Multi-centre derivation and validation of a colitis-associated colorectal cancer risk prediction web-tool
4 November 2020
A web tool has been developed that helps predict which ulcerative colitis patients have increased risk of developing colorectal cancer, to help target earlier intervention
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.