Symptomatic Assessment

Symptomatic-Publications

FIT for Symptomatic Assessment

The faecal immunochemical test in low risk patients with suspected bowel cancer

The National Institute for Health and Care Excellence produced guidance recommending use of the faecal immunochemical test in patients with low risk symptoms for colorectal cancer. At a cut off of 10 μg haemoglobin per gram of faeces, the National Institute for Health and Care Excellence estimated that the sensitivity of the faecal immunochemical test to detect colorectal cancer ranged from 89% to 100%. The authors evaluated the evidence and noted that the data for the use of the faecal immunochemical test were extrapolated from all comers including high risk patients. Data on low risk patients were scarce and weak. Furthermore, faecal immunochemical test results vary by age, sex, deprivation, ethnicity and symptoms.

D’Souza et al. (2018) British Journal of Hospital Medicine
Diagnostic accuracy of one or two faecal haemoglobin and calprotectin measurements in patients with suspected colorectal cancer

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.

Turvill, M. et al. (2019) Scandinavian Journal of Gastroenterology
Risk stratification of Symptomatic Patients Suspected of Colorectal Cancer using Faecal and Urinary Markers

When applied to FIT negative group, urinary VOCs improves CRC detection (sensitivity rises from 0.80 to 0.97)   thus showing promise as a second stage test to complement FIT in CRC detection.

Widlak, M. et al. (2018) Colorectal Disease
Faecal immunochemical tests (FIT) in the assessment of patents presenting with lower bowel symptoms: Concepts and challenges.

Moreover, the FIT results should not be taken in isolation, but clinical impressions and the results of other investigations, probably including the full blood count, should be considered. Challenges still exist, however, and harmonisation of aspects of the available FIT analytical systems is required. Moreover, a number of seemingly valid clinical concerns remain and these require resolution through further research and reporting of studies done in real clinical practice.

Fraser CG. (2018) The Surgeon, Journal of the Royal Colleges of Surgeons of Edinburgh and Ireland. Vol. 16, pp 302-308
Setting up a service for a faecal immunochemical test for haemoglobin (FIT): a review of considerations, challenges and constraints

Reporting of results should be done using µg Hb/g faeces units and with knowledge of the limit of detection and limit of quantitation of the analytical system used. FIT can be used successfully in an agreed diagnostic pathway, along with other clinical and laboratory information: this requires a multidisciplinary approach, providing opportunities for professionals in laboratory medicine involvement.

Godber IM et al. (2018) Journal of Clinical Pathology
Faecal immunochemical tests have the potential for correctly ruling out colorectal cancer in symptomatic patients

Nine studies reporting accuracy data for three FIT assays were included. The optimal test performance with the OC-Sensor assay appeared to occur with a positivity cut-off of 10 μg haemoglobin/ g faeces: the summary measures for sensitivity and specificity were 92.1% (95% CI 86.9 to 95.3) and 85.8% (95% CI 78.3 to 91.0); the NPV for CRC ranged between 99.4% and 100%. Similar results were observed for HM-JACKarc, while published data were insufficient to assess FOB Gold. Risk scores, combining FIT results with screenee’s age and gender, did not improve triage rule-out performance.

Senore C, Haug U (2018) BMJ Evidence-Based Medicine
The value of using the faecal immunochemical test in general practice on patients presenting with non-alarm symptoms of colorectal cancer

The FIT may be used as a supplementary diagnostic test in the diagnostic process of CRC and other serious bowel disease in individuals with non-alarm symptoms of CRC in general practice.

 Søgaard Juul et al. 2018 British Journal of Cancer 
Timely Diagnosis of Colorectal Cancer

An overwhelming majority of colorectal cancer patients worldwide are diagnosed via the clinical route. Screening programmes are not implemented in all countries, compliance rates are far from complete, and the screening test itself is likely not to be fully sensitive. The aim of this book is therefore to target the searchlight, not on screening but on the important and difficult task of diagnosing colorectal cancer in symptomatic patients.

 Olsson, L. (2018) Springer International Publishing 
Occult blood in faeces is associated with all-cause and non-colorectal cancer mortality

The presence of detectable f-Hb is associated with increased risk of death from a wide range of causes.

 Libby et al. 2018 Gut 
Faecal Tests for Blood – Think FIT, not FOB!

A blog entry by Prof. Callum Fraser published in 2015 outlines the progression in referral guidance for symptomatic bowel cancer, as laid out by NICE over recent years. Prof. Fraser, as part of the Scottish Cancer Prevention Network, examines the advantages of FIT over standard guaiac based methods, by comparing; the sample collection process, the specificity and sensitivity of the test, the functionality of the instrument (using HM-JACKarc by Kyowa Medex as opposed to the subjective colour changing testing), and the use of FIT as a ‘rule-out’ test for significant bowel disease. It concludes that as soon as feasibly possible, guaiac based faecal occult bloods tests should be replaced by FIT.

Fraser, C. (2015) Scottish Cancer Prevention Network Blog
Investigating Bowel Symptoms – Remember the Rule of Sixths

A brief investigation by Prof. Callum Fraser (from the Scottish Cancer Prevention Network) published in 2015, describes the efforts made by Cancer Research UK to improve the awareness of Bowel Cancer in the general population. CRUK advises that the most reliable and accurate methods of diagnosis are the colonoscopy and flexible sigmoidoscopy, and Prof. Fraser emphasises the impact of these tests according to the ‘Rule of Sixths’. With three-sixths of those referred for endoscopy having no detectable abnormality it is suggested that using FIT as a ‘rule-out’ test would ease the burden on endoscopy resource and safety net patients where no pathology was identified.

Fraser, C. (2015) Scottish Cancer Prevention Network Blog
Diagnostic accuracy of the faecal immunochemical test for colorectal cancer in symptomatic patients: comparison with NICE and SIGN referral criteria

A paper outlining a multisite, blind study into the effectiveness of FIT in the diagnosis of CRC in symptomatic patients. Comparing the use of FIT to the NICE and SIGN guidelines, showed FIT to be a more sensitive pathway, detecting more CRC than a patient following the current guidelines. The writers evidence that when FIT, with a 20 µg g-1 cut-off, is used instead of the NICE referral criteria, 19.6% fewer colonoscopies would be required to detect 42% additional CRCs. The paper focuses on the specificity and sensitivity of FIT, showing that FIT is able to identify more CRCs than the current NICE or SIGN pathways would, if the patient were following the exact referral recommendation.

 Cubiella, J., Salve, M., Díaz-Ondina, M., Vega, P., Alves, M., Iglesias, F., Sánchez, E., Macía, P., Blanco, I., Bujanda, L., Fernández-Seara, J. (2013) Colorectal Disease, vol. 16, no. 8, pp. 273–282 
Can an automated Faecal Immunochemical Test (FIT) determine whether faecal haemoglobin (f-Hb) concentrations can aid in stratifying symptomatic patients referred for colonoscopy

A poster presented by Ian Godber highlighting the use of FIT as a rule out test or CRC and SBD due to its high NPV. The poster also identified the value of FIT in the patient pathway, and possible combination with additional tests (for example calprotectin) as a solution to reduce the frequency of unnecessary endoscopy.

 Godber I. et al (2014) Poster presented at EuroLab FOCUS Meeting 2014.
Use of a faecal immunochemical test for haemoglobin can aid in the investigation of patients with lower abdominal symptoms

The high NPV for significant colorectal diseases suggests that f-Hb could be used as a rule-out test in this context. Potential exists for using f-Hb measurements to investigate symptomatic patients and guide the use of colonoscopy resources: detailed algorithms for the introduction of f-Hb measurements requires further exploration.

 Godber IM., et al. (2016) Clinical Chemistry and Laboratory Medicine. Vol. 54, no. 4, pp. 595-602
Diagnostic accuracy of faecal biomarkers in detecting colorectal cancer and adenoma in symptomatic patients

Undetectable faecal immunochemical test for haemoglobin is sufficiently sensitive to exclude colorectal cancer, with higher values in left‐sided lesions. FCP in combination does not appear to provide additional diagnostic information. Further studies to determine the health economic benefits of implementing faecal immunochemical test for haemoglobin in primary care are required.

 Widlak M.M., et al. (2016) Alimentary Pharmacology and Therapeutics. Vol 45, no. 2, pp. 354-363
The fecal hemoglobin concentration, age and sex test score: Development and external validation of a simple prediction tool for colorectal cancer detection in symptomatic patients

Prediction models for colorectal cancer (CRC) detection in symptomatic patients, based on easily obtainable variables such as fecal haemoglobin concentration (f-Hb), age and sex, may simplify CRC diagnosis. We developed, and then externally validated, a multivariable prediction model, the FAST Score, with data from five diagnostic test accuracy studies that evaluated quantitative fecal immunochemical tests in symptomatic patients referred for colonoscopy.

 Cubiella J., et al (2017) International Journal of Cancer. Vol. 140, no. 10, pp. 2201-2211

FIT Negative: Follow up and safety-netting

Faecal immunochemical tests for haemoglobin (FIT) in the assessment of patients with lower abdominal symptoms: current controversies

Faecal immunochemical tests for haemoglobin (FIT), as an adjunct to clinical information, assist in the triage of patients presenting in primary care with lower abdominal symptoms. Controversy remains regarding whether and which qualitative and quantitative FIT can be used, which groups of patients would benefit most from FIT, whether FIT should be done in primary and/or secondary care, and how FIT should be incorporated into diagnostic pathways. Controversy also exists as to the optimum cut-off used for referral for colonoscopy. A single sample of faeces may be sufficient. Reporting of results requires consideration. FIT provide a good rule in test for colorectal cancer and a good rule out test for significant bowel disease, but robust safety-netting is required for patients with negative results and ongoing symptoms. Risk scoring models have been developed, but their value is unclear as yet. Further evaluation of these topics is required to inform good practice.

 Fraser (2018) Gastroenterología y Hepatología

Analytical Significance

Detection capability of quantitative faecal immunochemical tests for haemoglobin (FIT) and reporting of low faecal haemoglobin concentrations

In this Opinion Paper proposals for interim APS are made, based on the current state of the art achieved with examinations of faecal samples. It is proposed that LoQ is determined at an examination imprecision of CV≤10% using faecal samples naturally positive for Hb rather than faeces spiked with haemolysate. Detailed proposals for reporting f-Hb data at low concentrations are also made.

 Fraser C., Benton S. (2018) Clinical Chemistry and Laboratory Medicine

Business Case

Faecal immunochemical tests to triage patients with lower abdominal symptoms for suspected colorectal cancer referrals in primary care: a systematic review and cost-effectiveness analysis

Faecal immunochemical testing is likely to be a clinically effective and cost-effective strategy for triaging people who are presenting, in primary care settings, with lower abdominal symptoms and who are at low risk for CRC. Further research is required to confirm the effectiveness of faecal immunochemical testing in primary care practice and to compare the performance of different FIT assays.

Westwood M. et al (2017) Health & Technology Assessment. Vol. 21, no. 33, pp. 1-234