First, blood-based CRC screening has limitations. Most importantly, it is less effective than other methods at detecting precancerous lesions and Stage I cancers, which means it can miss opportunities for prevention or early intervention. Sensitivity increases with later stage cancers, reaching up to 100% sensitivity for Stage IV CRC. While not ideal, this may help long-unwilling patients finally receive a diagnosis and treatment.

Because early detection is critical to patient outcomes, policymakers, medical directors, and public health, experts are actively considering the implications of blood-based CRC screening for health plans, providers, and patients.¹ Here are 3 insights on how health plans and providers can deploy it most effectively.

In 2021, more than 40% of eligible patients were not current with any CRC screening.² For patients unwilling to undergo colonoscopy or stool-based screening methods, blood-based screening may be an alternative.

Colonoscopy remains the most effective method for detecting and removing precancerous lesions, and blood-based screening should not replace it. Health plans and providers should prioritize USPSTF-endorsed screening methods first and offer blood-based screening only to patients who decline other options.³

The American Gastroenterological Association (AGA) and National Comprehensive Care Network (NCCN) have recognized blood-based screening only for those patients unwilling to complete guideline-endorsed methods, noting that while imperfect, it is more effective than no screening at all.

Health plans may wish to create differential incentives or other tools to encourage patients to choose USPSTF-endorsed screening methods. For example, patients who undergo colonoscopy or stool-based tests would receive high-level financial benefit or other reward, and patients who opt for blood-based screening receive a lower-level reward. This approach prevents missed diagnoses in patients who would have completed more sensitive screening methods.

The value of blood-based CRC screening depends on follow-up. Without colonoscopy confirmation, its benefits are limited. Yet, compliance is uneven: a 2025 study showed only 49% of patients with a positive blood test followed up with a colonoscopy within 6 months.⁴ In contrast, follow-up rates are 85% for mt-sDNA and 35% for FIT.⁵

The same barriers that kept patients from colonoscopy initially — time, transportation, preparation discomfort⁶ — often prevent follow-up. Addressing these barriers directly is essential when offering blood-based screening.

Patients need the right level of information to make an informed decision about CRC screening.

Because blood-based CRC testing has low sensitivity to precancerous lesions and Stage I cancer, false negative results may give patients a misplaced sense of security. Patients who delay re-screening may develop more advanced disease. 

At the same time, false positives can cause anxiety, especially since blood-based CRC tests are cross-reactive with nine other types of cancer.⁷ While a negative colonoscopy following a positive blood test rarely indicates hidden cancer elsewhere, patients may still feel uneasy without clear communication.

Providers should explain that:

• Blood-based CRC screening is less effective at early detection and is only recommended when patients decline colonoscopy or guideline-endorsed stool-based tests.
• A positive blood-based screening result must be followed by a colonoscopy.
• A positive blood-based screening with a negative colonoscopy does not usually indicate another cancer.
• Patients who receive a positive blood-based result and a negative colonoscopy should follow with routine screening and remain alert to symptoms.

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