We aimed to conduct a systematic review and meta-analysis assessing the incidence and risk factors of urethral recurrence (UR) as well as summarizing data on survival outcomes in patients with UR after radical cystectomy (RC) for bladder cancer. The MEDLINE and EMBASE databases were searched in February 2021 for studies of patients with UR after RC. Incidence and risk factors of UR were the primary endpoints. The secondary endpoint was survival outcomes in patients who experienced UR. Twenty-one studies, comprising 9,435 patients, were included in the quantitative synthesis. Orthotopic neobladder (ONB) diversion was associated with a decreased probability of UR compared to non-ONB (pooled OR: 0.44, 95% CI: 0.31-0.61, P < 0.001) and male patients had a significantly higher risk of UR compared to female patients (pooled OR: 3.16, 95% CI: 1.83-5.47, P < 0.001). Among risk factors, prostatic urethral or prostatic stromal involvement (pooled HR: 5.44, 95% CI: 3.58-8.26, P < 0.001; pooled HR: 5.90, 95% CI: 1.82-19.17, P = 0.003, respectively) and tumor multifocality (pooled HR: 2.97, 95% CI: 2.05-4.29, P < 0.001) were associated with worse urethral recurrence-free survival. Neither tumor stage (P = 0.63) nor CIS (P = 0.72) were associated with worse urethral recurrence-free survival. Patients with UR had a 5-year CSS that varied from 47% to 63% and an OS - from 40% to 74%; UR did not appear to be related to worse survival outcomes. Male patients treated with non-ONB diversion as well as patients with prostatic involvement and tumor multifocality seem to be at the highest risk of UR after RC. Risk-adjusted standardized surveillance protocols should be developed into clinical practice after RC.

Department of Urology and Oncologic Urology Wrocław Medical University Wroclaw Poland

Department of Urology Careggi Hospital University of Florence Florence Italy

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

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology Federal Armed Services Hospital Koblenz Koblenz Germany

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology King Fahad Specialist Hospital Dammam Saudi Arabia

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology Luzerner Kantonsspital Lucerne Switzerland; Department of Urology and Division of Experimental Oncology Urological Research Institute Milano Italy

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology Medical University of Silesia Zabrze Poland

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology University Hospital Zurich Zurich Switzerland

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Division of Urology Department of Special Surgery Jordan University Hospital The University of Jordan Amman Jordan

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Institute for Urology and Reproductive Health Sechenov University Moscow Russia

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Institute for Urology and Reproductive Health Sechenov University Moscow Russia; Division of Urology Department of Special Surgery Jordan University Hospital The University of Jordan Amman Jordan; Karl Landsteiner Institute of Urology and Andrology Vienna Austria; Department of Urology Weill Cornell Medical College New York New York NY; Department of Urology University of Texas Southwestern Dallas TX; Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Men's Health and Reproductive Health Research Center Shahid Beheshti University of Medical Sciences Tehran Iran

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Research Center for Evidence Based Medicine Tabriz University of Medical Sciences Tabriz Iran

Department of Urology Federal Armed Services Hospital Koblenz Koblenz Germany

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

Institute for Urology and Reproductive Health Sechenov University Moscow Russia

S H Ho Urology Centre Department of Surgery The Chinese University of Hong Kong Hong Kong China

Service d'Urologie Hôpital Erasme Université Libre de Bruxelles Bruxelles Belgium

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