Prognostic impact of variant histologies in urothelial bladder cancer treated with radical cystectomy

Abstract

ObjectivesTo evaluate variant histologies (VHs) for disease‐specific survival (DSS) in patients with invasive urothelial bladder cancer (BCa) undergoing radical cystectomy (RC).Materials and MethodsWe analysed a multi‐institutional cohort of 1082 patients treated with upfront RC for cT1‐4aN0M0 urothelial BCa at eight centres. Univariable and multivariable Cox’ regression analyses were used to assess the effect of different VHs on DSS in overall cohort and three stage‐based analyses. The stages were defined as ‘organ‐confined’ (≤pT2N0), ‘locally advanced’ (pT3‐4N0) and ‘node‐positive’ (pTanyN1‐3).ResultsOverall, 784 patients (72.5%) had pure urothelial carcinoma (UC), while the remaining 298 (27.5%) harboured a VH. Squamous differentiation was the most common VH, observed in 166 patients (15.3%), followed by micropapillary (40 patients [3.7%]), sarcomatoid (29 patients [2.7%]), glandular (18 patients [1.7%]), lymphoepithelioma‐like (14 patients [1.3%]), small‐cell (13 patients [1.2%]), clear‐cell (eight patients [0.7%]), nested (seven patients [0.6%]) and plasmacytoid VH (three patients [0.3%]). The median follow‐up was 2.3 years. Overall, 534 (49.4%) disease‐related deaths occurred. In uni‐ and multivariable analyses, plasmacytoid and small‐cell VHs were associated with worse DSS in the overall cohort (both P = 0.04). In univariable analyses, sarcomatoid VH was significantly associated with worse DSS, while lymphoepithelioma‐like VH had favourable DSS compared to pure UC. Clear‐cell (P = 0.015) and small‐cell (P = 0.011) VH were associated with worse DSS in the organ‐confined and node‐positive cohorts, respectively.ConclusionsMore than 25% of patients harboured a VH at time of RC. Compared to pure UC, clear‐cell, plasmacytoid, small‐cell and sarcomatoid VHs were associated with worse DSS, while lymphoepithelioma‐like VH was characterized by a DSS benefit. Accurate pathological diagnosis of VHs may ensure tailored counselling to identify patients who require more intensive management.