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Multicenter Study
. 2024 Dec;100(6):1061-1069.e3.
doi: 10.1016/j.gie.2024.06.015. Epub 2024 Jun 21.

Development of an algorithm combining blood-based biomarkers, fecal immunochemical test, and age for population-based colorectal cancer screening

Mathias M Petersen  1 , Jakob Kleif  2 , Jason Liggett  3 , Morten Rasmussen  4 , Lars N Jørgensen  4 , Jesper Vilandt  5 , Jakob B Seidelin  6 , Carla M T Beertsen  7 , Annemieke C Heijboer  7 , Claudia Jaensch  8 , Peter Bondeven  9 , Kåre A Gotschalck  10 , Uffe S Løve  11 , Susan H Gawel  12 , Berit Andersen  13 , Ib J Christensen  14 , Eric Mayer  3 , Gerard J Davis  12 , Christina Therkildsen  15
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Free article
Multicenter Study

Development of an algorithm combining blood-based biomarkers, fecal immunochemical test, and age for population-based colorectal cancer screening

Mathias M Petersen et al. Gastrointest Endosc. 2024 Dec.
Free article

Abstract

Background and aims: Implementation of screening modalities has 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 multicenter study, 8 blood-based biomarkers (carcinoembryonic antigen, ferritin, high-sensitivity C-reactive protein, human epididymis protein 4, Cyfra21-1, hepsin, interleukin 8, and osteoprotegerin) were investigated in 1977 FIT-positive individuals from the Danish national CRC screening program undergoing follow-up colonoscopy. Specimens were analyzed on Architect i2000, Architect c8000 (both from Abbott, Chicago, Ill, USA), or Luminex xMAP machines (MilliporeSigma, St. Louis, Mo, USA). FIT analyses and blood-based biomarker data were combined with clinical data (ie, 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 8 biomarkers, quantitative FIT result, and age performed superior to the FIT model in discriminating CRC versus non-CRC individuals (area under the receiver operating characteristic curve, 0.77 vs 0.67, respectively; P < .001). When discriminating individuals with either CRC or high- or medium-risk adenomas versus low-risk adenomas or clean colorectum, the areas under the receiver operating characteristic curve 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 adenoma detection rates or vice versa.

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Conflict of interest statement

Disclosure The following authors disclosed financial relationships: C. Therkildsen: Research grants from Abbott Diagnostics Division and New Day Diagnostics. J. Liggett: Full-time employee of New Day Diagnostics. C. M. T. Beertsen: Research grant from Abbott Diagnostics Division. S. Gawel: Full-time employee of Abbott Diagnostics Division. E. Mayer: Full-time employee of New Day Diagnostics. G. J. Davis: Full-time employee of Abbott Diagnostics Division. All analyses were made blinded to J. Liggett, S. Gawel, E. Mayer, and G. J. Davis, whereafter molecular data were merged with clinical data by the academic team at Copenhagen University Hospital, Hvidovre, which also performed statistical analyses. Although statistical analyses were discussed with the industrial partners, the academic research team at Hvidovre Hospital decided on and performed the formal analyses independently. All other authors disclosed no financial relationships. Patient inclusion, sample collection and storage, and salary for all of the clinical and academic research team was provided by external funding granted to Hans Jørgen Nielsen and the Colorectal Cancer Research Unit at Hvidovre Hospital. This work was supported by the Andersen Foundation, Augustinus Foundation, Beckett Foundation, Inger Bonnéns Fund, Hans and Nora Buchards Fund, Walter Christensen Fund, P. M. Christiansen Fund, Kong Chr. X’s Fund, Aase and Ejnar Danielsens Fund, Family Erichsens Fund, Knud and Edith Eriksens Fund, Svend Espersens Fund, Elna and Jørgen Fagerholts Cancer Research Foundation, Sofus Carl Emil Friis Scholarship, Torben and Alice Frimodts Fund, Eva and Henry Frænkels Fund, Gangsted Foundation, Thora and Viggo Groves Memorial Scholarship, H-Foundation, Erna Hamiltons Scholarship, Søren and Helene Hempels Scholarship, Sven and Ina Hansens Fund, Henrik Henriksen Fund, Carl and Ellen Hertz Scholarship, Jørgen Holm and Elisa F. Hansen Memorial Scholarship, Jochum Foundation, Kurt and Ingeborg Daell's Foundation, Kornerup Foundation, Linex Foundation, Dagmar Marshalls Fund, Midtjyske Fund, Axel Muusfeldts Fund, Børge Nielsens Fund, Michael Hermann Nielsens Memorial Scholarship, Arvid Nilssons Fund, Obelske Family Fund, Krista and Viggo Petersens Fund, Willy and Ingeborg Reinhards Fund, Kathrine and Vigo Skovgaards Fund, Toyota Foundation, Vissing Foundation, P. Carl Petersen Fund, Danish Cancer Research Foundation, and Hvidovre Hospitals Research Fund. Furthermore, the collaborative companies, Abbott Diagnostics Division and New Day Diagnostics, have sponsored the study by providing the reagents, facilities, and staff required for the molecular analyses as well as a sample fee to Hvidovre Hospital for sample requisition.

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