Combining faecal immunochemical testing with blood test results to identify patients with symptoms at risk of colorectal cancer: a consecutive cohort of 16,604 patients tested in primary care

Abstract

Objective: Faecal immunochemical tests (FITs) are used to triage primary care patients with low risk colorectal cancer symptoms for referral to colonoscopy. The aim of this study was to determine whether combining FIT with routine blood test results could improve the performance of FIT in the primary care setting. Design: Results of all consecutive FITs requested by primary care providers between March 2017 and December 2020 were retrieved from the Oxford University Hospital Trust. Demographic factors (age, sex), reason for referral, and results of blood tests within 90 days were also retrieved. Patients were followed up for incident colorectal cancer in linked hospital records. The sensitivity, specificity, positive and negative predictive values of FIT alone, FIT paired with blood test results, and several multivariable FIT models, were compared. Results: Among 16,604 eligible patients, 139 colorectal cancers were diagnosed (0.8%). Sensitivity and specificity of FIT alone at a threshold of 10 μg Hb/g were 92.1% and 91.5% respectively. Compared to FIT alone, blood test results did not improve the performance of FIT. Pairing blood test abnormalities with FIT reduced the number of abnormal results needed to detect one cancer but increased the number of cancers missed. Multivariable models retaining FIT, sex, and mean cell volume performed similarly to FIT alone. Conclusion: FIT is a highly sensitive tool for identifying higher risk individuals presenting to primary care with lower risk symptoms. Combining blood test results with FIT does not appear to lead to better discrimination for colorectal cancer than using FIT alone.

Faecal immunochemical testing (FIT) in patients with signs or symptoms of suspected colorectal cancer (CRC): a joint guideline from the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and the British Society of Gastroenterology (BSG)

“…A comparison of FIT at ≥10 µg Hb/g faeces alone, with the FAST score (combining FIT age and sex), and ColonFlag (a machine learning algorithm using age, sex and FBC indices to derive a risk score), showed that FIT and ColonFlag missed a different 18% of CRCs, respectively, and FAST score missed 27.3% 52. Combining simple blood tests with FIT at best matches the sensitivity of FIT alone in patients tested in primary care, whether as pairs of results or within multivariable model 20…”

“…When NICE set the threshold at ≥10 µg Hb/g faeces there was a paucity of data available on FIT in symptomatic patients tested in primary care prior to referral for colonic investigation 7. Since 2017, numerous studies have been published to inform the choice of FIT threshold in primary care,8–20 20–23 including some showing that FIT outperforms symptom-based referral criteria 24–26…”

“…The underlying prevalence of CRC directly influences a test’s performance at a chosen threshold. Individual prospective and retrospective cohort studies reporting FIT performance in populations of patients tested in primary care report CRC prevalence ranging from 0.8% to 1.8%, highlighting the variation in symptomatic patient groups eligible for FIT across primary care settings 8 11 13 18 20 21. In a subgroup analysis of the review, at a threshold of ≥10 µg Hb/g faeces, sensitivity was lower at 86% (95% CI 78% to 93%) versus 89% (95% CI 82% to 96%) and specificity significantly higher of 87% (95% CI 82% to 92%) versus 81% (95% CI 74% to 88%) when eight studies with a combined prevalence <3% were compared with seven studies with a prevalence of ≥3% 26…”

“…A number of groups have reported multivariate analyses including demographics (with symptoms, blood results and other factors) as covariates and fHb measured by FIT is consistently the most predictive factor by some margin 14 25 92–95. No other factor reaches significance consistently, although increasing age and male gender appear most frequently.…”

“…A much larger study by Withrow et al 93 reported on 16 604 patients tested in primary care (and includes the cohort from Nicholson et al )27 specifically focussing on the value of combining FIT with blood tests. However, the majority of patients were not investigated.…”