DAY 1 - Primary Sclerosing Cholangitis in the Absence of Inflammatory Bowel Disease Increases the Risk of Colorectal Cancer: A Propensity-Matched Cohort Study

Patients with both Primary sclerosing cholangitis (PSC) and Inflammatory bowel disease (IBD), particularly ulcerative colitis, face the risk of developing colorectal cancer (CRC). Recognizing this risk, the American College of Gastroenterology (ACG) and the American Gastroenterology Association (AGA) recommend annual surveillance colonoscopies for PSC patients with IBD. However, the risk of CRC in PSC patients without IBD has remained unclear, leaving a critical gap in our understanding of cancer risk in this population. This uncertainty has led to a lack of clear guidelines for CRC screening in PSC patients without IBD, potentially leaving a vulnerable group of patients at risk for undetected colorectal cancer.
 
At the ACG 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania, Dr. Saqr Alsakarneh, an Internal Medicine Resident from the University of Missouri - Kansas City School of Medicine, presented a retrospective study addressing this crucial issue. Dr. Alsakarneh's research aimed to evaluate the risk of colorectal cancer in patients with PSC without a history of IBD using a large national database, TriNetX, shedding light on a potentially overlooked risk factor. The study identified patients aged 18 years and older with PSC, dividing them into two groups: those with concomitant IBD (PSC-IBD cohort) and those without IBD (PSC non-IBD cohort). These groups were then matched with a control group of patients without a history of PSC or IBD using 1:1 propensity score matching.
 
The primary outcome of the study was the risk of the first CRC diagnosis within 14 years of the initial PSC diagnosis. Secondary outcomes included a comparison of CRC risk in PSC patients with IBD, subgroup analyses for ulcerative colitis and Crohn's disease, the risk of other gastrointestinal malignancies, and CRC risk stratified by age and gender.
Among 2,662 patients with PSC but no IBD, the risk of CRC was significantly elevated compared to the non-PSC/IBD cohort. Dr. Alsakarneh emphasized the importance of these results, stating, "For patients who had PSC alone, without a history of IBD before or after diagnosis of PSC, we found that they're at higher risk of CRC, with an adjusted hazard ratio of almost 2.9."
 
Even more alarming was the finding that PSC patients with concomitant IBD exhibited a 6.5-fold higher risk of CRC, with the risk being particularly pronounced in the ulcerative colitis cohort. These results were consistent across gender and age groups, underscoring the robustness of the findings. Interestingly, while males with PSC showed an increased risk of CRC, females did not demonstrate a significantly elevated risk compared to the general population. This gender disparity raises intriguing questions about the potential role of hormonal or other sex-specific factors in modulating CRC risk in PSC patients.
 
Dr. Alsakarneh stated: "Our study provides real-world evidence that PSC is an independent risk factor for CRC development, even in patients without IBD, compared to the general population. These findings suggest that current guidelines should incorporate the presence of PSC as an independent factor in CRC screening recommendations." By identifying PSC as an independent risk factor for CRC, this research will help clinicians better stratify their patients' CRC risk and tailor screening and surveillance strategies accordingly. This could lead to earlier detection of CRC, allowing for more effective treatment and improving the quality of life and long-term outcomes for patients with PSC.
 
While the study's findings are compelling, the authors acknowledge several limitations. The study's retrospective nature and the potential for inherent biases in the database used are important considerations. Dr. Alsakarneh noted, "We were not able to conduct separate analysis based on the timing of PSC and IBD diagnosis due to a limited number of patients in the database." Additionally, the limited patient numbers prevented separate analyses for different subgroups of PSC patients, which could have provided more nuanced insights.
 
These limitations point to several important avenues for future research, such as:
1. How can current CRC screening guidelines be optimally updated to incorporate PSC as an independent risk factor?
2. What are the potential reasons for the underdiagnosis of IBD in PSC patients, and how can this be addressed in clinical practice?
3. What is the relationship between the degree of cholangitis and the risk of CRC in PSC patients?
 
Furthermore, there is a need to understand the staging and treatment outcomes of CRC in PSC patients and explore potential mechanisms underlying the increased CRC risk in this population. The findings of this study have significant implications for clinical practice, suggesting that current CRC screening guidelines should be revised to incorporate PSC as a risk factor, regardless of IBD status.