Multicancer Early Detection Testing

POLICY NUMBER

A.2.04.158

DESCRIPTION

Many cancers appear to have a better prognosis if diagnosed early in their natural history. This has led to efforts to detect preclinical cancers in asymptomatic individuals through screening. Cancer screening tests such as ‘liquid biopsies’ that are minimally invasive and can simultaneously detect multiple types of cancer have been called multicancer early detection (MCED) tests.

Cancer is the second leading cause of death in the United States following heart disease, causing 1 in every 6 deaths. Excluding non-melanoma skin cancers, over 2 million new cancer cases are expected to be diagnosed in the US in 2025 and more than 618,000 people will die from the disease. Many cancers appear to have a better prognosis if diagnosed early in their natural history. This has led to efforts to detect preclinical cancers in asymptomatic persons through screening. However, screening tests have associated benefits and harms that must be considered when evaluating whether a test should be used in a population.

Early detection of cancer has 2 components: early diagnosis and screening. Early diagnosis is the early identification of cancer in symptomatic individuals with the aim of reducing the proportion of individuals diagnosed at a late stage. Screening is the identification of preclinical cancer or precursor lesions in apparently healthy, asymptomatic populations by tests that can be applied rapidly and widely in the target population. This policy focuses on tests for screening indications.

Cancer screening tests such as ‘liquid biopsies’ that are minimally invasive have been called multicancer early detection (MCED) tests. MCED tests are distinct from traditional cancer screening tests due to two main factors. Firstly, they employ a single blood test rather than x-rays, imaging tests like mammography, or procedures like colonoscopy. Secondly, they simultaneously screen for multiple types of cancer from various organs, including those not checked by existing methods. MCED tests predict the presence of cancer, rather than diagnose it. Depending on the biological signals measured, they may screen for multiple cancer types. Current development focuses on measuring signals in blood plasma, such as changes in DNA/RNA sequences, DNA methylation patterns, DNA fragmentation patterns, protein biomarker levels, and antibodies against cancer cell components. Researchers are continually developing new technological approaches to expand the range of measurable biological signals, such as those identified by immune cells.

No MCED tests have been approved or cleared by the U.S. Food and Drug Administration (FDA). Several tests, including Galleri® (GRAIL), CanScan™ (Geneseeq), and OverC™ Multi-Cancer Detection Blood Test (Burning Rock) have been granted breakthrough device designation by the FDA.

In February 2024, the National Cancer Institute (NCI) launched the Cancer Screening Research Network (CSRN) to evaluate emerging technologies for cancer screening. As part of this initiative, the CSRN began the Vanguard Study, which aims to enroll up to 24,000 participants to evaluate the feasibility and benefits of MCED tests. This study will focus on diverse populations across eight US sites led by the Fred Hutchinson Cancer Center, with further participation from the US Department of Defense and the Department of Veterans Affairs. Participants will be randomly assigned to a control group or one of two MCED test groups. The control group will have blood drawn without further testing, while the MCED test groups will receive assays - Avantect® from ClearNote Health and Shield™ from Guardant Health - at no cost. The study objectives include assessing participant willingness, adherence to testing, diagnostic follow-up, and evaluating the feasibility of diagnostic processes.

Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments. Galleri is available under the auspices of the Clinical Laboratory Improvement Amendments.

Laboratories that offer laboratory-developed tests must be licensed by the Clinical Laboratory Improvement Amendments for high-complexity testing. To date, the FDA has chosen not to require any regulatory review of this test.

Related medical policies –

• Urinary Biomarkers for Cancer Screening, Diagnosis, and Surveillance

• Circulating Tumor DNA and Circulating Tumor Cells for Cancer Management (Liquid Biopsy)

• Serologic Genetic and Molecular Screening for Colorectal Cancer

• Analysis of Human DNA in Stool Samples as a Technique for Colorectal Cancer Screening

POLICY

The use of multicancer early detection (MCED) tests (e.g., Galleri) is considered investigational for cancer screening.

POLICY EXCEPTIONS

None

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

The policy will focus on MCED tests that are available in the US. The Galleri test is the only commercially available MCED test in the US at this time. This policy will not include tests that screen for only 1 cancer (e.g., colon).

While advocates of the test might claim the simplicity of a blood test will improve compliance over existing cancer screening tests and offer screening for cancers that currently do not have recognized screening tests available, no evidence exists to support these claims or to estimate the potential harms of false positives.

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

03/15/2024: New policy added. Approved by the Medical Policy Advisory Committee.

07/22/2024: Policy description updated regarding tests. Policy statement unchanged.

08/21/2025: Policy description updated regarding new cancer data, MCED tests, and studies. Policy statement unchanged.

SOURCE(S)

Blue Cross Blue Shield Association policy # 2.04.158

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

Investigational Codes

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