Proposal for a Novel Histological Scoring System as a Potential Grading Approach for Muscle-invasive Urothelial Bladder Cancer Correlating with Disease Aggressiveness and Patient Outcomes.

Eckstein M, Matek C, Wagner P, Erber R, Büttner-Herold M, Wild PJ, Taubert H, Wach S, Sikic D, Wullich B, Geppert CI, Compérat EM, Lopez-Beltran A, Montironi R, Cheng L, van der Kwast T, Colecchia M, van Rhijn BWG, Amin MB, Netto GJ, Lehmann J, Stöckle M, Junker K, Hartmann A, Bertz S (2024)

Publication Language: English

Publication Type: Journal article

Publication year: 2024

Journal

Book Volume: 7

Pages Range: 128-138

Journal Issue: 1

DOI: 10.1016/j.euo.2023.07.011

Abstract

BACKGROUND: Grading of muscle-invasive bladder cancer (MIBC) according to the current World Health Organization (WHO) criteria is controversial due to its limited prognostic value. All MIBC cases except a tiny minority are of high grade. OBJECTIVE: To develop a prognostic histological scoring system for MIBC integrating histomorphological phenotype, stromal tumor-infiltrating lymphocytes (sTILs), tumor budding, and growth and spreading patterns. DESIGN, SETTING, AND PARTICIPANTS: Tissue specimens and clinical data of 484 patients receiving cystectomy and lymphadenectomy with curative intent with or without adjuvant chemotherapy. Histomorphological phenotypes, sTILs, tumor budding, and growth and spreading patterns were evaluated and categorized into four grade groups (GGs). GGs were correlated with molecular subtypes, immune infiltration, immune checkpoint expression, extracellular matrix (ECM) remodeling, and epithelial-mesenchymal transition (EMT) activity. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: GGs were associated with overall (OS), disease-specific (DSS), and progression-free (PFS) survival in univariable and multivariable analyses. Association with biological features was analyzed with descriptive statistics. RESULTS AND LIMITATIONS: Integration of two histomorphological tumor groups, three sTILs groups, three tumor budding groups, and four growth/spread patterns yielded four novel GGs that had high significance in the univariable survival analysis (OS, DSS, and PFS). GGs were confirmed as independent prognostic predictors with the greatest effect in the multivariable Cox regression analysis. Correlation with molecular data showed a gradual transition from basal to luminal subtypes from GG1 to GG4; a gradual decrease in survival, immune infiltration, and immune checkpoint activity; and a gradual increase in ECM remodeling and EMT activity. CONCLUSIONS: We propose a novel, prognostically relevant, and biologically based scoring system for MIBC in cystectomies applicable to routine pathological sections. PATIENT SUMMARY: We developed a novel approach to assess the aggressiveness of advanced bladder cancer, which allows improved risk stratification compared with the method currently proposed by the World Health Organization.

Authors with CRIS profile

Additional Organisation(s)

Related research project(s)

Involved external institutions

Brown University United States (USA) (US) Universitätsklinikum des Saarlandes (UKS) Germany (DE) Städtisches Krankenhaus Kiel Germany (DE) Medizinische Universität Wien Austria (AT) Università Politecnica delle Marche (UNIVPM) / Marche Polytechnic University Italy (IT) The University of Tennessee Health Science Center United States (USA) (US) University of Alabama at Birmingham (UAB) United States (USA) (US) Princess Margaret Cancer Centre / Princess Margaret Hospital Canada (CA) Universitätsklinikum Frankfurt am Main (KGU) Germany (DE) Università Vita-Salute San Raffaele (UniSR) Italy (IT) University of Cordoba / Universidad de Córdoba (UCO) Spain (ES) Universität Regensburg Germany (DE)

How to cite

APA:

Eckstein, M., Matek, C., Wagner, P., Erber, R., Büttner-Herold, M., Wild, P.J.,... Bertz, S. (2024). Proposal for a Novel Histological Scoring System as a Potential Grading Approach for Muscle-invasive Urothelial Bladder Cancer Correlating with Disease Aggressiveness and Patient Outcomes. European Urology Oncology, 7(1), 128-138. https://doi.org/10.1016/j.euo.2023.07.011

MLA:

Eckstein, Markus, et al. "Proposal for a Novel Histological Scoring System as a Potential Grading Approach for Muscle-invasive Urothelial Bladder Cancer Correlating with Disease Aggressiveness and Patient Outcomes." European Urology Oncology 7.1 (2024): 128-138.

BibTeX: Download