Predictors of Colorectal Neoplasia Outcomes in Indefinite and Low-Grade Dysplasia in Patients with Primary Sclerosing Cholangitis and Ulcerative Colitis: ACG IBD Research Award

Abstract

Purpose: Patients (pts) with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) are at an increased risk for colorectal neoplasia. We sought to examine the natural history of low-grade dysplasia (LGD) and indefinite dysplasia (IND) in order to identify factors associated with neoplasia progression or persistence in pts with PSC-UC. Methods: We performed a retrospective review of pts with PSC and UC who were diagnosed with LGD or IND (index lesion confirmed after review by a pathologist). LGD was classified as unifocal or multifocal and flat or raised. Raised lesions in an area of colitis were considered adenoma-like dysplasia (ALD). Sporadic adenomas were excluded. Pts were excluded if they had a prior colectomy, colorectal neoplasia, or liver transplant (LT) or did not follow up beyond 60 days of their index lesion. Pts were censored at the time of colectomy, last colonoscopy or LT, whichever was earliest. The primary end-point was neoplasia progression, or persistent LGD. Covariates were included into the multivariate model if they had a p-value of ≤0.05 in the univariate analysis. Results: Sixty-three pts (IND n=47, LGD n=16) were followed for 176 pt-years. The primary endpoint was reached in 56% of pts with LGD [cancer n=1; persistent LGD (multifocal n=2; ALD n=6)] and in 28% with IND (cancer n=3; HGD n=3; multifocal LGD n=2; ALD LGD n=1; flat LGD n=4). Compared to those with IND, pts with LGD were older (57 years versus 42 years, p<0.01), and had a longer duration of UC (28 years versus 10 years, p=0.03) and PSC (9 years versus 6 years, p=0.05). Compared to LGD, IND lesions were more likely to be flat (98% versus 50%, p<0.01) and found in an area of colitis (100% versus 81% p<0.01). Univariate analysis revealed that LGD (compared to IND) was associated with the primary endpoint, HR 4.02 (1.61-9.71) p<0.01. Of those with multifocal LGD at baseline, univariate analysis showed an association with the primary endpoint, HR 5.08 (0.97-23.79) p=0.05. PSC duration was associated with the endpoint, HR 0.87 (0.74-0.99) p=0.05, in pts with LGD. However, neither was associated with the primary outcome in the multivariate analysis. Among pts with IND, 5-ASA use was associated with a reduced risk of neoplasia progression, HR 0.18 (0.04-0.70) p=0.01 on univariate analysis. A multivariate analysis for the IND group was not performed since 5-ASA use was the only significant association detected. Conclusion: Pts with PSC and UC who developed LGD were more likely to have progressive or persistent neoplasia than those who had IND. However, more than one-quarter of IND pts also developed more advanced lesions. 5-ASA use appeared to protect against neoplasia progression in pts with IND.