Contemporary Grading and Staging of Urothelial Neoplasms of the Urinary Bladder: New Concepts and Approaches to Challenging Scenarios

Urothelial carcinoma of the bladder is one of the most common cancer types in the United States, and optimal patient management relies on accurate grading and staging of the tumor. Contemporary grading and staging of urothelial neoplasms is now performed in accordance with updates and recommendations provided by the recently published 4th edition of the World Health Organization (WHO) classification and the 8th edition of the American Joint Committee on Cancer (AJCC) TNM Cancer Staging Manual (8E AJCC).

The new WHO classification primarily offers refinements to the grading of noninvasive urothelial neoplasms. In particular, it now recognizes urothelial (low-grade) dysplasia as a flat lesion morphologically analogous to the cytologic features of non-invasive low grade papillary urothelial carcinoma. Additionally, the term “urothelial proliferation of unknown malignant potential” now replaces “urothelial hyperplasia” for cystoscopically-evident lesions demonstrating an undulating surface of thickened urothelium without cytologic atypia, and lacking true papillae. Recent evidence supports a clonal origin for these lesions, which may represent the shoulder of a previously resected papillary neoplasm.

A challenging situation arises when separate fragments of flat high-grade urothelial carcinoma are identified in the same specimen as high grade papillary urothelial carcinoma (HG PUC), which could represent a detached “shoulder” of HG PUC or a concurrent focus of urothelial carcinoma in situ (CIS). This becomes an important distinction because concurrent CIS in the setting of HG PUC is a high-risk feature and may influence management. To minimize this potential obstacle, urologists should consider submitting distinct transurethral resections (TURs) or biopsies with nonpapillary lesions in separate containers, so that each lesion can be evaluated independently and the presence of concurrent CIS can be recognized with more fidelity.

Staging in accordance with the 8E AJCC has seen multiple updates and recommendations. Due to the high rate of upstaging of pT1 tumors on TUR to pT2 tumors on cystectomy, the importance of pT1 subcategorization on TUR is now recognized. Although a preferred approach has not been standardized, the most promising strategy is by micrometric approach (microinvasive vs. extensive pT1). In other changes, staging of bladder diverticular tumors now skips pT2 staging and proceeds from pT1 (lamina propria invasion) to pT3 (perivesical soft tissue invasion), given the absence of a muscularis propria layer in these acquired diverticula. The updated guidelines also clarify staging of prostatic involvement by urothelial carcinoma based on the mechanism of spread. An intraurethral spread of urothelial carcinoma with subsequent prostatic stromal invasion is now staged as pT2 by urethral cancer staging and is associated with lower rates of lymph node metastases and higher overall survival in comparison to direct transmural spread of urothelial carcinoma to the prostate (pT4). Nodal (pN) staging now considers perivesical lymph nodes (LNs) to be regional, and therefore involvement of a single perivesicle LN is currently considered pN1. Metastatic (pM) staging has also been revised to distinguish nonregional LN metastases (pM1a) from the more aggressive distant non-nodal metastases (pM1b).

Refinement of tumor grading and staging is a dynamic process that reflects the constant and tireless advancement of knowledge within the field. The contemporary grading and staging of urothelial neoplasms of the bladder harness the most recent evidence-based advances in our knowledge to optimize patient management and improve clinical outcomes.

Written by: Alexander J. Gallan, MD¹, and Gladell P. Paner, MD²
1. Department of Pathology, University of Chicago, Chicago, Illinois
2. Department of Surgery, Section of Urology, University of Chicago, Chicago, Illinois

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