VANCOUVER –
In a blinded, prospective, cross-sectional study, researchers assessed a multitarget stool RNA test (mt-sRNA; Colosense, Geneoscopy) vs. colonoscopy for detection of advanced adenomas and CRC in average-risk individuals aged 45 years and older.
In a prospective, cross-sectional study, investigators evaluated the clinical performance of a next-generation multitarget stool DNA (mt-sDNA; Cologuard, Exact Sciences) and fecal hemoglobin assay for CRC screening in adults aged 40 years and older.
Both studies were presented at the ACG: American College of Gastroenterology 2023 Annual Scientific Meeting.
RNA as a biomarker
For CRC-PREVENT, which evaluated the mt-sRNA test, David Lieberman, MD, professor of medicine and former chief of the division of gastroenterology and hepatology at the Oregon Health & Science University, Portland, and colleagues recruited a diverse group of 8,289 adults undergoing colonoscopy at one of more than 3,800 endoscopy centers nationwide. Recruitment included outreach through social media, which could be used to improve future screening rates, Dr. Lieberman said.
The full study findings of CRC-PREVENT were also published online in the Journal of the American Medical Association.
Participants provided stool samples before colonoscopy. Colosense includes a commercially available fecal immunochemical test (FIT) and tests for eight different strands of RNA. The mt-sRNA test results were compared with the colonoscopy results.
The mt-sRNA test had 100% sensitivity for early, stage I cancers, which were detected in 12 patients. Advanced adenomas were detected with an overall sensitivity of 45%. When the advanced adenomas were ≥ 2 cm, sensitivity increased to 51%.
Specificity was 87% among patients with negative findings for hyperplastic polyps or lesions.
The mt-sRNA test showed significant improvements in sensitivity for CRC (94% vs. 77%; P = .029) and advanced adenomas (45% vs 29%; P < .001), when compared with the FIT results alone.
“This is the first large study to include the 45- to 49-year-old population, for whom screening is now recommended,” Dr. Lieberman told this news organization.
Results show a sensitivity of 100% for detecting CRC and 44% for advanced adenomas in this younger age group. That performance is “excellent,” said Dr. Lieberman.
Results also were reliable across all ages.
“The consistent performance across all age groups for whom screening is recommended is a key finding and was totally unknown” before this study, Dr. Lieberman said.
RNA-based testing may have an advantage over DNA biomarker tests, which can be prone to age-related DNA methylation changes, he added.
Detection by DNA
Thomas Imperiale, MD, distinguished professor of medicine at Indiana University, Indianapolis, and colleagues conducted the BLUE-C trial to validate the next-generation mt-sDNA test for CRC screening.
The mt-sDNA assay tests for three novel methylated DNA markers and fecal hemoglobin.
Dr. Imperiale and colleagues studied 20,176 adults (mean age, 63 years) scheduled for screening colonoscopy at one of 186 U.S. sites. Participants provided a stool sample for the mt-sDNA test and comparator FIT prior to colonoscopy preparation. They compared results to colonoscopy and FIT findings.
Colonoscopy revealed 98 people with CRC, 2,144 with advanced precancerous lesions, and 17,934 with no advanced neoplasia.
Sensitivity of the mt-sDNA test for detecting CRC was 93.9% (95% confidence interval, 87.1-97.7), advanced precancerous lesions was 43.4% (95% CI, 41.3-45.6), and advanced precancerous lesions with high-grade dysplasia was 74.6% (95% CI, 65.6-82.3).
Sensitivities of the mt-sDNA test for detecting CRC and advanced precancerous lesions were significantly higher than FIT (P < .0001).
In terms of specificity, the mt-sDNA test had a specificity of 90.6% (95% CI, 90.1-91.0) for the absence of advanced neoplasia. Specificity for non-neoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2-93.1).
The mt-sDNA test demonstrated high specificity and high CRC and advanced precancerous lesion sensitivity. The test outperformed FIT for these factors on sensitivity but not specificity, the authors noted.
Improved specificity was a goal of developing this next-generation assay. The BLUE-C trial demonstrated a 30% improvement in specificity that “will decrease the number of unnecessary colonoscopies performed for false-positive results,” said Dr. Imperiale.
“I was pleased to see the robust results support this new battery of markers,” Dr. Imperiale added. Improvements associated with this next-generation test could “help further reduce the incidence of and mortality from colorectal cancer.”
