DOI: 10.1002/cam4.71859 ISSN: 2045-7634

Navigating the Evolution of Urothelial Carcinoma Treatment: From Chemotherapy to Immunotherapy

Ben Li, Ziqi Yang, Yihao Pei, Yan Wang, Yumin Chen

ABSTRACT

Background

The urothelial carcinoma (UC) trial landscape has expanded over two decades, alongside a shift from chemotherapy to immunotherapy and targeted approaches. We characterized temporal patterns in trial phase, interventions, sponsorship, geographic footprint, and the uptake of biomarker specification and artificial intelligence (AI) terminology.

Methods

We conducted a trial registry‐based analysis of 823 interventional UC studies first posted on ClinicalTrials.gov during 2005–2024. Trials were classified by phase, recruitment status, and intervention, and further stratified by sponsor type and geographic region. Registry text was mined to flag biomarker‐specified and AI‐enabled registrations. Trends were summarized overall and for two periods: 2005–2014 and 2015–2024.

Results

Annual registrations increased after 2015, peaking in 2018. Early‐phase studies predominated overall, with expansion of Phase 3 activity in 2015–2024. Drug interventions remained dominant as immunotherapy displaced chemotherapy; pembrolizumab was the leading agent in the later period. The sponsor mix shifted toward industry, and the geographic footprint broadened: the United States/Canada remained the largest contributor, with growth in multinational activity and increased participation from East Asia. Biomarker‐specified language rose to roughly one quarter of registrations in 2015–2024, whereas explicit AI terminology was rare. Early‐phase termination rates were notable.

Conclusions

UC trials have scaled and globalized while consolidating immunotherapy and advancing genomically directed strategies. Priorities include precise preregistration of biomarker and computational endpoints, inclusive multinational accrual, and adequately powered comparative trials against current standards to accelerate durable clinical benefit.

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