Trends in the Diagnoses of Subtype Histologies in Bladder Cancer - Expert Commentary
The study included 28,160 patients with muscle-invasive bladder cancer who underwent cystectomy. Patients were stratified by confirmed cancer histology type, and researchers performed Spearman's rank-order correlation to assess temporal trends in proportions diagnosed with each histology category. The analysis period was divided into seven 3-year intervals with aggregated data to improve the precision of proportion estimates. Multivariable logistic regression was conducted to adjust for covariates, including TNM staging, sex, race, age at cystectomy, and prior cancer diagnosis.
In unadjusted analysis, the proportion of patients diagnosed with SCC decreased significantly over time from 5.8% in 2000-2002 to 3.7% in 2018-2020 (r = -0.86, P = 0.02). Conversely, the proportion diagnosed with other histological subtypes increased significantly from 2.0% to 5.2% (r = 1.00, P = 0.001). Temporal trends for AC and NC were not significant in univariate analysis. After adjusting for covariates, later year of diagnosis was associated with significantly increased odds of NC diagnosis (OR 1.07, 95% CI 1.03-1.12, P = 0.001) and other histological subtype diagnoses (OR 1.16, 95% CI 1.13-1.20, P < 0.001). SCC and other subtype histologies were associated with increased odds of ≥T3, >N1, and >M0 disease, while AC was associated with increased odds of ≥T3 and >M0 disease.
The increasing detection of variant histological subtypes over time likely reflects improved awareness among pathologists and enhanced diagnostic techniques. This trend corresponds with advances in World Health Organization pathology classification guidelines that occurred during the study period, which introduced expanded criteria for identifying divergent and subtype histologies through improved immunohistochemical and molecular techniques. The study's limitations include its retrospective design, coding inconsistencies in the SEER database, and inability to differentiate between pure subtypes and urothelial carcinoma with divergent differentiation due to database limitations. While our understanding of the molecular biology of these Subtypes has evolved over the past few years, significant work remains to be done to understand the colonial relationships between different subtypes within the same tumor or the pathways by which cancer cells transdifferentiate into these subtypes.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York
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