Towards Defining Follow-up Strategies for Patients with Primary Intermediate-risk Non-muscle-invasive Bladder Cancer

Roberto Contieri; Alberto Martini; Irene J. Beijert; Laura S. Mertens; Anouk E. Hentschel; Johannes Bründl; Eva M. Compérat; Karin Plass; Oscar Rodríguez; Jose D. Subiela Henríquez; Virginia Hernández; Enrique de la Peña; Isabel Alemany; Diana Turturica; Francesca Pisano; Francesco Soria; Otakar Čapoun; Lenka Bauerová; Michael Pešl; H. Maxim Bruins; Willemien Runneboom; Sonja Herdegen; Johannes Breyer; Antonin Brisuda; Ana Calatrava; José Rubio-Briones; Maximilian Seles; Sebastian Mannweiler; Judith Bosschieter; Venkata R. M. Kusuma; David Ashabere; Nicolai Huebner; Thomas Seisen; Francesco Claps; Alexandra Masson-Lecomte; Fredrik Liedberg; Daniel Cohen; Luca Lunelli; Olivier Cussenot; Soha El Sheikh; Dimitrios Volanis; Jean-François Côté; Morgan Rouprêt; Andrea Haitel; Shahrokh F. Shariat; A. Hugh Mostafid; Jakko A. Nieuwenhuijzen; Richard Zigeuner; Jose L. Dominguez-Escrig; Jaromir Hacek; Alexandre R. Zlotta; Maximilian Burger; Matthias Evert; Christina A. Hulsbergen-van de Kaa; Antoine G. van der Heijden; Lambertus A. L. M. Kiemeney; Viktor Soukup; Luca Molinaro; Rodolfo Hurle; Marco Paciotti; Marco Moschini; Benjamin Pradere; Sisto Perdonà; Paolo Gontero; Carlos Llorente; Ferran Algaba; Joan Palou; James N'Dow; Maria J. Ribal; Theo H. van der Kwast; Marko Babjuk; Richard J. Sylvester; Bas W. G. van Rhijn

doi:10.1016/j.euo.2025.04.010

Towards Defining Follow-up Strategies for Patients with Primary Intermediate-risk Non-muscle-invasive Bladder Cancer

Roberto Contieri
, Alberto Martini
, Irene J. Beijert
, Laura S. Mertens
, Anouk E. Hentschel
, Johannes Bründl
, Eva M. Compérat
, Karin Plass
, Oscar Rodríguez
, Jose D. Subiela Henríquez
, Virginia Hernández
, Enrique de la Peña
, Isabel Alemany
, Diana Turturica
, Francesca Pisano
, Francesco Soria
, Otakar Čapoun
, Lenka Bauerová
, Michael Pešl
, H. Maxim Bruins

Willemien Runneboom, Sonja Herdegen, Johannes Breyer, Antonin Brisuda, Ana Calatrava, José Rubio-Briones, Maximilian Seles, Sebastian Mannweiler, Judith Bosschieter, Venkata R. M. Kusuma, David Ashabere, Nicolai Huebner, Thomas Seisen, Francesco Claps, Alexandra Masson-Lecomte, Fredrik Liedberg, Daniel Cohen, Luca Lunelli, Olivier Cussenot, Soha El Sheikh, Dimitrios Volanis, Jean-François Côté, Morgan Rouprêt, Andrea Haitel, Shahrokh F. Shariat, A. Hugh Mostafid, Jakko A. Nieuwenhuijzen, Richard Zigeuner, Jose L. Dominguez-Escrig, Jaromir Hacek, Alexandre R. Zlotta, Maximilian Burger, Matthias Evert, Christina A. Hulsbergen-van de Kaa, Antoine G. van der Heijden, Lambertus A. L. M. Kiemeney, Viktor Soukup, Luca Molinaro, Rodolfo Hurle, Marco Paciotti, Marco Moschini, Benjamin Pradere, Sisto Perdonà, Paolo Gontero, Carlos Llorente, Ferran Algaba, Joan Palou, James N'Dow, Maria J. Ribal, Theo H. van der Kwast, Marko Babjuk, Richard J. Sylvester, Bas W. G. van Rhijn

Antoni van Leeuwenhoek Hospital
University of Cincinnati
University of Regensburg
European Association of Urology
Autonomous University of Barcelona
Fundacion Hospital Alcorcon
University of Turin
Charles University Praha
Radboud University Nijmegen
Instituto Valenciano de Oncologia
Medical University of Graz
Amsterdam UMC - University of Amsterdam
Royal Surrey Hospital
Medical University of Vienna
Hôpital Tenon
Royal Free London NHS Foundation Trust
Sorbonne Université
Princess Margaret Hospital Cancer Centre
IRCCS Istituto Clinico Humanitas - Rozzano (Milano)
Humanitas University
IRCCS Ospedale San Raffaele
Quint Fonsegrives
IRCCS Istituto nazionale tumori Fondazione Giovanni Pascale - Napoli

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

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Abstract

BACKGROUND AND OBJECTIVE: The current European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC) categorize patients into four risk groups. In 2024, a specific follow-up schedule was introduced for intermediate-risk (IR) disease. However, recommendations are based on expert opinion and restricted to patients with IR-NMIBC who have primary low-grade or high-grade/grade 2 disease. Our aim was to identify a subgroup of patients with IR-NMIBC who may require more stringent follow-up. METHODS: We conducted a retrospective analysis of 2086 patients with IR-NMIBC classified according to the World Health Organization 1973 grading scheme. Multivariable Cox-regression models were fitted to identify predictors of recurrence, which were then used to dichotomize groups with low risk of recurrence (IR-Low) versus high risk of recurrence (IR-High). Kaplan-Meier curves were plotted to estimate recurrence-free survival (RFS) and progression-free survival (PFS). Smoothed hazard estimates of first recurrence were plotted by risk group. KEY FINDINGS AND LIMITATIONS: Multifocality and tumor size ≥3 cm were significantly associated with higher risk of first recurrence and were used to define the IR-High and IR-Low (unifocal, size <3 cm; n = 1087) groups. The 3-yr RFS rate was significantly worse for the IR-High group (51%, 95% confidence interval [CI] 48-54%) than for IR-Low (68%, 95% CI 65-71%). The risk of progression was low (5-yr PFS rate 96%) with no significant difference between the IR-High and IR-Low groups. CONCLUSIONS AND CLINICAL IMPLICATIONS: During IR-NMIBC follow-up for recurrence, tumor size and focality should be considered rather than grade. If the primary objective is to ensure prompt detection of recurrence, follow-up schedules should be tailored according to the risk of recurrence, with more stringent protocols for patients with IR-NMIBC at higher risk of recurrence.

Original language	English
Pages (from-to)	977-985
Number of pages	9
Journal	European Urology Oncology
Volume	8
Issue number	4
DOIs	https://doi.org/10.1016/j.euo.2025.04.010
Publication status	Published - 1 Aug 2025

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Follow-up
Intermediate risk
Non–muscle-invasive bladder cancer
Risk
Stratification

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Towards-defining-follow-up-strategies-for-patients-with-primary-intermediate-risk-non-muscle-invasive-bladder-cancer.pdfFinal published version, 611 KBLicence: Taverne

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Contieri, R., Martini, A., Beijert, I. J., Mertens, L. S., Hentschel, A. E., Bründl, J., Compérat, E. M., Plass, K., Rodríguez, O., Subiela Henríquez, J. D., Hernández, V., de la Peña, E., Alemany, I., Turturica, D., Pisano, F., Soria, F., Čapoun, O., Bauerová, L., Pešl, M., ... van Rhijn, B. W. G. (2025). Towards Defining Follow-up Strategies for Patients with Primary Intermediate-risk Non-muscle-invasive Bladder Cancer. European Urology Oncology, 8(4), 977-985. https://doi.org/10.1016/j.euo.2025.04.010

@article{dfd0aa9fdb9a4dba8d4008d295fe1518,

title = "Towards Defining Follow-up Strategies for Patients with Primary Intermediate-risk Non-muscle-invasive Bladder Cancer",

abstract = "BACKGROUND AND OBJECTIVE: The current European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC) categorize patients into four risk groups. In 2024, a specific follow-up schedule was introduced for intermediate-risk (IR) disease. However, recommendations are based on expert opinion and restricted to patients with IR-NMIBC who have primary low-grade or high-grade/grade 2 disease. Our aim was to identify a subgroup of patients with IR-NMIBC who may require more stringent follow-up. METHODS: We conducted a retrospective analysis of 2086 patients with IR-NMIBC classified according to the World Health Organization 1973 grading scheme. Multivariable Cox-regression models were fitted to identify predictors of recurrence, which were then used to dichotomize groups with low risk of recurrence (IR-Low) versus high risk of recurrence (IR-High). Kaplan-Meier curves were plotted to estimate recurrence-free survival (RFS) and progression-free survival (PFS). Smoothed hazard estimates of first recurrence were plotted by risk group. KEY FINDINGS AND LIMITATIONS: Multifocality and tumor size ≥3 cm were significantly associated with higher risk of first recurrence and were used to define the IR-High and IR-Low (unifocal, size <3 cm; n = 1087) groups. The 3-yr RFS rate was significantly worse for the IR-High group (51\%, 95\% confidence interval [CI] 48-54\%) than for IR-Low (68\%, 95\% CI 65-71\%). The risk of progression was low (5-yr PFS rate 96\%) with no significant difference between the IR-High and IR-Low groups. CONCLUSIONS AND CLINICAL IMPLICATIONS: During IR-NMIBC follow-up for recurrence, tumor size and focality should be considered rather than grade. If the primary objective is to ensure prompt detection of recurrence, follow-up schedules should be tailored according to the risk of recurrence, with more stringent protocols for patients with IR-NMIBC at higher risk of recurrence.",

keywords = "Follow-up, Intermediate risk, Non{\textendash}muscle-invasive bladder cancer, Risk, Stratification",

author = "Roberto Contieri and Alberto Martini and Beijert, \{Irene J.\} and Mertens, \{Laura S.\} and Hentschel, \{Anouk E.\} and Johannes Br{\"u}ndl and Comp{\'e}rat, \{Eva M.\} and Karin Plass and Oscar Rodr{\'i}guez and \{Subiela Henr{\'i}quez\}, \{Jose D.\} and Virginia Hern{\'a}ndez and \{de la Pe{\~n}a\}, Enrique and Isabel Alemany and Diana Turturica and Francesca Pisano and Francesco Soria and Otakar {\v C}apoun and Lenka Bauerov{\'a} and Michael Pe{\v s}l and \{Maxim Bruins\}, H. and Willemien Runneboom and Sonja Herdegen and Johannes Breyer and Antonin Brisuda and Ana Calatrava and Jos{\'e} Rubio-Briones and Maximilian Seles and Sebastian Mannweiler and Judith Bosschieter and Kusuma, \{Venkata R. M.\} and David Ashabere and Nicolai Huebner and Thomas Seisen and Francesco Claps and Alexandra Masson-Lecomte and Fredrik Liedberg and Daniel Cohen and Luca Lunelli and Olivier Cussenot and Sheikh, \{Soha El\} and Dimitrios Volanis and Jean-Fran{\c c}ois C{\^o}t{\'e} and Morgan Roupr{\^e}t and Andrea Haitel and Shariat, \{Shahrokh F.\} and Mostafid, \{A. Hugh\} and Nieuwenhuijzen, \{Jakko A.\} and Richard Zigeuner and Dominguez-Escrig, \{Jose L.\} and Jaromir Hacek and Zlotta, \{Alexandre R.\} and Maximilian Burger and Matthias Evert and \{de Kaa\}, \{Christina A. Hulsbergen-van\} and \{van der Heijden\}, \{Antoine G.\} and Kiemeney, \{Lambertus A. L. M.\} and Viktor Soukup and Luca Molinaro and Rodolfo Hurle and Marco Paciotti and Marco Moschini and Benjamin Pradere and Sisto Perdon{\`a} and Paolo Gontero and Carlos Llorente and Ferran Algaba and Joan Palou and James N'Dow and Ribal, \{Maria J.\} and \{van der Kwast\}, \{Theo H.\} and Marko Babjuk and Sylvester, \{Richard J.\} and \{van Rhijn\}, \{Bas W. G.\}",

year = "2025",

month = aug,

day = "1",

doi = "10.1016/j.euo.2025.04.010",

language = "English",

volume = "8",

pages = "977--985",

journal = "European Urology Oncology",

issn = "2588-9311",

publisher = "Elsevier BV",

number = "4",

}

Contieri, R, Martini, A, Beijert, IJ , Mertens, LS, Hentschel, AE, Bründl, J, Compérat, EM, Plass, K, Rodríguez, O, Subiela Henríquez, JD, Hernández, V, de la Peña, E, Alemany, I, Turturica, D, Pisano, F, Soria, F, Čapoun, O, Bauerová, L, Pešl, M, Maxim Bruins, H, Runneboom, W, Herdegen, S, Breyer, J, Brisuda, A, Calatrava, A, Rubio-Briones, J, Seles, M, Mannweiler, S, Bosschieter, J, Kusuma, VRM, Ashabere, D, Huebner, N, Seisen, T, Claps, F, Masson-Lecomte, A, Liedberg, F, Cohen, D, Lunelli, L, Cussenot, O, Sheikh, SE, Volanis, D, Côté, J-F, Rouprêt, M, Haitel, A, Shariat, SF, Mostafid, AH, Nieuwenhuijzen, JA, Zigeuner, R, Dominguez-Escrig, JL, Hacek, J, Zlotta, AR, Burger, M, Evert, M, de Kaa, CAH, van der Heijden, AG, Kiemeney, LALM, Soukup, V, Molinaro, L, Hurle, R, Paciotti, M, Moschini, M, Pradere, B, Perdonà, S, Gontero, P, Llorente, C, Algaba, F, Palou, J, N'Dow, J, Ribal, MJ, van der Kwast, TH, Babjuk, M, Sylvester, RJ & van Rhijn, BWG 2025, 'Towards Defining Follow-up Strategies for Patients with Primary Intermediate-risk Non-muscle-invasive Bladder Cancer', European Urology Oncology, vol. 8, no. 4, pp. 977-985. https://doi.org/10.1016/j.euo.2025.04.010

TY - JOUR

T1 - Towards Defining Follow-up Strategies for Patients with Primary Intermediate-risk Non-muscle-invasive Bladder Cancer

AU - Contieri, Roberto

AU - Martini, Alberto

AU - Beijert, Irene J.

AU - Mertens, Laura S.

AU - Hentschel, Anouk E.

AU - Bründl, Johannes

AU - Compérat, Eva M.

AU - Plass, Karin

AU - Rodríguez, Oscar

AU - Subiela Henríquez, Jose D.

AU - Hernández, Virginia

AU - de la Peña, Enrique

AU - Alemany, Isabel

AU - Turturica, Diana

AU - Pisano, Francesca

AU - Soria, Francesco

AU - Čapoun, Otakar

AU - Bauerová, Lenka

AU - Pešl, Michael

AU - Maxim Bruins, H.

AU - Runneboom, Willemien

AU - Herdegen, Sonja

AU - Breyer, Johannes

AU - Brisuda, Antonin

AU - Calatrava, Ana

AU - Rubio-Briones, José

AU - Seles, Maximilian

AU - Mannweiler, Sebastian

AU - Bosschieter, Judith

AU - Kusuma, Venkata R. M.

AU - Ashabere, David

AU - Huebner, Nicolai

AU - Seisen, Thomas

AU - Claps, Francesco

AU - Masson-Lecomte, Alexandra

AU - Liedberg, Fredrik

AU - Cohen, Daniel

AU - Lunelli, Luca

AU - Cussenot, Olivier

AU - Sheikh, Soha El

AU - Volanis, Dimitrios

AU - Côté, Jean-François

AU - Rouprêt, Morgan

AU - Haitel, Andrea

AU - Shariat, Shahrokh F.

AU - Mostafid, A. Hugh

AU - Nieuwenhuijzen, Jakko A.

AU - Zigeuner, Richard

AU - Dominguez-Escrig, Jose L.

AU - Hacek, Jaromir

AU - Zlotta, Alexandre R.

AU - Burger, Maximilian

AU - Evert, Matthias

AU - de Kaa, Christina A. Hulsbergen-van

AU - van der Heijden, Antoine G.

AU - Kiemeney, Lambertus A. L. M.

AU - Soukup, Viktor

AU - Molinaro, Luca

AU - Hurle, Rodolfo

AU - Paciotti, Marco

AU - Moschini, Marco

AU - Pradere, Benjamin

AU - Perdonà, Sisto

AU - Gontero, Paolo

AU - Llorente, Carlos

AU - Algaba, Ferran

AU - Palou, Joan

AU - N'Dow, James

AU - Ribal, Maria J.

AU - van der Kwast, Theo H.

AU - Babjuk, Marko

AU - Sylvester, Richard J.

AU - van Rhijn, Bas W. G.

PY - 2025/8/1

Y1 - 2025/8/1

N2 - BACKGROUND AND OBJECTIVE: The current European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC) categorize patients into four risk groups. In 2024, a specific follow-up schedule was introduced for intermediate-risk (IR) disease. However, recommendations are based on expert opinion and restricted to patients with IR-NMIBC who have primary low-grade or high-grade/grade 2 disease. Our aim was to identify a subgroup of patients with IR-NMIBC who may require more stringent follow-up. METHODS: We conducted a retrospective analysis of 2086 patients with IR-NMIBC classified according to the World Health Organization 1973 grading scheme. Multivariable Cox-regression models were fitted to identify predictors of recurrence, which were then used to dichotomize groups with low risk of recurrence (IR-Low) versus high risk of recurrence (IR-High). Kaplan-Meier curves were plotted to estimate recurrence-free survival (RFS) and progression-free survival (PFS). Smoothed hazard estimates of first recurrence were plotted by risk group. KEY FINDINGS AND LIMITATIONS: Multifocality and tumor size ≥3 cm were significantly associated with higher risk of first recurrence and were used to define the IR-High and IR-Low (unifocal, size <3 cm; n = 1087) groups. The 3-yr RFS rate was significantly worse for the IR-High group (51%, 95% confidence interval [CI] 48-54%) than for IR-Low (68%, 95% CI 65-71%). The risk of progression was low (5-yr PFS rate 96%) with no significant difference between the IR-High and IR-Low groups. CONCLUSIONS AND CLINICAL IMPLICATIONS: During IR-NMIBC follow-up for recurrence, tumor size and focality should be considered rather than grade. If the primary objective is to ensure prompt detection of recurrence, follow-up schedules should be tailored according to the risk of recurrence, with more stringent protocols for patients with IR-NMIBC at higher risk of recurrence.

AB - BACKGROUND AND OBJECTIVE: The current European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC) categorize patients into four risk groups. In 2024, a specific follow-up schedule was introduced for intermediate-risk (IR) disease. However, recommendations are based on expert opinion and restricted to patients with IR-NMIBC who have primary low-grade or high-grade/grade 2 disease. Our aim was to identify a subgroup of patients with IR-NMIBC who may require more stringent follow-up. METHODS: We conducted a retrospective analysis of 2086 patients with IR-NMIBC classified according to the World Health Organization 1973 grading scheme. Multivariable Cox-regression models were fitted to identify predictors of recurrence, which were then used to dichotomize groups with low risk of recurrence (IR-Low) versus high risk of recurrence (IR-High). Kaplan-Meier curves were plotted to estimate recurrence-free survival (RFS) and progression-free survival (PFS). Smoothed hazard estimates of first recurrence were plotted by risk group. KEY FINDINGS AND LIMITATIONS: Multifocality and tumor size ≥3 cm were significantly associated with higher risk of first recurrence and were used to define the IR-High and IR-Low (unifocal, size <3 cm; n = 1087) groups. The 3-yr RFS rate was significantly worse for the IR-High group (51%, 95% confidence interval [CI] 48-54%) than for IR-Low (68%, 95% CI 65-71%). The risk of progression was low (5-yr PFS rate 96%) with no significant difference between the IR-High and IR-Low groups. CONCLUSIONS AND CLINICAL IMPLICATIONS: During IR-NMIBC follow-up for recurrence, tumor size and focality should be considered rather than grade. If the primary objective is to ensure prompt detection of recurrence, follow-up schedules should be tailored according to the risk of recurrence, with more stringent protocols for patients with IR-NMIBC at higher risk of recurrence.

KW - Follow-up

KW - Intermediate risk

KW - Non–muscle-invasive bladder cancer

KW - Risk

KW - Stratification

UR - https://www.scopus.com/pages/publications/105016598579

U2 - 10.1016/j.euo.2025.04.010

DO - 10.1016/j.euo.2025.04.010

M3 - Article

C2 - 40399193

SN - 2588-9311

VL - 8

SP - 977

EP - 985

JO - European Urology Oncology

JF - European Urology Oncology

IS - 4

ER -

Towards Defining Follow-up Strategies for Patients with Primary Intermediate-risk Non-muscle-invasive Bladder Cancer

Abstract

UN SDGs

Keywords

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