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



Tsuboi I1, 2, 3 ; Matsukawa A1, 4 ; Kardoust Parizi M1, 5 ; Schulz RJ1, 6 ; Mancon S1, 7 ; Fazekas T1, 8 ; Miszczyk M1, 9 ; Cadenar A1, 10 ; Laukhtina E1 ; Rajwa P1, 11 ; Kawada T1, 3 ; Katayama S1, 3 ; Iwata T1, 3 ; Bekku K1, 3 Show All Authors
Authors
  1. Tsuboi I1, 2, 3
  2. Matsukawa A1, 4
  3. Kardoust Parizi M1, 5
  4. Schulz RJ1, 6
  5. Mancon S1, 7
  6. Fazekas T1, 8
  7. Miszczyk M1, 9
  8. Cadenar A1, 10
  9. Laukhtina E1
  10. Rajwa P1, 11
  11. Kawada T1, 3
  12. Katayama S1, 3
  13. Iwata T1, 3
  14. Bekku K1, 3
  15. Yanagisawa T1, 4
  16. Miki J4
  17. Kimura T4
  18. Wada K1, 2
  19. Karakiewicz PI12
  20. Chlosta P13
  21. Teoh J14
  22. Araki M3
  23. Shariat SF1, 15, 16, 17, 18, 19, 20

Source: Clinical Genitourinary Cancer Published:2025


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. © 2025 The Author(s)
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