In the current European Association of Urology (EAU) non-muscle-invasive bladder cancer (NMIBC) guideline, two classification systems for grade are advocated: WHO1973 and WHO2004/2016.
To compare the prognostic value of these WHO systems.
Individual patient data for 5145 primary Ta/T1 NMIBC patients from 17 centers were collected between 1990 and 2019. The median follow-up was 3.9 yr.
Univariate and multivariable analyses of WHO1973 and WHO2004/2016 stratified by center were performed for time to recurrence, progression (primary endpoint), cystectomy, and duration of survival, taking into account age, concomitant carcinoma in situ, gender, multiplicity, tumor size, initial treatment, and tumor stage. Harrell's concordance (C-index) was used for prognostic accuracy of classification systems.
The median age was 68 yr; 3292 (64%) patients had Ta tumors. Neither classification system was prognostic for recurrence. For a four-tier combination of both WHO systems, progression at 5-yr follow-up was 1.4% in low-grade (LG)/G1, 3.8% in LG/G2, 7.7% in high grade (HG)/G2, and 18.8% in HG/G3 (log-rank, p < 0.001). In multivariable analyses with WHO1973 and WHO2004/2016 as independent variables, WHO1973 was a significant prognosticator of progression (p < 0.001), whereas WHO2004/2016 was not anymore (p = 0.067). C-indices for WHO1973, WHO2004, and the WHO systems combined for progression were 0.71, 0.67, and 0.73, respectively. Prognostic analyses for cystectomy and survival showed results similar to those for progression.
In this large prognostic factor study, both classification systems were prognostic for progression but not for recurrence. For progression, the prognostic value of WHO1973 was higher than that of WHO 2004/2016. The four-tier combination (LG/G1, LG/G2, HG/G2, and HG/G3) of both WHO systems proved to be superior, as it divides G2 patients into two subgroups (LG and HG) with different prognoses. Hence, the current EAU-NMIBC guideline recommendation to use both WHO classification systems remains correct.
At present, two classification systems are used in parallel to grade non-muscle-invasive bladder tumors. Our data on a large number of patients showed that the older classification system (WHO1973) performed better in terms of assessing progression than the more recent (WHO2004/2016) one. Nevertheless, we conclude that the current guideline recommendation for the use of both classification systems remains correct, since this has the advantage of dividing the large group of WHO1973 G2 patients into two subgroups (low and high grade) with different prognoses.
European urology oncology. 2021 Jan 08 [Epub ahead of print]
Bas W G van Rhijn, Anouk E Hentschel, Johannes Bründl, Eva M Compérat, Virginia Hernández, Otakar Čapoun, H Maxim Bruins, Daniel Cohen, Morgan Rouprêt, Shahrokh F Shariat, A Hugh Mostafid, Richard Zigeuner, Jose L Dominguez-Escrig, Maximilian Burger, Viktor Soukup, Paolo Gontero, Joan Palou, Theo H van der Kwast, Marko Babjuk, Richard J Sylvester, Multi-center EAU Non-Muscle-Invasive Bladder Cancer Guidelines Panel Study Consortium on the WHO1973 WHO 2004 2016 Classification Systems for Grade
European Association of Urology Non-Muscle Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; 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: ., Surgical Oncology (Urology), Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Urology, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, The Netherlands., 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; Pathology, Tenon Hospital, AP-HP, Sorbonne University, Paris, France., European Association of Urology Non-Muscle Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Urology, Hospital Universitario Fundación Alcorcón, Madrid, Spain., European Association of Urology Non-Muscle Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Urology, General Teaching Hospital and 1st Faculty of Medicine, Charles University Praha, Prague, Czech Republic., European Association of Urology Non-Muscle Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Urology, Radboud University Medical Center, Nijmegen, The Netherlands., European Association of Urology Non-Muscle Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Urology, Royal Free London - NHS Foundation Trust, Royal Free Hospital, London, UK., European Association of Urology Non-Muscle Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Urology, Pitié Salpétrière Hospital, AP-HP, GRC n°5, ONCOTYPE-URO, Sorbonne University, Paris, France., European Association of Urology Non-Muscle Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Urology, Teaching Hospital Motol and 2nd Faculty of Medicine, Charles University Praha, Prague, Czech Republic; 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; Urology, The Stokes Centre for Urology, Royal Surrey Hospital, Guildford, UK., European Association of Urology Non-Muscle Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Urology, Medical University of Graz, Graz, Austria., European Association of Urology Non-Muscle Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Urology, Fundación Instituto Valenciano de Oncología (I.V.O.), Valencia, Spain., European Association of Urology Non-Muscle Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; 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; 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; 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.