Understanding hepatopancreatobiliary cancer risks in a population-based primary sclerosing cholangitis-inflammatory bowel disease cohort

Background & Aims: Primary sclerosing cholangitis (PSC) is a pre-malignant condition with elevated risk of hepatopancreatobiliary cancers (HPBCa) and colorectal cancer (CRC) when inflammatory bowel disease (IBD) is present. We described cancer burden in a contemporary PSC-IBD cohort, and assessed rates of subsequent cancers, liver transplant and death post-colectomy or post-cholecystectomy status. Methods: Using linked health administrative databases, we calculated cause-specific cumulative incidences of HPBCa-related outcomes (diagnoses/deaths) and non-HPBCa-related transplant/death among individuals with PSC-IBD in Ontario, Canada (2002–2018) followed to 2021. Transition probabilities and transition intensity ratios (TIR) were evaluated using a multistate Markov model. Results: Amongst 476 individuals with incident PSC-IBD, there was a 54% probability of remaining event-free at 10 years, while approximately 1 in 20 experienced an HPBCa-related outcome, and up to 1 in 4 had a non-HPBCa-related transplant/death. During follow-up, 13% experienced multiple events. Age was associated with HPBCa (HR 1.02, 95% CI 1.01–1.04), but not male sex. Mortality occurred more frequently post-colectomy (TIR 3.08, 95% CI 1.7-5.59) and post-cholecystectomy (TIR 3.85, 95% CI 2.21-6.64) relative to event-free PSC-IBD, but there were no differences in post-surgery incidence of cancer or transplant. Conclusions: While some individuals with PSC-IBD experience an extended event-free disease course, a large proportion experienced disease-related cancer, colectomy, cholecystectomy and transplant events. Higher mortality rates observed after surgery are likely related to underlying disease processes that motivated surgical intervention (e.g. dysplasia/malignancy, refractory IBD), rather than the surgery itself. Understanding how PSC-IBD disease trajectories vary can inform individual management and patient counselling.