End Points for the Next-Generation Bladder-Sparing Perioperative Trials for Patients With Muscle-Invasive Bladder Cancer

Andrea Necchi; Matthew D Galsky; Nazli Dizman; David H Aggen; Neeraj Agarwal; Hikmat Al-Ahmadie; Andrea B Apolo; Leslie Ballas; Rick Bangs; Peter C Black; Maurizio Brausi; Giorgio Brembilla; Liang Cheng; Arturo Chiti; Alessia Cimadamore; Maurizio Colecchia; Siamak Daneshmand; Savino Di Stasi; Jason A Efstathiou; Alex Filicevas; Daniel M Geynisman; Petros Grivas; Shilpa Gupta; Alexia Iasonos; Nick D James; Seth P Lerner; Yohann Loriot; Lydia E Makaroff; Fernando Maluf; Marco Moschini; Irina Ostrovnaya; Sumanta K Pal; Elizabeth R Plimack; Gagan Prakash; Sarah P Psutka; Jonathan E Rosenberg; Sarmad Sadeghi; Bogdana Schmidt; Lawrence H Schwartz; Guru P Sonpavde; Marie-Pier St Laurent; Dingwei Ye; Philippe E Spiess; Ashish M Kamat

doi:10.1200/JCO-25-01608

End Points for the Next-Generation Bladder-Sparing Perioperative Trials for Patients With Muscle-Invasive Bladder Cancer

Andrea Necchi, Matthew D Galsky, Nazli Dizman, David H Aggen, Neeraj Agarwal, Hikmat Al-Ahmadie, Andrea B Apolo, Leslie Ballas, Rick Bangs, Peter C Black, Maurizio Brausi, Giorgio Brembilla, Liang Cheng, Arturo Chiti, Alessia Cimadamore, Maurizio Colecchia, Siamak Daneshmand, Savino Di Stasi, Jason A Efstathiou, Alex FilicevasDaniel M Geynisman, Petros Grivas, Shilpa Gupta, Alexia Iasonos, Nick D James, Seth P Lerner, Yohann Loriot, Lydia E Makaroff, Fernando Maluf, Marco Moschini, Irina Ostrovnaya, Sumanta K Pal, Elizabeth R Plimack, Gagan Prakash, Sarah P Psutka, Jonathan E Rosenberg, Sarmad Sadeghi, Bogdana Schmidt, Lawrence H Schwartz, Guru P Sonpavde, Marie-Pier St Laurent, Dingwei Ye, Philippe E Spiess, Ashish M Kamat

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	3536-3544
Number of pages	9
Journal	Journal of Clinical Oncology
Volume	43
Issue number	32
Early online date	Sep 11 2025
DOIs	https://doi.org/10.1200/JCO-25-01608
State	Published - Nov 10 2025

Keywords

Clinical Trials as Topic
Endpoint Determination
Humans
Neoplasm Invasiveness
Organ Sparing Treatments/methods
Perioperative Care/methods
Urinary Bladder Neoplasms/pathology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1200/JCO-25-01608

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Necchi, A., Galsky, M. D., Dizman, N., Aggen, D. H., Agarwal, N., Al-Ahmadie, H., Apolo, A. B., Ballas, L., Bangs, R., Black, P. C., Brausi, M., Brembilla, G., Cheng, L., Chiti, A., Cimadamore, A., Colecchia, M., Daneshmand, S., Di Stasi, S., Efstathiou, J. A., ... Kamat, A. M. (2025). End Points for the Next-Generation Bladder-Sparing Perioperative Trials for Patients With Muscle-Invasive Bladder Cancer. Journal of Clinical Oncology, 43(32), 3536-3544. https://doi.org/10.1200/JCO-25-01608

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title = "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.",

keywords = "Clinical Trials as Topic, Endpoint Determination, Humans, Neoplasm Invasiveness, Organ Sparing Treatments/methods, Perioperative Care/methods, Urinary Bladder Neoplasms/pathology",

author = "Andrea Necchi and Galsky, \{Matthew D\} and Nazli Dizman and Aggen, \{David H\} and Neeraj Agarwal and Hikmat Al-Ahmadie and Apolo, \{Andrea B\} and Leslie Ballas and Rick Bangs and Black, \{Peter C\} and Maurizio Brausi and Giorgio Brembilla and Liang Cheng and Arturo Chiti and Alessia Cimadamore and Maurizio Colecchia and Siamak Daneshmand and \{Di Stasi\}, Savino and Efstathiou, \{Jason A\} and Alex Filicevas and Geynisman, \{Daniel M\} and Petros Grivas and Shilpa Gupta and Alexia Iasonos and James, \{Nick D\} and Lerner, \{Seth P\} and Yohann Loriot and Makaroff, \{Lydia E\} and Fernando Maluf and Marco Moschini and Irina Ostrovnaya and Pal, \{Sumanta K\} and Plimack, \{Elizabeth R\} and Gagan Prakash and Psutka, \{Sarah P\} and Rosenberg, \{Jonathan E\} and Sarmad Sadeghi and Bogdana Schmidt and Schwartz, \{Lawrence H\} and Sonpavde, \{Guru P\} and \{St Laurent\}, Marie-Pier and Dingwei Ye and Spiess, \{Philippe E\} and Kamat, \{Ashish M\}",

year = "2025",

month = nov,

day = "10",

doi = "10.1200/JCO-25-01608",

language = "English",

volume = "43",

pages = "3536--3544",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "Lippincott Williams and Wilkins",

number = "32",

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Necchi, A, Galsky, MD, Dizman, N, Aggen, DH, Agarwal, N, Al-Ahmadie, H, Apolo, AB, Ballas, L, Bangs, R, Black, PC, Brausi, M, Brembilla, G, Cheng, L, Chiti, A, Cimadamore, A, Colecchia, M, Daneshmand, S, Di Stasi, S, Efstathiou, JA, Filicevas, A, Geynisman, DM, Grivas, P, Gupta, S, Iasonos, A, James, ND, Lerner, SP, Loriot, Y, Makaroff, LE, Maluf, F, Moschini, M, Ostrovnaya, I, Pal, SK, Plimack, ER, Prakash, G, Psutka, SP, Rosenberg, JE, Sadeghi, S, Schmidt, B, Schwartz, LH, Sonpavde, GP, St Laurent, M-P, Ye, D, Spiess, PE & Kamat, AM 2025, 'End Points for the Next-Generation Bladder-Sparing Perioperative Trials for Patients With Muscle-Invasive Bladder Cancer', Journal of Clinical Oncology, vol. 43, no. 32, pp. 3536-3544. https://doi.org/10.1200/JCO-25-01608

TY - JOUR

T1 - End Points for the Next-Generation Bladder-Sparing Perioperative Trials for Patients With Muscle-Invasive Bladder Cancer

AU - Necchi, Andrea

AU - Galsky, Matthew D

AU - Dizman, Nazli

AU - Aggen, David H

AU - Agarwal, Neeraj

AU - Al-Ahmadie, Hikmat

AU - Apolo, Andrea B

AU - Ballas, Leslie

AU - Bangs, Rick

AU - Black, Peter C

AU - Brausi, Maurizio

AU - Brembilla, Giorgio

AU - Cheng, Liang

AU - Chiti, Arturo

AU - Cimadamore, Alessia

AU - Colecchia, Maurizio

AU - Daneshmand, Siamak

AU - Di Stasi, Savino

AU - Efstathiou, Jason A

AU - Filicevas, Alex

AU - Geynisman, Daniel M

AU - Grivas, Petros

AU - Gupta, Shilpa

AU - Iasonos, Alexia

AU - James, Nick D

AU - Lerner, Seth P

AU - Loriot, Yohann

AU - Makaroff, Lydia E

AU - Maluf, Fernando

AU - Moschini, Marco

AU - Ostrovnaya, Irina

AU - Pal, Sumanta K

AU - Plimack, Elizabeth R

AU - Prakash, Gagan

AU - Psutka, Sarah P

AU - Rosenberg, Jonathan E

AU - Sadeghi, Sarmad

AU - Schmidt, Bogdana

AU - Schwartz, Lawrence H

AU - Sonpavde, Guru P

AU - St Laurent, Marie-Pier

AU - Ye, Dingwei

AU - Spiess, Philippe E

AU - Kamat, Ashish M

PY - 2025/11/10

Y1 - 2025/11/10

N2 - 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.

AB - 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.

KW - Clinical Trials as Topic

KW - Endpoint Determination

KW - Humans

KW - Neoplasm Invasiveness

KW - Organ Sparing Treatments/methods

KW - Perioperative Care/methods

KW - Urinary Bladder Neoplasms/pathology

U2 - 10.1200/JCO-25-01608

DO - 10.1200/JCO-25-01608

M3 - Article

C2 - 40934451

SN - 0732-183X

VL - 43

SP - 3536

EP - 3544

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 32

ER -

End Points for the Next-Generation Bladder-Sparing Perioperative Trials for Patients With Muscle-Invasive Bladder Cancer

Abstract

Keywords

UN SDGs

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