Blood test to detect colon cancer could move a step closer to FDA approval in the US

To screen for colon and rectal cancers, most people have colonoscopies, which can feel invasive and require anesthesia, or they may take an at-home stool test, which can be more convenient but also awkward — and not appealing for the squeamish.

But a simple blood test could soon become more broadly available.

Palo Alto, California-based biotechnology company Guardant Health has applied for US Food and Drug Administration approval of Shield, its blood test to screen for early signs of colorectal cancer, and on Thursday, a panel of expert advisers to the FDA gathered to discuss data on the screening test.

The FDA’s Molecular and Clinical Genetics Panel of the Medical Devices Advisory Committee met to discuss the benefits and risks of the test and vote on whether it’s safe and effective.

The panel voted 8-1 that the Shield test is safe for use in people who meet the criteria for testing, 6-3 that the test is effective for use in those meeting the criteria and 7-2 that the benefits of the test outweigh the risks.

The discussions and voting outcomes will be shared with the FDA, which takes into consideration but does not have to follow the committee’s advice when deciding whether to approve the test.

If Shield receives FDA approval, it will be the first approved blood screening test for colorectal cancer that meets requirements for Medicare reimbursement, said Dr. Craig Eagle, chief medical officer at Guardant Health.

Current options for colorectal cancer screening for people at average risk include a stool-based test done either annually or every three years; a traditional colonoscopy every 10 years; a virtual colonoscopy every five years; or a sigmoidoscopy procedure, which involves using a tube-like instrument called an endoscope to examine the lower part of the colon, every five years.

The Shield blood test is already available as a laboratory-developed test or LDT, so it does not necessarily require approval by the FDA to be performed under current regulations. However, the agency’s approval could make the test more widely available and broadly covered as another primary screening option.

The test would not replace the other screening methods that are commonly used. Rather, according to Guardant, it could be another noninvasive option, which could help boost the number of people who complete recommended screenings.

“Current primary non-invasive screening options are limited to stool-based tests,” Eagle wrote in an email. “Our Shield blood test offers patients a convenient option that has a proven level of performance within range of non-invasive tests.”

Several research teams and companies have been working to develop simple blood tests to screen for colon and rectal cancers.

“The argument is that a point-of-care blood test can actually significantly reduce the incidence rate of very advanced disease and save lives, even if it has lesser potential to prevent the disease,” said Robert Smith, senior vice president of early cancer detection science at the American Cancer Society.

A blood-based test would not be able to identify concerning lesions or polyps in the colon or rectum, as a colonoscopy would. With visual exams, like colonoscopies or sigmoidoscopies, a lesion or polyp that has the potential to develop into cancer can be identified and removed, thus preventing the disease.

“Most people would like to see a blood-based option that was more accurate with respect to finding precursor lesions in addition to cancers. But the rather remarkable thing about colorectal cancer screening is that people vary in their readiness to do one test or another,” Smith said. “You have to give people a choice.”

Guardant’s Shield test would be for colorectal cancer screening in people 45 or older who are at average risk of the disease, according to FDA meeting materials. The US Preventive Services Task Force recommends that screening for colorectal cancer start at age 45 for people at average risk.

The test would not be recommended for high-risk people, such as those with personal or family histories of the disease, and people who receive an “abnormal” test result using Shield would be referred for a colonoscopy.

Since the launch of the lab-developed version of the Shield test in May 2022, it has been used by more than 20,000 people, and more than 90% of those who were prescribed the test have completed it, according to Guardant Health.

“Any test developer knows that they have to get their test approved by the FDA for it to really gain traction,” Smith said.

Mixed vote on effectiveness

At Thursday’s meeting, the FDA advisers indicated some division about the test when answering three questions about its safety and effectiveness and whether the benefits outweigh any risks.

“I voted yes on all three, with the indication that this is to be used in asymptomatic individuals for the detection of colon cancer. I did feel like it met that indication,” panel member Dr. Sean Spencer, a gastroenterologist and physician scientist at Stanford University, said in the meeting.

“I think in the labeling, it should clearly indicate that this is not to detect adenomas and it is not designed as a preventive strategy,” Spencer said. Adenomas are tumors that are not cancerous.

Panel member Dr. Charity Morgan also voted yes to all three categories.

“My reasoning was very similar to Dr. Spencer’s: the indication is for detection of colorectal cancer. If the indication had said something about advanced adenomas, that would have changed my vote,” said Morgan, a professor at the University of Alabama at Birmingham.

“I was on the fence about the effectiveness because of the limited sensitivity for stage I. I think if the labeling was very clear that this test is strong as for detecting stages II, III and IV, that would turn my vote from a weak yes to a strong yes,” she said. “But ultimately, I concluded that they did show effectiveness as well as safety and a good risk-benefit profile.”

Meanwhile, panel member Dr. Padma Rajagopal voted that she thinks the test is safe and that the benefits outweigh the risks, but she does not think the test is effective due to its limitations in detecting advanced adenomas and says it’s not as effective in detecting stage I cancers as in detecting more advanced disease.

“If there were refinements to that indicated use or refinements in the way that providers and patients were educated, I will change my vote to a yes,” said Rajagopal, a physician-scientist at the National Cancer Institute.

Panel member Dr. William Brugge voted that, while he thinks the Shield test is safe, he does not think that it’s effective or that the benefits outweigh the risks.

“My primary concern here is that I don’t think Shield is a particularly good screening test for colon cancer,” said Brugge, a gastroenterologist at Mount Auburn Hospital in Cambridge, Massachusetts. He added that he thinks “many of the other existing tests” are better.

The FDA advisers’ votes will not immediately change or shift the American Cancer Society’s screening recommendations, Smith said.

“The American Cancer Society typically looks for FDA approval at this higher level before we would include a test in our guidelines,” Smith said.

“We really want to hear how the FDA thinks about this test, and then with respect to guidelines, I can’t tell you what any one organization – including ours – is going to do, because it’s a process that requires a great deal of literature review and evidence review and consideration of the FDA decision, as well as the implications,” he said. “It’s a process that takes some time.”

How the test works

The Shield test works by detecting tumor DNA in blood samples, and a physician would need to order the test and kit for their patient.

The test was found to have around 83% sensitivity and 90% specificity in a study published in March in the New England Journal of Medicine. Sensitivity refers to a test’s ability to accurately identify people with disease, designating them as positive. Specificity refers to its ability to accurately designate people without a disease as negative.

That study, which included nearly 8,000 people, was among the data that the FDA panel members reviewed in Thursday’s meeting.

“FDA seeks the Panel’s input on whether the information submitted by Guardant is adequate to support the safety and effectiveness of the Shield for the proposed intended use,” the meeting materials say.

The study found that about 83% of participants who had been diagnosed with colorectal cancer via colonoscopy tested positive for the disease on the Shield test, compared with about 17% who had a false negative.

The test showed about 88% sensitivity in detecting stage I, II or III colorectal cancer and a lower sensitivity, around 13%, in detecting precancerous lesions.

About 90% of the study participants without advanced colorectal cancer or precancerous lesions tested negative on the blood test, compared with about 10% who had a false positive test result.

Many people skip screening

The FDA meeting materials note that colorectal cancer occurs in about 150,000 people in the United States each year and is associated with more than 50,000 deaths annually.

The disease is the second most common cause of cancer deaths in the United States, and it’s estimated that more than 75% of people who die from colorectal cancer were not up to date with their screenings.

For the average person, the lifetime risk of developing colorectal cancer is about 1 in 23 for men and 1 in 25 for women, according to the American Cancer Society.

Signs and symptoms of colorectal cancer include changes in bowel habits, rectal bleeding or blood in the stool, cramping or abdominal pain, weakness and fatigue, and weight loss.

The share of colorectal cancer diagnoses among adults younger than 55 in the US has been rising since the 1990s, and when it comes to screening methods, new research suggests that the use of at-home stool tests for the disease has become more popular, especially among younger adults.

Data released last week by Epic Research, owned by the health-care software company Epic, shows that in early 2018, colonoscopies accounted for about 96% of colorectal cancer screenings, but that proportion fell below 70% by the third quarter of 2023.

Meanwhile, the use of DNA stool tests significantly rose in the second quarter of 2020, reaching 31% of screenings by the fourth quarter of 2023.

The study included data on more than 1.4 million first-time colorectal cancer screenings conducted by colonoscopy or DNA stool testing between 2018 and 2023.

Despite the current colorectal cancer screening recommendations, “a significant portion of the eligible population hesitates to participate in screenings. Common deterrents include the discomfort associated with stool-based tests, the preparation required for procedures, and anxiety surrounding colonoscopy examinations,” Dr. Jamin Brahmbhatt, a urologist and robotic surgeon with Orlando Health and past president of the Florida Urological Society, wrote in a CNN opinion piece in March.

“This apprehension may contribute to only about 60% of those eligible for colorectal cancer screenings staying up to date on the recommended tests,” Brahmbhatt wrote, adding that when it comes to blood-based screening tests, “the hope is, once approved by the US Food and Drug Administration, this blood test would increase screening for colorectal cancer.”

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