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

  • 2025-04
  • Clinical genitourinary cancer 23(2)
    • Ichiro Tsuboi
    • Akihiro Matsukawa
    • Mehdi Kardoust Parizi
    • Robert J Schulz
    • Stefano Mancon
    • Tamás Fazekas
    • Marcin Miszczyk
    • Anna Cadenar
    • Ekaterina Laukhtina
    • Pawel Rajwa
    • Tatsushi Kawada
    • Satoshi Katayama
    • Takehiro Iwata
    • Kensuke Bekku
    • Takafumi Yanagisawa
    • Jun Miki
    • Takahiro Kimura
    • Koichiro Wada
    • Pierre I Karakiewicz
    • Piotr Chlosta
    • Jeremy Teoh
    • Motoo Araki
    • Shahrokh F Shariat

Study Design

Type
Meta-Analysis
Population
4,593 patients with non-muscle-invasive bladder cancer
Methods
Systematic review and meta-analysis of prospective studies; 3 databases queried; standard pairwise meta-analyses using hazard ratios with random-effects model
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.

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