International Society of Urological Pathology Expert Opinion on Grading of Urothelial Carcinoma

Context: Grading is the mainstay for treatment decisions for patients with non–muscle-invasive bladder cancer (NMIBC). Objective: To determine the requirements for an optimal grading system for NMIBC via expert opinion. Evidence acquisition: A multidisciplinary working group established by the International Society of Urological Pathology reviewed available clinical, histopathological, and molecular evidence for an optimal grading system for bladder cancer. Evidence synthesis: Bladder cancer grading is a continuum and five different grading systems based on historical grounds could be envisaged. Splitting of the World Health Organization (WHO) 2004 low-grade class for NMIBC lacks diagnostic reproducibility and molecular-genetic support, while showing little difference in progression rate. Subdividing the clinically heterogeneous WHO 2004 high-grade class for NMIBC into intermediate and high risk categories using the WHO 1973 grading is supported by both clinical and molecular-genetic findings. Grading criteria for the WHO 1973 scheme were detailed on the basis of literature findings and expert opinion. Conclusions: Splitting of the WHO 2004 high-grade category into WHO 1973 grade 2 and 3 subsets is recommended. Provision of more detailed histological criteria for the WHO 1973 grading might facilitate the general acceptance of a hybrid four-tiered grading system or—as a preferred option—a more reproducible three-tiered system distinguishing low-, intermediate (high)-, and high-grade NMIBC. Patient summary: Improvement of the current systems for grading bladder cancer may result in better informed treatment decisions for patients with bladder cancer. A three-tiered grading system for non–muscle invasive bladder cancer derived by splitting the heterogeneous World Health Organization (WHO) 2004 high-grade category into WHO 1973 grade 2 and 3 subsets is recommended, as this may result in more informed treatment decisions