Definitions, End Points, and Clinical Trial Designs for Bladder Cancer: Recommendations From the Society for Immunotherapy of Cancer and the International Bladder Cancer Group

Abstract

PURPOSE There is a significant unmet need for new and efficacious therapies in urothelial cancer (UC). To provide recommendations on appropriate clinical trial designs across disease settings in UC, the Society for Immunotherapy of Cancer (SITC) and the International Bladder Cancer Group (IBCG) convened a multidisciplinary, international consensus panel. METHODS Through open communication and scientific debate in small- and whole-group settings, surveying, and responses to clinical questionnaires, the consensus panel developed recommendations on optimal definitions of the disease state, end points, trial design, evaluations, sample size calculations, and pathology considerations for definitive studies in low- and intermediate-risk nonmuscle-invasive bladder cancer (NMIBC), high-risk NMIBC, muscle-invasive bladder cancer in the neoadjuvant and adjuvant settings, and metastatic UC. The expert panel also solicited input on the recommendations through presentations and public discussion during an open session at the 2021 Bladder Cancer Advocacy Network (BCAN) Think Tank (held virtually). RESULTS The consensus panel developed a set of stage-specific bladder cancer clinical trial design recommendations, which are summarized in the table that accompanies this text. CONCLUSION These recommendations developed by the SITC-IBCG Bladder Cancer Clinical Trial Design consensus panel will encourage uniformity among studies and facilitate drug development in this disease.

Serum EZH2 is a novel biomarker for bladder cancer diagnosis and prognosis

“…For non-muscle invasive bladder cancer, progression is defined as an increase in T stage from CIS or Ta to T1; development of ≥T2 or lymph node (N+) disease or distant metastasis (M1); or an increase in grade from low to high. In the case of muscle-invasive bladder cancer, progression after treatment is defined by a tumor relapse with pathological evidence in the bladder with tumor stage ≥pT2 or distant relapse as N1-3 or M1 ( 25 , 26 ).…”

Toward standardization in bladder cancer clinical trials: Guidance from the SITC-IBCG expert panel

“…New comprehensive guidance from the SITC and IBCG Building on the success of the 2016 IBCG guidance, the Society for Immunotherapy of Cancer (SITC) and IBCG decided to collaborate and expand this approach to develop guidance encompassing all bladder cancer disease states. 6 SITC and IBCG gathered a multidisciplinary, international panel of clinical trial experts that included perspectives from medical oncology, pathology, urology, statistics, and patient advocacy. Throughout the development process, the patient's voice and consideration of the patient's journey were integral considerations during the panel deliberation and final recommendation formation.…”

“… Summary of recommendations from SITC and IBCG reproduced from Kamat et al . 6 IBCG, International Bladder Cancer Group; SITC, Society for Immunotherapy of Cancer. …”

Ablative therapy with UGN-102 for low-grade intermediate risk non-muscle-invasive bladder cancer: ready for primetime?

“…In fact, the Society for Immunotherapy of Cancer (SITC) and the International Bladder Cancer Group (IBCG) recently presented a consensus statement that recommends CR as the primary outcome for studies investigating ablative therapy for low and IR NMIBC ( 6 ). These organizations define recurrence as histologically proven tumor of any grade or stage within the bladder, progression to muscle invasive disease, or clinical stage/grade progression, rather than residual tumor at 3-month per the ATLAS trial ( 6 ). Next, the control TURBT arm could have allowed for adjuvant intravesical therapy, as it is expected to have high rates of recurrence with TURBT alone ( 1 ).…”