End Points for the Next-Generation Bladder-Sparing Perioperative Trials for Patients With Muscle-Invasive Bladder Cancer
Abstract
PURPOSE The evolving treatment landscape of muscle-invasive bladder cancer (MIBC) increasingly warrants novel trial design to evaluate perioperative strategies aimed at bladder preservation. To establish standardized outcome measures for evaluating organ preservation strategies in MIBC, the International Bladder Cancer Group (IBCG) and the Global Society of Rare Genitourinary Tumors (GSRGT) assembled an international, multidisciplinary consensus panel. METHODS The IBCG and GSRGT gathered global bladder cancer experts and patient advocates to establish a framework for risk-adapted bladder-sparing treatment approaches for MIBC. Working groups reviewed the literature and developed draft recommendations, which were discussed at a live meeting in December 2024 in Milan. This was followed by voting by the members using a modified Delphi process. Recommendations achieving ≥75% agreement during the meeting were further refined and presented. RESULTS Clinical complete response (cCR) definition should encompass the absence of high-grade malignancy on pathology and malignant cells on urine cytology and no evidence of local or metastatic disease on cross-sectional imaging. Although cCR remains immature as a primary or coprimary end point in registrational trials, it could serve as a suitable end point in early-phase studies and risk-adapted investigations. Event-free survival (EFS) remains the preferred primary end point as it could reliably capture the durability of clinically meaningful benefit after omittance of surgical consolidation or chemoradiation. Given the composite nature of EFS, events should be prespecified, evaluated in an intention-to-treat approach, and meticulously collected. Continuous assessment of individual patient preferences should begin at the outset of perioperative therapy discussions, with informed decision making prioritized throughout. CONCLUSION The consensus definition of cCR and the framework presented in this study can serve as a foundation for thorough testing of risk-adapted bladder-sparing treatment paradigms for MIBC.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (44)
Andrea Necchi
Department of Medical Oncology Fondazione IRCCS Istituto Nazionale dei Tumori University of Milan Milan Italy
Matthew D. Galsky
Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai
Nazli Dizman
The University of Texas MD Anderson Cancer Center, Houston, TX
David H. Aggen
Neeraj Agarwal
Division of Medical Oncology Department of Internal Medicine Huntsman Cancer Institute University of Utah Salt Lake City Utah USA
Hikmat Al-Ahmadie
Andrea B. Apolo
From the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda (A.B.A., N.S., S.N., L.L., L.C.), the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.H.-C.), and the Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville (H.S., E.S.) — all in Maryland; the Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN (K.V.B., M.O., C.M., G.P.B.); AdventHealth Cancer Institute and the University of Central Florida, Orlando (G.S.); Dana–Farber/Harvard Cancer Center, Boston (S.B., B.M.); UNC Lineberger Comprehensive Cancer Center, Chapel Hill (W.Y.K.), and Duke University Medical Center and Duke Cancer Institute, Durham (J.H., S.H.) — both in North Carolina; the University of Kansas Cancer Center, Westwood (R.P.); Memorial Sloan Kettering Cancer Center, New York (M.Y.T., M.J.M., J.E.R.), and Roswell Park Comprehensive Cancer Center, Buffalo (G.C.) — both in...
Leslie Ballas
Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA
Rick Bangs
Bladder Cancer Advocacy Network Bethesda Maryland USA
Peter C. Black
Maurizio Brausi
Department of Urology, Hesperia Hospital, Modena, Italy
Giorgio Brembilla
Department of Radiology, IRCCS San Raffaele Hospital, Comprehensive Cancer Center, Milan, Italy
Liang Cheng
Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices
Arturo Chiti
Alessia Cimadamore
Maurizio Colecchia
Department of Pathology, IRCCS San Raffaele Hospital, Comprehensive Cancer Center, Milan, Italy
Siamak Daneshmand
Department of Urology, Keck School of Medicine of University of Southern California, Norris Comprehensive Cancer Center
Savino Di Stasi
Catholic University “Our Lady of Good Counsel”, Tirana, Albania
Jason A. Efstathiou
Massachusetts General Hospital, Boston, MA
Alex Filicevas
World Bladder Cancer Patient Coalition, Brussels, Belgium
Daniel M. Geynisman
From the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda (A.B.A., N.S., S.N., L.L., L.C.), the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (J.H.-C.), and the Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville (H.S., E.S.) — all in Maryland; the Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN (K.V.B., M.O., C.M., G.P.B.); AdventHealth Cancer Institute and the University of Central Florida, Orlando (G.S.); Dana–Farber/Harvard Cancer Center, Boston (S.B., B.M.); UNC Lineberger Comprehensive Cancer Center, Chapel Hill (W.Y.K.), and Duke University Medical Center and Duke Cancer Institute, Durham (J.H., S.H.) — both in North Carolina; the University of Kansas Cancer Center, Westwood (R.P.); Memorial Sloan Kettering Cancer Center, New York (M.Y.T., M.J.M., J.E.R.), and Roswell Park Comprehensive Cancer Center, Buffalo (G.C.) — both in...
Petros Grivas
Division of Medical Oncology, Department of Medicine University of Washington Seattle Washington USA
Shilpa Gupta
Department of Hematology and Medical Oncology Taussig Cancer Institute Cleveland Clinic Cleveland Ohio USA
Alexia Iasonos
Nick D. James
Institute of Cancer Research, London, United Kingdom
Seth P. Lerner
Department of Urology, Baylor College of Medicine, Houston
Yohann Loriot
Université Paris-Saclay, Gustave Roussy, INSERM Unité Mixte de Recherche 981 — Prédicteurs Moléculaires et Nouvelles Cibles en Oncologie, Villejuif, France
Lydia E. Makaroff
World Bladder Cancer Patient Coalition, Brussels, Belgium
Fernando Maluf
Hospital Israelita Albert Einstein, São Paulo, Brazil
Marco Moschini
Irina Ostrovnaya
Sumanta K. Pal
Department of Medical Oncology and Therapeutics, City of Hope Comprehensive Cancer Center
Elizabeth R. Plimack
Fox Chase Cancer Center, Philadelphia, PA
Gagan Prakash
Department of Surgery, Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, India
Sarah P. Psutka
University of Washington School of Medicine, Seattle, WA
Jonathan E. Rosenberg
Genitourinary Oncology Service Department of Medicine Memorial Sloan Kettering Cancer Center New York New York USA
Sarmad Sadeghi
University of Southern California, Los Angeles, CA
Bogdana Schmidt
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT
Lawrence H. Schwartz
Guru P. Sonpavde
AdventHealth Cancer Institute Orlando, Orlando, FL
Marie-Pier St Laurent
Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada
Dingwei Ye
Fudan University Shanghai Cancer Center, Shanghai
Philippe E. Spiess
Ashish M. Kamat