Standardized Trial Design Proposed to Advance Bladder Cancer Trimodality Therapy
Key Insights
Expert panel recommends pragmatic eligibility criteria for trimodality therapy (TMT) clinical trials in bladder cancer (search), including ECOG performance status 0-2 and specific tumor stages.
Bladder Intact Event-Free Survival (BIEFS) is proposed as a primary endpoint for registration trials comparing TMT interventions, focusing on clinically meaningful outcomes.
Overall survival is deemed an appropriate secondary or co-primary endpoint, acknowledging recent advancements in systemic therapy and their impact on long-term survival.
An expert panel has proposed standardized eligibility criteria and endpoints for clinical trials evaluating trimodality therapy (TMT) in muscle-invasive bladder cancer (search). The recommendations aim to create uniformity in trial design, facilitating comparisons and advancing the field of bladder preservation. TMT, an alternative to radical cystectomy, combines maximal transurethral resection of bladder tumor (TURBT) with radiation and systemic therapy.
The panel, composed of clinicians, researchers, and patient advocates, reviewed published phase II/III trials assessing radiation's role in definitive bladder cancer (search) therapy. Their goal was to define pragmatic eligibility criteria and clinically meaningful endpoints. The recommendations emphasize inclusivity, patient-centricity, and endpoints that reflect real-world outcomes.
Eligibility Criteria
The panel recommends including patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, bladder cancer (search) stage T2-T4a N0±N1M0, unilateral tumor-associated hydronephrosis, and those who have undergone attempted maximal TURBT. Both pure urothelial carcinoma (search) and mixed histologic subtypes (excluding rare and aggressive small cell variants) should be eligible. The panel also suggests including patients who are non-cystectomy candidates.
Endpoints
Bladder Intact Event-Free Survival (BIEFS) is proposed as a primary endpoint for registration trials comparing different TMT interventions. BIEFS is defined as the time from randomization to muscle-invasive or locoregional recurrence, systemic recurrence, radical cystectomy from any cause, or death from any cause. Overall survival is deemed an appropriate secondary endpoint or a co-primary endpoint, especially given recent improvements in systemic therapy that can significantly improve long-term outcomes.
Quality of Life
The panel also emphasizes the importance of incorporating patient-reported quality of life assessments to support primary and secondary endpoints. This ensures that trial outcomes reflect the patient experience and the impact of treatment on their daily lives.
"The standardization of clinical trial design, eligibility criteria, and endpoints is essential for expediting progress in the field," the authors stated. "Inclusivity, patient-centricity, and clinically meaningful endpoints will facilitate the analysis, comparison, and meta-analysis of different trials, fostering advancements in bladder cancer (search) treatment."