Pure but Not Mixed Histologic Variants Are Associated With Poor Survival at Radical Cystectomy in Bladder Cancer Patients

The importance of a correct histologic variant classification in the decision making of bladder cancer patients have been recently highlighted by the new World Health Organization classification of the urothelial tract. Histologic variants at the time of radical cystectomy is a common finding, accounting for almost 30% of specimens, yet only pure histologic variants but not mixed histologic variants are associated with worse survival compared to pure urothelial cancer. Physicians should consider this parameter when counseling surgical patients. Purpose To evaluate the impact of pure and mixed histologic variant versus pure urothelial carcinoma in nonmetastatic bladder cancer (BCa) patients treated with radical cystectomy (RC). Patients and Methods We evaluated data from 1067 patients treated with RC and pelvic lymph node dissection between 1990 and 2013 at a single institution tertiary-care referral center. All specimens were evaluated by dedicated uropathologists. Univariable and multivariable Cox regression analyses tested the impact of the presence of pure and mixed histologic variants versus pure urothelial on recurrence, cancer-specific mortality, and overall mortality after accounting for all available confounders. Results In total, 201 (19%) and 137 (13%) patients were found with mixed and pure variants at RC, respectively. Mixed preponderant variants were sarcomatoid, lymphoepitelial, squamous, and glandular; small-cell and micropapillary variants were found mostly as pure variants. With a median follow-up of 6.5 years, patients who harbored pure variant were found by multivariable analyses to have lower survival outcomes compared to pure urothelial carcinoma (all P < .01). Conversely, no differences were found between mixed variant versus pure urothelial by multivariable Cox regression analyses predicting recurrence, cancer-specific mortality, and overall mortality (all P > .1). Conclusion The presence of histologic variants at RC is a common finding, accounting for approximately 30% of specimens. In this setting, the presence of a pure variant but not the presence of mixed variant with urothelial carcinoma is related to a detrimental effect on survival outcomes after RC.