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

Beijert, Irene J. ; Hagberg, Oskar LU ; Gårdmark, Truls ; Holmberg, Lars ; Häggström, Christel ; Johnston, Allan ; Trail, Matthew ; Hamid, Sami ; Dreyer, Barend A. and Padovani, Luisa , et al. (2024) In European Urology 86(5). p.391-399
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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Bladder, Cancer, Grading, Hybrid grade, World Health Organization 1973, World Health Organization 1999, World Health Organization 2004, World Health Organization 2016
in
European Urology
volume
86
issue
5
pages
9 pages
publisher
Elsevier
external identifiers
  • pmid:39209674
  • scopus:85202964808
ISSN
0302-2838
DOI
10.1016/j.eururo.2024.08.013
language
English
LU publication?
yes
id
1a29171b-5ae3-4b10-89f1-2321359a993d
date added to LUP
2024-12-16 10:24:07
date last changed
2025-07-01 02:16:44
@article{1a29171b-5ae3-4b10-89f1-2321359a993d,
  abstract     = {{<p>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 &lt; 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.</p>}},
  author       = {{Beijert, Irene J. and Hagberg, Oskar and Gårdmark, Truls and Holmberg, Lars and Häggström, Christel and Johnston, Allan and Trail, Matthew and Hamid, Sami and Dreyer, Barend A. and Padovani, Luisa and Garau, Roberta and Hasan, Rami and Ahmad, Imran and Hendry, David and Compérat, Eva M. and Burger, Maximilian and Rouprêt, Morgan and Gontero, Paolo and Ribal, Maria J. and van der Kwast, Theo H. and Babjuk, Marko and Sylvester, Richard J. and Mariappan, Paramananthan and Liedberg, Fredrik and van Rhijn, Bas W.G.}},
  issn         = {{0302-2838}},
  keywords     = {{Bladder; Cancer; Grading; Hybrid grade; World Health Organization 1973; World Health Organization 1999; World Health Organization 2004; World Health Organization 2016}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{391--399}},
  publisher    = {{Elsevier}},
  series       = {{European Urology}},
  title        = {{The Importance of Being Grade 3 : A Plea for a Three-tier Hybrid Classification System for Grade in Primary Non–muscle-invasive Bladder Cancer}},
  url          = {{http://dx.doi.org/10.1016/j.eururo.2024.08.013}},
  doi          = {{10.1016/j.eururo.2024.08.013}},
  volume       = {{86}},
  year         = {{2024}},
}