Johnson, Heather

e15647 Background: Colorectal cancer (CRC) screening offers an opportunity to prevent invasive disease by detecting and removing precancerous lesions. Colonoscopy-based detection of adenomas and serrated polyps is strongly associated with reduced risk of interval CRC. While the performance of noninvasive CRC screening tests is well described, comparative evidence on adenoma detection across screening colonoscopy and stool-based strategies with follow-up colonoscopy remains limited. We conducted a systematic review to compare adenoma detection across CRC screening modalities. Methods: MEDLINE (PubMed) and Embase were searched from January 1, 2000, through July 10, 2025, for peer-reviewed, U.S.-based studies reporting colonoscopy among average-risk adults aged ≥45 years, who underwent screening colonoscopy or follow-up colonoscopy after a positive stool-based screening test [fecal immunochemical test (FIT) or multi-target stool DNA (mt-sDNA) test]. The primary outcome was the detection of one or more adenomas at colonoscopy. High-risk or surveillance cohorts, AI-assisted colonoscopy, diagnostic accuracy trials, and non-U.S. studies were excluded. Results: Among 7,710 de-duplicated records, 147 studies underwent full-text review, and 47 studies were included in quantitative synthesis, with reported adenoma detection for screening colonoscopy alone (n = 31), follow-up colonoscopy after a positive FIT alone (n = 4), follow-up colonoscopy after a positive mt-sDNA test alone (n = 4), and for more than one of the screening strategies of interest (n = 8). Across included studies, overall adenoma detection differed by screening pathway. Follow-up colonoscopy after a positive mt-sDNA test demonstrated the highest adenoma detection (66.3%; 95% CI, 61.2-71.1), with lower adenoma detection observed for colonoscopy after a positive FIT (50.6%; 95% CI, 43.4-57.8) and screening colonoscopy alone (33.8%; 95% CI, 30.9-36.8) (Table 1). Conclusions: Detection of adenomas was highest following colonoscopy performed after a positive mt-sDNA test compared with FIT-positive follow-up or screening colonoscopy alone. These findings highlight differences in downstream detection across CRC screening tests and suggest that, in settings where colonoscopy resources are constrained, initial mt-sDNA screening with timely follow-up colonoscopy may help prioritize patients most likely to benefit. CRC screening modality No. of Studies Adenoma detected Study population Proportion, % (95% CI) Heterogeneity, I² (%) Between-study variance (τ 2 ) P-value* mt-sDNA 8 17,436 29,098 66.3 (61.2-71.1) 94.6 0.0924 <0.0001 FIT 11 17,588 32,630 50.6 (43.4-57.8) 94.0 0.2187 <0.0001 Screening colonoscopy 38 2,351,801 6,378,891 33.8 (30.9-36.8) 99.8 0.1710 NA *P-value represents adenoma detection vs. screening colonoscopy adenoma detection.

Abstract Introduction: Blood-based tests represent a compelling option for early detection and management of cancers and other chronic diseases. While blood-based tests may offer potential to increase patient engagement, the assumption of greater adherence in clinical practice requires further evaluation. This systematic review aimed to evaluate the real-world adherence to established blood-based tests for commonly recommended screening indications, to better inform expectations for proposed application to average-risk colorectal cancer (CRC) screening. Methods: A systematic search of PubMed, Embase, and citations was performed to identify literature published from 2010 to 2023. Studies examined adherence to routine blood-based laboratory tests with a Grade A or B recommendation per the United States Preventive Services Task Force (USPSTF) for diabetes, dyslipidemia, human immunodeficiency virus (HIV), and hepatitis C virus (HCV) in an average-risk patient population were included. In addition, prostate-specific antigen (PSA) testing adherence for prostate cancer screening (Grade-C USPSTF recommendation), the only commonly accessible blood-based single-cancer screening test for average-risk adults, was also included. Studies without venipuncture-derived blood were excluded. Results: Of 53,067 articles screened, 69 were included in the analysis. Overall, adherence rates of blood-based tests were highly variable, with median values (interquartile range, IQR) of 66.3% (11.8%), 67.8% (18.0%), 34% (28.7%), and 36.8% (30%) for diabetes, dyslipidemia, HCV, and HIV, respectively. PSA testing adherence was 37.2% (18.4%). Beyond disease type, adherence varied by study design, data source, patient characteristics, clinical setting, and study country. Information and selection bias were the most common risks of bias. Conclusions: Based on data from this comprehensive systematic review, real-world adherence to currently recommended, blood-based screening strategies is suboptimal. Future research is needed to identify the extent to which these data are generalizable to blood-based CRC screening, and to determine if/how this candidate strategy would impact clinical, economic, and health equity outcomes. Citation Format: Quang A. Le, Takako Kiener, Heather A. Johnson, Rukaiyya S. Khan, Joyce Kong, Kevin H. Li, Gina Thompson, A. Burak Ozbay, Mallik Greene, Paul J. Limburg, A. Mark Fendrick, John B. Kisiel, Derek W. Ebner. Systematic review of real-world adherence to blood-based laboratory tests for average-risk disease screening: potential implications for emerging colorectal cancer screening modalities [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A027.