An Adjustable Positivity Threshold for Non-invasive Screening Tests for Colorectal Neoplasms Can Improve Screening Program Effectiveness and Feasibility

Sep 22, 2026

Evaluation of two-step colorectal cancer screening examines how adjusting the fecal hemoglobin (f-Hb) “positivity threshold” changes who receives follow-up colonoscopy and how well programs perform. Using a literature review on quantitative FIT and modeling with f-Hb from a large population, the study characterizes the complex relationship between threshold choice and clinical accuracy, colonoscopy workload, feasibility, and cost-effectiveness. Lower thresholds increase sensitivity but reduce specificity, affecting incidence and mortality impact.

LanguageEnglish

CategoryHealthcare

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Pages12

Reading Time30 min

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Abstract

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Digestive Diseases and Sciences (2025) 70:1648–1659 [https://doi.org/10.1007/s10620-024-08657-6](https://doi.org/10.1007/s10620-024-08657-6) An Adjustable Positivity Threshold for Non‑invasive Screening Tests for Colorectal Neoplasms Can Improve Screening Program Effectiveness and Feasibility Graeme P. Young1 · Carlo Senore2 · Ronald Schoengold3 · Geri Laven‑Law1 · Hiroshi Saito4 · Erin L. Symonds1,5 Received: 28 August 2024 / Accepted: 19 September 2024 / Published online: 9 October 2024 © The Author(s) 2024 Abstract Background In two-step population screening for colorectal cancer (CRC), a simple non-invasive test, commonly a fecal immunochemical test for hemoglobin (FIT), is first undertaken to predict, based on the fecal hemoglobin concentration (f-Hb), who is more likely to have colorectal neoplasia and needs colonoscopy. Aim To evaluate the importance of being able to adjust the f-Hb threshold that triggers follow-up colonoscopy (the “positivity threshold”), we evaluated the predictive value of f-Hb for colorectal neoplasia and its implications for the configuration of new non-invasive tests. Methods A literature review was conducted on the use of quantitative FIT to select the positivity threshold, followed by using f-Hb from a large population to model how adjusting the positivity threshold enabled achievement of the desired program outcomes in a feasible manner. Extended author information available on the last page of the article Results The literature review and the modeling found that while the f-Hb positivity threshold is predictive for colorectal neoplasia across a wide range of f-Hb, there is a complex relationship between program outcomes and f-Hb. The threshold determines not just clinical accuracy (including true-and false-positive results for CRC and/or advanced precursor lesions), but also the colonoscopy workload. A lower f-Hb threshold is associated with a higher sensitivity for neoplasia but a lower specificity and a heavier load of follow-up colonoscopies. Consequently, the threshold determines a program’s impact on population CRC mortality and incidence, but also its feasibility and cost-effectiveness within a health-care system. Discussion We are entering a new era of non-invasive screening tests, where multiple biomarkers found in biological samples such as blood as well as feces, are being developed and evaluated. These typically specify a non-transparent algorithm, developed with machine learning, to provide a predictive dichotomous positive/negative result with a fixed associated clinical accuracy and colonoscopy workload. This will restrict use of new tests in jurisdictions where the accuracy and workload implications do not match the desired screening program outcomes. Conclusion However, similar to flexible FIT positivity thresholds, it would be ideal if new tests also provide capacity for screening program providers to select the positivity threshold that delivers their desired screening outcomes in a feasible manner. How marketing, distribution and reimbursement of non-invasive tests are approved, funded and implemented varies widely across jurisdictions and must be taken into account. Keywords Colorectal cancer · Non-invasive screening tests · Fecal immunochemical test accuracy · Positivity threshold adjustment · Screening program feasibility · Screening program outcomes Abbreviations FIT Fecal immunochemical test for hemoglobin gFOBT Guaiac fecal occult blood test CRC Colorectal cancer Hb Hemoglobin f-Hb Fecal hemoglobin concentration NNC Number needed to colonoscope OR Odds ratio ROC Receiver operating characteristic AUC Area under the curve PBOS Population-based organized screening Introduction The effectiveness of two-step screening for colorectal cancer (CRC)—which initially uses a non-invasive test to identify individuals at higher risk of CRC, followed by a diagnostic colonoscopy for those identified—has been proven to reduce population morbid

FAQs

What does the f-Hb positivity threshold determine in two-step colorectal screening?

It triggers which individuals proceed to follow-up colonoscopy by predicting colorectal neoplasia risk based on fecal hemoglobin concentration.

How does lowering the f-Hb threshold affect screening performance?

Lower thresholds raise sensitivity but lower specificity and increase the number of follow-up colonoscopies, increasing workload.

Why does the positivity threshold influence both clinical outcomes and program feasibility?

The threshold affects clinical accuracy (true/false positives) and the colonoscopy workload, which in turn determines how screening impacts CRC mortality and incidence as well as cost-effectiveness within healthcare systems.

Sep 22, 2026

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