OBJECTIVE: To investigate the influence of statins on the survival outcomes of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adjuvant intravesical bacille Calmette-Guérin (BCG) immunotherapy. PATIENTS AND METHODS: A retrospective cohort of consecutive patients with NMIBC who received intravesical BCG therapy from 2001 to 2020 and statins prescription were identified. Overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS) were analysed between the Statins Group vs No-Statins Group using Kaplan-Meier method and multivariable Cox regression. RESULTS: A total of 2602 patients with NMIBC who received intravesical BCG were identified. The median follow-up was 11.0 years. On Kaplan-Meier analysis, the Statins Group had significant better OS (P < 0.001), CSS (P < 0.001), and PFS (P < 0.001). Subgroup analysis indicated statins treatment started before BCG treatment had better CSS (P = 0.02) and PFS (P < 0.01). Upon multivariable Cox regression analysis, the 'statins before BCG' group was an independent protective factor for OS (hazard ratio [HR] 0.607, 95% confidence interval [CI] 0.514-0.716), and CSS (HR 0.571, 95% CI 0.376-0.868), but not RFS (HR 0.885, 95% CI 0.736-1.065), and PFS (HR 0.689, 95% CI 0.469-1.013). CONCLUSIONS: Statins treatment appears to offer protective effects on OS and CSS for patients with NMIBC receiving adjuvant intravesical BCG.

Department of Experimental and Clinical Biomedical Science University of Florence Florence Italy

Department of Experimental and Clinical Medicine University of Florence Florence Italy

Department of Surgical Oncology Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital Amsterdam The Netherlands

Department of Urology 2nd Faculty of Medicine Charles University Prague Czechia

Department of Urology GRC 5 Predictive Onco Urology AP HP Hôpital Pitié Salpêtrière Sorbonne Université Paris France

Department of Urology Hospital Clinico San Carlos Madrid Spain

Department of Urology Hospital Universitario La Ribera Valencia Spain

Department of Urology Luzerner Kantonsspital Lucerne Switzerland

Department of Urology Marienkrankenhaus Hamburg gGmbH Hamburg Germany

Department of Urology Medical University of Innsbruck Innsbruck Austria

Department of Urology Medical University of Vienna Vienna Austria

Department of Urology Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Okayama Japan

Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology University of Texas Southwestern Dallas TX USA

Department of Urology Weill Cornell Medical College New York NY USA

European Association of Urology Young Academic Urologists Renal Cancer Working Group Arnhem The Netherlands

European Association of Urology Young Academic Urologists Urothelial Carcinoma Working Group Arnhem Netherlands

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

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

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

Unit of Urological Robotic Surgery and Renal Transplantation Careggi Hospital University of Florence Florence Italy

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