Impact of histological variants on oncological outcomes of patients with urothelial carcinoma of the bladder treated with radical cystectomy

Objective To investigate the impact of variant histologies of urothelial carcinoma of the bladder (UCB) on oncologic outcomes after radical cystectomy (RC). Materials and Methods Data from 1984 UCB patients treated by RC without preoperative chemo- or radiotherapy were reviewed for histological differentiation and variants. We analysed the differences between pure UCB and UCB with variant histology, and those between the different histological variants using various stratifications. Results Overall, 488 (24.6%) patients had UCB variants with squamous cell (11.4%) and glandular differentiation (3.8%) being the most common. Histological UCB variants were associated with advanced tumour stage, lymphovascular invasion and lymph node metastasis (all p-values < 0.01) when compared to pure UCB. In univariable analyses, patients with non-squamous UCB variants were at significantly higher risk for disease recurrence and cancer-specific mortality than those with pure UCB patients (p-values = 0.001) and those with squamous cell differentiated UCB (p-values = 0.04); the latter two had the same risk. In multivariable analyses that adjusted for the effects of standard clinicopathologic characteristics, variant UCB histology was not associated with both survival end-points. In patients treated with adjuvant chemotherapy (n = 492) there was no difference in cancer-specific survival between pure UCB, squamous cell differentiated UCB and other histological UCB variants. Conclusions A quarter of UCB patients treated with RC harboured histological UCB variants. Variant UCB histologies were associated with features of biologically aggressive disease. While variant UCB histology was associated with worse outcomes in univariable analyses, this effect did not remain significant in multivariable analyses.