17December2019

Does the expanding armamentarium of medical options in IBD result in postponement of colectomy with an increased incidence of dysplasia and colorectal cancer?

Christianne Buskens, S-ECCO Member and Awardee of the ECCO-Pfizer Research Award 2019

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Christianne Buskens
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Patients with Inflammatory Bowel Disease (IBD) have an increased risk of colorectal cancer (CRC), principally resulting from the pro-neoplastic effects of chronic intestinal inflammation [1]. Epidemiological studies, however, have suggested that the incidence of CRC has decreased over time [2]. This is partly because the estimated incidence in older studies was based on data from referral centres, which likely included a different patient population with more severe and complicated disease. The declining incidence has also been attributed to successful CRC surveillance programmes and in addition has been hypothesised to be a consequence of improved control of mucosal inflammation [3]. The expanding armamentarium of medical options in IBD, such as anti-TNF and anti-adhesion biologic therapies, has substantially improved our ability to control severe inflammation, theoretically decreasing the risk of CRC.

However, population-based data show conflicting results. A Swedish population-based study demonstrated that the risk ratio of CRC among IBD patients decreased from 5.4 (95% CI, 2.2–11) in 1960–1969 to 1.8 (1.3–2.5) in 2000–2004 [4]. Comparable data were found in the Danish population, where the overall risk of CRC in patients with Ulcerative Colitis (UC) decreased over time from 1979 onwards, and no longer exceeded that of the general population in 2008 [5]. In contrast, a study from a Californian health organisation confirmed an elevated risk of CRC in IBD patients compared with the background population, but could not demonstrate any change in the risk ratio of CRC between the 1998–2001 and 2007–2010 study periods [6].

A key question in this discussion is whether current medication does have a true modifying effect on the natural history of the disease. Surgical rates are often used as a surrogate marker, and it is still being debated whether the use of biologic therapies really prevents patients from needing colectomy or only delays surgical intervention [7]. Most studies suggest that although there has been an overall decrease in surgical resections for Crohn’s Disease, colectomy rates in UC remain stable in long-term follow-up. If current treatment strategies indeed lead to postponement of colectomy, this might result in fewer operations being performed for therapy-refractory disease, and more patients being operated on for malignant degeneration.

Interestingly, recently published data on the role of appendectomy as a new therapeutic approach for patients with UC have fuelled this discussion. In a systematic review with meta-analysis on the suggested relation between appendectomy and increased risk of CRC in UC patients, we were able to confirm a higher incidence of CRC in colectomy specimens of patients who had previously undergone appendectomy [8]. This finding was related to longer disease duration and older age at colectomy after appendectomy (resulting in inequalities in at-risk exposure between groups), and emphasises the possible downside of positive clinical effects of therapies that decrease disease symptoms.

To analyse the hypothesis that the expanding medical options could lead to a shift in surgical indications in IBD patients, we have started a large international population-based study to analyse time trends. With the ECCO-Pfizer Research Award, we have inventoried all indications for colectomies performed in the Amsterdam UMC. Interestingly, we were able to demonstrate an increase in the percentage of IBD patients undergoing colectomy for CRC from 14% in 2010–2013 to 34% in 2014–2018. Obviously, we will have to compare these data to nationwide results and international IBD referral centre data to confirm the suggested time trend. In addition, patient and disease characteristics need to be collected in order to correlate findings to changes in treatment regimens and correct for the influence of possible confounding factors. However, we feel that the current findings confirm the importance of ongoing regular endoscopic surveillance of patients who are being exposed to the variety of treatment options that are currently available before being counselled for colectomy, as any postponement of colectomy will increase the CRC risk over the long term.

References

1. Dulai PS, Sandborn WJ, Gupta S. Colorectal cancer and dysplasia in inflammatory bowel disease: a review of disease epidemiology, pathophysiology, and management. Cancer Prev Res. 2016;9:887–94.

2. Olivera P, Spinelli A, Gower-Rousseau C, Danese S, Peyrin-Biroulet L. Risk of cancer in inflammatory bowel disease: going up, going down, or still the same? Curr Opin Gastroenterol. 2017;33:246–53.

3. Lopez A, Pouillon L, Beaugerie L, Danese S, Peyrin-Biroulet L. Colorectal cancer prevention in patients with ulcerative colitis. Best Pract Res Clin Gastroenterol. 2018;32:103–9.

4. Soderlund S, Brandt L, Lapidus A, et al. Decreasing time-trends of colorectal cancer in a large cohort of patients with inflammatory bowel disease. Gastroenterology 2009;136:1561–7.

 5. Jess T, Simonsen J, Jorgensen KT, et al. Decreasing risk of colorectal cancer in patients with inflammatory bowel disease over 30 years. Gastroenterology 2012;143:375–81.

6. Herrinton LJ, Liu L, Levin TR, et al. Incidence and mortality of colorectal adenocarcinoma in persons with inflammatory bowel disease from 1998 to 2010. Gastroenterology 2012;143:382–9.

7. Olivera P, Spinelli A, Gower-Rousseau C, Danese S, Peyrin-Biroulet L. Surgical rates in the era of biological therapy: up, down or unchanged? Curr Opin Gastroenterol 2017;33:246–53.

8. Stellingwerf ME, de Koning MA, Pinkney T, Bemelman WA, D’Haens GR, Buskens CJ. The risk of colectomy and colorectal cancer after appendectomy in patients with ulcerative colitis: a systematic review and meta-analysis. J Crohns Colitis 2019;13:309–18.

Posted in ECCO News, Committee News, S-ECCO, Volume 14, Issue 4

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