54 - Next-Generation Multitarget Stool DNA Test for Colorectal Cancer Screening: A Prospective Clinical Validation Study (BLUE-C) (Late-Breaking Abstract)

Thomas F. Imperiale, MD¹, Kyle Porter, MAS², Julia Zella, PhD², Zubin D. Gagrat, BS², Marilyn C. Olson, PhD², Sandi Statz, MS², Jorge Garces, PhD², Philip Lavin, PhD³, Humberto Aguilar, MD⁴, Don Brinberg, MD⁵, Charles Berkelhammer, MD⁶, John B. Kisiel, MD⁷, Paul J. Limburg, MD²; ¹Indiana University School of Medicine, Indianapolis, IN; ²Exact Sciences, Madison, WI; ³Boston Biostatistics Research Foundation, Framingham, MA; ⁴Louisiana Research Center, Shreveport, LA; ⁵Great Lakes Gastroenterology Research, Mentor, OH; ⁶Southwest Gastroenterology, Oak Lawn, IL; ⁷Mayo Clinic, Rochester, MN.


Introduction: The multitarget stool DNA (mt-sDNA) test is a non-invasive, average-risk colorectal cancer (CRC) screening test. To enhance clinical performance (particularly specificity), we developed a next-generation (next-gen) mt-sDNA test that combines 3 novel methylated DNA markers and fecal hemoglobin. We report results of a prospective, cross-sectional study (BLUE-C; NCT04144738) to determine next-gen mt-sDNA test performance.

Methods: Eligible adults (>40 years) scheduled for screening colonoscopy were consented, enrolled at 186 sites in the United States, and provided a stool sample for the next-gen mt-sDNA test and comparator fecal immunochemical test (FIT; OC-Auto^® Micro 80, Polymedco, Inc.) prior to colonoscopy preparation. Colonoscopy findings were categorized as CRC, advanced precancerous lesions (APL; lesions with high grade dysplasia, ≥25% villous morphology, or ≥10 mm in size), no advanced neoplasia (absence of CRC or APL), and non-neoplastic findings or negative colonoscopy. Next-gen mt-sDNA test markers, algorithm, and cut-off were locked prior to sample processing by a central laboratory blinded to clinical study data. Primary outcomes were CRC sensitivity and specificity for absence of advanced neoplasia. Secondary outcomes were APL sensitivity, specificity for non-neoplastic findings or negative colonoscopy, and comparison of CRC and APL sensitivity for the next-gen mt-sDNA test versus FIT.

Results: Among 26,758 participants enrolled from 11/15/2019 to 1/5/2023, 20,176 (75.4%) were evaluable (mean age 63.0 years; 53.2% female; 60.1% non-Hispanic White). Colonoscopy findings included 98 CRC, 2,144 APL, and 17,934 with no advanced neoplasia (6,973 with non-advanced adenomas; 10,961 with non-neoplastic findings or negative colonoscopy). Next-gen mt-sDNA test specificity for absence of advanced neoplasia was 90.6% (95% CI, 90.1-91.0; Table). CRC sensitivity was 93.9% (95% CI, 87.1-97.7). APL sensitivity was 43.4% (95% CI, 41.3-45.6); sensitivity for APL with high-grade dysplasia was 74.6% (95% CI, 65.6-82.3). Specificity for non-neoplastic findings or negative colonoscopy was 92.7% (95% CI, 92.2-93.1). Next-gen mt-sDNA test CRC and APL sensitivities were significantly higher than FIT (P<0.0001; Table).

Discussion: In this prospective clinical validation study, the next-gen mt-sDNA test demonstrated high specificity and high CRC and APL sensitivity, outperforming FIT for CRC and APL sensitivity but not specificity.


Disclosures:


Thomas F. Imperiale, MD¹, Kyle Porter, MAS², Julia Zella, PhD², Zubin D. Gagrat, BS², Marilyn C. Olson, PhD², Sandi Statz, MS², Jorge Garces, PhD², Philip Lavin, PhD³, Humberto Aguilar, MD⁴, Don Brinberg, MD⁵, Charles Berkelhammer, MD⁶, John B. Kisiel, MD⁷, Paul J. Limburg, MD²; ¹Indiana University School of Medicine, Indianapolis, IN; ²Exact Sciences, Madison, WI; ³Boston Biostatistics Research Foundation, Framingham, MA; ⁴Louisiana Research Center, Shreveport, LA; ⁵Great Lakes Gastroenterology Research, Mentor, OH; ⁶Southwest Gastroenterology, Oak Lawn, IL; ⁷Mayo Clinic, Rochester, MN. 54 - Next-Generation Multitarget Stool DNA Test for Colorectal Cancer Screening: A Prospective Clinical Validation Study (BLUE-C) (Late-Breaking Abstract), ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.