Urothelial carcinoma (UC) is a challenging malignancy with suboptimal outcomes following surgical treatment. Antibody-drug conjugates (ADCs), a novel class of targeted therapies, have demonstrated promising efficacy. However, high-quality randomized controlled trials (RCTs) evaluating ADCs in UC are still lacking. Limited data are available from prospective non-randomized studies and meta-analyses. In recent years, with the advancement of ADC research, more high-quality clinical trials have been published. This study aims to summarize the existing literature and assess the efficacy and safety of ADCs in UC patients, particularly those with advanced disease.

A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science to identify prospective single-arm or multi-arm clinical studies evaluating ADC monotherapy in UC. Studies involving non-ADC interventions, combination therapies, non-English publications, or those without relevant outcome data were excluded. Key efficacy and safety outcomes, including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs) were extracted. An updated meta-analysis was performed to evaluate the clinical impact of ADCs in UC comprehensively.

A total of 16 studies comprising 1,594 patients were included in the meta-analysis. Regarding tumor response, the pooled ORR was 40% (95% CI: 36–45%), and the DCR was 74% (95% CI: 70–78%). Survival analysis showed a median PFS of 5.9 months (95% CI: 5.09–6.7 months) and a median OS of 12.91 months (95% CI: 11.9–13.92 months). The 6-month PFS and OS rates were 46% (95% CI: 40–51%) and 82% (95% CI: 77–87%), respectively, while the 1-year PFS and OS rates were 20% (95% CI: 16–25%) and 55% (95% CI: 51–60%), respectively. Regarding safety, the overall incidence of TRAEs was high, with 52% (95% CI: 46–58%) of patients experiencing grade III or higher TRAEs. The most common TRAEs included alopecia (any grade: 44% [95% CI: 42–47%]; grade III or higher: 0% [95% CI: 0–0%]), decreased appetite (any grade: 35% [95% CI: 29–42%]; grade III or higher: 2% [95% CI: 1–3%]), dysgeusia (any grade: 37% [95% CI: 25–49%]; grade III or higher: 0% [95% CI: 0–1%]), fatigue (any grade: 37% [95% CI: 31–44%]; grade III or higher: 5% [95% CI: 4–7%]), nausea (any grade: 35% [95% CI: 25–47%]; grade III or higher: 1% [95% CI: 0–2%]), peripheral sensory neuropathy (any grade: 39% [95% CI: 31–48%]; grade III or higher: 2% [95% CI: 0–5%]), and pruritus (any grade: 28% [95% CI: 22–34%]; grade III or higher: 2% [95% CI: 1–3%]).

This meta-analysis demonstrates that ADCs have clinical utility in the treatment of advanced UC, providing strong support for their adoption in clinical practice. Compared to previous studies, our findings further enhance the robustness of existing evidence. Future high-quality RCTs are needed to validate the efficacy of ADCs in different UC immunophenotypes and explore potential combination therapy strategies.