Double faecal immunochemical testing in patients with symptoms suspicious of colorectal cancer

Abstract

Background: Faecal immunochemical test (FIT)-directed pathways based on a single test have been implemented for symptomatic patients. However, with a single test, the sensitivity is 87 per cent at 10 µg haemoglobin (Hb) per g faeces. This aims of this study were to define the diagnostic performance of a single FIT, compared with double FIT in symptomatic populations.

Methods: Two sequential prospective patient cohorts referred with symptoms from primary care were studied. Patients in cohort 1 were sent a single FIT, and those in cohort 2 received two tests in succession before investigation. All patients were investigated, regardless of having a positive or negative test (threshold 10 µg Hb per g).

Results: In cohort 1, 2260 patients completed one FIT and investigation. The sensitivity of single FIT was 84.1 (95 per cent c.i. 73.3 to 91.8) per cent for colorectal cancer and 67.4 (61.0 to 73.4) per cent for significant bowel pathology. In cohort 2, 3426 patients completed at least one FIT, and 2637 completed both FITs and investigation. The sensitivity of double FIT was 96.6 (90.4 to 99.3) per cent for colorectal cancer and 83.0 (77.4 to 87.8) per cent for significant bowel pathology. The second FIT resulted in a 50.0 per cent reduction in cancers missed by the first FIT, and 30.0 per cent for significant bowel pathology. Correlation between faecal Hb level was only modest (rs = 0.58), and 16.8 per cent of double tests were discordant, 11.4 per cent in patients with colorectal cancer and 18.3 per cent in those with significant bowel pathology.

Conclusion: FIT in patients with high-risk symptoms twice in succession reduces missed significant colorectal pathology and has an acceptable workload impact.

Fig. 1

Flow diagram showing single- and double-faecal immunochemical test cohorts from eligible referrals to completed faecal immunochemical test and colorectal investigation *Completed single-faecal immunochemical test (FIT) protocol; †completed double-test protocol; ‡completed at least one FIT. EPR, electronic patient record; n.a., not applicable.

Fig. 2

Receiver operating characteristic (ROC) curve analysis for the detection of colorectal cancer between cohorts Area under the curve 0.85 (95% c.i. 0.80 to 0.90) for the single-faecal immunochemical test (FIT) cohort, 0.90 (0.87 to 0.93) for the first FIT analysed (FIT1) of patients who completed at least one test and investigation in the double-FIT cohort, and 0.91 (0.88 to 0.93) for the greatest FIT result (FIT_MAX) in those who completed the double-test (DT) protocol.

Fig. 3

Discordance between first and second faecal immunochemical tests over time and in the absence and presence of significant bowel pathology a Total number of patients with concordant and dicordant faecal immunochemical test (FIT) results, and percentage discordance, over time; b direction of percentage discordance over time; and c FIT discordance according to presence of significant bowel pathology overall (upper panels) and over time (lower panels). There was no significant difference in discordance in the absence versus presence of significant bowel pathology (P = 0.508, Chi-squared test). Hb, haemoglobin.

Fig. 4

Consequences of increasing the diagnostic threshold on number needed to investigate and percentage of colorectal cancers missed in the double-faecal immunochemical test cohort a First sample analysed (FIT1) from all who completed at least one faecal immunochemical test (FIT) and b greatest FIT result (FIT_MAX) for those who completed double-test (DT) protocol. NNI, number needed to investigate; CRC, colorectal cancer; Hb, haemoglobin.

Fig. 5

Clinical implementation of double-faecal immunochemical test strategy Values in parentheses are percentage of referrals. Where both faecal immunochemical tests (FITs) show 10 μg haemoglobin (Hb) per g or more, the colorectal cancer (CRC) prevalance is 19.9%.