The Importance of Being Grade 3: A Plea for a Three-tier Hybrid Classification System for Grade in Primary Non–muscle-invasive Bladder Cancer

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.

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Publication Details

Journal
European Urology
Published
2024-08-29
DOI
https://doi.org/10.1016/j.eururo.2024.08.013
Citations
9
Primary Topic
Bladder and Urothelial Cancer Treatments
Type
article
Field-Weighted Citation Impact
5.15

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article

The Importance of Being Grade 3: A Plea for a Three-tier Hybrid Classification System for Grade in Primary Non–muscle-invasive Bladder Cancer

Matthew Trail, María J. Ribal, Lars Holmberg, Luisa Padovani et al.
9 citations
European Urology
Bladder and Urothelial Cancer Treatments
5.15
article

The Importance of Being Grade 3: A Plea for a Three-tier Hybrid Classification System for Grade in Primary Non–muscle-invasive Bladder Cancer

Matthew Trail, María J. Ribal, Lars Holmberg, Luisa Padovani, Richard Sylvester, Irene Beijert, David Hendry, Paramananthan Mariappan, Truls Gårdmark, Fredrik Liedberg, Paolo Gontero, Oskar Hagberg, Theodorus van der Kwast, Éva Compérat, Morgan Rouprêt, Christel Häggström, Imran Ahmad, Roberta Garau, Rami Hasan, Allan Johnston, Sami Hamid, Marko Babjuk, Maximilian Burger, Bas W.G. van Rhijn, B. Dreyer
article en
9 citations

Abstract

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 UrologyVol. 86(5)
Uppsala University (SE), University Health Network (CA), University of Toronto (CA), Lund University (SE), Western General Hospital (GB), University Hospital Ayr (GB), European Association of Urology (NL), Vienna General Hospital (AT), Ninewells Hospital (GB), Edinburgh Cancer Research (GB), Princess Margaret Cancer Centre (CA), Karolinska Institutet (SE), Sorbonne Université (FR), Assistance Publique – Hôpitaux de Paris (FR), Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (NL), Victoria Hospital (GB), Queen Elizabeth University Hospital (GB), Onco-Urologie Prédictive (FR), Umeå University (SE)
Univerzita Karlova v Praze, Swedish Movement Disorder Society, Scottish Government, Bladder Cancer Canada, Swedish Council of America, Amsterdam University Medical Centers, King's College London, University of Glasgow, Radboud Universiteit, European Association of Urology, Lunds Universitet, Linköpings Universitet, Karolinska Institutet, Umeå Universitet, Universität Regensburg, Sahlgrenska Universitetssjukhuset, Göteborgs Universitet, Radboud Universitair Medisch Centrum, Uppsala Universitet, Karl-Franzens-Universität Graz, Medizinische Universität Graz, Skånes universitetssjukhus, Universitat Autònoma de Barcelona, Sorbonne Université, Sahlgrenska Akademin, Faculty of Medicine and Health, University of Sydney
Zero hunger
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Bladder and Urothelial Cancer Treatments
5.15
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