Risk of Intestinal and Extraintestinal Malignancies in Inflammatory Bowel Disease With and Without Primary Sclerosing Cholangitis.

[INTRODUCTION] Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease frequently associated with inflammatory bowel disease (IBD). While both conditions independently increase cancer risk, the comparative burden of cancer in patients with coexisting IBD and PSC (IBD-PSC), isolated IBD, and isolated PSC remains inadequately defined.

[METHODS] We conducted a retrospective cohort study using the TriNetX nationwide electronic health records database. Patients with IBD-PSC were compared to individuals with isolated IBD and isolated PSC. Propensity score matching (PSM) was employed to balance key baseline characteristics across groups. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were calculated for intestinal and extraintestinal malignancies across three pairwise comparisons: IBD-PSC vs isolated IBD, IBD-PSC vs isolated PSC, and isolated PSC vs isolated IBD.

[RESULTS] After matching, 4,187 patients were included in each of the IBD-PSC and isolated IBD groups. IBD-PSC was associated with increased risks of colorectal cancer (aHR 4.01, 95% CI: 2.79-5.75, p < 0.001), cholangiocarcinoma (aHR 27.54, 95% CI: 15.05-50.38, p < 0.001), liver cancer (aHR 13.41, 95% CI: 7.42-24.26, p < 0.001), pancreatic cancer (aHR 2.37, 95% CI: 1.18-4.76, p = 0.013), and gallbladder cancer (aHR 36.26, 95% CI: 4.94-266.23, p < 0.001). Compared to isolated PSC, IBD-PSC had higher risks of colorectal (aHR 5.72, 95% CI: 3.17-10.31, p < 0.001) and gallbladder cancer (aHR 4.14, 95% CI: 1.69-10.14, p = 0.001).

[CONCLUSION] IBD-PSC is associated with substantially elevated risks of both intestinal and extraintestinal malignancies compared to isolated IBD or PSC. These findings highlight the synergistic oncogenic potential of coexisting IBD and PSC and underscore the need for tailored surveillance and early detection strategies in this high-risk population.