Combining faecal immunochemical testing with blood test results for colorectal cancer risk stratification: a consecutive cohort of 16,604 patients presenting to primary care

Abstract

Background Faecal immunochemical tests (FITs) are used to triage primary care patients with symptoms that could be caused by colorectal cancer 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. Methods Results of all consecutive FITs requested by primary care providers between March 2017 and December 2020 were retrieved from the Oxford University Hospitals NHS Foundation 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 One hundred thirty-nine 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 results with FIT increased specificity but decreased sensitivity. Multivariable models including blood tests performed similarly to FIT alone. Conclusions 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)

“…An analysis from the Southwest of England discussed moving from population risk to individual risk 11. The cancer risk in the ≥10 µg Hb/g faeces population was 7%, in line with larger data sets from low prevalence primary care populations 18 23 26 27. Although cautious about the uncertainty in their estimate, they calculated that the individualised risk was 3% at the threshold ≥37 Hb/g faeces (95% CI 26 to 50) suggesting safety netting may be warranted between 10 and 36 Hb/g faeces.…”

“…The corresponding proportion of positive tests were 11, 10, 7, 4, 3, 3 and 2%, the proportion of cancers detected 91, 91, 85, 74, 61, 57 and 54%, the NNS to detect one cancer was 11, 10, 8, 6, 5, 5 and 4, and the NMC per 1000 FITs was 1, 1, 2, 3, 4, 5 and 5. Reducing the threshold of ≥10 to ≥2 µg Hb/g faeces resulted in increase in the NNS to 21 and a reduction in the NMC to 4 per 100 000 patients tested 23…”

“…Reducing the threshold of ≥10 to ≥2 µg Hb/g faeces resulted in increase in the NNS to 21 and a reduction in the NMC to 4 per 100 000 patients tested. 23 At a higher prevalence of 1.6%, a smaller Spanish retrospective cohort of 4543 symptomatic patients reported the NMC per 1000 patients tested to be 3.7 (2.2-6.3) at a threshold of ≥10 µg Hb/g faeces compared with 4.1 (2.5-6.6) using ≥20 µg Hb/g faeces, and the NNS was 13.8 (10.8-17.7) compared with 10.9 (8.5-14.0). 27 The authors concluded that the use of ≥20 µg Hb/g in preference to ≥10 µg Hb/g could reduce referrals for colonoscopy without missing more than one CRC per 1000 patients tested.…”

“…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…”

“…All dichotomous FIT thresholds, from the LoD upwards, identify a population with CRC risk ≥3% as recommended by NICE for urgent referral. For example, the PPV for ≥2 µg Hb/g faeces was 4.7% (4.0% to 5.5%) in the Oxfordshire Primary Care cohort, rising to 8.4% (7.1% to 9.9%) using ≥10 µg Hb/g faeces 23. An analysis from the Southwest of England discussed moving from population risk to individual risk 11.…”