Y-ECCO Literature Review: Rohit Rao

A PCCRC is defined as a CRC diagnosed 6–36 months after a colonoscopy negative for CRC and is accepted as a key quality indicator for colonoscopy. Definitions of the PCCRC rate vary in the literature, although a standardised definition has now been proposed: the number of PCCRCs divided by the sum of the number of PCCRCs and detected CRCs (diagnosed within 6 months of colonoscopy) [8]. Using this definition, the PCCRC rate has been calculated as 8.6% in the normal population [8] but remains unclear in those with IBD. Increased PCCRC rates in IBD have been described in previous literature; elderly patients with IBD have a reported rate of 15% [9], whilst a Dutch study reported a rate of 45% [10]. These two studies used differing definitions and highlight the importance of using a standardised definition. In this cohort study by Stjärngrim et al., the authors sought to provide clarity on PCCRC rates using the adult Swedish IBD population. They also aimed to identify associated risk factors for PCCRC in the IBD and non-IBD populations.

Key Findings

National registers were used to identify patients who underwent colonoscopy between 2001 and 2010 and those with a diagnosis of IBD. All individuals without a previous CRC in whom a CRC was diagnosed within 0–36 months after a colonoscopy were selected. For individuals who underwent multiple colonoscopies, only the first colonoscopy that detected the CRC and the first colonoscopy that failed to detect the CRC were included in the calculation. PCCRC rates were calculated using the definition proposed by Morris et al. [8].

In total, 348,232 colonoscopies were performed in 270,918 individuals between 2001 and 2010, 23% of which were on patients with IBD [8% Crohn’s Disease (CD), 15% Ulcerative Colitis (UC)]. In total, 13,731 cases of CRC in the interval 0–36 months were identified. The PCCRC rate in the non-IBD group was 6.3%. Contrastingly, the corresponding figure was 28.3% in the CD group and 41% in the UC group. Approximately half of the PCCRCs were diagnosed as stage T3 or T4. The proportion of IBD patients with co-existing primary sclerosing cholangitis (PSC) was less than 3%, but interestingly, nearly all of the CRCs in this group were PCCRCs. The authors report that when patients with PSC were excluded, there was little change in the overall PCCRC rate.

Patients in the IBD group were, on average, younger than those in the non-IBD group. Moreover, IBD patients with PCCRCs were significantly younger than those with detected CRC (p=0.030). In the UC group it was also reported that the younger the individual, the higher the rate of PCCRC. This was not the case in the CD cohort. It was, however, noted that within the CD group there was an increased risk of a CRC being a PCCRC if it was located in the rectum. There was no observed increased risk of PCCRC in right-sided tumours or in diverticulosis – both of which have been described in previous literature [8]. The presence of a polyp at a previous colonoscopy in an individual with UC did not affect the risk of future PCCRC, while in the non-IBD population, a three times increased risk was observed.

Overall, in the multivariate analysis, the relative risk for an IBD-CRC to be a PCCRC compared with a CRC in an individual without IBD was significantly increased: 3.82 (95% CI 2.92–4.96, p<0.001) in the CD group and 5.89 (95% CI 5.10–6.80, p<0.001) in the UC group.

Conclusion

This national cohort study demonstrates an increased rate of PCCRC in those with IBD when compared to the non-IBD population. Furthermore, the characteristics of PCCRC in the IBD population appear different: there is an increased risk for younger age groups and an increased risk for rectal cancer location for those with CD. This supports previous studies describing increased rates in selected IBD populations [9, 10] and provides an insight into PCCRC rates on a national level.

The nature of a register-based study does, however, have inherent weaknesses. Information was not available on the extent of colitis, disease severity or the quality of the index colonoscopy (such as completeness and bowel preparation). Furthermore, information on dysplasia at previous colonoscopy was not available – a known risk factor for advanced neoplasia.

Early dysplasia detection is essential to preventing CRC. This remains challenging in the IBD population and was highlighted in a recent study which found that unknown high-grade dysplasia was identified in 29% of colectomy specimens from IBD patients [11]. As such, missed lesions at index or surveillance colonoscopy are of significant concern. Advancements in endoscopic technology have improved dysplasia detection but given the predilection for PCCRC in younger age, it may be time to consider alternative surveillance strategies.

References

1. Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001;48:526–35.
2. Jess T, Rungoe C, Peyrin-Biroulet L. Risk of colorectal cancer in patients with ulcerative colitis: a meta-analysis of population-based cohort studies. Clin Gastroenterol Hepatol. 2012;10:639–45.
3. Annese V, Daperno M, Rutter MD, et al. European evidence based consensus for endoscopy in inflammatory bowel disease. J Crohn’s Colitis. 2013;7:982–1018.
4. Cairns SR, Scholefield JH, Steele RJ, et al. Guidelines for colorectal cancer screening and surveillance in moderate and high risk groups (update from 2002). Gut. 2010;59:666–89.
5. Bye WA, Ma C, Nguyen TM, Parker CE, Jairath V, East JE. Strategies for detecting colorectal cancer in patients with inflammatory bowel disease: a Cochrane systematic review and meta-analysis. Am j Gastroenterol. 2018;13:1801–9.
6. Jess T, Simonsen J, Jorgensen KT, Pedersen BV, Nielsen NM, Frisch M. Decreasing risk of colorectal cancer in patients with inflammatory bowel disease over 30 years. Gastroenterology. 2012;143:375–81.
7. Herszényi L, Barabás L, Miheller P, Tulassay Z. Colorectal cancer in patients with inflammatory bowel disease: The true impact of the risk. Dig Dis. 2015;33:52–7.
8. Morris EJA, Rutter MD, Finan PJ, Thomas JD, Valori R. Post-colonoscopy colorectal cancer (PCCRC) rates vary considerably depending on the method used to calculate them: A retrospective observational population-based study of PCCRC in the English National Health Service. Gut. 2015;64:1248–56.
9. Wang YR, Cangemi JR, Loftus EV Jr, Picco MF. Rate of early/missed colorectal cancers after colonoscopy in older patients with or without inflammatory bowel disease in the United States. Am J Gastroenterol. 2013;108:444–9.
10. Wintjens DSJ, Bogie RMM, van den Heuvel TRA, et al. Incidence and classification of postcolonoscopy colorectal cancers in inflammatory bowel disease: A Dutch population-based cohort study. J Crohn’s Colitis. 2018;12:777–83.
11. Eluri S, Parian AM, Limketkai BN, et al. Nearly a third of high-grade dysplasia and colorectal cancer is undetected in patients with inflammatory bowel disease. Dig Dis Sci. 2017;62:3586–93.

Rohit Rao is a gastroenterology trainee at the Royal London Hospital, United Kingdom. He has a particular interest in complex polypectomy and advancing imaging techniques in IBD endoscopy.