasma, bronchial brushings, and
sputum. Circulating blood-based and serum based biomarkers are convenient samples as they are
relatively easy and inexpensive to collect.

It is important to note that screening tests are not diagnostic tests. The results from a screening test
put an individual into a lower risk or higher risk status. For an individual that is put into the higher
risk status, following up with an appropriate diagnostic test would be necessary to make a
definitive diagnosis of cancer.

For lung cancer, approaches where a biomarker based initial screen is followed by LDCT, or in
which a biomarker test is combined with LDCT, show promise for use in early detection. However,
more high quality evidence is needed to support and guide the implementation of these tests.

Concert Genetic Oncology: Cancer Screening
V1.2025
Date of Last Revision: 11/2024
CENTENE Corporation

POLICY REFERENCE TABLE
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
2023, American Medical Association. All rights reserved. CPT codes and 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.

The tests, associated laboratories, CPT codes, and ICD codes contained within this document serve
only as examples to help users navigate claims and corresponding criteria; as such, they are not
comprehensive and are not a guarantee of coverage or non-coverage. Please see the Concert
Platform for a comprehensive list of registered tests.

| Criteria Sections | Example Tests (Labs) | Common CPT Codes | Common ICD Codes | Ref |
|-------------------|---------------------|-----------------|-----------------|-----|
| Colorectal Cancer Screening Tests | | | | |
| FIT-DNA Testing (Stool DNA Testing) | Cologuard (Exact Sciences Corporation, LLC) | 81528 | Z12.10-Z12.13 | 1, 2 |
| Urinary Biomarker Tests for Pre-cancerous Colon Polyps | PolypDx (Metabolomic Technologies) | 0002U | Z12.10-Z12.13 | 1 |
| Blood-based Biomarker Colorectal Cancer Screening Tests | BeScreened-CRC (Beacon Biomedical) | 0163U | Z12.10-Z12.13 | 4 |
| | FirstSight (CellMax Life) | 0091U | | |
| | ColonSentry (StageZero Life Sciences) | 81599 | | |
| | Epi proColon (Epigenomics) | 81327, G0327 | | |
| | ColoVantage (Quest Diagnostics) | | | |
| | ColoScape Colorectal Cancer Detection (DiaCarta Clinical Lab) | 0368U | | |

Concert Genetic Oncology: Cancer Screening
V1.2025
Date of Last Revision: 11/2024
CENTENE Corporation

| | Guardant Shield (Guardant Health) | 81479 | | |
| Lung Cancer Screening Tests | | | | |
| Blood-based Biomarker Lung Cancer Screening Tests | FirstLook (Delfi Diagnostics) | | Z12.2 | 3 |

OTHER RELATED POLICIES
This policy document provides criteria for cancer screening tests. 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: Algorithmic Testing for criteria related to gene expression profiling and tumor
  multianalyte assays with algorithmic analyses.
- 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.
- Genetic Testing: General Approach to Genetic and Molecular Testing for criteria related
  to cancer screening that is not specifically discussed in this or another non-general policy.

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:

Concert Genetic Oncology: Cancer Screening
V1.2025
Date of Last Revision: 11/2024
CENTENE Corporation

COLORECTAL CANCER SCREENING TESTS
FIT-DNA Testing (Stool DNA Testing)
I. The use of FIT-DNA Testing (stool DNA testing) (81528) to screen for colorectal cancer
   may be considered medically necessary when:
   A. The member/enrollee is 45 years of age or older, AND
   B. The member/enrollee is an individual who is at average risk for colorectal cancer,
      because the member/enrollee does not have any of the following:
      1. A personal history of colorectal cancer or adenoma or sessile serrated polyp,
         OR
      2. A family history of colorectal cancer in close relatives, OR
      3. A personal history of inflammatory bowel disease (ulcerative colitis or
         Crohn’s disease), OR
      4. A personal history of cystic fibrosis, OR
      5. A confirmed or suspected hereditary colorectal cancer syndrome, such as
         familial adenomatous polyposis (FAP) or Lynch syndrome (hereditary non-
         polyposis colon cancer or HNPCC), OR
      6. A personal history of receiving radiation to the abdomen (belly) or pelvic
         area to treat a prior cancer.
II. The use of FIT-DNA Testing (stool DNA testing) (81528) to screen for colorectal cancer is
    considered investigational for all other indications.

**NOTE:** Fecal immunochemical testing (FIT) alone is not in the scope of this policy (see definitions)

Urinary Biomarker Tests for Pre-cancerous Polyps
I. The use of urinary biomarker tests for pre-cancerous polyps (0002U) is considered
   investigational.
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Concert Genetic Oncology: Cancer Screening
V1.2025
Date of Last Revision: 11/2024
CENTENE Corporation

Blood-based Biomarker Colorectal Cancer Screening Tests
I. The use of blood-based biomarkers to screen for colorectal cancer (0091U, 0163U, 0368U,
   81327, 81479, 81599, G0327) is considered investigational.
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LUNG CANCER SCREENING TESTS
Blood-based Biomarker Lung Cancer Screening Tests
I. The use of blood-based biomarker tests for lung cancer screening are considered
   investigational.
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## DEFINITIONS
1. Fecal immunohistochemical testing (FIT): Screening test for colon cancer that detects
   human blood in the lower intestines. (FIT testing alone does not involve any genetic test
   and is outside of the scope of this policy).
2. FIT-DNA test: Combination of the fecal immunochemical (FIT), which uses antibodies to
   detect blood in the stool, with a test that detects abnormal DNA from cancer or polyp cells
   in the stool.
3. Low-dose computed tomography (LDCT): Proposed as a method of screening
   asymptomatic, high risk individuals for lung cancer; it refers to a non-contrast study with a
   multi-detector CT scanner during a single maximal inspiratory breath-hold with a scanning
   time of under 25 seconds. It has been suggested that LDCT may be an improved early lung
   cancer detection tool based on the advantages it appears to have over CXR and sputum
   cytology to detect lung cancer at an earlier stage.
4. MicroRNAs (miRNAs): Tissue specific, small, non-coding RNAs regulating gene
   expression which may identify candidates for early detection of lung cancer.
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Concert Genetic Oncology: Cancer Screening
V1.2025
Date of Last Revision: 11/2024
CENTENE Corporation

BACKGROUND AND RATIONALE
COLON CANCER SCREENING TESTS
FIT-DNA Testing (Stool DNA Testing)
National Comprehensive Cancer Network (NCCN)

Current NCCN guidelines on Colorectal Cancer Screening (1.2024) support the use of FIT-DNA
for colorectal cancer screening in average-risk individuals aged 45-75 with a life expectancy
greater than or equal to 10 years, and notes that the decision to screen individuals aged 76-85
should be individualized. (p. CSCR-1A) The choice of screening modality should be based on
patient preference and availability after discussion. (p. CSCR-1).

Food and Drug Administration (FDA)

Cologuard (Exact Sciences):

On August 12, 2014, Cologuard (Exact Sciences) was approved by the U.S. Food and Drug
Administration (FDA) through the premarket approval process as an automated fecal DNA testing
product (P130017). Cologuard is intended for the qualitative detection of colorectal neoplasia
associated with DNA markers and occult hemoglobin in human stool. A positive result may
indicate the presence of CRC or advanced adenoma and should be followed by diagnostic
colonoscopy. (p. 1)

On September 20, 2019, the FDA approved the expansion of the Cologuard label to include adults
ages 45 years or older. Cologuard was previously indicated for those aged 50 years or older.
Cologuard is not a replacement for diagnostic colonoscopy or surveillance colonoscopy in high-
risk individuals.

Urinary Biomarker Tests for Pre-cancerous Colon Polyps
National Comprehensive Cancer Network (NCCN)

Current NCCN guidelines on Colon Cancer Screening (1.2024) do not include a recommendation
for colorectal cancer screening via urine-based screening.

Concert Genetic Oncology: Cancer Screening
V1.2025
Date of Last Revision: 11/2024
CENTENE Corporation

There is insufficient evidence to support the use of this test. No recommendations for or against
this testing within standard professional society guidelines covering this area of testing were
identified.

Blood-based Biomarker Colorectal Cancer Screening Tests
Concert Evidence Review for Coverage Determination (Published 12/21/2023)

Multiple studies have been published on BeScreened, FirstSight CRC, ColonSentry, Epi
proColon, Colovantage, ColoScape Colorectal Cancer Detection, and Guardant Shield and their
ability to screen for increased risk of colorectal cancer, including several meta-analyses and
validation studies. Most of these studies include a measure of clinical validity measured by
sensitivity and specificity, and several studies compared these measures to those of colonoscopy,
FIT or FOBT testing. The evidence for clinical validity does not consistently demonstrate
superior sensitivity or specificity for these tests across studies. This lack of consistency
highlights the importance of understanding the mechanism of these biomarkers in colorectal
cancer in order to explain the observed variability. Further, there is limited evidence to
demonstrate that these tests promote a safe and effective alternative to colonoscopy or useful
screening test to prioritize patients who should get colonoscopies. While the United States
Preventive Services Task Force (USPSTF) and the National Comprehensive Cancer Network
(NCCN) address blood-based tests for colon cancer screening in their most recent
recommendations, neither recommend the testing.

At the present time, blood-based biomarker tests such as BeScreened, FirstSight CRC,
ColonSentry, Epi proColon, Colovantage, ColoScape Colorectal Cancer Detection and Guardant
Shield have INSUFFICIENT EVIDENCE in peer-reviewed publications to effectively result in
improved health outcomes compared to the current standard of care.

LUNG CANCER SCREENING TESTS
Blood-based Biomarker Lung Cancer Screening Tests
National Comprehensive Cancer Network (NCCN)

Current NCCN guidelines on Lung Cancer Screening (2.2024) do not include a recommendation
for lung cancer screening via blood-based or micro-RNA based screening. Current NCCN
guidelines support lung cancer screening using LDCT for individuals with high risk factors.

Concert Genetic Oncology: Cancer Screening
V1.2025
Date of Last Revision: 11/2024
CENTENE Corporation

There is insufficient evidence to support the use of this test. No recommendations for or against
this testing within standard professional society guidelines covering this area of testing were
identified.
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| Reviews, Revisions, and Approvals | Revision Date | Approval Date |
|----------------------------------|--------------|--------------|
| Policy developed. | 03/23 | 03/23 |
| Semi-annual review. Updated title to reflect V1.2024 version. Overview, coding, reference-table, background and references updated. Throughout policy: replaced “coverage criteria” with “criteria”. For Policy Reference Table: Cancer Screening Tests: added G0328. For Other Related Policies: added “and Molecular”. For Criteria: Blood-based Biomarker Colorectal Cancer Screening Tests: added G0327 and G0328. For Background and Rationale: Colon Cancer Screening Tests- Blood-based Biomarker Colorectal Cancer Screening Tests: removed “Technical Assessment 2021”; removed “October 2021...”, added “May 2023.” | 10/23 | 10/23 |
| Semi-annual review. Updated title to reflect V2.2024 version. Minor rewording for clarity throughout. Coding, reference-table, background and references updated. | 04/24 | 04/24 |
| Semi-annual review. Updated title to reflect V1.2025 version. Urinary Biomarker Tests for Pre-cancerous Colon Polyps: Reformatted Background and Rationale; Updated NCCN version. Blood-based Biomarker Colorectal Cancer Screening Tests: Streamlined portions of Background and Rationale section for brevity; Updated NCCN version. Blood-based Biomarker Lung Cancer Screening Tests: Updated example test in Policy Reference Table; Streamlined and clarified portions of Background and Rationale section. FIT-DNA Testing (Stool DNA Testing): Updated NCCN version in Background and Rationale and references. | 11/24 | 11/24 |

Concert Genetic Oncology: Cancer Screening
V1.2025
Date of Last Revision: 11/2024
CENTENE Corporation



Note: For Medicaid member/enrollees, when state Medicaid coverage provisions conflict with
the coverage provisions in this clinical policy, state Medicaid coverage provisions take precedence.
Please refer to the state Medicaid manual for any coverage provisions pertaining to this clinical
policy.

Note: For Medicare member/enrollees, to ensure consistency with the Medicare National
Coverage Determinations (NCD) and Local Coverage Determinations (LCD), all applicable NCDs
and LCDs and Medicare Coverage Articles should be reviewed prior to applying the criteria set
forth in this clinical policy. Refer to the CMS website at http://www.cms.gov for additional
information.

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