The Use of Blood-Based Biomarkers in the Prediction of Colorectal Neoplasia at the Time of Primary Screening Colonoscopy Among Average-Risk Patients: A Systematic Literature Review

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Abstract
Background/Objectives: Risk prediction models (RPMs) for colorectal cancer (CRC) could facilitate risk-based screening. Models incorporating biomarkers may improve the utility of current RPMs. We performed a systematic review of studies reporting RPMs for CRC that evaluated the impact of blood-based biomarkers on clinical outcome prediction at the time of screening colonoscopy in average-risk populations. Methods: We conducted a search of MEDLINE, Web of Science, and PubMed databases from inception through April 2024. Studies that developed or validated a model to predict risk of CRC or its precursors were included. Studies were limited to those including patients undergoing average-risk CRC screening. Results: Sixteen studies published between 2015 and 2024 were included. Outcomes included CRC (16 studies) and high-risk adenomas (1 study). Using a complete blood count was the most common biomarker and was able to achieve an AUC of 0.82 and a specificity of 0.88. Other blood-based biomarkers included were various serum proteins/metabolites/enzymes, plasma metabolites, insulin-related factors, and anemia markers. The highest-performing model, with an AUC of 0.99, involved the use of a plasma metabolite panel. Conclusions: The evidence base of RPMs for CRC screening is expanding and incorporating biomarkers, which remain a prominent aspect of model discovery. Most RPMs included a lack of internal/external validation or discussion as to how the model could be implemented clinically. As biomarkers improve the discriminatory potential of RPMs, more research is needed for the evaluation and implementation of RPMs within existing CRC screening frameworks.

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