Mathias M. Petersen, Jakob Kleif, Jason Liggett, Morten Rasmussen, Lars N. Jørgensen, Jesper Vilandt, Jakob B. Seidelin, Carla M.T. Beertsen, Annemieke C. Heijboer, Claudia Jaensch, Peter Bondeven, Kåre A. Gotschalck, Uffe Schou Løve, Susan H. Gawel, Berit Andersen, Ib J. Christensen, Eric Mayer, Gerard J. Davis, Christina Therkildsen
This paper is only available as a PDF. To read, Please Download here.
Abstract:
Background and aims
Implementation of screening modalities have reduced the burden of colorectal cancer (CRC), but high false positive rates pose a major problem for colonoscopy capacity. We aimed to create a tailored screening algorithm that expands the fecal immunochemical test (FIT) with a blood specimen and current age to improve selection of individuals for diagnostic colonoscopy.
Methods
In this prospective multi-center study, eight blood-based biomarkers (CEA, Ferritin, hsCRP, HE4, Cyfra21-1, Hepsin, IL-8 and OPG) were investigated in 1,977 FIT positive individuals from the Danish national CRC screening program undergoing follow-up colonoscopy. Specimens were analyzed on ARCHITECT i2000®, ARCHITECT c8000® or Luminex xMAP® machines. FIT analyses and blood-based biomarker data were combined with clinical data (i.e., age and colonoscopy findings) in a cross-validated logistic regression model (algorithm) benchmarked against a model solely using the FIT result (FIT model) applying different cutoffs for FIT positivity.
Results
The cohort included individuals with CRC (n = 240), adenomas (n = 938) or no neoplastic lesions (n = 799). The cross-validated algorithm combining the eight biomarkers, quantitative FIT result and age performed superior to the FIT model in discriminating CRC versus non-CRC individuals (AUC 0.77 versus 0.67, p < 0.001). When discriminating individuals with either CRC or high- or medium-risk adenomas versus low-risk adenomas or clean colorectum, the AUCs were 0.68 versus 0.64 for the algorithm and FIT model, respectively.
Conclusions
The algorithm presented here can improve patient allocation to colonoscopy, reducing colonoscopy burden without compromising cancer and adenomas detection rates or vice versa.
