Role of the faecal immunochemical test in patients with risk-stratified suspected colorectal cancer symptoms: A systematic review and meta-analysis to inform the ACPGBI/BSG guidelines

Abstract

Background: The UK National Institute for Health and Care Excellence (NICE), recommended in 2017 the use of the faecal immunochemical test (FIT) to guide investigations in patients presenting with NICE-defined low-risk symptoms suspicious for colorectal cancer (CRC). At that time, NICE did not recommend FIT use for high-risk symptoms. This is the first systematic review to evaluate the diagnostic accuracy of FIT in NICE-defined high and low-risk symptoms and was designed to inform the joint ACPGBI/BSG guidelines.

Methods: We performed a systematic literature review and meta-analysis. PROSPERO registration number CRD42021224674. Medline and EMBASE databases were searched from inception to 31^st March 2022. We included studies recruiting adult patients presenting with suspected CRC symptoms in whom FIT was performed and diagnostic accuracy data for CRC detection could be derived at a limit of detection (LoD) and/or 10 µg haemoglobin/gram faeces threshold in four commonly used analysers. FIT performance was assessed for high-risk, low-risk and individual symptoms where possible. Bivariate meta-analysis was performed where study numbers allowed.

Findings: Thirty-one studies (79566 patients) met inclusion criteria. At 10 µg/g, for "all symptoms" (n = 35,945) sensitivity and specificity were 91.0% (95% CI: 88.9, 92.7) and 75.2% (95% CI: 69.6, 80.1); for "high-risk" symptoms (n = 18,264), 88.7% (95% CI: 84.4, 92.0) and 78.5% (95% CI: 73.0, 83.2); and for "low-risk" symptoms (n = 2161), 88.7% (95% CI: 78.1, 95.3) and 88.5% (95% CI: 87.1, 89.9), respectively. At LoD, for "all symptoms" (n = 26,056) sensitivity and specificity were 94.7% (95% CI: 90.5, 97.1) and 66.5% (95% CI: 58.7, 73.6); for "high-risk" symptoms (n = 16,768), 92.8% (95% CI: 86.4, 96.3) and 70.3% (95% CI: 66.5, 73.8); and for "low-risk" symptoms (n = 2082), 94.7% (95% CI: 85.4, 98.9) and 71.9% (95% CI: 69.9, 73.9), respectively. Summary estimates were similar across different analysers.

Interpretation: FIT sensitivity for CRC detection is maximised at the LoD; its performance is similar in high and low-risk symptoms, and across different analysers where a common threshold is used. FIT performance for CRC detection is adequate and transferrable to clinical diagnostic pathways.

Funding: This review was part-funded by NHS England awarded to RM Partners. RB and RC were funded by research fellowships awarded by Croydon University Hospital.

Keywords: Clinical decision making; Colorectal cancer; FOB Gold; Faecal immunochemical test, FIT; HM-JACKarc; High-risk symptoms; Low-risk symptoms; Meta-analysis; NICE DG30; NICE NG12; OC-Sensor; QuikRead go; Stool markers; Systematic review.

Figure 1

PRISMA diagram showing selection of articles for inclusion in the review.

Figure 2

HSROC curves for pooled assays at an LoD cutoff for patients with unstratified presenting symptoms, high-risk symptoms or low-risk symptoms, where studies were conducted in any setting (primary care, secondary care, both or unclear). 95% confidence region for each summary estimate is represented by the dashed-line curve.

Figure 3

HSROC curves for pooled assays at a cutoff of 10 µg/g for patients with unstratified presenting symptoms, high-risk symptoms or low-risk symptoms, where studies were conducted in any setting (primary care, secondary care, both or unclear). Curves generated using only OC-Sensor data for Chapman 2021 study to avoid double counting. 95% confidence region for each summary estimate is represented by the dashed-line curve.

Figure 4

HSROC curves for pooled assays at an LoD cutoff, for tier 1 studies and for tier 2 studies, for patients with unstratified presenting symptoms where studies were conducted in any setting (primary care, secondary care, both or unclear). 95% confidence region for each summary estimate is represented by the dashed-line curve.

Figure 5

HSROC curves for pooled assays at cutoff of 10 µg/g, for tier 1 studies and for tier 2 studies, for patients with unstratified presenting symptoms where studies were conducted in any setting (primary care, secondary care, both or unclear). 95% confidence region for each summary estimate is represented by the dashed-line curve.

Figure 6

FIT and colonoscopy outcomes comparing a LoD threshold with a threshold of 10 µg/g for a hypothetical 1000 patients with a CRC prevalence of 3.3%.