Non Invasive Strategies for Detection and Monitoring of Colorectal Diseases

In recent years there has been increasing demand for endoscopy services in Ireland. This is related to the establishment of the national colorectal cancer screening program which was established in 2012 to increase early detection of colorectal cancer and improve survival among patients. Since March 2020 endoscopy capacity has come under increasing pressure due to the COVID-19 pandemic which has reduced endoscopy service provision nationally and has led to increases in waiting lists compared with previous years. In a large single centre retrospective study examining >19,000 colonoscopies we have shown that the majority of colonoscopies performed were in symptomatic patients triaged as routine. This cohort had a lower rate of CRC compared with screening patients and symptomatic patients meeting urgent criteria. Screening patients accounted for the majority of CRC diagnosed and were more likely to have earlier stage disease at diagnosis compared with any other group. Current referral pathways for symptomatic patients are insufficient and have poor diagnostic accuracy for detecting CRC and significant bowel pathology. Improving identification of high risk patients through the use of non-invasive faecal biomarkers, namely FIT and faecal calprotectin (FC) will reduce the volume of referrals for urgent colonoscopy, thereby improving access for screening patients and increasing early CRC detection and survival. A prospective evaluation of FIT and FC to identify organic bowel disease in low risk patients was performed. Among this patient cohort the rate of significant bowel disease, including CRC, IBD and advanced adenomas, was 3.8%. A combination of FIT ≥10μg/g with FC ≥50μg/g was the most accurate diagnostic test for identifying significant bowel disease. A prospective study was performed to examine the diagnostic accuracy of FC and FIT in patients with IBD undergoing colonoscopy and their potential application in disease monitoring. In this study, among IBD patients referred for CRC surveillance, over 50% had active inflammation present at colonoscopy, 0 patients with a FC ≥250μg/g had mucosal healing at colonoscopy and 0 dysplastic lesions were detected among this cohort. The presence of disease activity was associated with higher levels of both FC and FIT. In those undergoing assessment for treatment de-escalation 62.5% had mucosal healing at colonoscopy and none of those had FC ≥250μg/g. GOAL-ARC is a randomised multicentre two arm trial studying the effectiveness of dose optimisation of Golimumab based on FC and drug levels as compared to treatment according to the SmPC. An assessment of induction data to week 6 was performed. Following Golimumab induction at week 6 there was significant improvement in both clinical and biochemical markers. Median modified partial Mayo score improved from 4 to 2, median FC improved from 1300μg/g to 227 μg/g, median combined Short Health Scale improved from 24.5 to 18. The rate of early clinical response was 50.6% in an intention to treat analysis. Factors associated with early clinical response included lower week 6 FC levels, lower week 6 combined SHS score and higher week 6 trough Golimumab levels. Week 6 trough Golimumab level was inversely proportional to week 6 FC level. Patients with higher drug levels measured at week 6 were more likely to achieve early clinical response.