Objective Ulcerative colitis (UC) patients diagnosed with low-grade dysplasia (LGD) have increased risk of developing advanced neoplasia (AN; high-grade dysplasia or colorectal cancer). We aimed to develop and validate a predictor of AN risk in UC patients with LGD and create a visual web-tool to effectively communicate the risk.

Design In our retrospective multi-centre validated cohort study, adult UC patients with an index diagnosis of LGD, identified from four UK centres between 2001-2019, were followed until progression to AN. In the discovery cohort (n=246), a multivariate risk prediction model was derived from clinicopathological features using Cox regression. Validation used data from 3 external centres (n=198). The validated model was embedded in a web-tool to calculate patient-specific risk.

Results Four clinicopathological variables were significantly associated with AN progression in the discovery cohort: endoscopically visible LGD > 1 cm (HR = 2.7; 95% CI 1.2-5.9), unresectable or incomplete endoscopic resection (HR = 3.4; 95% CI 1.6-7.4), moderate/severe histological inflammation within 5 years of LGD diagnosis (HR = 3.1; 95% CI 1.5-6.7), and multifocality (HR = 2.9; 95% CI 1.3-6.2). In the validation cohort, this 4-variable model accurately predicted future AN cases with overall calibration Observed/Expected = 1 (95% CI 0.63-1.5), and achieved 100% specificity for the lowest risk group over 13 years of available follow-up.

Conclusion Multi-cohort validation confirms that patients with large, unresected, multifocal LGD and recent moderate/severe inflammation are at highest risk of developing AN. Personalised risk prediction provided via the Ulcerative Colitis-Cancer Risk Estimator (www.UC-CaRE.uk) can support treatment decision-making.