Colon cancer blood test effective for average-risk population

A new study appearing in The New England Journal of Medicine (NEJM) investigated the effectiveness of an emerging colon cancer screening option—a cell-free DNA (cfDNA) blood-based test known as Shield—that researchers and clinicians hope will encourage more people to be screened for colorectal cancer (CRC) (doi:10.1056/NEJMoa2304714).

Allison Rosen, MS, from Houston, Texas, is a 12-year CRC survivor who says that she is alive today because of timely colon cancer screening. “Unfortunately,” says Ms Rosen, “after talking with the community about the importance of screening and even with the knowledge that screening can save their life, people tell me every day that they refuse to get screened because both stool-based tests and colonoscopies have very negative stigmas.”

Ms Rosen points to American Cancer Society (ACS) data showing that one third of the screening-eligible population is not getting screened even though 90% of CRC deaths can be prevented with timely screening. Ms Rosen is the director of the ACS’s Project ECHO (Extension for Community Healthcare Outcomes) in Houston, Texas.

The Shield test is a blood-based CRC screening test meant for average-risk people with no family history of CRC and no personal history of CRC or advanced polyps (large polyps). Targeted patients are also CRC symptom–free.

The researchers who conducted the NEJM study believe that this screening test option could be key to improving screening rates, leading to fewer colon cancer deaths.

According to study author William M. Grady, MD, medical director of the Gastrointestinal Cancer Prevention Program at the Fred Hutchinson Cancer Center in Seattle, Washington, the test is on par with stool-based CRC screening tests, such as the fecal immunochemical test (FIT) and the Cologuard multitarget stool DNA test, for the detection of CRC.

The results of the NEJM study were derived from the ECLIPSE (Evaluation of the ctDNA LUNAR Test in an Average Patient Screening Episode) study, a multisite clinical trial of nearly 8000 people aged 45–84 years. The study was underwritten and led by Guardant Health (based in Palo Alto, California). The focus of the study was the comparison of the effectiveness of the blood test and colonoscopies for CRC sensitivity and for advanced neoplasia, including CRC and advanced precancerous lesions. Also investigated was the sensitivity for discovering if advanced precancerous lesions had a negative cfDNA blood-based test.

Of the 7861 patients who met the study criteria, 83.1% with colonoscopy-detected CRC registered a positive cfDNA test; 16.9% had a negative test (i.e., a colonoscopy detected CRC, but a circulating tumor DNA [ctDNA] test did not). Overall, the researchers found that the blood test was most sensitive for CRCs, including early-stage cancers. They also found that it was less sensitive for advanced precancerous lesions, which may become cancerous later.

Furthermore, the researchers found that 89.6% of patients without any advanced colorectal neoplasia—CRC or advanced precancerous lesions from earlier colonoscopies—had a negative cfDNA blood-based test, whereas 10.4% had a positive cfDNA blood-based test. By comparison, they reported that 89.9% of colonoscopies found no CRC, advanced precancerous lesions, or nonadvanced precancerous lesions.

The Guardant Health test is one of approximately 20 blood tests being developed. Although the Guardant test is for CRC, other tests are being developed to screen for other cancers or for multiple cancers. One feature being developed with a few of the tests is the identification of the source of the tumors, which is important for the multicancer detection tests.

“Any screening is better than no screening,” says Cathy Eng, MD, a professor of medicine at Vanderbilt University Medical Center in Nashville, Tennessee. Dr Eng notes that a blood test administered in a clinician’s office might be preferential for patients who shun colonoscopies or do not want to take a fecal test at home and could reduce the wait time for results. “This screening tool will provide impetus for clinicians to offer another non-invasive approach to screening in their clinic quickly.” Dr Eng is the David H. Johnson Endowed Chair in Surgical and Medical Oncology and codirector of gastrointestinal oncology at Vanderbilt. “However, primary care physicians need to recommend and remind their patients about the need for timely screening, and patients have to be willing to be screened. One thing that confounds everything—and which is the same as with the Cologuard fecal test—is we still have no way to ensure that patients who test positive will follow up with a colonoscopy to determine if they are at risk for colon cancer,” she adds.

Reid M. Ness, MD, associate professor of medicine in gastroenterology, hepatology, and nutrition at Vanderbilt University Medical Center, says that it is important to note one strong caveat about the screening tool. “This is a colon cancer detection test, but it is not useful for colon cancer prevention,” says Dr Ness. “Still, our hope is more people will get screened because of this test.”

Another concern that Dr Ness has is what happens when there is a positive test result for circulating cancerous DNA but the follow-up colonoscopy does not detect the source. “The question then becomes, where did the circulating DNA come from? Do patients have to needlessly worry about an increased risk for cancer elsewhere in the body with a positive from this test leading to additional tests that are unnecessary?”

Dr Grady says that the blood test is already an option for CRC screening that can be discussed with a primary care physician when someone is deciding what type of CRC screening test to use. “This is significant given that at this time when people are given the option of doing CRC screening with a stool-based test or with colonoscopy, currently roughly one-third are electing to do neither.”

Two other things are notable about the ECLIPSE trial and the Shield test, says Dr Grady. The first is that the people enrolled in the trial reflected the demographics of the general US population and included proportional enrollment of African Americans/Blacks, Hispanics, and Asian Americans. “This means the results of the Shield test are generally applicable to all people living in the US.”

Dr Grady says that the second key point is that the technology used in the Shield test (ctDNA methylomic and fragmentomic pattern analysis) is novel in a screening test. “It is a very promising technology for blood-based cancer screening tests and is the basis for other blood-based cancer screening tests that are under investigation for screening for cancers like breast cancer, lung cancer, and other types of cancer.”

Screening advocate Ms Rosen believes that a blood test that is available during a visit to a primary care physician could prove to be preferred over a stool-based test or a colonoscopy, and adherence could increase. “I believe the best screening test is the one that gets done. As more tests come on the market, as long as the sensitivity and specificity are comparable to stool-based tests, this will be a great option to offer patients.”

Ms Rosen adds, “As an advocate, I work daily to break the stigmas that exist and stress that screening can save lives. The community needs to understand that they need to be screened before they experience symptoms because, by the time they start to have symptoms, the likelihood of being diagnosed with cancer at a later stage is high. The goal of this test is prevention. I have lost numerous friends to colorectal cancer, so the possibility of getting more people screened is a goal of mine. I want to prevent someone from having to go through what I went through.”