key: cord-1017106-4ew6ixr9
authors: Kamel, Faddy; Zulfiqar, Saadia; Penfold, WIlliam; Weatherell, Stephanie; Madani, Rana; Nisar, Pasha; Bearn, Philip
title: The use of the faecal immunochemical test during the COVID‐19 pandemic to triage urgent colorectal cancer referrals
date: 2022-03-31
journal: Colorectal Dis
DOI: 10.1111/codi.16120
sha: 8cd0ff734aab96d76653d655c459231e06509583
doc_id: 1017106
cord_uid: 4ew6ixr9

AIM: During the first wave of the COVID‐19 pandemic in 2020, elective gastrointestinal endoscopy services were abbreviated for fear of viral transmission. However, urgent suspected colorectal cancer (CRC) referrals continued. Serendipitously, a national study suggested that a new faecal immunochemical test (FIT) might be helpful in triaging patients with colorectal alarm symptoms. METHODS: This was a single centre observational study of patients referred using NG12 criteria between March and August 2020. Patients were triaged to the urgent cancer pathway for FIT ≥ 10 μg/g and investigated using the latest National Health Service England guidance. Demographic data, method of investigations, cancer and polyp detection rates were compared to patients referred in the 6 months prior to the use of FIT as a triage tool. RESULTS: In all, 1192 patients (median age 70) were referred using NG12 guidelines during the pandemic period, compared with 1592 patients (median age 72) in the previous 6 months. CRC detection was similar in both groups (n = 45, 2.8% vs. n = 38, 3.5%; P = 0.248). Two patients with a negative FIT (0.36%) had CRC. Using FIT as a triage tool resulted in a significant reduction in the use of endoscopy (n = 477, 43.6% vs. n = 1186, 74.5%; P > 0.001) with a significant increase in CT scanning (n = 696, 63.6% vs. n = 750, 47.1%; P < 0.001). CONCLUSION: The use of FIT in NG12 patients triaged during the first wave of the COVID‐19 pandemic reduced endoscopy but not CT scanning and did not compromise CRC detection rates. It is a safe method that aids in reducing the burden on services greatly. A negative FIT test does not absolutely exclude CRC.

During the first wave of the COVID-19 pandemic in March 2020, the British Society of Gastroenterologists and the Association of Coloproctology of Great Britain and Ireland (ACPGBI) issued guidance that only urgent colonoscopy should be performed. This reflected colonoscopy being potentially aerosol generating and the subsequent COVID-19 risk posed to staff and patients [4] . The guidelines recommended that clinicians should identify high risk patients, determined by the nature of clinical signs and symptoms, and proceed to plain contrast CT imaging or, if available, CT colonography to identify any cancers. This was at a time of reduced staffing due to illness, self-isolation and redeployment.

In order to address the growing concerns and disturbance on healthcare services caused by the COVID-19 pandemic, we adopted the local alliance guidelines which stated that secondary care should use FIT to triage patients to an urgent and non-urgent pathway and that this should be issued but not interpreted by primary care [5] .

The primary outcome of this study was to establish whether using FIT to triage patients referred under the urgent suspected cancer (USC) pathway was safe, in terms of any cases of CRC being missed in FIT-negative patients. Its sensitivity and specificity for CRC and significant polyps was also assessed. The secondary aim was to assess the impact on CT imaging and endoscopy utilization.

Local ethical approval was granted by the trust's audit department where this study was registered as an audit (Local registration number TASCC Colo 2020-06).

This was a single centre retrospective study based in a district general hospital in Surrey, UK, that serves a population of around 400 000 people. The study focused on all patients referred under the USC pathway as per NICE NG12 guidelines for suspected lower gastrointestinal cancer. Two cohorts of referrals were analysed: first, patients referred between 1 September 2019 and 28 February 2020 prior to the implementation of the FIT based triage (pre-FIT triage cohort); second, patients referred between 1 March 2020 and 31

August 2020 after the implementation of FIT triage (FIT triage cohort). Patients from the FIT triage cohort were followed up until the end of August 2021 in order to identify any FIT-negative pathology.

Data between September 2019 and February 2020 were recorded retrospectively.

Patient eligibility included any patient above the age of 18 years who was referred under the USC pathway as per the NICE NG12 criteria pathway for CRC [6] (Table 1) . Any patients who declined investigation or were lost to follow-up were excluded from this study. Lost to follow-up was defined as patients who did not attend consultations or booked investigations. Eligible patients were identified by the local cancer services department that keep a record of all patients referred under the USC pathway. Individual patient data were collected from the electronic patient records system available in the trust. All patient data were pseudonymized to maintain patient confidentiality.

The primary end-point measured was whether the use of FIT triage to assess the need for further investigations in patients referred under the USC pathway for suspected lower gastrointestinal cancer was safe. Safety was defined by any cases of CRC that were diagnosed in patients with a negative FIT (faecal haemoglobin [f-Hb] < 10 μg/g). Alongside CRC, other diagnoses that were focused on included significant polyps as per the current ACPGBI guidelines [7] , diverticular disease, haemorrhoids and colitis.

Secondary end-points were the utilization of CT imaging and endoscopy in both pre-FIT and FIT triage based on the proportion of patients referred in each cohort undergoing these investigations compared to the total number of patients referred.

Each referral was triaged by a colorectal specialist nurse or consultant colorectal surgeon, where a combination of the f-Hb level from an FIT sample was assessed if it was available alongside patient symptoms. If the clinician triaging the patient felt that the patient suffered from any red flag symptoms that warranted urgent investigation, then this was performed regardless of the FIT level.

The choice of investigation, either CT imaging or endoscopy, was determined by the assessing clinician, being dependent on patient symptoms, comorbidity and frailty. A summary of the referral pathway for patients when FIT triage was implemented is displayed in 

Statistical analysis was performed using IBM SPSS® version 25.

Non-parametric data were expressed as median (interquartile range, IQR). Categorical data were compared using the chi-squared test.

Numerical data were compared using the Mann-Whitney U test.

Sensitivity and specificity of colonoscopy based on the various FIT cut-off levels were estimated by plotting a receiver operating characteristic curve. This was expressed along with their 95% confidence interval (CI). Statistical significance was defined as P < 0.05. Table 2 demonstrates that there was no significant difference in baseline demographics. The most common reason for referral within both cohorts was change in bowel habit, accounting for over 40% of referrals ( Figure 2 ). Patients who were lost to follow-up were those who did not attend initial consultation or investigation.

There was no difference in the overall CRC detection rates be- (40.6%) were positive (f-Hb ≥ 10 μg/g). These were divided into three groups: group 1 (f-Hb < 10 μg/g), n = 561; group 2 (f-Hb = 10-100 μg/g), n = 236, 61.6%; group 3 (f-Hb > 100 μg/g), n = 147, 38.4%.

A total of 13.7% (150/1094) of patients did not return an FIT sample.

The introduction of FIT triage was associated with a significant n = 96, 20.1%; P = 0.008). The most common findings at endoscopy were a combination of diverticular disease, haemorrhoids or absence of pathology and these accounted for more than 60% of diagnoses in both pre-FIT and FIT triage cohorts, with the overall endoscopic findings shown in Table 3 .

More patients underwent CT imaging after the introduction of Table 4 ). P < 0.001). There was no difference in low risk polyp detection rates (Table 6) .

Overall CRC detection rates were highest in group 3 (f-Hb > 100 μg/g) at 16.3% (n = 24/147) and lowest in patients with a negative FIT (f-Hb < 10 μg/g), with two patients (n = 2/561, 0.36%) in this cohort who did have CRC. Both patients had alarm symptoms:

one presented with anaemia and the other with rectal bleeding. The overall CRC detection rates across the different cohorts are summarized in Figure 5 . The specificity of a negative FIT in this study was 91.5% (95% CI 88.7-94.3), with a sensitivity in group 2 of 80.0%

(95% CI 55.2-99.9) and 92.3% (95% CI 88.9-95.6) in group 3 (Table 7 and Figure 6 ). 

COVID-19 has changed surgical practice in both the primary and secondary care setting. This study reflects a change in practice which was necessary when endoscopy services were limited due to the real fear of COVID-19 cross-infection to patients and staff.

This coincided with a temporary reduction in urgent CRC referrals reported nationally [8] . The use of FIT to triage patients to CT scanning and endoscopy was supported by the guidelines which evolved during the pandemic, and which our hospital trust rapidly adopted [9, 10] .

Since there was no statistical difference in the age and gender of pre-FIT and FIT triage patients, we felt we were justified in comparing the two cohorts. triage; and since one study was from a local trust the local cancer alliance had even more confidence in the FIT as a triage tool [12] [13] [14] .

Follow-up data enabled us to calculate a sensitivity of 80.0%

(95% CI 89.8-95.8) in group 2 patients (f-Hb = 10-100 μg/g) and

92.2% (95% CI 89.8-95.6) in group 3 patients (f-Hb > 100 μg/g).

There was a specificity of 91.5% (95% CI 88.7-84.3) in patients with a negative FIT (f-Hb < 10 μg/g). Compared to a recent multicentre double blinded study, the levels were lower in group 2 (f-Hb = 10-100 μg/g) and higher for a negative FIT (f-Hb < 10 μg/g) and those in group 3 (f-Hb > 100 μg/g), which may reflect the disparity in sample sizes [12] . Two patients (0.36%) had CRC despite a negative FIT (f-Hb < 10 μg/g), which is similar to the 0.31% reported by the D'Souza et al. [12] multicentre study. The two FIT-negative CRC patients suffered from anaemia and per rectum bleeding. Both symptoms led to them being investigated along the urgent pathway.

Despite this, 0.36% is much lower than the 4%-6% of cancers which may be missed when colonoscopy is used as a screening tool [15] [16] [17] . A recent subgroup analysis of a multicentre trial looking into the use of FIT as a predictive tool for CRC has shown that a positive f-Hb using FIT on symptomatic patients under the age of 50 may indicate the need for referral for investigation of CRC or serious bowel TA B L E 6 Subgroup analysis of the endoscopic findings within the FIT triage cohort based on FIT cut-off levels compared to the total number of patients within the FIT triage cohort [18] . The age group is significantly younger than the median age of the cohort in our study (72 years). However, the conclusion is still similar to what we have found in our study given the significantly higher detection rates of CRC and high risk polyps in the FIT-positive (f-Hb > 10 μg/g) cohort.

Colorectal cancer is the most important pathology that must be ruled out when investigating patients referred under a USC pathway. Following this, the detection and subsequent removal of polyps is also of upmost importance, given the adenoma cancer pathway that is involved in the pathogenesis of CRC [19] . Therefore, it is imperative that these lesions are detected at an early stage and excised to prevent the subsequent development of a malignant lesion. A recent meta-analysis showed a 33% (95% CI 0.26-0.41) rate of missed high risk adenomas in symptomatic patients undergoing colonoscopy [20] . A recent single centre study comparing adenoma detection rates in patients who underwent FIT testing to screening colonoscopies showed significantly higher adenoma detection rates in those patients who underwent FIT testing but did not differentiate between high and low risk lesions [21] . A greater detection of adenomas can lead to a subsequent reduction in progression to CRC.

The proportion of patients returning an FIT sample in our study was 86.4%. This is higher than many other studies and may reflect the fact that, as part of our CRC triage, patients are telephoned on referral by a health professional in secondary care rather than primary care where uptake rates can be as low as 63.9%, as seen in the Scottish Bowel Screening Programme [22] . This may be relevant to primary care where FIT is being proposed as a triage tool for urgent CRC referral as per the NICE guidelines [3] . TA B L E 7 The diagnostic accuracy of FIT for colorectal cancer based on the different f-Hb cut-off values 

The use of CT imaging increased after the implementation of FIT triage. This was no surprise as CT was carried out during COVID-19 in both FIT-positive as well as FIT-negative patients who had symptoms suggestive of CRC. This triage system inevitably increased the radiology workload which has been acknowledged elsewhere [25] . In our study, CRC detection rates were similar between the two cohorts despite the change in practice and suggests that CT scanning remains a good tool for CRC detection as reported elsewhere [26, 27] . Although less expensive than colonoscopy, CT scan interpretation requires radiologist expertise and the Royal College of Radiologists reports a 33%

shortage in workforce which is predicted to rise up to 44% by 2025 [28] . Ironically, there is a similar issue in endoscopy [29] . Artificial intelligence and development of training schemes for non-medical practitioners may help in the future for both disciplines [30, 31] .

All of the data for pre-FIT triage patients were collected retrospectively, and even with the authors best attempts these results are still open to selection bias. Despite the large cohort of patients in the FIT triage group, overall there were fewer patients who underwent endoscopic investigations compared to some other studies, which can account for the difference in sensitivities and specificities observed.

Our trust is one of the first in the UK to have implemented the use of FIT for triage to investigation for urgent suspected CRC referrals secondary to the COVID-19 pandemic. This system helped our hospital cope in the management of patients referred on the USC pathway. There was a decreased use of endoscopy and an increased use of radiology during this period. This change in practice did not lead to a decrease in detection of CRC.

In the future, we will continue to use this system for triaging patients for urgent investigation, as it is both safe and aids in reducing the overall burden on endoscopic services which was already an issue prior to the pandemic.

All authors listed contributed to either data collection or manuscript editing or both.

Ethical approval was gained locally from the trust research and development department and registered as an audit (TASCC Colo 2020-06).

None.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

NHS Bowel Screening

NHS Bowel Screening Transition to quantitative faecal immunochemical testing from guaiac faecal occult blood testing in a fully rolled-out population-based national bowel screening programme

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SSCA Lower GI Cancer pathway: diagnostic priortisation. Prepared by: Surrey and Sussex Cancer Alliance

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British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England postpolypectomy and post-colorectal cancer resection surveillance guidelines

A reflection on the impact of COVID-19 on primary care in the United Kingdom

BSG (British society of gastroenterolgists). GI Endoscopy Activity and COVID-19: Next steps

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