Blood Test for Colon Cancer Screening May Miss Some Precancers, FDA Staff Says

FDA reviewers questioned the potential benefits of Guardant Health’s blood-based test for colorectal cancer (CRC) screening in documents released ahead of an advisory committee meeting on Thursday.

The Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee will be asked to discuss several issues involving the Shield test, including whether its performance supports its use as a primary CRC screening option, especially given its low sensitivity for advanced adenomas.

The Shield test is an in vitro diagnostic blood test intended to detect CRC-derived alterations in cell-free DNA. Guardant is seeking approval for Shield as a screening test for individuals 45 years or older at average risk for the disease. The company suggests the test “should be considered alongside other CRC screening modalities, like colonoscopy, and is not a replacement for diagnostic colonoscopy or surveillance colonoscopy in high-risk individuals.”

FDA staffers indicated that the benefit of the test is that it may increase compliance with CRC screening and detect earlier-stage cancer, “which may potentially cure the patient and also potentially prolong survival when treated,” they wrote in an executive summary.

On the other hand, the test comes with the risk of failing to detect a patient with advanced adenoma, “which can later become neoplastic, losing the opportunity to prevent or prolong the onset of colorectal cancer,” the staffers wrote.

Shield was evaluated in the pivotal ECLIPSE trial — a multisite, prospective, non-randomized, observational study designed to evaluate the clinical performance of the blood-based test in patients 45 to 84 years of age who were of average risk for CRC.

Results from the study showed that the cell-free DNA blood-based test had a sensitivity of 83.1% for CRC and a specificity of 89.6% for advanced neoplasia. However, among 1,116 participants with advanced precancerous lesions, the test was positive for only 147, for a sensitivity of 13.2%.

Thus, the FDA wants the panel to discuss the risks and benefits of a CRC screening test with such low sensitivity for the detection of advanced adenomas, and to discuss “potential mitigations which might be deployed to ensure physicians and patients are able to make informed choices regarding screening test options to mitigate clinical risks of the Shield test’s advanced adenoma sensitivity.”

In its own executive summary ahead of Thursday’s panel, Guardant acknowledged Shield’s limited advanced adenoma detection could result in harm “if the screening test is used only once in a lifetime.”

“Given Shield’s expected higher adherence and the extended dwell time of adenomas progressing to CRC, the risk of limited advanced adenoma detection and accrued harm would be reduced,” the company said. It added that it expects Shield to improve overall CRC screening rates, “which outweighs the harm from individuals pursuing Shield over other CRC screening options.”

The FDA also wants the advisors to discuss whether a post-approval study evaluating the benefits and risk of programmatic CRC screening over time with Shield would be beneficial.

While the FDA is not required to follow the advice of its advisory committees, it typically does.

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