Erica Barnell, MD, PhD1, Elizabeth Wurtzler, PhD2, Julie La Rocca, MS2, Thomas Fitzgerald, MS2, Jessica Petrone, MD1, Yansheng Hao, MD, PhD3, Faith Holmes, MD4, David Lieberman, MD5 1Washington University School of Medicine, St. Louis, MO; 2Geneoscopy, St. Louis, MO; 3University of Rochester Medical Center, Rochester, NY; 4Elligo Health Research, Austin, TX; 5Oregon Health & Science University, Portland, OR
Introduction: Noninvasive tests for colorectal cancer (CRC) screening must include sensitive detection of CRC and precancerous lesions. These tests must be validated for the intended-use population, which includes average-risk patients ≥ 45 years of age. While recent guidance changes have lowered the recommended age for CRC screening, minimal data has been reported to demonstrate performance characteristics of noninvasive screening tests in individuals 45-49 years old.
Methods: This pivotal clinical trial was a blinded, prospective cross-sectional study that evaluated a novel multi-target stool RNA test (Colosense™, mt-sRNA) when compared to a colonoscopy. Participants were identified online using social media platforms and enrolled using decentralized call centers. Stool samples were collected prior to a colonoscopy. The mt-sRNA test incorporated a commercially available fecal immunochemical test (FIT) and RNA concentrations for eight transcripts. The mt-sRNA test results (positive or negative) were compared to the results of a colonoscopy.
Results: Using a decentralized clinical trial approach, 8,289 participants were recruited from 49 states within the U.S. and participants obtained colonoscopies at > 3,800 different endoscopy centers. The mt-sRNA test sensitivity for detecting CRC was 94%, with 100% sensitivity for early stage (Stage I) cancers (n = 12). Sensitivity for detecting advanced adenomas (AA) was 45%, with 51% sensitivity for AAs >2cm in size. Specificity for no findings (hyperplastic polyps and no lesions on colonoscopy) was 87%. Notably, 24% of participants were between the ages of 45 and 49. For participants in the younger age bracket, sensitivity for CRC was 100% and sensitivity for AAs was 44%. The mt-sRNA test showed significant improvements in CRC sensitivity (94% vs. 77%, p = 0.029) and AA sensitivity (45% vs. 29%, p < 0.001) when compared to the results of the FIT in isolation.
Discussion: The mt-sRNA test demonstrated high sensitivity and specificity across all age groups with significant improvement in sensitivity for colorectal neoplasia (CRC and AA) when compared to a FIT. Maintenance of sensitivity in participants aged 45-49 was likely attributable to the use of RNA biomarkers, which are not subject to DNA age-related methylation patterns that may impact test results across age groups. Specificity for no findings on colonoscopy were comparable to existing molecular diagnostic tests (Funded by Geneoscopy Inc.; ClinicalTrials.gov: NCT04739722).
Figure: The CRC-PREVENT clinical trial demonstrated high accuracy and consistent performance in a diverse patient population to support the novel mt-sRNA test (Colosense™) for CRC screening.
Disclosures:
Erica Barnell: Geneoscopy – Employee, Stock Options, Stock-privately held company.
Elizabeth Wurtzler: Geneoscopy – Employee, Stock Options, Stock-privately held company.
Julie La Rocca: Geneoscopy – Employee, Stock Options, Stock-privately held company.
Thomas Fitzgerald: Geneoscopy – Employee, Stock Options, Stock-privately held company.
David Lieberman: ColoWrap – Advisory Committee/Board Member. Geneoscopy – Advisor or Review Panel Member. UDX – Consultant.
Erica Barnell, MD, PhD1, Elizabeth Wurtzler, PhD2, Julie La Rocca, MS2, Thomas Fitzgerald, MS2, Jessica Petrone, MD1, Yansheng Hao, MD, PhD3, Faith Holmes, MD4, David Lieberman, MD5, 47, CRC-PREVENT: Multi-Target Stool RNA Test for Detection of Colorectal Cancer and Advanced Adenomas in Average-Risk Individuals 45 and Older, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.
