Unmet Treatment Need and Challenges Associated with Comparative Evidence Generation in BCG-unresponsive...

Area of Science:

• Urology
• Oncology
• Clinical Trials

Background:

• Non-muscle-invasive bladder cancer (NMIBC) that is unresponsive to Bacillus Calmette-Guérin (BCG) treatment presents a significant unmet need.
• A substantial portion of these patients are unfit for or unwilling to undergo radical cystectomy (RC).

Purpose of the Study:

• To achieve consensus among European experts on the unmet need in BCG-unresponsive NMIBC.
• To define appropriate clinical evidence generation strategies and trial endpoints for this patient population.

Main Methods:

• A modified Delphi panel study involving 12 European clinical experts.
• Online surveys were conducted, followed by a consensus meeting to finalize statements.
• Consensus was defined as agreement by ≥80% of panelists.

Main Results:

• Experts agreed on a substantial unmet need, particularly for patients unfit for RC.
• Randomized controlled trials (RCTs) face ethical and technical barriers (recruitment, homogeneity, defining unfitness).
• Single-arm trials (SATs) were deemed appropriate and ethical, with consensus on measuring complete response, duration of response, and safety.

Conclusions:

• While RCTs are feasible, unresolved challenges necessitate alternative evidence generation methods.
• Data from SATs are considered an acceptable alternative to address the unmet need.
• These findings provide a pathway forward for developing novel therapies for BCG-unresponsive NMIBC.