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Medical Policy Multicancer Early Detection Testing
Table of Contents • Policy: Commercial • Coding Information
• Information Pertaining to All Policies
• Policy: Medicare • Description
• References
• Authorization Information • Policy History

Policy Number: 124 BCBSA Reference Number: 2.04.158 (For Plan internal use only) NCD/LCD: N/A Related Policies
Analysis of Human DNA in Stool Samples as a Technique for Colorectal Cancer Screening, #557 Policy Commercial Members: Managed Care (HMO and POS), PPO, and Indemnity
Medicare HMO BlueSM and Medicare PPO BlueSM Members

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

Policy guidelines The review 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 review 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.

Plans may need to alter local coverage medical policy to conform to state law regarding coverage of biomarker testing.

Prior Authorization Information
Inpatient • For services described in this policy, precertification/preauthorization IS REQUIRED for all products if the procedure is performed inpatient.
Outpatient • For services described in this policy, see below for products where prior authorization might be required if the procedure is performed outpatient.

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Outpatient Commercial Managed Care (HMO and POS) This is not a covered service. Commercial PPO and Indemnity This is not a covered service. Medicare HMO BlueSM This is not a covered service. Medicare PPO BlueSM This is not a covered service.

CPT Codes / HCPCS Codes / ICD Codes
Inclusion or exclusion of a code does not constitute or imply member coverage or provider reimbursement. Please refer to the member’s contract benefits in effect at the time of service to determine coverage or non-coverage as it applies to an individual member.

Providers should report all services using the most up-to-date industry-standard procedure, revenue, and diagnosis codes, including modifiers where applicable. CPT Codes There are not any specific codes for this service. Description Cancer is the second leading cause of death in the United States following heart disease, causing 1 in every 6 deaths.1, 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.2, 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.3, This review 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.4, 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.

Summary
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.

Summary of Evidence For individuals who are being screened for cancer who receive multicancer early detection (MCED) testing, the relevant published evidence includes a systematic review, and one US-based prospective study. Relevant outcomes are overall survival, disease-specific survival, functional outcomes, quality of life, treatment-related mortality, and treatment-related morbidity. A systematic review of 36 studies on MCED tests highlighted variability in diagnostic accuracy. Evidence was limited, with no completed RCTs. While

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the tests exhibited high specificity, sensitivity varied depending on study design, population, reference tests, and follow-up duration. Insufficient follow-up for negative results led to high risk of bias across studies. Currently, the Galleri test is the only commercially available MCED test in the United States. One prospective study of the Galleri test reported a positive predictive value of 38% (95% CI, 29 to 48) and specificity and negative predictive value of approximately 99%. The specifics regarding the practical application of the test, including the appropriate at-risk target populations, frequency of testing, and follow- up for positive and negative results, have not been fully described. There is a need for performance characteristics for both the prediction of overall cancer likelihood and the tissue of origin. No clinical utility studies have been published to date, and estimates of changes in cancer-specific mortality, quality of life, functional outcomes, and rates of overdiagnosis and overtreatment remain unknown. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Policy History Date Action 8/2025 Annual policy review. Policy updated with literature review through May 16, 2025; references added. Policy statements unchanged. 8/2024 Annual policy review. Policy updated with literature review through April 16, 2024; references added. Policy statements unchanged. 11/2023 New medical policy describing investigational indications. Effective 11/1/2023. Information Pertaining to All Blue Cross Blue Shield Medical Policies Click on any of the following terms to access the relevant information: Medical Policy Terms of Use Managed Care Guidelines Indemnity/PPO Guidelines Clinical Exception Process Medical Technology Assessment Guidelines References

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4. National Cancer Institute. Questions and Answers about Multi-Cancer Detection Tests. Accessed May 22, 2025.
5. National Cancer Institute. NIH launches research network to evaluate emerging cancer screening technologies 2024. Accessed, May 19, 2025.
6. National Cancer Institute. Vanguard Study. Accessed May 10, 2025.
7. Bossuyt PM, Irwig L, Craig J, et al. Comparative accuracy: assessing new tests against existing diagnostic pathways. BMJ. May 06 2006; 332(7549): 1089-92. PMID 16675820
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12. GRAIL, LLC. Frequently asked questions for healthcare providers interested in ordering the Galleri test. Accessed May 13, 2025.
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15. Cuzick J, Cafferty FH, Edwards R, et al. Surrogate endpoints for cancer screening trials: general principles and an illustration using the UK Flexible Sigmoidoscopy Screening Trial. J Med Screen. 2007; 14(4): 178-85. PMID 18078562
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22. Nicholson BD, Oke J, Virdee PS, et al. Multi-cancer early detection test in symptomatic patients referred for cancer investigation in England and Wales (SYMPLIFY): a large-scale, observational cohort study. Lancet Oncol. Jul 2023; 24(7): 733-743. PMID 37352875
23. Wade R, Nevitt S, Liu Y, et al. Multi-cancer early detection tests for general population screening: a systematic literature review. Health Technol Assess. Jan 2025; 29(2): 1-105. PMID 39898371
24. Schrag D, Beer TM, McDonnell CH, et al. Blood-based tests for multicancer early detection (PATHFINDER): a prospective cohort study. Lancet. Oct 07 2023; 402(10409): 1251-1260. PMID 37805216
25. Neal RD, Johnson P, Clarke CA, et al. Cell-Free DNA-Based Multi-Cancer Early Detection Test in an Asymptomatic Screening Population (NHS-Galleri): Design of a Pragmatic, Prospective Randomised Controlled Trial. Cancers (Basel). Oct 01 2022; 14(19). PMID 36230741
26. National Comprehensive Cancer Network. Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic; Version 3.2025. Accessed May 16, 2025.