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.
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.
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.
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.
European urology oncology. 2025 May 20 [Epub ahead of print]
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
Department of Surgical Oncology (Urology), Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Department of Biochemical Science, Humanitas University, Milan, Italy; Department of Urology, Humanitas Clinical and Research Institute IRCCS, Rozzano, Italy., Department of Urology, University of Cincinnati, Cincinnati, OH, USA., Department of Surgical Oncology (Urology), Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Department of Urology, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, The Netherlands., Department of Surgical Oncology (Urology), Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands., Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany., European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Pathology, Tenon Hospital, AP-HP, Sorbonne University, Paris, France., European Association of Urology Guidelines Office, Arnhem, The Netherlands., Department of Urology, Fundacio Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain., European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Urology, Hospital Universitario Fundación Alcorcón, Madrid, Spain., Department of Urology, Hospital Universitario Fundación Alcorcón, Madrid, Spain., Department of Pathology, Hospital Universitario Fundación Alcorcón, Madrid, Spain., Department of Urology, Città della Salute e della Scienza, University of Torino School of Medicine, Torino, Italy., Department of Urology, Fundacio Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain; Department of Urology, Città della Salute e della Scienza, University of Torino School of Medicine, Torino, Italy., European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Urology, General Teaching Hospital and 1st Faculty of Medicine, Charles University Praha, Prague, Czechia., Department of Pathology, General Teaching Hospital and 1st Faculty of Medicine, Charles University Praha, Prague, Czechia., Department of Urology, General Teaching Hospital and 1st Faculty of Medicine, Charles University Praha, Prague, Czechia., European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands., Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands., Department of Urology, Teaching Hospital Motol and 2nd Faculty of Medicine, Charles University Praha, Prague, Czechia., Department of Pathology, Fundación Instituto Valenciano de Oncología, Valencia, Spain., Department of Urology, Fundación Instituto Valenciano de Oncología, Valencia, Spain., Department of Urology, Medical University of Graz, Graz, Austria., Department of Pathology, Medical University of Graz, Graz, Austria., Department of Urology, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, The Netherlands., Department of Urology, Stokes Centre for Urology, Royal Surrey Hospital, Guildford, UK., Department of Urology, Comprehensive Cancer Center, Medical University Vienna, Vienna General Hospital, Vienna, Austria., European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; 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Department of Urology, Teaching Hospital Motol and 2nd Faculty of Medicine, Charles University Praha, Prague, Czechia; Department of Urology, Comprehensive Cancer Center, Medical University Vienna, Vienna General Hospital, Vienna, Austria., European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Urology, Stokes Centre for Urology, Royal Surrey Hospital, Guildford, UK., European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Urology, Medical University of Graz, Graz, Austria., European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Urology, Fundación Instituto Valenciano de Oncología, Valencia, Spain., Department of Pathology, Teaching Hospital Motol and 2nd Faculty of Medicine, Charles University Praha, Prague, Czechia., Department of Surgical Oncology (Urology), University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, Canada., Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany; European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands., Department of Pathology, University of Regensburg, Regensburg, Germany., Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands., IQ Health and Urology, Radboud University Medical Center, Nijmegen, The Netherlands., Department of Pathology, Città della Salute e della Scienza, University of Torino School of Medicine, Torino, Italy., Department of Urology, Humanitas Clinical and Research Institute IRCCS, Rozzano, Italy., Department of Biochemical Science, Humanitas University, Milan, Italy; Department of Urology, Humanitas Clinical and Research Institute IRCCS, Rozzano, Italy., Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy., Department of Urology UROSUD, La Croix du Sud Hôpital, Quint Fonsegrives, France., Uro-Gynecological Department, Istituto Nazionale Tumori di Napoli G. Pascale IRCCS, Naples, Italy., European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Urology, Città della Salute e della Scienza, University of Torino School of Medicine, Torino, Italy., Department of Pathology, Fundacio Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain., European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Urology, Fundacio Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain., Laboratory Medicine Program, University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, Canada., European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands., Department of Surgical Oncology (Urology), Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany; European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Surgical Oncology (Urology), University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, Canada. 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