ReviewEuropean urology open science2026
Re-evaluating Treatments for Advanced Urothelial Carcinoma Using Restricted Mean Survival Time: A Systematic Review and Network Meta-analysis.
Review in European urology open science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Time-dependent effects of BCG plus immune checkpoint inhibitors in BCG-naive high-risk non-muscle-invasive bladder cancer: a reconstructed patient-level analysis.International urology and nephrology · 2026Article
- Treatment Patterns and Outcomes After Recurrence Following Adjuvant Nivolumab for Urothelial Carcinoma: An AGEHA Real-World Study.International journal of urology : official journal of the Japanese Urological Association · 2026Observational
- A Qualitative Study of Factors Affecting Medication Adherence in Patients with Open-Angle Glaucoma.Clinical ophthalmology (Auckland, N.Z.) · 2026Article
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background and objective: The proportional hazards (PH) assumption may not hold for immune checkpoint inhibitor (ICI) trials because of delayed treatment effects. We assessed PH validity in trials of first-line treatment in advanced urothelial carcinoma (UC) and compared treatments using restricted mean survival time (RMST). Methods: We conducted a systematic review and network meta-analysis (NMA) of phase 2/3 randomized controlled trials published between 2015 and 2025 evaluating ICIs or antibody-drug conjugates. Seven trials involving 5321 patients with ten treatment comparisons were analyzed. Individual patient data were reconstructed from Kaplan-Meier curves. The PH assumption was tested using Schoenfeld residuals ( Key findings and limitations: The PH assumption was violated in 50% of overall survival (OS) comparisons and 60% of progression-free survival comparisons. ICI monotherapy regimens demonstrated a significant early detriment at 12 mo in comparison to chemotherapy (PD-1 inhibitors: -0.8 mo, Conclusions and clinical implications: Half of modern UC trials violate PH assumptions, with time-dependent treatment effects that can be obscured by traditional analyses. RMST analysis quantifies the magnitude and clinical impact of early ICI monotherapy detriment that is not captured by nonsignificant hazard ratios. Enfortumab vedotin plus pembrolizumab demonstrated the largest RMST benefit in this analysis, although this finding is based on a single pivotal trial and requires validation in additional studies and real-world settings. These findings support the value of RMST analysis as a complementary approach for evaluating time-dependent treatment effects in immunotherapy trials. Patient summary: We analyzed clinical trials of treatments for advanced bladder cancer and found that traditional statistical methods may miss important treatment patterns. Our analysis shows that immunotherapy alone may perform worse than chemotherapy initially, but the treatment effect improves over time. The combination of enfortumab vedotin and pembrolizumab provides the best outcomes for patients at all time points.
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