High-risk symptoms and quantitative faecal immunochemical test accuracy: Systematic review and meta-analysis

Abstract

Background: The quantitative faecal immunochemical test for haemoglobin (FIT) has been revealed to be highly accurate for colorectal cancer (CRC) detection not only in a screening setting, but also in the assessment of patients presenting lower bowel symptoms. Therefore, the National Institute for Health and Care Excellence has recommended the adoption of FIT in primary care to guide referral for suspected CRC in low-risk symptomatic patients using a 10 µg Hb/g faeces threshold. Nevertheless, it is unknown whether FIT´s accuracy remains stable throughout the broad spectrum of possible symptoms.

Aim: To perform a systematic review and meta-analysis to assess FIT accuracy for CRC detection in different clinical settings.

Methods: A systematic literature search was performed using MEDLINE and EMBASE databases from inception to May 2018 to conduct a meta-analysis of prospective studies including symptomatic patients that evaluated the diagnostic accuracy of quantitative FIT for CRC detection. Studies were classified on the basis of brand, threshold of faecal haemoglobin concentration for a positive test result, percentage of reported symptoms (solely symptomatic, mixed cohorts) and CRC prevalence (< 2.5%, ≥ 2.5%) to limit heterogeneity and perform subgroup analysis to assess the influence of clinical spectrum on FIT´s accuracy to detect CRC.

Results: Fifteen cohorts including 13073 patients (CRC prevalence 0.4% to 16.8%) were identified. Pooled estimates of sensitivity for studies using OC-Sensor at 10 µg Hb/g faeces threshold (n = 10400) was 89.6% [95% confidence interval (CI): 82.7% to 94.0%). However, pooled estimates of sensitivity for studies formed solely by symptomatic patients (n = 4035) and mixed cohorts (n = 6365) were 94.1% (95%CI: 90.0% to 96.6%) and 85.5% (95%CI: 76.5% to 91.4%) respectively (P < 0.01), while there were no statistically significant differences between pooled sensitivity of studies with CRC prevalence < 2.5% (84.9%, 95%CI: 73.4% to 92.0%) and ≥ 2.5% (91.7%, 95%CI: 83.3% to 96.1%) (P = 0.25). At the same threshold, OC-Sensor^® sensitivity to rule out any significant colonic lesion was 78.6% (95%CI: 75.6% to 81.4%). We found substantial heterogeneity especially when assessing specificity.

Conclusion: The results of this meta-analysis confirm that, regardless of CRC prevalence, quantitative FIT is highly sensitive for CRC detection. However, FIT ability to rule out CRC is higher in studies solely including symptomatic patients.

Keywords: Bowel disease; Colorectal cancer; Diagnostic accuracy; Faecal haemoglobin; Faecal immunochemical test; Faecal occult blood test; Inflammatory bowel disease; Significant colonic lesion.

Figure 1

Summary of evidence search and selection.

Figure 2

Quality Assessment of Diagnostic Accuracy Studies.

Figure 3

Pooled sensitivity and specificity of faecal immunochemical tests for colorectal cancer detection based on threshold and branch (DerSimonian´s method). CI: Confidence interval; DC: Derivation cohort; VC: Validation cohort.

Figure 4

Summary receiver operating characteristic curve for colorectal cancer detection at different thresholds and branches (DerSimmonian and Lair´s model). LoD: Limit of detection; AUC: Area under the curve; SROC: Summary receiver operating characteristic.

Figure 5

Funnel scatterplot to evaluate publication bias for studies using OC-Sensor^® with different thresholds to detect colorectal cancer. Each point in the plot represents a study with its diagnostic odds ratio (dOR) and sample size. A symmetric image around an axis traced by the pooled dOR value suggests absence of publication bias. Asymmetry with study concentration on the right side (the side with higher diagnostic odds ratio values) suggests publication bias with less negative studies published. dOR: Diagnostic odds ratio.

Figure 6

OC-Sensor^® pooled sensitivity estimates for colorectal cancer detection (subgroup analysis using DerSimonian´s method). CRC: Colorectal cancer.

Figure 7

Hierarchical summary receiver-operating characteristic curves for colorectal cancer detection generated using different subgroups of studies. A: All studies; B: 100% symptomatic; C: Mixed cohorts. HSROC: Hierarchical summary receiver operating characteristic.

Figure 8

Relationship between colorectal cancer prevalence, clinical spectrum and accuracy of faecal immunochemical test for haemoglobin to rule out colorectal cancer. A: There is no correlation between colorectal cancer (CRC) prevalence and faecal immunochemical test for haemoglobin (FIT) sensitivity; B: Pooled FIT sensitivity to detect CRC cancer estimated from studies with ‘Mixed cohorts’ is significantly lower than estimated with ‘100% symptomatic’ cohorts; C: Number of missed CRC per 1000 assessed symptomatic patients with colorectal cancer calculated through Fagan nomograms under various assumptions (FIT accuracy parameters estimated with mixed cohorts or 100% symptomatic cohorts) and CRC prevalence. CRC: Colorectal cancer; FIT: Faecal immunochemical test for haemoglobin.

Figure 9

Fagan nomograms used to calculate post-test probabilities based on different scenarios defined by colorectal cancer prevalence and supposed accuracy of OC-Sensor (Threshold 10 µg Hb/g faeces). A-C; These scenarios are defined by colorectal cancer (CRC) prevalence of 1%, 3% and 13% respectively and faecal immunochemical test for haemoglobin (FIT) accuracy parameters used were the pooled estimates calculated with ‘mixed cohorts’ studies; D-F; These scenarios are defined by CRC prevalence of 1%, 3% and 13% respectively and FIT accuracy parameters used were the pooled estimates calculated with ‘100% symptomatic’ studies. CRC: Colorectal cancer; FIT: Faecal immunochemical test for haemoglobin.