Colorectal Cancer in Inflammatory Bowel Disease: towards an improved surveillance guideline

Abstract

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a group of chronic disorders with varying phenotypes and disease severity. The worldwide incidence and prevalence rates are rising. It has been estimated that around 90,000 Dutch inhabitants had IBD by the end of 2003, which makes IBD, in order of magnitude, comparable to diseases such as breast cancer, sporadic colorectal cancer and dementia. One of the most feared long-term complications of IBD is colorectal cancer. It is considered best medical practice to prevent colorectal cancer in IBD by colonoscopic surveillance to detect asymptomatic cancer or precancerous dysplastic lesions. The aim of this thesis is to provide better evidence for colonoscopic surveillance in IBD in order to improve guidelines. In the period 2008-2013, we published or submitted for publication 6 studies that all focused on colonoscopic surveillance in patients with inflammatory bowel disease (IBD). We showed that a large proportion of patients (10-20%) do not benefit from surveillance because they already had developed colorectal cancer before the recommended starting date of surveillance as they were published in 2002-2003. Despite this shortcoming, we found that patients who underwent colonoscopic surveillance had improved colorectal cancer-related survival and overall survival compared to patients in whom no surveillance was performed. In our meta-analysis we found that both Crohn’s colitis and ulcerative colitis are associated with an increased risk of colorectal cancer with a relative risk of 1.7. We confirmed that extensive disease is a risk factor. Using the Leuven University IBD-database for validation, we showed that it is possible to predict colorectal cancer risk in IBD patients by scoring 4 characteristics: IBD-type, primary sclerosing cholangitis, post-inflammatory polyps, and extensive disease. In 2009 and 2010 the British Society of Gastroenterology (BSG) and the American Gastroenterological Association updated their surveillance guidelines. The BSG guideline recommends a risk stratification approach that we have adopted for clinical practice as well. Employing Markov modeling, we showed that the BSG surveillance strategy with different colonoscopy intervals of 5 years, 3 years and 1 year is more cost-effective as compared to conventional annual surveillance for IBD with primary sclerosing cholangitis and bi-annual surveillance for all other IBD patients as proposed by the AGA. In order to further improve surveillance guidelines, we propose that future studies need to focus on the following items: 1) Validation of the risk profiling approach in prospectively followed cohorts of IBD patients; 2)Validation of the proposed surveillance intervals of 1, 3 and 5 years for the corresponding low, intermediate and high risk groups; 3)Addition of molecular biomarkers for neoplastic progression to the current risk profiling. This will undoubtedly aid in further tailoring surveillance guidelines to the individual patient and in achieving the most cost-efficient way of preventing colorectal cancer in IBD.