Faecal occult blood loss accurately predicts future detection of colorectal cancer. A prognostic model

Reinier G. S. Meester, Hilliene J. van de Schootbrugge-Vandermeer, Emilie C. H. Breekveldt, Lucie de Jonge, Esther Toes-Zoutendijk, Arthur Kooyker, Daan Nieboer, Christian R. Ramakers, Manon C. W. Spaander, Anneke J. van Vuuren, Ernst J. Kuipers, Folkert J. van Kemenade, Iris D. Nagtegaal, Evelien Dekker, Monique E. van Leerdam, Iris Lansdorp-Vogelaar

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Abstract

Objectives To examine the prognostic potential of repeated faecal haemoglobin (F-Hb) concentration measurements in faecal immunochemical test (FIT)-based screening for colorectal cancer (CRC). Design Prognostic model. Setting Dutch biennial FIT-based screening programme during 2014-2018. Participants 265 881 participants completing three rounds of FIT, with negative test results (F-Hb <47 μg Hb/g faeces) in rounds 1 and 2. Interventions Colonoscopy follow-up in participants with a positive FIT (F-Hb ≥47 μg Hb/g faeces). Main outcomes We evaluated prognostic models for detecting advanced neoplasia (AN) and CRC in round 3, with as predictors, participant age, sex, F-Hb in rounds 1 and 2, and categories/combinations/non-linear transformations of F-Hb. Primary evaluation criteria included: risk prediction accuracy (calibration), discrimination of participants with versus without AN or CRC (optimism-adjusted C-statistics, range 0.5-1.0), the degree of risk stratification and C-statistics in external validation. Results Among study participants, 8806 (3.3%) had a positive FIT result, 3254 (1.2%) had AN detected and 557 (0.2%) had cancer. F-Hb concentrations in rounds 1 and 2 were the strongest outcome predictors, with adjusted ORs of up to 9.4 (95% CI 7.5 to 11.7) for the highest F-Hb category. Risk predictions matched the observed risk for most participants (calibration intercept -0.008 to -0.099; slope 0.982-0.998), and discriminated participants with versus without AN or CRC with C-statistics of 0.78 (95% CI 0.77 to 0.79) and 0.73 (95% CI 0.71 to 0.75), respectively. The predicted risk ranged from 0.4% to 36.7% for AN and from 0.0% to 5.5% for CRC across participants. In external validation, the model retained similar discrimination accuracy for AN (C-statistic 0.77, 95% CI 0.66 to 0.87) and CRC (C-statistic 0.78, 95% CI 0.66 to 0.91). Conclusion Participants at lower versus higher risk of future AN or CRC can be accurately identified based on their age, sex and particularly, prior F-Hb concentrations. Risk stratification should be considered based on this information.

Original languageEnglish
Pages (from-to)101-108
Number of pages8
JournalGut
Volume72
Issue number1
DOIs
Publication statusPublished - 10 May 2022

Keywords

  • colorectal neoplasm
  • screening
  • stool markers

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