Purpose: To determine the prognostic effect of upper tract urothelial carcinoma (UTUC) with variant histology (VH) after radical nephroureterectomy (RNU). Patients and Methods: The data of 1173 patients who received RNU for UTUC without neoadjuvant chemotherapy in 11 institutions between 2002 and 2016 were retrospectively reviewed. A matched propensity score analysis was performed. Clinicopathologic variables, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were compared between patients with pure UTUC and patients with UTUC and VH. Univariate and multivariate Cox proportional regression models were used to determine the independent variables associated with oncologic outcomes. Results: UTUC with VH was observed in 93 patients (7.9%). After propensity score matching, UTUC with VH showed no difference in clinicopathologic features compared to pure UTUC; however, it was associated with shorter RFS, CSS, and OS (log rank, P =.011, P =.002, P =.006, respectively). Additionally, the multivariate analysis revealed that VH was independently associated with a poor RFS [hazard ratio (HR) = 1.92; 95% confidence interval (CI), 1.27-2.89; P =.002], CSS (HR = 4.47; 95% CI, 1.99-10.1; P =.001), and OS (HR = 3.00; 95% CI, 1.55-5.78; P =.001). However, the Kaplan-Meier method revealed that differences in RFS, CSS, and OS were not significant in patients who received adjuvant chemotherapy (log rank, P =.562, P =.060, P =.153, respectively). Conclusion: UTUC with VH was independently associated with poor oncologic outcomes in patients with UTUC after RNU. Although patients with UTUC and VH had a poor prognosis compared to patients with pure UTUC, adjuvant chemotherapy would be helpful in improving the survival rates of these patients. Because of its rarity, reports focusing on patients with upper tract urothelial carcinoma (UTUC) and variant histology (VH) are limited. The current study results suggest that VH is an independent prognostic factor associated with recurrence-free survival, cancer-specific survival, and overall survival in patients with UTUC after radical nephroureterectomy. Although patients with UTUC and VH had a poor prognosis compared to those with pure UTUC, the results suggest that adjuvant chemotherapy could improve oncologic outcomes in these patients.
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