Introduction:

The diagnosis of variant histology bladder cancer (VBC) carries significant clinical implications, yet can represent a diagnostic challenge for pathologists. Our objective was to characterize the trends in VBC diagnosis over time, subtype, and facility type within a national retrospective cohort.  

Methods:

The National Cancer Database was queried for all cases of pure urothelial and VBC using International Classification of Disease-O-3 morphologic codes from 2004-2021. The diagnosis of each type of VBC was trended from 2004-2021 to identify significant differences. This was performed in total and across varying facility types with multivariable regression demonstrating significant associations with VBC diagnosis.

Results:

Between 2004 and 2021, 753,880 patients with pure urothelial carcinoma (UC) and 30,884 patients with VBC were identified. The diagnosis of VBC across all bladder cancer cases increased from 3.5% of cases in 2004-2009 (first tertile) to 4.3% of cases in 2016-2021 (third tertile) [p<0.001]. This increase in VBC diagnosis was concentrated in micropapillary, sarcomatoid, and neuroendocrine carcinoma subtypes (p<0.001). Squamous differentiation did not demonstrate a significant change in diagnosis across time (p=0.20). VBC diagnosis was increased across all facility types, including both community cancer facilities (3.0% of cases in 2004-2009 to 3.7% of cases in 2016-2021) and academic research facilities (4.4% of cases in 2004-2009 to 7.4% of cases in 2016-2021), with academic and comprehensive cancer centers experiencing the most increase.

Conclusion:

Our findings suggest that the diagnosis of VBC is increasing nationally. The increase in diagnosis is among micropapillary, sarcomatoid, and neuroendocrine subtypes, and mostly among academic and comprehensive cancer centers, reflecting the need for specialized pathologic review.

Funding: N/A