An investigational, blood-based test for circulating tumor DNA shows “reasonable accuracy” for detecting colorectal cancer (CRC) among people at average risk, researchers report, but its ability to reveal early-stage lesions presents more of a challenge.
The clinical validation results of the PREEMPT CRC study, reported in JAMA, suggest further improvements are needed for it to replace traditional colonoscopy and stool-based screening.
In an editorial accompanying the findings, Jason Dominitz, MD, from the VA Puget Sound Health Care System in Seattle, and colleagues wrote that the results present a complex message to patients and primary care physicians.
“We are excited about the prospect of a CRC screening test that may increase participation,” they maintained.
“The ability to detect a CRC signal in blood is a major scientific advance. However, the illusion of simplicity is deceptive: the new test may paradoxically result in inferior outcomes if substituted for currently recommended tests or if follow-up colonoscopy is not completed in those with abnormal result.”
CRC is the second leading cause of cancer deaths in the U.S. and most of this mortality could be prevented if the 42% of Americans aged 45 to 75 years who are not up to date with screening would participate.
However, people may be reluctant to undertake screening with lower intestinal endoscopy or repeated rounds of occult blood–based stool screening tests due to inconvenience, discomfort, embarrassment, aversion to handling stools, or fear of complications.
In an attempt to find a more acceptable, non-invasive test, researchers studied the value of an investigational blood test for circulating tumor DNA in asymptomatic adults aged 45 to 85 years who were at average CRC risk at 201 centers across the U.S. and United Arab Emirates.
The prospective, population-based, observational study enrolled 48,995 participants, with a final total of 27,010 evaluable participants.
Participants had blood collected, after which they underwent a screening colonoscopy.
The primary end points were sensitivity for colorectal cancer, specificity for advanced colorectal neoplasia—consisting of colorectal cancer or advanced precancerous lesions—negative predictive value for advanced colorectal neoplasia, and positive predictive value for advanced colorectal neoplasia.
The secondary end point was sensitivity for advanced precancerous lesions.
Aasma Shaukat, MD, from NYU Grossman School of Medicine, and co-workers report that all primary end points met the prespecified acceptance criteria, with the test demonstrating 79.2% sensitivity for colorectal cancer and 91.5% specificity for advanced colorectal neoplasia.
However, it did not meet prespecified criterion for sensitivity for advanced precancerous lesions, with a value of just 12.5% that was lower than fecal immunochemical testing, multitarget stool DNA, and multitarget stool RNA.
The researchers concluded: “In an average-risk colorectal cancer screening population, a blood-based test demonstrated acceptable accuracy for colorectal cancer detection, but detection of advanced precancerous lesions remains a challenge, and ongoing efforts are needed to improve test sensitivity.”
Editorialists Dominitz and colleagues added: “If a blood test is offered, clinicians should educate their patients about its lower detection of advanced precancerous lesions and early-stage CRC compared with colonoscopy and stool-based testing. This is a complex message for patients and primary care clinicians.
“In increasingly busy clinical practice, to avoid the lure of offering a seemingly simple option that could actually increase population-level CRC cases and deaths if supplanting accepted tests, it may be prudent to emphasize that colonoscopy and stool-based tests are first line and that blood-based tests should only be considered if the alternative is no screening at all.”
