Richard J Sylvester1, Oscar Rodríguez2, Virginia Hernández3, Diana Turturica4, Lenka Bauerová5, Harman Max Bruins6, Johannes Bründl7, Theo H van der Kwast8, Antonin Brisuda9, José Rubio-Briones10, Maximilian Seles11, Anouk E Hentschel12, Venkata R M Kusuma13, Nicolai Huebner14, Juliette Cotte15, Laura S Mertens16, Dimitrios Volanis17, Olivier Cussenot17, Jose D Subiela Henríquez2, Enrique de la Peña18, Francesca Pisano19, Michael Pešl20, Antoine G van der Heijden21, Sonja Herdegen7, Alexandre R Zlotta22, Jaromir Hacek23, Ana Calatrava24, Sebastian Mannweiler25, Judith Bosschieter26, David Ashabere13, Andrea Haitel27, Jean-François Côté28, Soha El Sheikh29, Luca Lunelli30, Ferran Algaba31, Isabel Alemany32, Francesco Soria4, Willemien Runneboom33, Johannes Breyer7, Jakko A Nieuwenhuijzen26, Carlos Llorente18, Luca Molinaro34, Christina A Hulsbergen-van de Kaa33, Matthias Evert35, Lambertus A L M Kiemeney36, James N'Dow37, Karin Plass37, Otakar Čapoun38, Viktor Soukup38, Jose L Dominguez-Escrig39, Daniel Cohen40, Joan Palou41, Paolo Gontero42, Maximilian Burger43, Richard Zigeuner44, Amir Hugh Mostafid45, Shahrokh F Shariat46, Morgan Rouprêt47, Eva M Compérat48, Marko Babjuk46, Bas W G van Rhijn49. 1. European Association of Urology Non-Muscle-Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands. Electronic address: richard.sylvester@skynet.be. 2. Department of Urology, Fundacio Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain. 3. European Association of Urology Non-Muscle-Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Urology, Hospital Universitario Fundación Alcorcón, Madrid, Spain. 4. Department of Urology, Città della Salute e della Scienza, University of Torino School of Medicine, Torino, Italy. 5. Department of Pathology, General Teaching Hospital and 1st Faculty of Medicine, Charles University Praha, Prague, Czech Republic. 6. European Association of Urology Non-Muscle-Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands. 7. Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany. 8. Laboratory Medicine Program, University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, Canada. 9. Department of Urology, Teaching Hospital Motol and 2nd Faculty of Medicine, Charles University Praha, Prague, Czech Republic. 10. Department of Urology, Fundación Instituto Valenciano de Oncología, Valencia, Spain. 11. Department of Urology, Medical University of Graz, Graz, Austria. 12. Department of Urology, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, The Netherlands; Department of Surgical Oncology (Urology), Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. 13. Department of Urology, The Stokes Centre for Urology, Royal Surrey Hospital, Guildford, UK. 14. Department of Urology, Comprehensive Cancer Center, Medical University Vienna, Vienna General Hospital, Vienna, Austria. 15. Department of Urology, Pitié Salpétrière Hospital, AP-HP, Sorbonne University, Paris, France. 16. Department of Surgical Oncology (Urology), Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. 17. Department of Urology, Royal Free London NHS Foundation Trust, Royal Free Hospital, London, UK. 18. Department of Urology, Hospital Universitario Fundación Alcorcón, Madrid, Spain. 19. 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. 20. Department of Urology, General Teaching Hospital and 1st Faculty of Medicine, Charles University Praha, Prague, Czech Republic. 21. Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands. 22. Department of Surgical Oncology (Urology), University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, Canada. 23. Department of Pathology, Teaching Hospital Motol and 2nd Faculty of Medicine, Charles University Praha, Prague, Czech Republic. 24. Department of Pathology, Fundación Instituto Valenciano de Oncología, Valencia, Spain. 25. Department of Pathology, Medical University of Graz, Graz, Austria. 26. Department of Urology, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, The Netherlands. 27. Department of Pathology, Comprehensive Cancer Center, Medical University Vienna, Vienna General Hospital, Vienna, Austria. 28. Department of Pathology, Pitié Salpétrière Hospital, AP-HP, Pierre et Marie Curie Medical School, Sorbonne University, Paris, France. 29. Department of Pathology, Royal Free London NHS Foundation Trust, Royal Free Hospital, London, UK. 30. Department of Urology, Tenon Hospital, AP-HP, Sorbonne University, Paris, France. 31. Department of Pathology, Fundacio Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain. 32. Department of Pathology, Hospital Universitario Fundación Alcorcón, Madrid, Spain. 33. Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands. 34. Department of Pathology, Città della Salute e della Scienza, University of Torino School of Medicine, Torino, Italy. 35. Department of Pathology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany. 36. Department of Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands. 37. European Association of Urology Guidelines Office, Arnhem, The Netherlands. 38. 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, Czech Republic. 39. European Association of Urology Non-Muscle-Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Urology, Fundación Instituto Valenciano de Oncología, Valencia, Spain. 40. European Association of Urology Non-Muscle-Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Urology, Royal Free London NHS Foundation Trust, Royal Free Hospital, London, UK. 41. 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. 42. 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. 43. European Association of Urology Non-Muscle-Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany. 44. European Association of Urology Non-Muscle-Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Urology, Medical University of Graz, Graz, Austria. 45. European Association of Urology Non-Muscle-Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Urology, The Stokes Centre for Urology, Royal Surrey Hospital, Guildford, UK. 46. European Association of Urology Non-Muscle-Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Urology, Teaching Hospital Motol and 2nd Faculty of Medicine, Charles University Praha, Prague, Czech Republic; Department of Urology, Comprehensive Cancer Center, Medical University Vienna, Vienna General Hospital, Vienna, Austria. 47. European Association of Urology Non-Muscle-Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Urology, Pitié Salpétrière Hospital, AP-HP, Sorbonne University, Paris, France. 48. 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. 49. 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.
Abstract
BACKGROUND: The European Association of Urology (EAU) prognostic factor risk groups for non-muscle-invasive bladder cancer (NMIBC) are used to provide recommendations for patient treatment after transurethral resection of bladder tumor (TURBT). They do not, however, take into account the widely used World Health Organization (WHO) 2004/2016 grading classification and are based on patients treated in the 1980s. OBJECTIVE: To update EAU prognostic factor risk groups using the WHO 1973 and 2004/2016 grading classifications and identify patients with the lowest and highest probabilities of progression. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for primary NMIBC patients were collected from the institutions of the members of the EAU NMIBC guidelines panel. INTERVENTION: Patients underwent TURBT followed by intravesical instillations at the physician's discretion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable Cox proportional-hazards regression models were fitted to the primary endpoint, the time to progression to muscle-invasive disease or distant metastases. Patients were divided into four risk groups: low-, intermediate-, high-, and a new, very high-risk group. The probabilities of progression were estimated using Kaplan-Meier curves. RESULTS AND LIMITATIONS: A total of 3401 patients treated with TURBT ± intravesical chemotherapy were included. From the multivariable analyses, tumor stage, WHO 1973/2004-2016 grade, concomitant carcinoma in situ, number of tumors, tumor size, and age were used to form four risk groups for which the probability of progression at 5 yr varied from <1% to >40%. Limitations include the retrospective collection of data and the lack of central pathology review. CONCLUSIONS: This study provides updated EAU prognostic factor risk groups that can be used to inform patient treatment and follow-up. Incorporating the WHO 2004/2016 and 1973 grading classifications, a new, very high-risk group has been identified for which urologists should be prompt to assess and adapt their therapeutic strategy when necessary. PATIENT SUMMARY: The newly updated European Association of Urology prognostic factor risk groups for non-muscle-invasive bladder cancer provide an improved basis for recommending a patient's treatment and follow-up schedule.
BACKGROUND: The European Association of Urology (EAU) prognostic factor risk groups for non-muscle-invasive bladder cancer (NMIBC) are used to provide recommendations for patient treatment after transurethral resection of bladder tumor (TURBT). They do not, however, take into account the widely used World Health Organization (WHO) 2004/2016 grading classification and are based on patients treated in the 1980s. OBJECTIVE: To update EAU prognostic factor risk groups using the WHO 1973 and 2004/2016 grading classifications and identify patients with the lowest and highest probabilities of progression. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for primary NMIBC patients were collected from the institutions of the members of the EAU NMIBC guidelines panel. INTERVENTION: Patients underwent TURBT followed by intravesical instillations at the physician's discretion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable Cox proportional-hazards regression models were fitted to the primary endpoint, the time to progression to muscle-invasive disease or distant metastases. Patients were divided into four risk groups: low-, intermediate-, high-, and a new, very high-risk group. The probabilities of progression were estimated using Kaplan-Meier curves. RESULTS AND LIMITATIONS: A total of 3401 patients treated with TURBT ± intravesical chemotherapy were included. From the multivariable analyses, tumor stage, WHO 1973/2004-2016 grade, concomitant carcinoma in situ, number of tumors, tumor size, and age were used to form four risk groups for which the probability of progression at 5 yr varied from <1% to >40%. Limitations include the retrospective collection of data and the lack of central pathology review. CONCLUSIONS: This study provides updated EAU prognostic factor risk groups that can be used to inform patient treatment and follow-up. Incorporating the WHO 2004/2016 and 1973 grading classifications, a new, very high-risk group has been identified for which urologists should be prompt to assess and adapt their therapeutic strategy when necessary. PATIENT SUMMARY: The newly updated European Association of Urology prognostic factor risk groups for non-muscle-invasive bladder cancer provide an improved basis for recommending a patient's treatment and follow-up schedule.
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