Original Study Survival Effect of Chemotherapy in Metastatic Upper Urinary Tract Urothelial Carcinoma Sebastiano Nazzani, 1,2,3 Felix Preisser, 1,2,4 Elio Mazzone, 1,2,5 Michele Marchioni, 1,2 Marco Bandini, 1,2,5 Zhe Tian, 2 Francesco A. Mistretta, 6 Shahrokh F. Shariat, 7 Denis Soulières, 2 Emanuele Montanari, 8 Pietro Acquati, 3 Alberto Briganti, 5 Luca Carmignani, 3 Pierre I. Karakiewicz 1,2 Abstract Chemotherapy (CHT) might offer a survival benefit in patients with nonsurgically treated metastatic primary upper tract urothelial carcinoma (mUTUC). We tested this hypothesis within 539 patients with mUTUC: 277 (51.4%) underwent CHT. In nonadjusted and fully adjusted Kaplan-Meier analyses, CHT was associated with better overall survival (9 vs. 2 months; P < .001 in both analyses). In multivariable Cox regression models, CHT administration independently predicted lower overall mortality (hazard ratio, 0.31; 95% confidence interval, 0.25-0.39; P < .001). Our analyses suggest a survival benefit of CHT in primary mUTUC. Background: Few data examined the potential survival benefit of chemotherapy (CHT) in the setting of metastatic upper urinary tract urothelial carcinoma (mUTUC). We hypothesized that a survival benefit might be associated with the use of CHT in nonsurgically treated primary mUTUC and tested this hypothesis within a large population-based cohort. Patients and Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2014), we identified 539 patients with nonsurgically treated primary mUTUC. Inverse probability of treatment weighting (IPTW)- adjusted Kaplan-Meier plots, as well as multivariable Cox regression models relying on IPTW and landmark analyses, were used to test the effect of CHT versus no CHT on overall mortality and cancer-specific mortality. Results: Of 539 patients with metastatic UTUC, 277 (51.4%) underwent CHT. In nonadjusted and IPTW-adjusted Kaplan-Meier plots, CHT was associated with better overall survival (9 vs. 2 months; P < .001 in both analyses). In multivariable Cox regression models, CHT administration independently predicted lower overall mortality before IPTW (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.25-0.39; P < .001), as well as after IPTW adjustment (HR, 0.31; 95% CI, 0.25- 0.38; P < .001). Similar results were recorded in landmark analyses (HR, 0.52; 95% CI, 0.38-0.70; P < .001). Finally, virtually the same results were obtained for cancer-specific mortality. Conclusions: Our analyses suggest a survival benefit after CHT in the setting of nonsurgically treated primary mUTUC. Clinical Genitourinary Cancer, Vol. -, No. -, --- ª 2018 Elsevier Inc. All rights reserved. Keywords: Chemotherapy, Inverse probability after treatment weighting, Metastatic, SEER, Upper urinary tract urothelial carcinoma Introduction Upper urinary tract urothelial carcinoma (UTUC) accounts for 5% of all urothelial cancers and for less than 10% of kidney malignancies. 1 Rates of localized UTUC at diagnosis are decreasing, 2 and the presence of metastatic disease represents the most important determinant of overall mortality (OM) and cancer- 1 Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Quebec, Canada 2 Centre de recherche du Centre Hospitalier de l’Université de Montréal (CR-CHUM) and Institut du cancer de Montréal, Montréal, Québec, Canada 3 Academic Department of Urology, IRCCS Policlinico San Donato, University of Milan, Milan, Italy 4 Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany 5 Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy 6 Department of Urology, Istituto Europeo di Oncologia, Milan, Italy 7 Department of Urology, Medical University of Vienna, Vienna, Austria 8 Department of Urology, IRCCS Fondazione Ca’Granda-Ospedale Maggiore Policli- nico University of Milan, Milan, Italy Submitted: Jun 26, 2018; Revised: Sep 8, 2018; Accepted: Sep 21, 2018 Address for correspondence: Sebastiano Nazzani, MD, Academic Urology Department, IRCCS Policlinico San Donato, Università degli Studi di Milano, Milan, Italy E-mail contact: sebastiano.nazzani@yahoo.com 1558-7673/$ - see frontmatter ª 2018 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.clgc.2018.09.017 Clinical Genitourinary Cancer Month 2018 - 1