Understanding colorectal cancer risk for symptomatic patients in primary care: A cohort study utilising faecal immunochemical tests and blood results in England

Abstract

Background: A faecal immunochemical tests (FIT) cut-off of ≥10 μg Hb/g faeces is now recommended in the UK as a gateway to urgent (suspected cancer) investigation for colorectal cancer (CRC), based on an expected CRC risk threshold of 3%. Aims:To quantify the risk of CRC at FIT cut-offs by age, haemoglobin and platelet strata.Methods: A cohort study of a symptomatic CRC pathway based on primary care FIT tests in Nottingham, UK (November 2017-2021) with 1-year follow-up. Heat maps showed the cumulative 1-year CRC risk using Kaplan-Meier estimates. Results:In total, 514 (1.5%) CRCs were diagnosed following 33,694 index FIT requests. Individuals with a FIT ≥ 10 μg Hb/g faeces had a >3% risk of CRC, except patients under the age of 40 years (CRC risk 1.45% [95% CI: 0.03%-2.86%]). Nonanaemic patients with a FIT < 100 μg Hb/g faeces had a CRC risk of <3%, except those between the age of 70 and 85 years (5.26% 95% CI: 2.72%-7.73%). Using a ≥3% CRC threshold in patients <55 years calculated using FIT, age and anaemia might allow 160-220 colonoscopies per 10,000 FITs to be re-purposed, at a cost of missing 1-2 CRCs.Conclusions: FIT alone with a single cut-off is unlikely to be a panacea for optimising CRC diagnosis, as risk varies by FIT, age and anaemia when faecal haemoglobin levels are below 100 μg Hb/g. Tailored FIT cut-offs for investigation on a CRC pathway could reduce the number of investigations needed at a 3% CRC risk threshold.

‘Low’ faecal immunochemical test (FIT) colorectal cancer: a 4‐year comparison of the Nottingham ‘4F’ protocol with FIT10 in symptomatic patients

“…However, this inevitably diverts a 'false-positive' population towards the urgent pathway, which may explain why demand has not reduced. Recent analysis of our cohort shows that the CRC risk is often <3% even above our thresholds [15], highlighting the need to consider adjuncts to FIT.…”

“…Trust data and electronic patient records and databases were used for crosschecking and diagnostic validation for all patients sent a FIT between November 2017 and 31 October 2021. This is described in depth elsewhere [14,15]. Ethical was approval granted locally (NUH registration number 20-135C).…”

COLOFIT: Development and internal-external validation of models using age, sex, faecal immunochemical and blood tests to optimise diagnosis of colorectal cancer in symptomatic patients

“…This would determine the diagnostic yield and health service burden all stakeholders are willing and able to accept and deliver. For example, if a 3% risk of CRC were to be implemented this would be equivalent to enacting a f-Hb threshold of ≥40 µg/g 10 . This would reduce the number of normal colonoscopies required substantially but at a cost of more missed cancers.…”

“…Recent evidence from Nottingham suggests that stratifying by age and the presence or absence of anaemia could identify those people with a FIT ≥10 µg/g at a low CRC risk, well below the defined 3%, who do not need investigation 10 . While stratified approaches could work, an alternative approach, is to use a clinical prediction model to estimate risk of CRC at an individual level to tailor investigation.…”

Editorial: Less is more for colorectal cancer diagnosis – FIT leads the way

“…5 Crooks et al tackled this issue and posited a more sophisticated pathway, including age (in 15-year bands) and haemoglobin values. 6 The study, from a cohort of over 33,000 patients with FIT and haemoglobin results, introduced these two variables by identifying adjusted FIT thresholds above which the risk of cancer was 3%. In those with a normal haemoglobin and a FIT level between 20 and 40 μg/g faeces, only those aged over 85 years had a risk of cancer exceeding 3%.…”