Elsevier

European Journal of Cancer

Volume 49, Issue 14, September 2013, Pages 3049-3054
European Journal of Cancer

Superior diagnostic performance of faecal immunochemical tests for haemoglobin in a head-to-head comparison with guaiac based faecal occult blood test among 2235 participants of screening colonoscopy

https://doi.org/10.1016/j.ejca.2013.04.023Get rights and content

Abstract

There is increasing evidence that faecal immunochemical tests (FITs) for haemoglobin offer a number of advantages over traditional guaiac based faecal occult blood tests (gFOBTs). However, evidence on diagnostic performance from direct comparisons with colonoscopy findings in all participants in the average risk population is still sparse. We aimed for a head-to-head comparison of three quantitative FITs with a gFOBT among participants of the German screening colonoscopy programme. Pre-colonoscopy stool samples and colonoscopy reports were obtained from 2235 participants of screening colonoscopy in 2005–2009. To enhance comparability of diagnostic performance of the various tests, we assessed sensitivity, specificity, predictive values and likelihood ratios of FITs after adjusting the FIT cut-off haemoglobin (Hb) concentrations in such a way that FIT positivity rates equalled the positivity rate of the gFOBT. Colorectal cancer, advanced adenomas and other adenomas were found in 15 (0.7%), 207 (9.3%) and 398 (17.8%) participants. The gFOBT was positive in 111 (5.0%) participants, with sensitivities (specificities) for detecting colorectal cancer, any advanced neoplasm or any neoplasm of 33.3% (95.2%), 8.6% (95.4%) and 5.5% (95.2%). At the same positivity rate, all three FITs outperformed the gFOBT in all indicators. In particular, all sensitivities of FITs were approximately two to three times higher at increased levels of specificity. All differences were statistically significant, except for some of the performance indicators for colorectal cancer. In conclusion, FITs can detect much larger proportions of colorectal neoplasms even if their cut-offs are set to levels that ensure equally low positivity rates as gFOBT.

Introduction

Screening by faecal occult blood tests (FOBTs) has been shown in randomised trials to reduce colorectal cancer (CRC) incidence and mortality.1 In these trials, guaiac based FOBTs (gFOBTs) have been used which have high specificity but relatively low sensitivity to detect CRC and its precursors.2 Meanwhile, faecal immunochemical tests (FITs) for haemoglobin in stool have been developed. FITs offer a number of advantages over gFOBTs,3, 4, 5, 6 including being specific for human blood and hence removing any need for dietary restrictions. Furthermore, some quantitative tests enable automated processing and easy adjustment of cut-off concentrations that are most adequate for population-based screening. Also, adherence seems to be higher with FIT than with gFOBT-based screening.7

Diagnostic performance, sensitivity and detection rates of advanced neoplasms were reported to be higher for FITs than for gFOBTs at commonly used cut-offs for test positivity.3, 4, 5, 6, 8, 9, 10, 11, 12, 13 This major advantage seems to come at the price of higher positivity rates and lower specificity though,8, 9, 10, 11, 12, 13 and hence a higher load of work-up colonoscopies, which makes final judgement of the superiority of either test difficult. Furthermore, evidence from direct ‘head-to-head’ comparisons of both types of tests in the screening setting, including comparisons with ‘gold standard’ examinations by colonoscopy among all participants, is still sparse.10, 13

We aimed for a head-to-head comparison of three quantitative FITs with a gFOBT among participants of screening colonoscopy in Germany. To enhance comparability, we assessed sensitivity, specificity, predictive values and likelihood ratios of FITs after adjusting cut-offs in such a way that their positivity matched the positivity rate of the gFOBT.

Section snippets

Study design and study population

Our analysis is based on data from the ongoing BLITZ-study, the design of which has been described in detail elsewhere.14, 15, 16, 17 Briefly, participants of screening colonoscopy were recruited in 20 gastroenterology practices in Southern Germany and invited to provide blood and stool samples for evaluation of novel CRC screening tests. Patients were informed about the study at a preparatory visit in the practice, typically about one week prior to colonoscopy. Patients willing to participate

Results

Characteristics of the study population are shown in Table 1. Half of the 2235 participants were men, and approximately 80% were 55–69 years of age (mean: 62.7 years). Colonoscopy was complete in 98% of cases. In a clear majority of >70% of participants, no neoplasm was found at screening colonoscopy. The most advanced finding was CRC, advanced adenoma or non-advanced adenoma in 15 (0.7%), 207 (9.3%) or 398 (17.8%) of participants.

Overall, 111 participants (5.0%) had a positive gFOBT. The same

Discussion

In this large diagnostic study conducted in the screening setting, we aimed for a head-to-head comparison of the ability of three quantitative FITs and one gFOBT to detect colorectal neoplasms. Comparability was ensured by defining cut-offs of the FITs yielding the same positivity rate as the (qualitative) gFOBT. Presence of colorectal neoplasms was verified by screening colonoscopy in all participants. At the same levels of test positivity rates, all three FITs showed substantially better

Conflict of interest statement

The test kits were provided free of charge by the manufacturers and Eiken Chemical Co. provided support for conduction of the OC SENSOR tests.

Acknowledgements

The authors gratefully acknowledge excellent cooperation of physicians conducting screening colonoscopies in patient recruitment, excellent contributions of Isabel Lerch, Utz Benscheid and Dr. Sabrina Hundt (Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg) in data collection, monitoring and documentation and excellent cooperation with Labor Limbach (Heidelberg) in test execution.

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    Financial support: This study was supported in part by the German Research Foundation (Deutsche Forschungsgemeinschaft) within the framework of a PhD programme (Graduiertenkolleg 793) and by a grant from the German Federal Ministry of Education and Research (No. O1ESO72). The test kits were provided free of charge by the manufacturers and Eiken Chemical Co. provided support for conduction of the OC SENSOR tests. The sponsors had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review, or approval of the manuscript.

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