Despite currently used intravesical therapies in non-muscle-invasive bladder cancer (NMIBC), the rate of intravesical recurrence remains very high. We aimed to evaluate the effectiveness of adding nonintravesical interventions to standard intravesical therapies to prevent intravesical recurrence. In April 2024, 3 databases were queried for prospective studies evaluating nonintravesical interventions in addition to standard intravesical therapies for NMIBC (CRD42024490988). The primary outcome was intravesical recurrence-free survival (iRFS). Standard pairwise meta-analyses were performed using hazard ratios (HR) and 95% confidence intervals (95% CI) with a random-effects model. We identified 18 eligible studies (14 RCTs and 4 prospective trials) comprising 4,593 NMIBC patients, which investigated pharmacological interventions (eg, selenium, vitamins, Lactobacillus casei, celecoxib, metformin, mistletoe lectin) and lifestyle modifications (diet). The addition of Lactobacillus casei significantly improved iRFS (HR: 0.50; 95% CI: 0.34-0.73; P < .001). A high western diet pattern significantly worsened iRFS (HR:1.48, 95%CI:1.06-2.06, P = .03). The other nonintravesical interventions were not associated with iRFS. Our comprehensive review of the published literature highlights the need for further research into the efficacy of nonvesical interventions for NMIBC. While Lactobacillus was shown to improve iRFS in 2 RCTs, additional high-quality randomized studies are required to evaluate the effectiveness of other interventions.

Cancer Prognostics and Health Outcomes Unit University of Montreal Health Centre Montreal Quebec Canada

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

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

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Collegium Medicum Faculty of Medicine WSB University Dąbrowa Górnicza Poland

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Experimental and Clinical Medicine Unit of Oncologic Minimally Invasive Urology and Andrology Careggi Hospital University of Florence Florence Italy

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

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 Semmelweis University Budapest Hungary

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology Shariati Hospital Tehran University of Medical Sciences Tehran Iran

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology Shimane University Faculty of Medicine Shimane Japan

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology Shimane University Faculty of Medicine Shimane Japan; 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 University Medical Center Hamburg Eppendorf Hamburg Germany

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Department of Urology University of Texas Southwestern Medical Center Dallas TX; Department of Urology Weill Cornell Medical College New York NY; Department of Urology 2nd Faculty of Medicine Charles University Prague Czechia; Division of Urology Department of Special Surgery The University of Jordan Amman Jordan; Karl Landsteiner Institute of Urology and Andrology Vienna Austria; Research Center for Evidence Medicine Urology Department Tabriz University of Medical Sciences Tabriz Iran

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Division of Surgery and Interventional Science University College London London UK

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria; Humanitas University Department of Biomedical Sciences Pieve Emanuele Italy

Department of Urology Jagiellonian University Medical College Krakow Poland

Department of Urology Jikei University School of Medicine Tokyo Japan

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

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