Faye, Adam S

ABSTRACT Introduction Patients with primary sclerosing cholangitis (PSC) and concomitant inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC). However, the risk of CRC in patients with PSC without IBD remains uncertain. We aimed to evaluate the risk of CRC in patients with PSC without a history of IBD using a large national database. Methods We conducted a retrospective cohort study using the TriNetX database to identify patients ≥ 18 years with PSC. Patients were then divided into two groups, PSC with IBD (PSC‐IBD cohort) and PSC without IBD (PSC non‐IBD cohort), and were matched with patients without a history of PSC or IBD (non‐PSC/non‐IBD group) by using 1:1 propensity score matching. The primary outcome was the risk of first diagnosis of CRC. With censoring applied, Kaplan–Meier analysis with hazard ratios (HRs) and 95% CIs was used to compare time‐to‐event rates at daily time intervals. Results PSC patients without IBD were at increased risk of CRC compared to the non‐PSC/IBD cohort (aHR = 2.91; 95% CI: 1.6–6.0). Patients with PSC and IBD exhibited a higher risk of CRC (aHR = 6.5; 95% CI: 3.78–11.2), especially among the UC cohort (aHR = 6.3; 95% CI: 3.2–12.4). Patients with PSC were at increased risk of various gastrointestinal malignancies (aHR = 10.5; 95% CI: 7.3–15; p < 0.0001), including hepatobiliary cancers, pancreatic cancer, and hepatocellular carcinoma. Discussion Our findings provide real‐world evidence that PSC is an independent risk factor for colorectal cancer, even in the absence of concomitant IBD. These results support the need for further research to determine whether patients with isolated PSC may benefit from tailored CRC surveillance strategies.