Risk of hepatobiliary and colorectal malignancies in primary sclerosing cholangitis: Crohn's disease with colonic involvement versus ulcerative colitis - a propensity-matched cohort study.

OBJECTIVE: Primary sclerosing cholangitis (PSC) increases malignancy risk in inflammatory bowel disease (IBD), but whether this risk differs between Crohn's disease (CD) and ulcerative colitis (UC) remains poorly defined. This study compared the risk of colorectal cancer (CRC), gallbladder cancer (GBC) and cholangiocarcinoma (CCA) in patients with CD with colonic involvement and concomitant PSC (CD+PSC) versus UC with concomitant PSC (UC+PSC). METHODS: This retrospective propensity score-matched cohort study used the TriNetX Network (2001-2024) to identify adults with PSC and either CD with colonic involvement (ICD-10-CM K50.1, K50.8) or UC (K51). Cohorts were matched 1:1 on age, sex, race, body mass index, smoking status, C-reactive protein and erythrocyte sedimentation rate. The primary analysis employed Kaplan-Meier survival estimation with Cox proportional hazards regression. RESULTS: After matching, 1,084 pairs were analyzed (mean follow-up 5.3 ± 2.6 years). CRC risk did not differ between groups (30/1084 = 2.8% in both; HR 1, 95% CI 0.765-2.112). CD+PSC was associated with significantly lower risk of both GBC (0.9% vs. 1.2%; HR 0.199, 95% CI 0.045-0.885) and CCA (2.8% vs. 5.9%; HR 0.625, 95% CI 0.406-0.961) versus UC+PSC. The CCA finding was consistent across both time-to-event and odds ratio analyses, while the GBC difference reached significance only in the time-to-event analysis. CONCLUSIONS: Among patients with PSC-IBD, CRC risk appears comparable regardless of IBD subtype, suggesting that PSC may be the predominant contributor to CRC risk in this population. However, CD+PSC carries significantly lower risk of both GBC and CCA than UC+PSC, which may reflect differences in biliary disease phenotype or surveillance intensity and warrants prospective validation.