Symptomatic Assessment

Aim: Access to colonoscopy was limited during the Coronavirus disease-2019 (COVID-19) pandemic peak. It was, therefore, of great importance that a tool such as faecal immunochemical test (FIT) be used to identify patients with a greater likelihood of colorectal cancer (CRC).
Conclusion: The yield for CRC is minimal in a FIT negative patient – such patients may be safely discharged, as long as a clinical safety net is in place. Using sensitivity and specificity analysis, patients with a FIT above 19 µgHb/g should be investigated urgently to exclude cancer.

Almost a quarter of this primary care cohort of symptomatic patients with FIT testing were found to be positive. However, there was low agreement between patient-reported and GP-recorded symptoms. This may impact cancer risk assessment and optimal patient management in primary care.

Objective: To provide a clear strategy for the use of faecal immunochemical testing (FIT) in the diagnostic pathway of people with signs or symptoms of a suspected diagnosis of colorectal cancer (CRC).

The inevitable direction of travel will be to use FIT as a triage tool to decide which patients to investigate, and how urgently to investigate them. FIT’s sensitivity, and positive and negative predictive values make it a once-in-a-lifetime tool that could revolutionise the way bowel symptoms are investigated.

FIT is a highly sensitive tool for identifying higher risk individuals presenting to primary care with lower risk symptoms. Combining blood test results with FIT does not appear to lead to better discrimination for colorectal cancer than using FIT alone.

FIT is the test of choice to evaluate patients with new-onset lower gastrointestinal symptoms in primary healthcare.

Studies have concluded that if the FIT is negative and clinical assessment and full blood count normal then the risk of underlying significant bowel disease (SBD) is extremely small. Furthermore, pa­tients with f-Hb ≥400 μgHb/g faeces have >50% risk of SBD and should be investigated urgently. Thus, a single f-Hb requested by GPs provides both a reliable prediction of the absence of SBD, and an objective assessment of the need and urgency of further investigation.

Faecal haemoglobin is not always detectable in patients with RB; 56% of patients had undetectable f‐Hb (<2µg/g) and CRC was present in 0.1%. The high sensitivity of FIT can be used to rule out CRC in patients with RB and triage them more appropriately for investigation.

This evaluation of FIT from the South West Cancer Alliance provides some key information regarding patient management, particularly during these difficult times. “FIT performs exceptionally well to triage patients with low-risk symptoms of colorectal cancer in primary care; a higher threshold may be appropriate in the wake of the COVID-19 crisis.”

In primary care, f-Hb, in conjunction with clinical assessment, can safely and objectively determine individual risk of CRC and decide on simple reassurance or urgent, or routine referral.

A perspective on the use of FIT in the symptomatic cohort during the COVID-19 pandemic, to alleviate pressure on already overburdened endoscopy resource.

This study shows that the faecal immunochemical test is a promising technology that detected colorectal cancer in all high- or low-risk symptomatic patients in our cohort at a threshold of detectable faecal haemoglobin. Data from adequately powered cohort studies will elucidate the true diagnostic accuracy of the test and the rate and patterns of undetected colorectal cancer.

Members of the Scottish Cancer Prevention Network (SCPN) were asked about their favourite paper published in 2019. Prof. Callum Fraser, Senior Research Fellow, University of Dundee and Founding Member of the Expert Working Group on FIT for Screening, CRCSC, World Endoscopy Organization has chosen this 2019 paper which discusses the increasing incidence for CRC in young adults.

This study shows that the faecal immunochemical test is a promising technology that detected colorectal cancer in all high- or low-risk symptomatic patients in our cohort at a threshold of detectable faecal haemoglobin. Data from adequately powered cohort studies will elucidate the true diagnostic accuracy of the test and the rate and patterns of undetected colorectal cancer.

An entry by Prof. Fraser on the Scottish Cancer Prevention Network (SCPN) blog regarding patient sampling and the possible implications of this on both screening and symptomatic assessment.

Our survey findings suggest that GPs’ awareness of using FIT as a triage test in primary care is currently low and there is limited insight into the perceived barriers and facilitators associated with GPs’ use of the test. Successful early adoption of the FIT test in primary care will require extensive primary care engagement to raise awareness of the NICE guideline and the updated diagnostics guidance in parallel with providing access to the FIT test.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.