PURPOSE: To evaluate stage at presentation and cancer-specific mortality (CSM) in upper urinary tract tumors according to histologic subtype. METHODS: Within the Surveillance, Epidemiology, and End Results registry (SEER, 2004-2016), we identified patients with upper urinary tract tumors with pure variant histology (UTVH) and pure upper urinary tract urothelial carcinoma (UTUC). Cumulative incidence plots, after propensity score matching for tumor and patient characteristics, addressed CSM. Subgroup analyses addressed efficacy of radical nephroureterectomy (RNU) in stage T1-2 and of chemotherapy in metastatic UTVH patients. RESULTS: Of all 11,809 upper urinary tract tumor patients, 154 (1.3%) harbored squamous cell carcinoma (SCC), 86 (0.7%) adenocarcinoma, 39 (0.3%) neuroendocrine carcinoma, 38 (0.3%) other UTVH, and 11,492 (97.3%) UTUC. UTVH patients were more likely to exhibit metastatic stage disease at diagnosis than UTUC (odds ratio, 1.9; 95% confidence interval, 1.3-2.8; P < .01). After detailed matching for performance status, only SCC showed significantly higher CSM than UTUC (multivariate HR = 1.71; P < .01). Subgroup analyses in stage T1-2 RNU patients showed, relative to UTUC patients, no CSM differences for SCC or adenocarcinoma patients. No significant survival benefit for chemotherapy administration was identified in patients with metastatic SCC or metastatic adenocarcinoma. This study is limited by its sample size and the missing centralized pathologic review. CONCLUSIONS: Disease stage at diagnosis is more advanced in UTVH patients than UTUC. Across all stages, CSM is higher for SCC than for UTUC. However, in T1-2 stage disease, RNU results in similar survival in SCC or adenocarcinoma versus UTUC.
