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

Patients with colonic inflammatory bowel disease (IBD) have an overall 40%–70% increased risk of developing colorectal cancer (CRC) [1]. Surveillance colonoscopy is recommended to detect and—where possible—endoscopically remove dysplasia, and guide individualised surgical recommendations in partnership with the IBD multidisciplinary team [2, 3]. Patients with colonic high-grade dysplasia (HGD) are among the highest risk for CRC development. However, data on the natural history of this group are limited, and guidelines rely on small retrospective case series [1]. For patients not undergoing proctocolectomy, intensive colonoscopic surveillance is advised, initially at 3–6 months, then, depending on findings, annually for 5 years [1, 4]. Further high-quality data are needed to inform best practice. Derks et al. have presented the largest retrospective cohort study to date of patients with IBD and HGD, aiming to determine the 1, 5, and 10 years incidence of CRC and colorectal neoplasia (CRN: including indefinite for dysplasia (IND), low-grade dysplasia (LGD), HGD and CRC) [5]. Using the Dutch nationwide pathology databank, 1220 patients with colonic IBD and histologically confirmed HGD were identified. The cohort had a cumulative follow-up from index HGD of 8426 years, with a median of 5.2 years per patient. Of these, 1034 had ≥ 1 year, 627 ≥ 5 years, and 312 ≥ 10 years of follow-up. Index HGD was treated endoscopically in 890 patients (73%) and surgically in 329 (26.9%) including 69 proctocolectomies. CRC was diagnosed in 348 patients (28.5%) after a median of 0.3 years post-HGD. Of these, 204 (16.7%) were synchronous CRC (within 6 months of index HGD). Among the remaining 1016 patients, 144 metachronous CRCs (after 6 months) were diagnosed after a median of 3.6 years. The cumulative CRC incidence at 1, 5, and 10 years after HGD was 20.2%, 28.1% and 34.9%. Additionally, 638 patients (62.8%) developed metachronous CRN of any grade after a median of 2.2 years. Independent risk factors for metachronous CRC following HGD included post-inflammatory polyps (consistent with inflammation being a key risk factor for neoplasia), prior IND or LGD, disease duration of ≥ 20 years, invisible index HGD, academic follow-up and endoscopic (vs surgical) treatment. Moreover, post-inflammatory polyps, primary sclerosing cholangitis, prior IND or LGD, age at HGD diagnosis, IBD duration at index HGD diagnosis, year of index HGD in 2010 or later, multifocal index HGD, and endoscopic treatment of index HGD were independent risk factors for metachronous CRN. Limitations include lack of data on IBD extent, severity, prior IBD treatment and differentiation between IBD-related and sporadic neoplasia. Nonetheless, the finding that 1 in 6 patients had synchronous CRC underscores the importance of surgical consideration and early endoscopic surveillance after identifying HGD, and supports counselling of patients regarding their future risk. Notably, nine out of ten synchronous cancers were in the same colonic segment as HGD, often with high clinical suspicion of malignancy at the time of HGD diagnosis. This underscores the risk of sampling error and challenges in histopathology assessment. High-quality colonoscopy, expert histopathological assessment, and multidisciplinary team discussion are essential for optimal management of this high-risk group. Alexandra Hickey: writing – original draft, writing – review and editing. Chaonan Dong: writing – original draft, writing – review and editing. Christopher A. Lamb: writing – original draft, conceptualization, writing – review and editing, supervision. Chaonan Dong and Christopher A. Lamb acknowledge research support from the NIHR Newcastle Biomedical Research Centre. Christopher A. Lamb acknowledges research support from the Medical Research Council, The Leona M. and Harry B. Helmsley Charitable Trust, Crohn's & Colitis UK, EU Innovative Medicines Initiative, Wellcome Trust, Open Targets, European Bioinformatics Institute (EMBL-EBI), Janssen, Takeda, Abbvie, AstraZeneca, Eli Lilly, Orion, Pfizer, Roche, Sanofi Aventis, UCB, Biogen, Genentech, Bristol Myers Squibb (BMS), GSK and Merck Sharp and Dohme (MSD); acknowledges consultancy for MSD, Takeda, Janssen and BMS; has received honoraria for development and/or delivery of education from Takeda, Ferring, Janssen, Dr. Falk, and Nordic Pharma; participated in a data safety monitoring board for the MARVEL: Mitochondrial Anti-oxidant therapy to Resolve Inflammation in Ulcerative Colitis trial; was previously the IBD Section Secretary for the British Society of Gastroenterology, sits on the Steering Committee and attends Board meetings at IBD UK; and has received conference attendance support from Tillotts Pharma UK, Janssen, British Society of Gastroenterology (BSG), International Organisation of IBD (IOIBD) and the European Crohn's & Colitis Organisation (ECCO). A.H. declares no conflicts of interest. See Acknowledgements section for the remaining authors. 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.70473. The authors have nothing to report.