VANCOUVER, British Columbia — The novel multitarget stool RNA test (ColoSense) showed high sensitivity for detecting colorectal neoplasia among adults ages 45 and older, according to the phase III prospective CRC-PREVENT trial.
Among 8,920 participants, the test sensitivity for detecting colorectal cancer was 94%, and 46% for detecting advanced adenomas, while specificity for no lesions on colonoscopy was 88%, reported David Lieberman, MD, of Oregon Health & Science University in Portland, during the American College of Gastroenterology (ACG) annual meeting.
The test also showed significant improvement in sensitivity for colorectal cancer compared with results of fecal immunochemical testing (FIT; 94% vs 78%, McNemar P=0.01) and advanced adenomas (46% vs 29%, McNemar P<0.001), Lieberman and colleagues noted in their study, which was simultaneously published in JAMA.
The test met primary endpoints and is being considered for approval by the FDA, Lieberman said.
Session moderator Irving Pike, MD, a past president of the ACG and a gastroenterologist in Alamo, California, said that “this is a unique test based on RNA rather than DNA. This will give us another modality for screening people for colon cancer. It is not approved yet, and there are several more steps before it will be available.”
The U.S. Preventive Services Task Force (USPSTF) recommends both invasive and noninvasive approaches for colorectal cancer screening, with colonoscopy being the standard for identifying and removing colorectal lesions, including polyps, the authors noted.
Currently, the most sensitive FDA-approved or -cleared noninvasive screening test for colorectal cancer is the multitarget stool DNA test (Cologuard).
Lieberman and his co-authors pointed to the similar noninvasiveness of the multitarget stool RNA test and its comparable level of false-positive results versus existing molecular screening tests.
“Moreover,” they wrote, “the test characteristics in a younger cohort (45-49 years), now recommended for screening, [are] preserved.”
While most colorectal cancers occur in adults older than 50, about 12% of all cases are observed in people under 50.
Lieberman said that one of the hallmarks of CRC-PREVENT was that it used social media to recruit participants.
“Unlike prior clinical trials, subjects were not recruited from gastrointestinal doctors’ offices where participants had prescheduled colonoscopies,” he explained. “We used a novel decentralized recruitment strategy to enroll participants via social media.”
Interested participants completed a self-reported online survey to screen for the intended use population and to obtain socioeconomic and demographic information. Information on race and ethnicity was collected to ensure diverse representation in the clinical trial.
For this blinded cross-sectional study, 8,920 participants ages 45 and older were identified online using social media platforms and enrolled from 49 states from June 2021 to June 2022 using a decentralized nurse call center. They completed the multitarget stool RNA test, which was comprised of commercially available FIT, concentration of eight RNA transcripts, and participant-reported smoking status. Stool samples were collected prior to participants completing a colonoscopy at their local endoscopy center.
Mean participant age was 55, 60% were women, 84% were white, 11% were Black, and 7% were Hispanic or Latino.
Of the participants, 0.4% had colorectal cancer and 6.8% had advanced adenomas.
The multitarget stool RNA test had 100% sensitivity for stage I colorectal cancer, and 65% sensitivity for high-grade dysplasia or 10 or more adenomas. Positive predictive value for colorectal neoplasia was 20.6%.
Within colorectal cancer categories, the test sensitivity for stage I/II colorectal cancer was not significantly different from sensitivity for stage III/IV colorectal cancer (92.3% vs 100%; P=0.39).
Lieberman and team noted that study limitations were mostly due to use of a decentralized clinical trial for participant recruitment, which could have led to variations in colonoscopy quality metrics and differences in participant treatment.
The trial was funded by Geneoscopy.
Lieberman disclosed relationships with Geneoscopy, ColoWrap, and CapCheck.
Pike disclosed no relevant relationships with industry.
Source Reference: Barnell EK, et al “Multitarget stool RNA test for colorectal cancer screening” JAMA 2023; DOI: 10.1001/jama.2023.22231.