OBJECTIVES: To identify correlates of survival and perioperative outcomes of upper tract urothelial carcinoma (UTUC) patients undergoing open (ORNU), laparoscopic (LRNU), and robotic (RRNU) radical nephroureterectomy (RNU). METHODS: We conducted a retrospective, multicenter study that included non-metastatic UTUC patients who underwent RNU between 1990-2020. Multiple imputation by chained equations was used to impute missing data. Patients were divided into three groups based on their surgical treatment and were adjusted by 1:1:1 propensity score matching (PSM). Survival outcomes per group were estimated for recurrence-free survival (RFS), bladder recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS). Perioperative outcomes: Intraoperative blood loss, hospital length of stay (LOS), and overall (OPC) and major postoperative complications (MPCs; defined as Clavien-Dindo > 3) were assessed between groups. RESULTS: Of the 2434 patients included, 756 remained after PSM with 252 in each group. The three groups had similar baseline clinicopathological characteristics. The median follow-up was 32 months. Kaplan-Meier and log-rank tests demonstrated similar RFS, CSS, and OS between groups. BRFS was found to be superior with ORNU. Using multivariable regression analyses, LRNU and RRNU were independently associated with worse BRFS (HR 1.66, 95% CI 1.22-2.28, p = 0.001 and HR 1.73, 95%CI 1.22-2.47, p = 0.002, respectively). LRNU and RRNU were associated with a significantly shorter LOS (beta -1.1, 95% CI -2.2-0.02, p = 0.047 and beta -6.1, 95% CI -7.2-5.0, p < 0.001, respectively) and fewer MPCs (OR 0.5, 95% CI 0.31-0.79, p = 0.003 and OR 0.27, 95% CI 0.16-0.46, p < 0.001, respectively). CONCLUSIONS: In this large international cohort, we demonstrated similar RFS, CSS, and OS among ORNU, LRNU, and RRNU. However, LRNU and RRNU were associated with significantly worse BRFS, but a shorter LOS and fewer MPCs.

Department of Urology 2nd Faculty of Medicine Charles University 150 06 Prague Czech Republic

Department of Urology Azienda Ospedaliera Universitaria Integrata of Verona University of Verona 37126 Verona Italy

Department of Urology Comprehensive Cancer Center Medical University of Vienna 1090 Vienna Austria

Department of Urology Erasmus MC Cancer Institute University Medical Center 3015 GD Rotterdam The Netherlands

Department of Urology Icahn School of Medicine at Mount Sinai New York NY 10029 USA

Department of Urology Kindai University Faculty of Medicine Osaka 589 8511 Japan

Department of Urology Lions Gate Hospital North Vancouver BC V7L 2L7 Canada

Department of Urology Luzerner Kantonsspital 6004 Lucerne Switzerland

Department of Urology Mayo Clinic Rochester MN 55902 USA

Department of Urology Medical University of Silesia 40 752 Katowice Poland

Department of Urology Paracelsus Medical University Salzburg University Hospital Salzburg 5020 Salzburg Austria

Department of Urology Penn State Health Hershey PA 17033 USA

Department of Urology St Marianna University School of Medicine Kawasaki 214 8525 Japan

Department of Urology The James Buchanan Brady Urological Institute The Johns Hopkins University School of Medicine Baltimore MD 21231 USA

Department of Urology University Hospital Zurich 8091 Zurich Switzerland

Department of Urology University Medical Center Hamburg Eppendorf 20251 Hamburg Germany

Department of Urology University of Florence Careggi Hospital 50100 Florence Italy

Department of Urology University of Rennes 35000 Rennes France

Department of Urology University of Texas Southwestern Dallas TX 75390 USA

Department of Urology Uro Oncology Robot Assisted and Specialized Urologic Surgery University Hospital Cologne 50937 Cologne Germany

Department of Urology UROSUD La Croix Du Sud Hospital 31130 Quint Fonsegrives France

Department of Urology USC Norris Comprehensive Cancer Center University of Southern California Los Angeles CA 90033 USA

Department of Urology Weill Cornell Medical College New York NY 10065 USA

Division of Urology Department of Surgical Sciences San Giovanni Battista Hospital University of Studies of Torino 10124 Turin Italy

Hourani Center for Applied Scientific Research Al Ahliyya Amman University Amman 19328 Jordan

Institute for Urology and Reproductive Health Sechenov University 119991 Moscow Russia

Karl Landsteiner Institute of Urology and Andrology 1090 Vienna Austria

Urology Department Fundació Puigvert Autonomous University of Barcelona 08025 Barcelona Spain

Urology Department GRC n°5 Predictive Onco Uro AP HP Pitié Salpêtrière Hospital Sorbonne University 75013 Paris France

USC Institute of Urology Keck Medicine of USC University of Southern California Los Angeles CA 90007 USA

Vattikuti Urology Institute Henry Ford Hospital Detroit MI 48202 USA

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