International Bladder Cancer Group Consensus Statement on Clinical Trial Design for Patients with Bacillus Calmette-Guérin-exposed High-risk Non-muscle-invasive Bladder Cancer.

A large proportion of patients with non-muscle-invasive bladder cancer (NMIBC) fall in the gap between bacillus Calmette-Guérin (BCG)-naïve and BCG-unresponsive disease. As multiple therapeutic agents move into this gray area, there is a critical need to define the disease state and establish recommendations for optimal trial design.

To develop a consensus on optimal trial design for patients with BCG-exposed NMIBC, defined as high-grade recurrence after BCG treatment that does not meet the criteria for BCG-unresponsive disease.

We conducted a literature review using the Cochrane Library, Medline, and Embase and a review of clinical trials in as a basis to generate consensus recommendations for clinical trial design in BCG-exposed NMIBC.

BCG-exposed NMIBC encompasses BCG resistance (presence of high-grade Ta or carcinoma in situ [CIS] at 3-mo evaluation after induction BCG) and delayed relapse. Randomized controlled trials are required to compare experimental therapies to a control arm receiving additional BCG, although ongoing BCG shortages may impact our ability to follow an optimal trial design. A placebo should be used in combination with BCG if the treatment arm includes BCG plus a study drug. Trials will either need to separate patients with and without CIS into two cohorts, or stratify by the presence of CIS at the time of randomization. If two cohorts are used, the primary endpoint for CIS patients should be complete response within a predetermined time. The primary endpoint in a cohort with Ta/T1 only, or if a single combined cohort is used, should be the duration of event-free survival. Suggested efficacy thresholds and corresponding sample sizes are provided.

The International Bladder Cancer Group has developed recommendations regarding definitions, endpoints, and clinical trial design for BCG-exposed NMIBC to encourage uniformity among studies in this disease state.

Our consensus provides a precise definition of the disease state for bladder cancer not invading the bladder muscle and exposed to bacillus Calmette-Guérin (BCG) treatment. Clear guidance for conducting optimal clinical trials in this disease setting was established and we believe that this will promote further progress in this field.

European urology. 2021 Dec 23 [Epub ahead of print]

Mathieu Roumiguié, Ashish M Kamat, Trinity J Bivalacqua, Seth P Lerner, Wassim Kassouf, Andreas Böhle, Maurizio Brausi, Roger Buckley, Raj Persad, Marc Colombel, Donald Lamm, Juan Palou-Redorta, Mark Soloway, Ken Brothers, Gary Steinberg, Yair Lotan, Richard Sylvester, J Alfred Witjes, Peter C Black

Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, Canada; Department of Urology, Toulouse Cancer Institute and Toulouse University Hospital, Toulouse, France., Department of Urology, MD Anderson Cancer Center, Houston, TX, USA., Perelman Center for Advanced Medicine, University of Pennsylvania, Division of Urology, Department of Surgery, Philadelphia, PA. Electronic address: ., Scott Department of Urology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA., Department of Surgery (Urology), Faculty of Medicine, McGill University, Montreal, Canada., Departments of Urology, University of Lübeck, Lübeck, Germany; HELIOS Agnes-Karll-Krankenhaus, Bad Schwartau, Germany., Department of Urology, Hesperia Hospital, Modena, Italy., North York General Hospital, Toronto, Ontario, Canada., Department of Urology, Southmead Hospital, North Bristol Hospitals Trust, Bristol, UK., Claude Bernard University, Hôpital Edouard Herriot, Lyon, France., University of Arizona and BCG Oncology, Phoenix, AZ, USA., Department of Urology, Fundació Puigvert, Universidad Autónoma de Barcelona, Barcelona, Spain., Division of Urology, Memorial Cancer Institute, Memorial Hospital, Hollywood, FL, USA., Patient Advocate, National Cancer Institute Bladder Cancer Task Force, Snowbasin, UT, USA., Department of Urology, NYU Langone Health, New York, NY, USA., Department of Urology, UT Southwestern Medical Center at Dallas, Dallas, TX, USA., European Association of Urology Guidelines Office, Brussels, Belgium., Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands., Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, Canada. Electronic address: .