Survival impact of variant histology in patients with upper tract urothelial carcinoma after radical nephroureterectomy

•Variant histology is associated with aggressive clinicopathological features.•Variant histology is associated with inferior survival outcomes.•Variant histology is not a risk factor for poor outcomes in localized patients (pT≤2).•Adenocarcinoma differentiation is not a risk factor for poor outcomes.•Regional squamous cell differentiation is not a risk factor for poor outcomes. To investigate the prognostic impact of variant histology (VH) on survival outcomes in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). Data from 635 UTUC patients who underwent RNU at our institution from May 2003 to June 2019 were retrospectively acquired and analyzed. After propensity score matching (PSM), we investigated the impact of VH on overall survival (OS) and cancer-specific survival (CSS) by using cumulative incidence plots with the log-rank test, Cox regression models, and competing risk regression models. Overall, 121 (19.1%) patients were diagnosed with VH, including 68 (10.7%) with squamous cell differentiation (SCD) and 28 (4.4%) with adenocarcinoma differentiation (AD). After PSM, the presence of VH was significantly associated with worse OS (HR 1.70, 95% CI 1.25–2.32) and CSS (HR 1.64, 95% CI 1.17–2.31) only in locally advanced UTUC patients (pT>2). In the subgroup analysis, SCD revealed inferior outcomes (OS: HR 1.81, 95% CI 1.28–2.57; CSS: HR 1.73, 95% CI 1.18–2.54) compared with pure urothelial carcinoma (pUC), whereas AD conferred comparable outcomes. In addition, compared with pUC patients, SCD patients with extensive squamous components had significantly decreased OS (HR 4.17, 95% CI 1.84–9.44) and CSS (HR 1.10, 95% CI 0.61–1.99), whereas those with regional squamous components had similar survival outcomes. For UTUC patients after RNU, the presence of VH is associated with aggressive clinicopathological features and inferior survival outcomes. However, the survival outcomes of localized UTUC patients (pT≤2) with VH, and patients with the AD or regional SCD subtype are comparable to those of patients with pUC.