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Variation in diagnostic performance of fecal immunochemical test (FIT) by cutoffs used in screening programs globally

Ola, Idris ; Seum, Teresa ; Carlsson, Sigrid V. LU ; Hoffmeister, Michael and Brenner, Hermann (2026) In EClinicalMedicine 94.
Abstract

Background: Quantitative fecal immunochemical test (FIT) is widely used for colorectal cancer (CRC) screening, with substantial variation in positivity thresholds across countries. This study examines how these thresholds affect FIT's diagnostic performance for detecting CRC and advanced precancerous lesions (APCL). Methods: We analyzed data from a single round screening of 7398 men and women aged 50–79 years, enrolled between 2008 and 2020 in the German BLITZ study, who provided a stool sample for FIT prior to screening colonoscopy. Using FIT positivity thresholds from 30 countries across five continents, we estimated positivity rates, sensitivities for CRC, APCL, and any advanced neoplasia (AN), as well as specificity for no AN, with... (More)

Background: Quantitative fecal immunochemical test (FIT) is widely used for colorectal cancer (CRC) screening, with substantial variation in positivity thresholds across countries. This study examines how these thresholds affect FIT's diagnostic performance for detecting CRC and advanced precancerous lesions (APCL). Methods: We analyzed data from a single round screening of 7398 men and women aged 50–79 years, enrolled between 2008 and 2020 in the German BLITZ study, who provided a stool sample for FIT prior to screening colonoscopy. Using FIT positivity thresholds from 30 countries across five continents, we estimated positivity rates, sensitivities for CRC, APCL, and any advanced neoplasia (AN), as well as specificity for no AN, with colonoscopy as the reference standard. Subgroup analyses were conducted by age and sex. Findings: FIT positivity thresholds across the included countries ranged from 8.5 (Belgium, Flanders) to 120 μg Hb/g feces (England, Wales and Northern Ireland). This wide range went along with very wide ranges of positivity rates and diagnostic performance parameters: positivity rate, 17.6% (95% CI: 16.7–18.5) to 2.6% (95% CI: 2.3–3.0); sensitivity for CRC, 98.1% (95% CI: 90.1–100.0) to 55.6% (41.4–69.1); sensitivity for APCL, 45.5% (95% CI: 41.9–49.0) to 12.2% (95% CI: 10.0–14.7); sensitivity for any AN, 48.9% (95% CI: 45.4–52.4) to 15.0% (95% CI: 12.7–17.7); specificity for no AN, 86.3% (95% CI: 85.5–87.2) to 98.9% (95% CI: 98.7–99.2). Interpretation: The broad range of FIT positivity thresholds across countries goes along with very different diagnostic performance parameters. While this limits comparability of results between countries, our results underscore the potential of FIT as a flexible screening tool that can be adapted to the evolving healthcare system capacities in different countries. Funding: German Research Council, the Federal Ministry of Education and Research, and the German Cancer Aid.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Colonoscopy, Colorectal cancer screening, FIT thresholds, Sensitivity, Specificity, Stool-based test
in
EClinicalMedicine
volume
94
article number
103835
publisher
Lancet Publishing Group
external identifiers
  • scopus:105035646604
  • pmid:41884490
ISSN
2589-5370
DOI
10.1016/j.eclinm.2026.103835
language
English
LU publication?
yes
id
fad9e4c3-b352-4451-8c3c-43dd41d6c662
date added to LUP
2026-05-29 12:35:48
date last changed
2026-05-30 03:00:06
@article{fad9e4c3-b352-4451-8c3c-43dd41d6c662,
  abstract     = {{<p>Background: Quantitative fecal immunochemical test (FIT) is widely used for colorectal cancer (CRC) screening, with substantial variation in positivity thresholds across countries. This study examines how these thresholds affect FIT's diagnostic performance for detecting CRC and advanced precancerous lesions (APCL). Methods: We analyzed data from a single round screening of 7398 men and women aged 50–79 years, enrolled between 2008 and 2020 in the German BLITZ study, who provided a stool sample for FIT prior to screening colonoscopy. Using FIT positivity thresholds from 30 countries across five continents, we estimated positivity rates, sensitivities for CRC, APCL, and any advanced neoplasia (AN), as well as specificity for no AN, with colonoscopy as the reference standard. Subgroup analyses were conducted by age and sex. Findings: FIT positivity thresholds across the included countries ranged from 8.5 (Belgium, Flanders) to 120 μg Hb/g feces (England, Wales and Northern Ireland). This wide range went along with very wide ranges of positivity rates and diagnostic performance parameters: positivity rate, 17.6% (95% CI: 16.7–18.5) to 2.6% (95% CI: 2.3–3.0); sensitivity for CRC, 98.1% (95% CI: 90.1–100.0) to 55.6% (41.4–69.1); sensitivity for APCL, 45.5% (95% CI: 41.9–49.0) to 12.2% (95% CI: 10.0–14.7); sensitivity for any AN, 48.9% (95% CI: 45.4–52.4) to 15.0% (95% CI: 12.7–17.7); specificity for no AN, 86.3% (95% CI: 85.5–87.2) to 98.9% (95% CI: 98.7–99.2). Interpretation: The broad range of FIT positivity thresholds across countries goes along with very different diagnostic performance parameters. While this limits comparability of results between countries, our results underscore the potential of FIT as a flexible screening tool that can be adapted to the evolving healthcare system capacities in different countries. Funding: German Research Council, the Federal Ministry of Education and Research, and the German Cancer Aid.</p>}},
  author       = {{Ola, Idris and Seum, Teresa and Carlsson, Sigrid V. and Hoffmeister, Michael and Brenner, Hermann}},
  issn         = {{2589-5370}},
  keywords     = {{Colonoscopy; Colorectal cancer screening; FIT thresholds; Sensitivity; Specificity; Stool-based test}},
  language     = {{eng}},
  publisher    = {{Lancet Publishing Group}},
  series       = {{EClinicalMedicine}},
  title        = {{Variation in diagnostic performance of fecal immunochemical test (FIT) by cutoffs used in screening programs globally}},
  url          = {{http://dx.doi.org/10.1016/j.eclinm.2026.103835}},
  doi          = {{10.1016/j.eclinm.2026.103835}},
  volume       = {{94}},
  year         = {{2026}},
}