Does repeating faecal immunochemical tests provide reassurance and improve colorectal cancer detection?
Creators: name: Farkas, Nicholas George
Publisher: name: University of Surrey
Year: 2025
Subjects: faecal immunochemical test
symptomatic cohort
Colorectal Cancer

description: BackgroundColorectal cancer (CRC) is the fourth most common cancer in the UK, with nearly 43,000 cases diagnosed per annum. Primary care physicians use NICE guidance to refer suspected cancer patients onwards to secondary care. In recent years, the NHS has come under ever-increasing pressure to deliver high quality care in a timely and cost-efficient manner. The broadening of the referral net has resulted in significant increases in the volume of two-week wait (TWW) referrals. This change came into force in 2015, with the timing of symptoms prior to referral and anaemia thresholds removed, whilst a broader spectrum of symptoms meeting referral criteria were included.(1)Since 2017, faecal immunochemical tests for haemoglobin (FIT) have been recommended as a diagnostic aide for CRC.CRC and pre-cancerous lesions can bleed, and the presence of haemoglobin in faeces acts as a surrogate marker, indicating increased risk. FIT assess the concentration of haemoglobin in faecal matter.FIT have superseded the previously used guaiac faecal occult blood tests (FOBT) in both screening and symptomatic cohorts. Determining whether repeating a FIT is of benefit remains unknown. Understanding whether repetition of this cheap, non-invasive test can provide additional reassurance (that a patient does not have CRC) has the potential to deliver significant cost savings at national levels. Referral practice may alter, decreasing demand on limited resources such as endoscopy and CT.AimsThe primary aims of the thesis were to determine the clinical utility of replicate and repeat FIT for the triage of symptomatic patients referred via the TWW pathway for suspected CRC; to assess patient satisfaction, ease of use, and acceptance of FIT as a non-invasive alternative to conventional diagnostic methods; to evaluate whether multiple FIT results improve diagnostic accuracy and reduce the risk of missed colorectal cancer or significant bowel disease (SBD) when compared to single laboratory FIT. To ascertain this, the correlation between repeat FIT (FIT 2 and FIT 3) and colonoscopy/pathology results were analysed. A secondary aim was to determine whether there is homogeneity or heterogeneity in faecal haemoglobin concentrations from multiple FIT returned by an individual patient.Design and SettingThe MD can be split into five clear, logical chapters. The first chapter assesses why this subject is of importance, through analysis of data from Royal Surrey Hospital regarding referral rates and the application of FIT. The second chapter is a systematic review of repeat and replicate FIT in symptomatic patients and discusses the (limited) pertinent literature on the subject. Chapter three relates to the acceptability of FIT as a strategy for patients. Chapter four highlights a single centre experience of repeat FIT which serves as a feasibility pilot study for the larger Repeat FIT (RFIT) study (Chapter 5), which was a single centre observational cohort study that was run from Royal Surrey Hospital. MethodsThis thesis comprises five interconnected studies investigating the impact, utility, and patient perceptions of FIT in the symptomatic urgently referred patient cohort:&lt;strong&gt;Chapter 1&lt;/strong&gt;: A retrospective study analysed TWW referral data from 2009–2021 to assess the impact of introducing FIT on referral volumes, CRC detection rates, and diagnostic pathways. FIT results were stratified (&lt;10, 10–100, &gt;100 µg Hb/g faeces), and correlations with subsequent investigations were explored.&lt;strong&gt;Chapter 2&lt;/strong&gt;: A systematic review synthesized evidence on replicate and repeat FIT strategies in symptomatic patients. Data from seven studies were analysed to determine the clinical utility of multiple FITs in minimizing missed diagnoses and optimizing diagnostic pathways.&lt;strong&gt;Chapter 3: &lt;/strong&gt;A telephone-based survey of 109 symptomatic patients evaluated patient-reported outcomes, including expectations, satisfaction, and ease of FIT compared to conventional colonic investigations (colonoscopy, CT colonography, sigmoidoscopy). Responses were collected on a 1–5 Likert scale.&lt;strong&gt;Chapter 4&lt;/strong&gt;: A prospective observational study assessed replicate FIT in symptomatic patients referred via the TWW pathway. Participants provided an initial (FIT 1) and second FIT (FIT 2), with results categorized into double-negative, double-positive, and discordant groups. Findings were compared to endoscopic and radiological outcomes.&lt;strong&gt;Chapter 5&lt;/strong&gt;: The RFIT study evaluated the value of repeating FIT three times in symptomatic patients. Diagnostic accuracy measures (sensitivity, specificity, negative predictive value) were calculated for one, two, and three FITs, correlating results with CRC and significant bowel disease (SBD) diagnoses.ResultsIn the first study, TWW referrals increased by 360%, yet CRC detection rates remained static at 3–4%. FIT was effective in guiding secondary care resource allocation. Despite the increased referral burden, FIT helped avoid delays in CRC diagnosis particularly during the COVID pandemic.The systematic review outlined both limited and conflicting evidence on replicate and repeat FIT. While some studies suggested repeat FIT could minimize missed CRC diagnoses, others showed no significant improvement in diagnostic accuracy. The findings emphasized the need for further research to determine the clinical value of replicate FIT testing in symptomatic patients.The patient-reported outcome study demonstrated that FIT was well-accepted, with most patients finding it easy to perform. Many patients expressed satisfaction with a negative FIT to rule out CRC, 32% were dissatisfied, preferring the reassurance of conventional investigations like colonoscopy. The fourth study examined the utility of replicate FIT results and demonstrated that double negative FITs (&lt;10 μg Hb/g) were highly reassuring, with no CRC cases detected in this group. However, discordant FIT results (one positive, one negative) were less reliable, with one missed CRC case reported. The findings highlighted the need for careful clinical evaluation of discordant results to avoid missed diagnoses.The RFIT study investigated the impact of repeating FIT on diagnostic accuracy. Sensitivity for CRC remained high (&gt;95%) across one, two, and three negative FIT results, while specificity declined with additional testing. Patients with multiple negative FITs had very low CRC risk (negative predictive value &gt;99%), providing strong reassurance. In contrast, multiple positive FITs increased CRC detection rates, from 8.3% with a single positive result to 20.9% with three positive FITs, offering better stratification of patients for further investigation.ConclusionsThis thesis highlights the valuable role FIT plays in the symptomatic TWW pathway, offering a non-invasive, accessible, and patient-acceptable triage strategy for CRC. Multiple FIT provide incremental diagnostic reassurance for CRC and SBD, but at the cost of reduced specificity and increased investigations. The clinical utility of repeat FIT can be improved, risk stratification may help refine its use in the triage of symptomatic patients.