Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2019; 25(19): 2383-2401
Published online May 21, 2019. doi: 10.3748/wjg.v25.i19.2383
High-risk symptoms and quantitative faecal immunochemical test accuracy: Systematic review and meta-analysis
Noel Pin Vieito, Sara Zarraquiños, Joaquín Cubiella
Noel Pin Vieito, Sara Zarraquiños, Joaquín Cubiella, Department of Gastroenterology, Complexo Hospitalario Universitario de Ourense, Ourense 32005, Spain
Noel Pin Vieito, Sara Zarraquiños, Joaquín Cubiella, Instituto de Investigación Sanitaria Galicia Sur, Ourense 32005, Spain
Noel Pin Vieito, Department of Biochemistry, Genetics and Immunology, Faculty of Biology University of Vigo, Vigo 36310, Pontevedra, Spain
Author contributions: Pin Vieito N and Cubiella J conception and design of the study; Pin Vieito N, Zarraquiños S, and Cubiella J acquisition of data, analysis and interpretation of data, and final approval; Pin Vieito N and Cubiella J drafted the article; Cubiella J contributed to critical revision.
Conflict-of-interest statement: Dr. Pin reports non-financial support from ABBVIE, non-financial support from GILEAD SCIENCES, outside the submitted work; Dr. Zarraquiños reports non-financial support from CASEN RECORDATI, non-financial support from MYLAN, non-financial support from ALLERGAN, non-financial support from OLYMPUS, non-financial support from ABBVIE, outside the submitted work; Dr. Cubiella reports grants from Instituto de Investigación Sanitaria Galicia Sur, grants from Fondo de Investigaciones Sanitarias (FIS), during the conduct of the study; personal fees from NORGINE, personal fees from IMC, outside the submitted work;
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Noel Pin Vieito, MD, Staff Physician, Statistician, Department of Gastroenterology, Complexo Hospitalario Universitario de Ourense, C/ Ramón Puga 52-54, Ourense 32005, Spain.
Telephone: +34-988385399 Fax: +34-988385399
Received: February 3, 2019
Peer-review started: February 6, 2019
First decision: March 5, 2019
Revised: March 20, 2019
Accepted: March 29, 2019
Article in press: March 30, 2019
Published online: May 21, 2019
Research background

Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth leading cause of cancer-related death. The majority of cancers are still diagnosed after symptomatic presentation, and the quantitative faecal immunochemical test for haemoglobin (FIT) has been revealed to be more accurate for the detection of CRC than multiple clinical referral criteria in symptomatic patients referred for colonoscopy. Hence, The National Institute for Health and Care Excellence (NICE) has recently issued referral guidance for suspected CCR in which FIT is recommended for certain low risk symptomatic patients using a 10 µg Hb/g faeces threshold.

Research motivation

Although NICE recommendation applies only to patients with low risk symptoms in primary care, the studies done to date were mainly concerned with patients who had already been referred to secondary care and were not only concerned with patients with low risk symptoms. Thus, further work is required to find out if FIT´s ability to rule out CRC may change through the broad spectrum of symptomatic patients.

Research objectives

We aimed to systematically review the literature for published studies out of CRC screening programme setting, to compare FIT accuracy for CRC detection in different clinical spectrum through a meta-analysis. Secondary goal included assessing the usefulness of FIT to detect significant colonic lesions (SCLs) in symptomatic patients.

Research methods

We performed an electronic search in MEDLINE and EMBASE databases (from database inception to May 2018) using a sensitive search of “FIT for CRC” narrowing our search to prospective cohort studies performed on adult patients when at least a fraction of symptomatic patients was included. To identify further relevant studies, we checked the reference lists of all articles extracted. We classified studies on the basis of brand and threshold of faecal haemoglobin (f-Hb) concentration for a positive test result to limit heterogeneity. Finally, a bivariate model was fitted for subgroups defined by CRC prevalence and percentage of symptoms, for direct comparison between them.

Research results

We identified fourteen studies that matched the search criteria, and individual unpublished data from cohorts included in the COLONPREDICT study were also used enrolling 10400 patients using OC-Sensor® at the f-Hb cut-off of 10 mg Hb/g faeces. Pooled estimates of sensitivity for studies formed solely by symptomatic patients (94.1%) were significantly higher than for mixed cohorts (85.5%), while there were no statistically significant differences between pooled sensitivity of studies with different CRC prevalence (< 2.5% and ≥ 2.5%). At the same threshold, OC-Sensor® sensitivity to rule out any SCL was 78.6%.

Research conclusions

This meta-analysis suggests that FIT sensitivity to detect CRC is higher in studies solely including symptomatic patients irrespective of CRC prevalence, but may not be sensitive enough to rule out all SCLs. We hypothesize that differences between both groups could be justified due to cohorts solely including symptomatic patients could present a higher percentage of symptoms related to higher amounts of f-Hb as rectal bleeding or diarrhoea, but the study design is not suitable to prove this hypothesis.

Research perspectives

More data are warranted in order to compare FIT accuracy for CRC detection in patients with different clinical spectrum, to identify a subgroup of symptomatic patients where FIT can safely rule out CRC. Future prospective cohort studies solely concerned with patients consulting for low risk symptoms and stratifying by sex and age could help to get this aim.