Nonintravesical Interventions for Preventing Intravesical Recurrence in Patients With Nonmuscle-Invasive Bladder Cancer: A Systematic Review and Meta-Analysis.

Pawel Rajwa, Jeremy Teoh, Marcin Miszczyk, Mehdi Kardoust Parizi, Anna Cadenar, Satoshi Katayama, Tatsushi Kawada, Tamás Fazekas, Stefano Mancon, Ichiro Tsuboi, Akihiro Matsukawa, Shahrokh F Shariat, Takafumi Yanagisawa, Pierre I Karakiewicz, Piotr Chlosta, Motoo Araki, Koichiro Wada, Robert J Schulz, Takahiro Kimura, Jun Miki, Ekaterina Laukhtina, Takehiro Iwata, Kensuke Bekku

Journal: Clinical genitourinary cancer 2025;23(2):102306

PMID: 39952876

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Abstract

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.

Address: 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, Jikei University School of Medicine, Tokyo, Japan.; 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, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Italy.; 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; 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, 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; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.; 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, Shimane University Faculty of Medicine, Shimane, Japan.; Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Quebec, Canada.; Department of Urology, Jagiellonian University, Medical College, Krakow, Poland.; Department of Surgery, S.H. Ho Urology Centre, The Chinese University of Hong Kong, Hong Kong SAR, China.; 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 of Texas Southwestern Medical Center, Dallas, TX; Department of Urology, Weill Cornell Medical College, New York, NY; Department of Urology, Second 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. Electronic address: [email protected].

DOI: 10.1016/j.clgc.2025.102306