To evaluate oncological outcomes of primary versus secondary muscle-invasive bladder cancer treated with radical cystectomy. Medline, Embase, Scopus and Cochrane Library were searched for eligible studies. Hazard ratios for overall survival (OS), cancer specific survival (CSS) and progression free survival (PFS) were calculated using survival data extracted from Kaplan-Meier curves. A total of 16 studies with 5270 patients were included. Pooled analysis showed similar 5-year and 10-year OS (HR 1, p = 0.96 and HR 1, p = 0.14) and CSS (HR 1.02, p = 0.85 and HR 0.99, p = 0.93) between primMIBC and secMIBC. Subgroup analyses according to starting point of follow-up and second-look transurethral resection revealed similar results. Subgroup analyses of studies in which neoadjuvant chemotherapy was administered demonstrated significantly worse 5-year CSS (HR 1.5, p = 0.04) but not 10-year CSS (HR 1.36, p = 0.13) in patients with secMIBC. Patients with secMIBC had significantly worse PFS at 5-year (HR 1.41, p = 0.002) but not at 10-year follow-up (HR 1.25, p = 0.34). This review found comparable oncologic outcomes between primMIBC and secMIBC patients treated with RC regarding OS and CSS. Subgroup analysis showed worse 5-year CSS but not 10-year CSS for neoadjuvant chemotherapy in the secMIBC group. Prospective clinical trials incorporating molecular markers, that allow precise risk stratification of secMIBC and further research uncovering underlying molecular and clinical drivers of the heterogeneous group of secMIBC is needed.

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

Department of Pathology Medical University of Vienna 1090 Vienna Austria

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

Department of Urology Luzerner Kantonsspital 6000 Luzern Switzerland

Department of Urology Medical University of Vienna 1090 Vienna Austria

Department of Urology The Jikei University School of Medicine Tokyo 3 25 8 Japan

Department of Urology University of Jordan Amman 11942 Jordan

Department of Urology University of Texas Southwestern Dallas TX 5323 USA

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

European Association of Urology Research Foundation 6803 Arnhem The Netherlands

Institute of Urology and Reproductive Health Imperial Moscow Sechenov 1st Moscow State Medical University 119992 Moscow Russia

Karl Landsteiner Institute of Urology and Andrology 1090 Vienna Austria

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The Impact of Primary Versus Secondary Muscle-invasive Bladder Cancer at Diagnosis on the Response to Neoadjuvant Chemotherapy

Comparative Outcomes of Primary Versus Recurrent High-risk Non-muscle-invasive and Primary Versus Secondary Muscle-invasive Bladder Cancer After Radical Cystectomy: Results from a Retrospective Multicenter Study