Is histological grade a useful parameter in muscle-invasive urothelial bladder cancer? Results from a multicenter study on the impact of different grading systems on disease-free survival after upfront radical cystectomy

The prognostic value of histopathological grade in muscle-invasive urothelial carcinoma (MIBC) to predict disease-specific survival (DSS) is understudied. While grading systems like WHO1973 and WHO2004 are established in non-muscle-invasive bladder cancer (NMIBC), their relevance in MIBC remains controversial. This study assessed the prognostic impact of histopathological grade on DSS in a multicenter cohort. We included 1,123 cN0M0 MIBC patients treated with upfront radical cystectomy (1987–2020) at nine centers. Tumors were graded using WHO1973 (G1 + G2 combined as G1/2 due to low numbers vs. G3), WHO2004 (low-grade [LG] vs. high-grade [HG]), and a hybrid three-tier system. Slides were locally reviewed by uro-pathologists. DSS was analyzed using Kaplan-Meier and Cox models, adjusting for age, stage, lympho-vascular invasion, surgical margins, lymph-node status, adjuvant chemotherapy, treatment center, and era of cystectomy. Among all cases, 74 (6.6%) were G1/2 and 1,049 (93.4%) G3; 27 (2.4%) were LG and 1,096 (97.6%) HG. Median follow-up was 5.3 years (IQR 2.9–8.5). Univariable analyses showed significantly better DSS for LG and G1/2 tumors across grading systems. However, multivariable models showed no independent association between grade and DSS. Although LG and G1/2 MIBC tumors demonstrated superior DSS in univariable analyses, the lack of independent prognostic significance in multivariable models questions the relevance of histopathological grade in MIBC. Further studies should explore the clinical utility of grade, define new grading schemes including features of epithelial-mesenchymal transition or tumor microenvironment, and explore alternative prognostic (bio)markers.

Authors

Institutions

Publication Details

Journal
World Journal of Urology
Published
2025-11-20
DOI
https://doi.org/10.1007/s00345-025-06089-z
Primary Topic
Bladder and Urothelial Cancer Treatments
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Is histological grade a useful parameter in muscle-invasive urothelial bladder cancer? Results from a multicenter study on the impact of different grading systems on disease-free survival after upfront radical cystectomy

Laura S. Mertens, Alexandre R. Zlotta, Y. Neuzillet, Tahlita C.M. Zuiverloon et al.
World Journal of Urology
Bladder and Urothelial Cancer Treatments
article

Is histological grade a useful parameter in muscle-invasive urothelial bladder cancer? Results from a multicenter study on the impact of different grading systems on disease-free survival after upfront radical cystectomy

Laura S. Mertens, Alexandre R. Zlotta, Y. Neuzillet, Tahlita C.M. Zuiverloon, B. Wullich, Carlo Trombetta, Yair Lotan, Rossana Bussani, Roman Mayr, Theodorus van der Kwast, Roger Lijnen, Nicola Pavan, Francesco Claps, Damien Pouessel, Bas W.G. van Rhijn, Shahrokh François Shariat, Joost L. Boormans, Geert J.L.H. van Leenders, Markus Eckstein, Peter J. Boström, Arndt Hartmann, Yves Allory, Maximilian Burger, Emily Rinderknecht
article en

Abstract

The prognostic value of histopathological grade in muscle-invasive urothelial carcinoma (MIBC) to predict disease-specific survival (DSS) is understudied. While grading systems like WHO1973 and WHO2004 are established in non-muscle-invasive bladder cancer (NMIBC), their relevance in MIBC remains controversial. This study assessed the prognostic impact of histopathological grade on DSS in a multicenter cohort. We included 1,123 cN0M0 MIBC patients treated with upfront radical cystectomy (1987–2020) at nine centers. Tumors were graded using WHO1973 (G1 + G2 combined as G1/2 due to low numbers vs. G3), WHO2004 (low-grade [LG] vs. high-grade [HG]), and a hybrid three-tier system. Slides were locally reviewed by uro-pathologists. DSS was analyzed using Kaplan-Meier and Cox models, adjusting for age, stage, lympho-vascular invasion, surgical margins, lymph-node status, adjuvant chemotherapy, treatment center, and era of cystectomy. Among all cases, 74 (6.6%) were G1/2 and 1,049 (93.4%) G3; 27 (2.4%) were LG and 1,096 (97.6%) HG. Median follow-up was 5.3 years (IQR 2.9–8.5). Univariable analyses showed significantly better DSS for LG and G1/2 tumors across grading systems. However, multivariable models showed no independent association between grade and DSS. Although LG and G1/2 MIBC tumors demonstrated superior DSS in univariable analyses, the lack of independent prognostic significance in multivariable models questions the relevance of histopathological grade in MIBC. Further studies should explore the clinical utility of grade, define new grading schemes including features of epithelial-mesenchymal transition or tumor microenvironment, and explore alternative prognostic (bio)markers.

World Journal of UrologyVol. 43(1)
Centre National de la Recherche Scientifique (FR), University of Trieste (IT), University of Turku (FI), Sechenov University (RU), University of Augsburg (DE), Friedrich-Alexander-Universität Erlangen-Nürnberg (DE), Université de Versailles Saint-Quentin-en-Yvelines (FR), Cornell University (US), Charles University (CZ), Université Paris Sciences et Lettres (FR), Université Paris-Saclay (FR), Turku University Hospital (FI), University Hospital Augsburg (DE), Princess Margaret Cancer Centre (CA), The Netherlands Cancer Institute (NL), Universitätsklinikum Erlangen (DE), Comprehensive Cancer Center Vienna (AT), Institut universitaire du cancer de Toulouse Oncopole (FR), Institut Claudius Regaud (FR), Erasmus MC Cancer Institute (NL), Hôpital Foch (FR), Caritas-Krankenhaus St. Josef (DE), Biologie cellulaire et Cancer (FR), University of Regensburg (DE), Medical University of Vienna (AT), Institut Curie (FR), The University of Texas Southwestern Medical Center (US), University of Palermo (IT)
Openalex Percentile: Top 46%
Bladder and Urothelial Cancer Treatments
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.