VANCOUVER, BC — Two multitarget stool tests in development compare favorably for colorectal cancer (CRC) screening in average-risk people, suggest two new studies.
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 American College of Gastroenterology (ACG) 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 and Science University in Portland, and colleagues recruited a diverse group of 8289 adults undergoing colonoscopy at one of more than 3800 endoscopy centers nationwide. Recruitment included outreach through social media, which could be used to improve future screening rates, Lieberman said.
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,” Lieberman told Medscape Medical News.
Results show a sensitivity of 100% for detecting CRC and 44% for advanced adenomas in this younger age group. That performance is “excellent,” said 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, 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 School of Medicine in 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.
Imperiale and colleagues studied 20,176 adults (mean age, 63 years) scheduled for screening colonoscopy at one of 186 US 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, 2144 with advanced precancerous lesions, and 17,934 with no advanced neoplasia.
Sensitivity of the mt-sDNA test for detecting CRC was 93.9% (95% CI, 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 Imperiale.
“I was pleased to see the robust results support this new battery of markers,” Imperiale added. Improvements associated with this next-generation test could “help further reduce the incidence of and mortality from colorectal cancer.”
Tests to Provide More Noninvasive Options
Both are “important studies” that look at a large, average-risk screening population in the United States, said Aasma Shaukat, MD, MPH, who was not affiliated with the research. “Both show high sensitivity for detecting CRC and decent specificity for advanced adenomas.”
While we will have to wait for the full publications, US Food and Drug Administration approvals, and insurance coverage, gastroenterologists can expect to see these tests in clinical use in the near future, added Shaukat, professor of medicine and population health at NYU Grossman School of Medicine, New York City, and lead author of the ACG 2021 Colorectal Cancer Screening Guidelines.
These tests provide more noninvasive options for CRC screening and are more accurate, which hopefully will translate into increased screening and a reduced burden of CRC, she said.
“It also will mean more stool test positive colonoscopies can be expected in our practices,” Shaukat said.
American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting. Abstracts 47 and 54. Presented October 22, 2023.
Geneoscopy funded the CRC-PREVENT trial. Exact Sciences funded the BLUE-C trial. Lieberman is an advisor or review panel member for Geneoscopy. Imperiale receives grant or research support from Exact Sciences. Shaukat reports no relevant financial relationships.
Damian McNamara is a staff journalist based in Miami, Florida. He covers a wide range of medical specialties, including infectious diseases, gastroenterology, and critical care. Follow Damian on Twitter: @MedReporter.
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