P0445 High risk of colorectal cancer after high-grade dysplasia in Inflammatory Bowel Disease patients

Abstract Background Colonic high-grade dysplasia (HGD) is the highest-risk precursor of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients with reported incidence rates of 1.0-3.5%.1-4 Data on metachronous CRC risk after HGD in IBD are limited and outdated. The aim of this study was to determine the long-term risk of CRC and colorectal neoplasia (including indefinite for dysplasia, low-grade dysplasia, HGD and CRC) after a first diagnosis of HGD in IBD, and to assess HGD treatment strategies. Methods In this nationwide retrospective cohort study, patients with both a colonic IBD and HGD diagnosis between 1991 and 2021 were extracted from the Dutch nationwide pathology databank (PALGA). The primary outcome was the cumulative incidence of metachronous CRC and colorectal neoplasia. Cox proportional hazard models were used to assess associations with metachronous CRC. Kaplan Meier curves were used to show proctocolectomy free survival per decade. Results CRC was diagnosed in 358 of 1,223 patients with HGD (29.3%) after a median 0.3 years (IQR 0.1-2.7, figure 1). Of these, 203 patients (16.6%) were diagnosed with CRC within 6 months after the first HGD diagnosis and were considered synchronous CRC patients. Metachronous CRC was diagnosed in 155 of 1,020 patients (15.2%) after a median 4.1 years (IQR 1.3-11.0). The 1-, 5-, and 10-year cumulative incidences of metachronous CRC after HGD were 2.9%, 10.4%, and 17.2%, respectively. After a median of 2.2 years (IQR 1.0-5.7), 642 patients (62.9%) developed metachronous colorectal neoplasia (indefinite for dysplasia as highest grade: n=12 [1.9%]; low-grade dysplasia: n=243 [37.9%]; HGD: n=220 [34.3%]; CRC: n=155 [24.1%], figure 1). The 1-, 5- and 10-year cumulative incidences of metachronous colorectal neoplasia were 18.0%, 53.9% and 75.0%, respectively. Post-inflammatory polyps (aHR 1.88, 95% CI 1.33-2.65, p<0.01), strictures (aHR 1.62, 95% CI 1.02-2.58, p=0.04), invisible index HGD (aHR 2.04, 95% CI 1.24-3.35, p<0.01), academic follow-up (aHR 1.54, 95% CI 1.10-2.17, p=0.01), and endoscopic vs. surgical treatment (aHR 2.31, 95% CI 1.17-4.57, p=0.02) were associated with metachronous CRC. Proctocolectomy was performed in 209 (17.1%) patients after a median 4.7 years (IQR 1.5-9.7) after index HGD diagnosis. Proctocolectomy free survival did not differ between decades of HGD diagnosis after 8 years of follow-up (p=0.58). Conclusion The high cumulative incidence of synchronous and metachronous CRC after a diagnosis of HGD underlines the high-risk profile for this subgroup of IBD patients. The possible advantages of colon sparing treatment for HGD should be balanced with the subsequent higher risk of metachronous CRC and colorectal neoplasia and resulting need for stringent endoscopic surveillance. References 1.Choi CH, Rutter MD, Askari A, et al. Forty-Year Analysis of Colonoscopic Surveillance Program for Neoplasia in Ulcerative Colitis: An Updated Overview. Am J Gastroenterol. Jul 2015;110(7):1022-34. doi:10.1038/ajg.2015.65 2.Mooiweer E, van der Meulen-de Jong AE, Ponsioen CY, et al. Incidence of Interval Colorectal Cancer Among Inflammatory Bowel Disease Patients Undergoing Regular Colonoscopic Surveillance. Clin Gastroenterol Hepatol. Sep 2015;13(9):1656-61. doi:10.1016/j.cgh.2015.04.183 3.Shah SC, Ten Hove JR, Castaneda D, et al. High Risk of Advanced Colorectal Neoplasia in Patients With Primary Sclerosing Cholangitis Associated With Inflammatory Bowel Disease. Clin Gastroenterol Hepatol. Jul 2018;16(7):1106-1113 e3. doi:10.1016/j.cgh.2018.01.023 4.Singh K, Al Khoury A, Kurti Z, et al. High Adherence to Surveillance Guidelines in Inflammatory Bowel Disease Patients Results in Low Colorectal Cancer and Dysplasia Rates, While Rates of Dysplasia are Low Before the Suggested Onset of Surveillance. J Crohns Colitis. Sep 27 2019;13(10):1343-1350. doi:10.1093/ecco-jcc/jjz066