Diagnostic accuracy of one or two faecal haemoglobin and calprotectin measurements in patients with suspected colorectal cancer

Abstract

Background: The role of faecal biomarkers in patients at ‘high risk’ of colorectal cancer (CRC) is not yet defined. Pre-analytical factors, such as heterogeneity of biomarker distribution within faeces, may influence their optimisation in clinical practice. We undertook to determine whether repeat or combined biomarker testing improves diagnostic accuracy for CRC or clinically significant disease.

Methods: Patients referred with suspected CRC provided two separate faecal samples each for faecal immunochemical testing (FIT) and faecal calprotectin (FC) prior to investigation. Diagnostic accuracy of FIT and FC were evaluated based on final diagnoses.

Results: Five hundred fifteen patients completed a full colorectal evaluation. The optimal cut-off for CRC using a single FIT was ≥12 µgHb/g faeces (84.6% sensitivity, 88.5% specificity). For two FIT, the cut-off was ≥43 µgHb/g faeces if either and ≥2 µgHb/g faeces if both were positive. There was no advantage in their diagnostic accuracy compared with a single FIT. FC had a lower diagnostic accuracy for CRC than FIT, which was not improved by repeat FC. No benefit was identified with FIT-FC combined.

For CRC, significant adenomatous polyps and organic enteric disease combined, FIT and FC performed similarly to each other but were poorer predictors (AUC 0.677 and 0.660). There was no uplift in diagnostic accuracy when the tests were repeated or combined.

Conclusion: This study supports using a single FIT at a cut-off close to that recommended by NICE DG30 to improve diagnostic accuracy for ‘two-week wait’ patients referred with suspected CRC.

Keywords:

• Colorectal cancer
• faecal biomarkers
• faecal immunochemical test
• faecal calprotectin
• diagnostic accuracy

Acknowledgements

We are indebted to Dr Deborah Phillips, Research Advisor, Department of Research and Development, York Teaching Hospital NHS Foundation Trust for her support and to Helen Sweeting, Research Nurse supported by Olatunde Fagbayimu. It was supported by Alpha Laboratories Ltd, Eastleigh SO50 4NU who provided the HM-JACKarc analyser and supplied collection devices and reagents free of charge. AK is a member of the York Teaching Hospital NHS Foundation Trust Research and Development committee.

Disclosure statement

No potential conflict of interest was reported by the authors.

Authorship statement

JLT is the guarantor of the article.

JLT was the chief investigator, directed the study and wrote the first draft.

SM, LJ and SB conducted the laboratory analysis.

AK performed the statistical analysis.

DT provided laboratory oversight, advice to JLT and assisted in the preparation of the manuscript.

SM, LJ, SB and AK assisted in the preparation of the manuscript.

The final version is approved by all the authors.

Additional information

Funding

This study has been funded by an Elsie May Sykes award, York Teaching Hospital NHS Foundation Trust, York Against Cancer (Registered Charity Number: 1130835) and Gastroenterology Departmental research funds.