The Importance of Being Grade 3: A Plea for a Three-tier Hybrid Classification System for Grade in Primary Non-muscle-invasive Bladder Cancer.
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Beijert Irene J, Hagberg Oskar, Gårdmark Truls, Holmberg Lars, Häggström Christel, Johnston Allan, Trail Matthew, Hamid Sami, Dreyer Barend A, Padovani Luisa, Garau Roberta, Hasan Rami, Ahmad Imran, Hendry David, Compérat Eva M, Burger Maximilian, Rouprêt Morgan, Gontero Paolo, Ribal Maria J, van der Kwast Theo H, Babjuk Marko, Sylvester Richard J, Mariappan Paramananthan, Liedberg Fredrik, van Rhijn Bas W G, 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
Аннотация
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.