Editorial: High‐Grade Dysplasia in Colonic Inflammatory Bowel Disease Is Associated With a High Risk of Synchronous or Metachronous Colorectal Cancer—Authors' Reply

We thank Dr. Hickey and colleagues for their insightful editorial on outcomes and clinical implications of our study on colorectal cancer (CRC) risk following high-grade dysplasia (HGD) in inflammatory bowel disease (IBD) [1, 2]. Patients with IBD and HGD indeed carry a high risk for CRC but supportive evidence is derived from small studies with historical data. The nationwide design of our study enabled us to establish the largest cohort to date of IBD patients with HGD with over 1200 subjects. We acknowledge certain limitations noted in the editorial [1]. The lack of data on disease extent and severity within the PALGA registry limited our ability to estimate the individual inflammatory burden. The cumulative inflammatory burden, calculated as the sum of the average inflammation score between surveillance endoscopies multiplied by the interval in years between procedures, was previously shown to be associated with colorectal neoplasia (CRN) risk and is a confounder that should be considered [3]. Importantly, the high metachronous CRN and CRC rates observed after endoscopic resection suggest that endoscopic treatment should only be considered when complete resection is feasible and close surveillance is possible without impaired mucosal visualisation from active inflammation, strictures or post-inflammatory polyps. An individualised treatment strategy is warranted, considering patients' age, comorbidity and CRC risk. The high risk of CRC detected within 6 months after HGD diagnosis, predominantly in the same colorectal segment, underlines the potential for sampling error and histopathological challenges in distinguishing HGD from early cancer in IBD. When we separately performed histopathology revision on 54 HGD lesions, we found an increased risk of metachronous CRC after confirmation of HGD by a second pathologist [4]. This underlines the necessity of obtaining sufficient biopsies and histopathological revision of HGD in daily practice. Our findings help refine CRC risk classification in this subgroup of patients with IBD and may assist clinicians in selecting the appropriate treatment strategy for HGD, where the benefits of endoscopic resection, including avoidance of surgery and preserving bowel function, should be balanced against the elevated risk of metachronous CRC. We agree that optimal management of HGD requires a multidisciplinary approach integrating gastroenterology, pathology and surgery teams, as recommended in the most recent British Society of Gastroenterology (BSG) guideline [5]. Our study underscored the limitations of current evidence, which largely relies on expert opinion and small retrospective series. Ideally, gastroenterologists and surgeons should apply personalised surveillance and treatment strategies, guided by individualised CRN risk and patient preferences. A CRC prediction calculator for daily practice is available and recommended in the latest BSG guideline, based on a Dutch prediction model using data from large well-characterised international IBD cohorts [5, 6]. Building on this, future research should generate high-quality data on synchronous and metachronous CRN risk using up-to-date endoscopic surveillance techniques, intervals and treatment modalities, as well as the impact of disease- and lesion-specific factors. Given the low and declining incidence of CRC and the required long follow-up, multicentre international collaborations will be essential to produce robust, prospective data with broad external validity. Monica E. W. Derks: conceptualization, writing – original draft. Frank Hoentjen: writing – review and editing, supervision. The authors have nothing to report. This article is linked to Derks et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70429 and https://doi.org/10.1111/apt.70442. The authors have nothing to report.