State and School Employees' Health Insurance Plan - Analysis of Human DNA in Stool Samples as a Technique for Colorectal Cancer Screening

POLICY NUMBER

L.2.04.444

DESCRIPTION

Detection of DNA abnormalities associated with colorectal cancer (CRC) in stool samples has been proposed as a screening test for CRC. This technology is another potential alternative to currently available screening approaches such as fecal occult blood testing, fecal immunochemical testing (FIT), and colonoscopy.

Colorectal Cancer

Several cellular genetic alterations have been associated with colorectal cancer (CRC). In the proposed multistep model of carcinogenesis, the tumor suppressor gene p53 and the proto-oncogene KRAS are most frequently altered. Variants in adenomatous polyposis coli genes and epigenetic markers (e.g., hypermethylation of specific genes) have also been detected. Colorectal cancer is also associated with DNA replication errors in microsatellite sequences (termed microsatellite instability) in patients with Lynch syndrome (formerly known as hereditary nonpolyposis colorectal cancer) and in subgroups of patients with sporadic colon carcinoma. Tumor-associated gene variants and epigenetic markers can be detected in exfoliated intestinal cells in stool specimens. Since cancer cells are shed into stool, tests have been developed to detect these genetic alterations in the DNA from shed colorectal cancer cells isolated from stool samples.

On August 12, 2014, Cologuard® (Exact Sciences Corporation) was approved by the U.S. Food and Drug Administration (FDA) through the premarket approval process as an automated fecal DNA testing product for use in average risk adults aged 50 to 84 years (P130017). Cologuard is intended for the qualitative detection of colorectal neoplasia associated DNA markers and of occult hemoglobin in human stool. A positive result may indicate the presence of CRC or advanced adenoma and should be followed by diagnostic colonoscopy. On September 20, 2019, the FDA approved the expansion of the Cologuard label to include average risk adults aged ≥45 years. Cologuard is not a replacement for diagnostic colonoscopy or surveillance colonoscopy in high-risk individuals. On August 26, 2020, the FDA approved the post-approval study (PAS) protocol titled: "A Real-World Study of Patients Under the Age of 50 Screened for Colorectal Cancer (CRC) Using Cologuard in the U.S. (Tidal)." On October 3, 2024, Cologuard Plus^TMwas approved by the FDA. On March 31, 2025, Exact Sciences Corporation launched the Cologuard Plustest with plans to phase out Cologuard.

POLICY

The use of an FDA-approved fecal DNA test (Cologuard or Cologuard Plus) is considered medically necessary once every 3 years under preventive care benefits as a screening technique for individuals age 45 - 75 at average risk for colorectal cancer for whom colorectal cancer preventive screening is indicated AND meet ALL of the following criteria:

1. Has not had any of the following United States Preventive Services Task Force (USPSTF) recommended (A rating) colorectal cancer screening performed during the recommended screening interval:

2. • Colonoscopy in the past 10 years, or

   • Flexible sigmoidoscopy in the past 5 years, or

   • Guaiac-based fecal occult blood test (gFOBT) in the past year, or

   • Fecal DNA test in the past 3 years (Cologuard or Cologuard Plus),AND

3. Has no signs or symptoms of colorectal disease, including lower gastrointestinal pain, blood in stool, positive guaiac fecal occult blood test or fecal immunochemical test,          AND

4. Remains at average risk of developing colorectal cancer defined by the following:

5. • No personal history of adenomatous polyps, colorectal cancer, or inflammatory bowel disease, including Crohn's Disease and ulcerative colitis, and

   • No family history of colorectal cancers or adenomatous polyps, familial adenomatous polyposis, or hereditary nonpolyposis colorectal cancer.

The use of an FDA-approved fecal DNA test is considered investigational for all other indications including post colorectal cancer diagnosis surveillance.

The use of non-FDA approved fecal DNA test and all other methods for the analysis of DNA in stool samples are considered investigational.

If a fecal DNA test has been used as a colorectal cancer preventive screening, then the following services are not medically necessary and not eligible for coverage as a colorectal cancer preventive screening within three years of the fecal DNA test screening:

• Colonoscopy

• Flexible sigmoidoscopy

• Guaiac-based fecal occult blood test (gFOBT) in the past year

• Fecal DNA test (Cologuard or Cologuard Plus)

POLICY EXCEPTIONS

None

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy should not be used in lieu of the Mississippi State and School Employees’ Life and Health Insurance Plan.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  Consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  Appropriate with regard to standards of good medical practice; and

C.  Not solely for the convenience of the Member, his or her Provider; and

D.  The most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

03/20/2019: New policy added effective 01/01/2018.

12/09/2021: Policy updated to state that effective 01/01/2022, the use of an FDA-approved fecal DNA test is considered medically necessary once every 3 years under preventive care benefits as a screening technique beginning at age 45.

01/27/2022: Policy Description updated regarding indications for Cologuard. Policy statements unchanged. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity."

01/19/2023: Policy description updated. Policy statements unchanged.

12/21/2023: Policy reviewed. Policy statements unchanged. Code Reference section updated to add new 2024 CPT code 0421U, effective 01/01/2024.

03/15/2024: Policy reviewed; no changes.

03/26/2025: Policy reviewed; no changes.

01/01/2026: Policy criteria updated to add Cologuard Plus. Added CPT Code 0464U to the Code Reference section. 

SOURCE(S)

1. Blue Cross Blue Shield Association medical policy # 2.04.29

2. U.S. Preventive Services Task Force Recommendations

   https://www.uspreventiveservicestaskforce.org/BrowseRec/Index/browse-recommendations

CODE REFERENCE

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Medically Necessary Codes

Investigational Codes

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