Blood Test for Colon Cancer Screening Gets Guideline Backing

The American Cancer Society (ACS) updated its colorectal cancer (CRC) screening guidelines to include new molecular-based screening tests that have received FDA approval since the release of the 2018 guidelines.

While the new recommendations reaffirm that average-risk adults should begin CRC screening at age 45 and continue through age 75 for those with a life expectancy greater than 10 years, the ACS has added guidelines for new blood-based screening tests, as well as one updated and one new at-home stool-based screening options, reported Robert A. Smith, PhD, of the ACS’s Center for Early Cancer Detection, and colleagues.

“Consistent with prior guidelines, the ACS emphasizes that offering multiple, recommended screening options supports informed patient choice and may improve participation, because the most effective screening test is the one that the patient completes,” they wrote in CA: A Cancer Journal for Clinicians.

While confirming that colonoscopy remains the gold standard for CRC screening, and that blood-based testing is not a preferred option, Smith and co-authors suggested that it can be used for individuals who decline or do not complete preferred screening tests, with the proviso that it should be followed by a colonoscopy if the test is positive.

The FDA approved the Shield circulating cell-free DNA blood-based test for CRC screening in adults ages 45 and older at average risk in 2024, based on results from the ECLIPSE study, which showed that the test had a sensitivity of 83% for CRC and a specificity of 90% for advanced neoplasia.

Another blood-based test, the Freenome multiomics blood test, has been submitted to the FDA for review.

Smith and team cautioned that compared with established stool-based tests, blood-based tests have “demonstrated lower sensitivity for both advanced precancerous lesions and stage I cancers, with modeling studies predicting less effectiveness in reducing CRC incidence and mortality.”

They also pointed out that Medicare covers just one brand of blood-based test and that coverage by private insurers is uncertain.

The update also included guidance on two stool-based tests, which were both approved in 2024: the next-generation multi-target stool DNA test (Cologuard Plus), an updated version of an already-recommended at-home test analyzing stool samples for specific DNA markers and hemoglobin, and the multi-target stool RNA test (ColoSense), a new at-home test that analyzes stool samples for specific RNA markers and hemoglobin.

These tests demonstrate high sensitivity for colorectal cancer and moderate sensitivity for advanced precancerous lesions and are recommended for screening every 3 years, noted Smith and colleagues.

“Ongoing evaluation of adherence, real-world implementation, and clinical outcomes will inform future updates for these new tests,” they wrote. “For screening to be effective, a positive result on any noncolonoscopy screening test requires timely follow-up with colonoscopy, preferably within 6 months, to complete the screening process.”

In an accompanying editorial, Gloria D. Coronado, PhD, of the University of Arizona in Tucson, and David A. Lieberman, MD, of Oregon Health and Science University in Portland, emphasized that adherence to follow-up colonoscopy among patients who obtain a blood test “will be important.”

They pointed out that they conducted a study that showed lower adherence to follow-up colonoscopy at 6 months in patients with an abnormal blood-based test result versus an abnormal fecal immunochemical test result.

“We need to know which methods work best in achieving high adherence and at what cost,” they wrote. “Importantly, future studies should measure trade-offs, such as how many patients complete a blood test who might have completed a more accurate test had conditions been optimized.”

Coronado and Lieberman also expressed concern that blood-based testing will not be confined to the group that it is recommended for in the guidelines, and that some patients incorrectly believe a blood test is more accurate than a stool-based test for detecting CRC.

Going forward, “providers need information on real-world implementation to accurately communicate the risks and benefits of each test,” as well as data on clinical outcomes, they added.

The impact of the guidelines “will depend on how well implementation is monitored and guided by real-world evidence,” the editorialists concluded. “Achieving the full potential of these guidelines will require rigorous tracking of adherence across the full screening cascade; transparent reporting of test performance, including individual components; and sustained attention to clinical outcomes, including precursor lesion detection, cancer stage at diagnosis, and mortality.”