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Papillary urothelial neoplasm of low malignant potential (PUN-LMP): Still a meaningful histo-pathological grade category for Ta, noninvasive bladder tumors in 2019?

  • Anouk E. Hentschel
  • , Bas W. G. van Rhijn*
  • , 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. Max Bruins
  • , Willemien Runneboom
  • , Sonja Herdegen
  • , Johannes Breyer
  • Antonin Brisuda, Andrea Scavarda-Lamberti, Ana Calatrava, José Rubio-Briones, Maximilian Seles, Sebastian Mannweiler, Judith Bosschieter, Venkata R. M. Kusuma, David Ashabere, Nicolai Huebner, Juliette Cotte, Laura S. Mertens, Daniel Cohen, Luca Lunelli, Olivier Cussenot, Soha El Sheikh, Dimitrios Volanis, Jean-François Coté, 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, Paolo Gontero, Carlos Llorente, Ferran Algaba, Joan Palou, James N'Dow, Marko Babjuk, Theo H. van der Kwast, Richard J. Sylvester
*Corresponding author for this work
  • Vrije Universiteit Amsterdam
  • Antoni van Leeuwenhoek Hospital
  • University of Regensburg
  • Princess Margaret Cancer Centre
  • Sorbonne Université
  • European Association of Urology
  • Autonomous University of Barcelona
  • Fundacion Hospital Alcorcon
  • University of Turin
  • Charles University
  • Radboud University Medical Center
  • Instituto Valenciano de Oncologia
  • Medical University of Graz
  • Royal Surrey County Hospital NHS Foundation Trust
  • Medical University of Vienna
  • Lysosomal Storage Disorders Unit, Royal Free Hospital NHS Foundation Trust and University College London, London, UK
  • Surgical Oncology (Urology), Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands; Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany; Surgical Oncology (Urology), University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, Canada. Electronic address: [email protected].
  • Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany.
  • Pathology, Tenon Hospital, AP-HP, UPMC Paris VI, Sorbonne University, Paris, France.
  • EAU Guidelines Office Board, European Association of Urology, Arnhem, the Netherlands.
  • Urology, Fundacio Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • Urology, Hospital Universitario Fundación Alcorcón, Madrid, Spain.
  • Pathology, Hospital Universitario Fundación Alcorcón, Madrid, Spain.
  • Urology Clinic, Citta' della Salute e della Scienza, University of Studies of Torino, Torino, Italy.
  • Urology, Fundacio Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain; Urology Clinic, Citta' della Salute e della Scienza, University of Studies of Torino, Torino, Italy.
  • Urology, General Teaching Hospital and 1st Faculty of Medicine, Charles University Praha, Prague, Czech Republic.
  • Pathology, General Teaching Hospital and 1st Faculty of Medicine, Charles University Praha, Prague, Czech Republic.
  • Department of Urology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
  • Tumor Immunology Laboratory, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands (P.R.G., B.M.S., E.D.K.-R., G.J.A.); Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands (K.V., P.W.); Department of Neurosurgery, Radboud University Medical Center, Nijmegen, the Netherlands (S.A.J.H.B., M.L.); Department of Pathology...
  • Urology,Teaching Hospital Motol, Prague, Czech Republic.
  • Pathology, Fundación Instituto Valenciano de Oncología (I.V.O.), Valencia, Spain.
  • Urology, Fundación Instituto Valenciano de Oncología (I.V.O.), Valencia, Spain.
  • Urology, Medical University of Graz, Graz, Austria.
  • Pathology, Medical University of Graz, Graz, Austria.
  • Urology, Royal Surrey County Hospital-NHS Foundation Trust, Guildford, Surrey, United Kingdom.
  • Urology, Comprehensive Cancer Center, Medical University Vienna, Vienna General Hospital, Vienna, Austria.
  • Urology, Pitié Salpétrière Hospital, AP-HP, GRC n 5, ONCOTYPE-URO, Sorbonne University, Paris, France.
  • Department of Urology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Department of Urology, Royal Free London NHS Foundation Trust, University College London, United Kingdom.
  • Urology, Tenon Hospital, AP-HP, UPMC Paris VI, Sorbonne University, Paris, France.
  • Pathology, Royal Free London-NHS Foundation Trust, Royal Free Hospital, London, United Kingdom.
  • Pathology, Pitié Salpétrière Hospital, AP-HP, Pierre et Marie Curie Medical School, Sorbonne University, Paris, France.
  • Pathology, Comprehensive Cancer Center, Medical University Vienna, Vienna General Hospital, Vienna, Austria.
  • Urology,Teaching Hospital Motol, Prague, Czech Republic; Urology, Comprehensive Cancer Center, Medical University Vienna, Vienna General Hospital, Vienna, Austria.
  • Pathology, Teaching Hospital Motol, Prague, Czech Republic.
  • Surgical Oncology (Urology), University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, Canada.
  • Pathology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany.
  • Department for Health Evidence, Radboud university medical center, Nijmegen, the Netherlands.
  • Pathology, Citta' della Salute e della Scienza, University of Studies of Torino, Torino, Italy.
  • Pathology, Fundacio Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • Pathology, University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, Canada.

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Papillary urothelial neoplasm of low malignant potential (PUN-LMP) was introduced as a noninvasive, noncancerous lesion and a separate grade category in 1998. Subsequently, PUN-LMP was reconfirmed by World Health Organization (WHO) 2004 and WHO 2016 classifications for urothelial bladder tumors. Objectives: To analyze the proportion of PUN-LMP diagnosis over time and to determine its prognostic value compared to Ta-LG (low-grade) and Ta-HG (high-grade) carcinomas. To assess the intraobserver variability of an experienced uropathologist assigning (WHO) 2004/2016 grades at 2 time points. Materials and methods: Individual patient data of 3,311 primary Ta bladder tumors from 17 hospitals in Europe and Canada were available. Transurethral resection of the tumor was performed between 1990 and 2018. Time to recurrence and progression were analyzed with cumulative incidence functions, log-rank tests and multivariable Cox-regression stratified by institution. Intraobserver variability was assessed by examining the same 314 transurethral resection of the tumorslides twice, in 2004 and again in 2018. Results: PUN-LMP represented 3.8% (127/3,311) of Ta tumors. The same pathologist found 71/314 (22.6%) PUN-LMPs in 2004 and only 20/314 (6.4%) in 2018. Overall, the proportion of PUN-LMP diagnosis substantially decreased over time from 31.3% (1990–2000) to 3.2% (2000–2010) and to 1.1% (2010–2018). We found no difference in time to recurrence between the three WHO 2004/2016 Ta-grade categories (log-rank, P = 0.381), nor for LG vs. PUN-LMP (log-rank, P = 0.238). Time to progression was different for all grade categories (log-rank, P < 0.001), but not between LG and PUN-LMP (log-rank, P = 0.096). Multivariable analyses on recurrence and progression showed similar results for all 3 grade categories and for LG vs. PUN-LMP. Conclusions: The proportion of PUN-LMP has decreased to very low levels in the last decade. Contrary to its reconfirmation in the WHO 2016 classification, our results do not support the continued use of PUN-LMP as a separate grade category in Ta tumors because of the similar prognosis for PUN-LMP and Ta-LG carcinomas.
Original languageEnglish
Article numberdoi: 10.1016/j.urolonc.2019.10.002
Pages (from-to)440-448
Number of pages9
JournalUrologic oncology
Volume38
Issue number5
Early online date5 Nov 2019
DOIs
Publication statusPublished - 1 May 2020

UN SDGs

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

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • Bladder
  • Cancer
  • Carcinomas
  • Grade
  • Nonmuscle-invasive
  • Urothelial
  • WHO

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