Abstract

Abstract Background The expanding medical armamentarium in ulcerative colitis (UC) has contributed to increased control of inflammation. However, simultaneously, postponed colonic resection with an accumulative inflammatory burden might lead to an increased risk of CRC. Recent studies have reported conflicting results regarding the incidence of colorectal cancer (CRC) in UC patients. Aim To analyse the impact of advanced medical therapies (defined as biologicals and small molecules) on time to colonic resection and risk of CRC in UC patients. Methods Consecutive patients ≥18 years with established UC who underwent colonic resection between January 2003 and October 2022 at the Academic Medical Centre Amsterdam or the University Hospital Leuven were included. Primary outcomes were time to colonic resection and CRC rate in colonic specimens, compared between four time periods: P1 (2003-2007), P2 (2008-2012), P3 (2013-2017) and P4 (2018-2022). Secondary outcomes were the effect of advanced medical therapy on time to resection, cancer stage and risk of CRC. CRC was staged according to the AJCC TNM classification (advanced cancer defined as T3/T4, N1/2 or M1). Results A total of 716 patients were included. The usage of advanced medical therapies prior to surgery increased from 38.2% in P1 to 90.2% in P4 (p<0.001). However, this did not result in an increased time to colonic resection (P1: 7 years (2-12) vs P2: 6 years (2-14) vs P3: 7 years (3-14) vs P4: 7 years (2-14), p=0.94). CRC was diagnosed in 72 (10.1%) patients, and this incidence did also not change over time. Time to resection was significantly longer (median 18 years, IQR 10-24) in CRC patients compared to the overall cohort. The majority of CRC patients (64.8%) were diagnosed with advanced cancer, which did not decrease over time. Patients using advanced medical therapies had significantly shorter follow-up compared to therapy-naïve patients (6 years vs. 10 years, p<0.001), which resulted in a decreased risk of CRC (OR 0.17, p=<0.001). However, the finding of an incidental carcinoma rate (i.e. not preoperatively diagnosed) in this group was 18% whereas this was only 4% in patients without advanced medical therapy (p=0.08). Moreover, the incidence of advanced CRC was numerically higher in UC patients who received ≥2 therapies (83.3% vs 61.0%, p=0.14). Conclusion This study demonstrated that in the last two decades, the increased usage of advanced medical therapies did not result in an increased time to resection, nor in a decreased CRC rate in UC patients undergoing colonic resection. A higher incidence of incidental and advanced cancers was seen in patients with ≥2 therapies. Therefore, care should be taken with improved tailored surveillance in this group.

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