INTRODUCTION & OBJECTIVES: It is currently recommended to perform open radical nephroureterectomy (oRNU) with bladder cuff excision in patients with locally advanced (cT3-4 or cN1-2) upper tract urothelial carcinoma (laUTUC). We tested the hypothesis that bladder recurrence-free survival (BRFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) are not influenced by the surgical approach in patients with laUTUC using a large multicenter series. MATERIAL & METHODS: This was a multicenter retrospective cohort study including 361 patients with preoperative cT3-4 cM0 or cN1-2 cM0 laUTUC treated with open or minimally invasive RNU from 1999 to 2019 at 21 academic centers in Europe, Asia, and the United States. Missing values of relevant baseline characteristics were estimated through multiple imputation of chained equations. Baseline patients' heterogeneity was balanced using a 1:1 propensity score matching estimated using logistic regression. Uni- and multivariable Cox regression analyses for bladder recurrence, metastasis, cancer-specific death and overall death were performed according to clinical and pathological characteristics. Kaplan Meier (KM) estimates and log-rank test were used to compare BRFS, MFS, CSS and OS according to clinical and pathological features. RESULTS: Median follow-up was 28 months. After propensity score matching, two cohorts of 115 laUTUC patients each with similar baseline and preoperative tumor characteristics were obtained. In the matched cohort, pT ≥ 3 stage was found in 84 (73%) and 67 (58.3%) patients in the oRNU and miRNU groups, respectively. Positive lymph nodes were detected in 27 (23.5%) and 32 (27.8%) patients in the oRNU and miRNU groups, respectively. In the multivariable regression analysis, pT ≥ 3 and positive lymph nodes were associated with an increased risk of metastasis (HR 3.22, 95% CI 1.26-8.23, and HR 4.03, 95% CI 2.05-7.89, respectively). The surgical approach (oRNU vs. mi RNU) did not influence oncological outcomes as shown by uni- and multivariable analyses as well as Kaplan-Meier estimates, regardless of pT stage. CONCLUSIONS: The oncological outcomes of laUTUC for cT3-4 cM0 or cN1-2 cM0 disease are comparable whether RNU is performed via an open or minimally invasive approach. Therefore, the decision to opt for oRNU or miRNU should be guided by the surgeon's expertise and the patient's comorbidities, rather than concerns over long-term oncological outcomes associated with either surgical technique.

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

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

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

Department of Urology Fundació Puigvert Barcelona Spain

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

Department of Urology Kantonsspital Aarau Aarau Switzerland

Department of Urology Kindai University Faculty of Medicine Osaka Japan

Department of Urology Lions Gate Hospital North Vancouver BC Canada

Department of Urology Luzerner Kantonsspital Lucerne Switzerland

Department of Urology Mayo Clinic Rochester MN USA

Department of Urology Penn State Health Hershey PA USA

Department of Urology San Raffaele Hospital and Scientific Institute Milan Italy

Department of Urology St Marianna University School of Medicine Kawasaki Kanagawa Japan

Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology University of Florence Careggi Hospital Florence Italy

Department of Urology University of Rennes Rennes France

Department of Urology University of Texas Southwestern Dallas TX USA

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

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

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

Department of Urology Weill Cornell Medical College New York NY USA

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

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

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

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

Sorbonne University AP HP Pitie Salpetriere Hospital GRC 5 Predictive Onco Uro Urology PARIS F 75013 France

Vattikuti Urology Institute Henry Ford Hospital Detroit MI USA

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