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Background: We aimed to evaluate the impact of advanced medical therapies (biologicals and small molecules) on time to colectomy and oncological outcomes in UC., Methods: This cohort study included UC patients who underwent colectomy between 2003 and 2022 at two referral centres in Belgium and the Netherlands. Exposure was use of advanced medical therapies. Primary outcomes were time to colectomy and colorectal cancer (CRC) rate, compared between four periods: P1 (2003-2007), P2 (2008-2012), P3 (2013-2017), P4 (2018-2022). Secondary outcomes were oncological outcomes, including incidental cancers found unexpectedly in resection specimens or during endoscopic follow-up for medication switch., Results: Among 716 patients, the usage of advanced therapies increased from 36.8% in P1 to 89.7% in P4 (p<0.0001). Median time to colectomy remained comparable (P1: 7.1 years [IQR, 2.8-12.9] vs P4: 7.2 years [IQR, 2.7-14.6]; p=not significant). CRC was diagnosed in 72 (10.1%) patients, with no significant change over time (p=0.44). Proportion of CRC was lower in patients treated with advanced therapies (4.7% vs 23.6%, p<0.0001), related to a shorter follow-up (median 6.1 vs 10.3 years, p<0.0001). Advanced therapy patients had higher incidental cancer rates (37.5% vs 8.3%, p=0.002), which was associated with reduced CRC-related survival (HR for CRC-related death: 3.3, 95% CI 1.17-9.4; p=0.02)., Conclusion: Despite increased usage of advanced medical therapies, time to resection and CRC rates have remained unchanged in UC patients undergoing colectomy over the past two decades. Advanced therapy patients had higher incidental cancers rates, associated with decreased CRC-survival. Awareness of timely colectomy is crucial for this group., (© The Author(s) 2025. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)