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Eur Urol. 2019 Nov 16. pii: S0302-2838(19)30763-8. doi: 10.1016/j.eururo.2019.09.035. [Epub ahead of print]

EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer-An International Collaborative Multistakeholder Effort: Under the Auspices of the EAU-ESMO Guidelines Committees.

Witjes JA1, Babjuk M2, Bellmunt J3, Bruins HM4, De Reijke TM5, De Santis M6, Gillessen S7, James N8, Maclennan S9, Palou J10, Powles T11, Ribal MJ12, Shariat SF13, Der Kwast TV14, Xylinas E15, Agarwal N16, Arends T17, Bamias A18, Birtle A19, Black PC20, Bochner BH21, Bolla M22, Boormans JL23, Bossi A24, Briganti A25, Brummelhuis I4, Burger M26, Castellano D27, Cathomas R28, Chiti A29, Choudhury A30, Compérat E31, Crabb S32, Culine S33, De Bari B34, De Blok W35, J L De Visschere P36, Decaestecker K37, Dimitropoulos K38, Dominguez-Escrig JL39, Fanti S40, Fonteyne V41, Frydenberg M42, Futterer JJ43, Gakis G44, Geavlete B45, Gontero P46, Grubmüller B47, Hafeez S48, Hansel DE49, Hartmann A50, Hayne D51, Henry AM52, Hernandez V53, Herr H54, Herrmann K55, Hoskin P56, Huguet J10, Jereczek-Fossa BA57, Jones R58, Kamat AM59, Khoo V60, Kiltie AE61, Krege S62, Ladoire S63, Lara PC64, Leliveld A65, Linares-Espinós E66, Løgager V67, Lorch A68, Loriot Y69, Meijer R70, Mir MC39, Moschini M71, Mostafid H72, Müller AC73, Müller CR74, N'Dow J75, Necchi A76, Neuzillet Y77, Oddens JR5, Oldenburg J78, Osanto S79, J G Oyen W80, Pacheco-Figueiredo L81, Pappot H82, Patel MI83, Pieters BR84, Plass K85, Remzi M47, Retz M86, Richenberg J87, Rink M88, Roghmann F89, Rosenberg JE90, Rouprêt M91, Rouvière O92, Salembier C93, Salminen A94, Sargos P95, Sengupta S96, Sherif A97, Smeenk RJ98, Smits A4, Stenzl A99, Thalmann GN100, Tombal B101, Turkbey B102, Lauridsen SV103, Valdagni R104, Der Heijden AGV4, Van Poppel H105, Vartolomei MD106, Veskimäe E107, Vilaseca A12, Rivera FAV108, Wiegel T109, Wiklund P110, Williams A111, Zigeuner R112, Horwich A113.

Author information

1
Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Fred.Witjes@radboudumc.nl.
2
Depatment of Urology, 2nd Faculty of Medicine, Hospital Motol, Charles University, Prague, Czech Republic; Department of Urology, Medical University of Vienna, Vienna, Austria.
3
IMIM-Hospital del Mar Medical Research Institute, Barcelona, Spain; Harvard Medical School, Boston, Massachusetts, USA.
4
Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
5
Department of Urology, Amsterdam University Medical Centers, University of Amsterdam, The Netherlands.
6
Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Charité University Hospital, Berlin, Germany.
7
Division of Cancer Sciences, University of Manchester, Manchester, UK; The Christie NHS Foundation Trust, Manchester, UK; Division of Oncology and Haematology, Kantonsspital St Gallen, St Gallen, Switzerland; University of Bern, Bern, Switzerland.
8
University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.
9
Academic Urology Unit, University of Aberdeen, Aberdeen, UK.
10
Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain.
11
The Royal Free NHS Trust, London, UK; Barts Cancer Institute, Queen Mary University of London, London, UK.
12
Uro-Oncology Unit, Hospital Clinic, University of Barcelona, Spain.
13
Depatment of Urology, 2nd Faculty of Medicine, Hospital Motol, Charles University, Prague, Czech Republic; Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Weill Cornell Medical College, New York, New York, USA; Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA; Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia.
14
Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands.
15
Department of Urology, Bichat-Claude Bernard Hospital, Assistance Publique Hôpitaux de Paris, Paris, France; Paris Descartes University, Paris, France.
16
Huntsman Cancer Institute, University of Utah (NCI-CCC), Salt Lake City, Utah, USA.
17
Urology Department, Canisius-Wilhelmina Ziekenhuis Nijmegen, The Netherlands.
18
2nd Propaedeutic Dept of Internal Medicine, Medical School, National & Kapodistrian University of Athens, Athens, Greece.
19
Division of Cancer Sciences, University of Manchester, Manchester, UK; Rosemere Cancer Centre, Lancashire Teaching Hospitals, Preston, UK.
20
Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, British Colombia, Canada.
21
Department of Urology, Weill Cornell Medical College, New York, New York, USA; Urology Service, Department of Urology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
22
Emeritus Professor of Radiation Oncology, Grenoble - Alpes University, Grenoble, France.
23
Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
24
Department of Radiation Oncology, Gustave Roussy Institute, Villejuif, France.
25
Department of Urology, Urological Research Institute, Milan; Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy.
26
Department of Urology, Caritas-St. Josef Medical Center, University of Regensburg, Regensburg, Germany.
27
Medical Oncology Department, 12 de Octubre University Hospital (CIBERONC), Madrid, Spain.
28
Departement Innere Medizin, Abteilung Onkologie und Hämatologie, Kantonsspital Graubünden, Chur, Switzerland.
29
Department of Biomedical Sciences, Humanitas University, Milan, Italy; Humanitas Research Hospital, Milan, Italy.
30
Division of Cancer Sciences, University of Manchester, Manchester, UK; The Christie NHS Foundation Trust, Manchester, UK.
31
Department of Pathology, Tenon hospital, HUEP, Paris, France; Sorbonne University, Paris, France.
32
Cancer Sciences Unit, University of Southampton, Southampton, UK.
33
Department of Cancer Medicine, Hôpital Saint Louis, Paris, France.
34
Radiation Oncology Department, Centre Hospitalier Régional Universitaire "Jean Minjoz" of Besançon, INSERM UMR 1098, Besançon, France; Radiation Oncology Department, Centre Hospitalier Universitaire Vaudois, Université de Lausanne, Lausanne, Switzerland.
35
Department of Urology, University Medical Center Utrecht, Utrecht, The Netherlands.
36
Department of Radiology and Nuclear Medicine, Division of Genitourinary Radiology and Mammography, Ghent University Hospital, Ghent, Belgium.
37
Department of Urology, Ghent University Hospital, Ghent, Belgium.
38
Department of Urology, Aberdeen Royal Infirmary, Aberdeen, UK.
39
Servicio de Urología, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
40
Department of Nuclear Medicine, Policlinico S Orsola, University of Bologna, Italy.
41
Department of Radiotherapy Oncology, Ghent University Hospital, Ghent, Belgium.
42
Department of Surgery, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Australia.
43
Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
44
Department of Urology and Paediatric Urology, University Hospital of Würzburg, Julius-Maximillians University, Würzburg, Germany.
45
Department of Urology, Saint John Emergency Clinical Hospital, Bucharest, Romania.
46
Division of Urology, Molinette Hospital, University of Studies of Torino, Torino, Italy.
47
Department of Urology, Medical University of Vienna, Vienna, Austria.
48
Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK; Department of Clinical Oncology, The Royal Marsden NHS Foundation Trust, London, UK.
49
Department of Urology, University of California, San Diego Pathology, La Jolla, California, USA.
50
Institute of Pathology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, Erlangen, Germany.
51
Department of Urology, UWA Medical School, University of Western Australia, Perth, Australia.
52
Leeds Institute of Medical Research, University of Leeds, Leeds, UK.
53
Department of Urology, Hospital Universitario Fundación de Alcorcón, Madrid, Spain.
54
Urology Service, Department of Urology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
55
Department of Nuclear Medicine, Universitätsklinikum Essen, Essen, Germany.
56
Division of Cancer Sciences, University of Manchester, Manchester, UK; The Christie NHS Foundation Trust, Manchester, UK; Mount Vernon Centre for Cancer Treatment, London, UK.
57
Department of Oncology and Hemato-oncology, University of Milan, Milan; Division of Radiotherapy, IEO European Institute of Oncology, IRCCS, Milan, Italy.
58
Institute of Cancer Sciences, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
59
Department of Urology - Division of Surgery, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
60
Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK; Department of Clinical Oncology, The Royal Marsden NHS Foundation Trust, London, UK; Department of Medicine, University of Melbourne; Monash University, Melbourne, Australia.
61
CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK.
62
Department of Urology, Pediatric Urology and Urologic Oncology, Kliniken Essen-Mitte, Essen, Germany.
63
Department of Medical Oncology, Centre Georges François Leclerc, Dijon, France.
64
Department of Oncology, Hospital Universitario San Roque; Universidad Fernando Pessoa, Canarias, Spain.
65
Department of Urology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
66
Department of Urology, University Hospital La Paz, Madrid, Spain.
67
Department of Radiology, Copenhagen University Hospital Herlev and Gentofte, Herlev, Denmark.
68
Department of Medical Oncology and Hematology, University Hospital Zürich, Zürich, Switzerland.
69
Département de Médecine Oncologique, Gustave Roussy, INSERM U981, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
70
UMC Utrecht Cancer Center, MS Oncologic Urology, Utrecht, The Netherlands.
71
Department of Urology, Luzerner Kantonsspital, Luzern, Switzerland.
72
Department of Urology, Royal Surrey County Hospital, Guildford, UK.
73
Department of Radiation Oncology, Eberhard Karls University, Tübingen, Germany.
74
Cancer Treatment Centre, Sorlandet Hospital, Kristiansand, Norway.
75
Academic Urology Unit, University of Aberdeen, Aberdeen, UK; Department of Urology, Aberdeen Royal Infirmary, Aberdeen, UK.
76
Department of Medical Oncology, Istituto Nazionale Tumori of Milan, Milan, Italy.
77
Department of Urology, Hospital Foch, University of Versailles-Saint-Quentin-en-Yvelines, Suresnes, France.
78
Department of Oncology, Akershus University Hospital, Lørenskog, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
79
Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
80
Department of Biomedical Sciences, Humanitas University, Milan, Italy; Humanitas Research Hospital, Milan, Italy; Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Radiology and Nuclear Medicine, Rijnstate Hospital, Arnhem, The Netherlands.
81
Department of Urology, Centro Hospitalar São João, Porto, Portugal; Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
82
Department of Oncology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
83
Department of Urology, Westmead Hospital, University of Sydney, Sydney, Australia.
84
Department Radiation Oncology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands.
85
EAU Guidelines Office, Arnhem, The Netherlands.
86
Department of Urology, Rechts der Isar Medical Center, Technical University of Munich, Munich, Germany.
87
Department of Imaging and Nuclear Medicine, Royal Sussex County Hospital, Brighton, UK; Brighton and Sussex Medical School, Brighton, UK.
88
Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
89
Department of Urology, Ruhr-University Bochum, Marien Hospital, Herne, Germany.
90
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA; Weill Cornell Medical College, New York, New York, USA.
91
Department of Urology, Sorbonne Université, GRC n°5, ONCOTYPE-URO, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France.
92
Hospices Civils de Lyon, Service d'Imagerie Urinaire et Vasculaire, Hôpital Edouard Herriot, Lyon, France; Université de Lyon, Université Lyon 1, faculté de médecine Lyon Est, Lyon, France.
93
Department of Radiation Oncology, Europe Hospitals Brussels, Belgium.
94
Department of Urology, University Hospital of Turku, Finland.
95
Department of Radiotherapy, Institut Bergonié, Bordeaux, France.
96
Department of Surgery, Austin Health, University of Melbourne, Melbourne, Australia; Eastern Health Clinical School, Monash University, Melbourne, Australia.
97
Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå university, Umeå, Sweden.
98
Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
99
Department of Urology, Eberhard Karls University Tübingen, Tübingen, Germany.
100
Department of Urology, Inselspital, Bern University Hospital, Bern, Switzerland.
101
Division of Urology, IREC, Cliniques Universitaires Saint Luc, UCL, Brussels, Belgium.
102
Molecular Imaging Program, National Cancer Institute, Bethesda, Maryland, USA.
103
Department of Urology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
104
Department of Oncology and Hemato-oncology, Università degli Studi di Milano, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
105
Department of Urology, University Hospitals Leuven, Belgium.
106
Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Cell and Molecular Biology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania.
107
Department of Urology, Tampere University Hospital, Tampere, Finland.
108
Clinica HematoOncologica Bonadona Prevenir, Universidad Metropolitana, Clinica Club de Leones, Barranquilla, Colombia.
109
Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany.
110
Icahn School of Medicine, Mount Sinai Health System New York City, New York, USA; Department of Urology, Karolinska Institutet, Stockholm, Sweden.
111
Department of Urology, Auckland City Hospital, Auckland, New Zealand.
112
Department of Urology, Medizinische Universität Graz, Graz, Austria.
113
Emeritus Professor, The Institute of Cancer Research, London, UK.

Abstract

BACKGROUND:

Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.

OBJECTIVE:

To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.

DESIGN:

A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference.

SETTING:

Online Delphi survey and consensus conference.

PARTICIPANTS:

The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:

Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).

RESULTS AND LIMITATIONS:

Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease.

CONCLUSIONS:

These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach.

PATIENT SUMMARY:

This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.

KEYWORDS:

Bladder cancer; Consensus; Delphi; Diagnosis; Follow-up; Treatment

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