Grade is an important determinant of progression in non-muscle-invasive bladder cancer. Although the World Health Organization (WHO) 2004/2016 grading system is recommended, other systems such as WHO1973 and WHO1999 are still widely used. Recently, a hybrid (three-tier) system was proposed, separating WHO2004/2016 high grade (HG) into HG/grade 2 (G2) and HG/G3 while maintaining low grade. We assessed the prognostic performance of HG/G3 and HG/G2. Three independent cohorts with 9712 primary (first diagnosis) Ta-T1 bladder tumors were analyzed. Time to progression was analyzed with cumulative incidence functions and Cox regression models. Harrell's C-index was used to assess discrimination. Time to progression was significantly shorter for HG/G3 than for HG/G2 in multivariable analyses (cohort 1: hazard ratio [HR] = 1.92; cohort 2: HR = 2.51, and cohort 3: HR = 1.69). Corresponding progression risks at 5 yr were 18%, 20%, and 18% for HG/G3 versus 7.3%, 7.5%, and 9.3% for HG/G2, respectively. Cox models using hybrid grade performed better than models with WHO2004/2016 (all cohorts; p < 0.001). For the three cohorts, C-indices for WHO2004/2016 were 0.69, 0.62, and 0.75, while, for hybrid grade, C-indices were 0.74, 0.68, and 0.78, respectively. Subdividing the HG category into HG/G2 and HG/G3 stratifies time to progression and supports the recommendation to adopt the hybrid grading system for Ta/T1 bladder cancers.
European urology. 2024 Aug 28 [Epub ahead of print]
Irene J Beijert, Oskar Hagberg, Truls Gårdmark, Lars Holmberg, Christel Häggström, Allan Johnston, Matthew Trail, Sami Hamid, Barend A Dreyer, Luisa Padovani, Roberta Garau, Rami Hasan, Imran Ahmad, David Hendry, Eva M Compérat, Maximilian Burger, Morgan Rouprêt, Paolo Gontero, Maria J Ribal, Theo H van der Kwast, Marko Babjuk, Richard J Sylvester, Paramananthan Mariappan, Fredrik Liedberg, Bas W G van Rhijn, BladderBaSe-Consortium , Scot BC Quality OPS Collaborative , Multi-center EAU Non-Muscle-Invasive Bladder Cancer Guidelines Panel Study Consortium on the WHO1973 , WHO2004/2016 Classification Systems for Grade
Surgical Oncology (Urology), Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; Urology, Amsterdam University Medical Centers, Vrije Universiteit, Amsterdam, The Netherlands., Institution of Translational Medicine, Lund University, Malmö, Sweden., Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden., Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; School of Cancer and Pharmaceutical Sciences, King's College London, London, UK., Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Northern Registry Centre, Department of Diagnostics and Intervention, Umeå University, Umeå, Sweden., Department of Urology, Queen Elizabeth University Hospital, Glasgow, UK., Department of Urology, Ninewells Hospital, Dundee, UK., Department of Urology, Victoria Hospital, Kirkcaldy, UK., Edinburgh Bladder Cancer Surgery, Department of Urology, Western General Hospital, Edinburgh, UK., Edinburgh Bladder Cancer Surgery, Department of Urology, Western General Hospital, Edinburgh, UK; Department of Urology, University Hospital Ayr, Ayr, UK., Department of Urology, Queen Elizabeth University Hospital, Glasgow, UK; School of Cancer Sciences, University of Glasgow, Glasgow, UK., 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, 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, 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, Città della Salute e della Scienza, University of Torino School of Medicine, Torino, Italy., European Association of Urology, Guidelines Office Board, Arnhem, The Netherlands., 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; 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., Edinburgh Bladder Cancer Surgery, Department of Urology, Western General Hospital, Edinburgh, UK; European Association of Urology, Non-Muscle Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; University of Edinburgh, Edinburgh, UK. Electronic address: ., Institution of Translational Medicine, Lund University, Malmö, Sweden; European Association of Urology, Non-Muscle Invasive Bladder Cancer Guidelines Panel, Arnhem, The Netherlands; Department of Urology, Skåne University Hospital, Malmö, Sweden. Electronic address: ., Surgical Oncology (Urology), Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; 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; Surgical Oncology (Urology), University Health Network, Princess Margaret Cancer Center, University of Toronto, Toronto, Canada. Electronic address: .