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Article Open Access

Intravesical gemcitabine vs. intravesical Bacillus‑Calmette-Guérin for non‑muscle invasive bladder cancer: A systematic review and meta‑analysis

  • Authors:
    • Fakhri Zuhdian Nasher
    • Agus Rizal Ardy Hariandy Hamid
    • Chaidir Arif Mochtar
    • Fakhri Rahman
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
    Copyright: © Nasher et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].
  • Article Number: 108
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    Published online on: September 22, 2025
       https://doi.org/10.3892/wasj.2025.396
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Abstract

Non‑muscle invasive bladder cancer (NMIBC) remains a major disease burden worldwide. Although Bacillus Calmette‑Guérin (BCG) immunotherapy is among the first‑line treatments for NMIBC, it is associated with a high rate of adverse events. The present systematic review aimed to compare the efficacy and safety of intravesical gemcitabine and BCG immunotherapy in patients with NMIBC. For this purpose, a literature search was conducted using the PubMed, Cochrane, ProQuest and EBSCOhost databases, accompanied by citation searching. Eligible articles were critically appraised, assessed for risk of bias and analyzed using random‑effects meta‑analysis. In total, five studies comprising 447 patients were included. From four randomized controlled trials, gemcitabine was shown to be non‑inferior to BCG in terms of preventing recurrence [relative risk (RR), 0.97; 95% confidence interval (CI), 0.58‑1.60; high heterogeneity (I2=72.9%, P=0.011) and progression, 1.02 (0.54‑1.93); and low heterogeneity (I2=0.0%, P=0.766)]. The overall risk of adverse events (RR, 0.78; 95% CI, 0.53‑1.13; I2=11.8%, P=0.322) and severe adverse events were similar between the groups (RR, 0.67; 95% CI, 0.25‑1.77; I2=0.0%, P=0.402). However, gemcitabine was associated with a lower risk of developing dysuria (four studies; RR, 0.59; 95% CI, 0.39‑0.89); I2=0.0%, P=0.674) and fever (three studies; RR, 0.17; 95% CI, 0.04‑0.76; I2=0.0%, P=0.569), and urinary frequency (one study; RR, 0.22; 95% CI, 0.13‑0.37) and itching (one study; RR, 0.34; 95% CI, 0.18‑0.64) were lower in patients receiving gemcitabine. Stratified analyses yielded consistent results in patients both at high‑risk and low‑to‑intermediate risk. On the whole, the present study demonstrates that intravesical gemcitabine was non‑inferior to BCG immunotherapy in preventing the recurrence and progression of NMIBC. Although the overall adverse event rates were similar, gemcitabine was less frequently associated with dysuria, fever, urinary frequency and itching. 
View Figures

Figure 1

PRISMA flow chart.

Figure 2

Risk of bias assessment using the
Cochrane risk-of-bias tool for randomized control studies (RoB 2.0)
for RCTs and Risk of Bias in Non-randomized Studies of
Interventions (ROBINS-I) tool for observational studies checklists.
The studies included were the following: Porena et al
(17), Di Lorenzo et al
(18), Bendary et al
(19), Gontero et al
(16) and Prasanna et al
(20).

Figure 3

Comparison of (A) recurrence and (B)
progression rates between intravesical gemcitabine and BCG
immunotherapy in non-muscle invasive bladder cancer. BCG, Bacillus
Calmette-Guérin.

Figure 4

Comparison of (A) any adverse events
and (B) severe adverse events (grade ≥3) between intravesical
gemcitabine and BCG immunotherapy in non-muscle invasive bladder
cancer. BCG, Bacillus Calmette-Guérin.
View References

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Copy and paste a formatted citation
Spandidos Publications style
Nasher FZ, Hamid AR, Mochtar CA and Rahman F: Intravesical gemcitabine vs. intravesical Bacillus‑Calmette-Guérin for non‑muscle invasive bladder cancer: A systematic review and meta‑analysis. World Acad Sci J 7: 108, 2025.
APA
Nasher, F.Z., Hamid, A.R., Mochtar, C.A., & Rahman, F. (2025). Intravesical gemcitabine vs. intravesical Bacillus‑Calmette-Guérin for non‑muscle invasive bladder cancer: A systematic review and meta‑analysis. World Academy of Sciences Journal, 7, 108. https://doi.org/10.3892/wasj.2025.396
MLA
Nasher, F. Z., Hamid, A. R., Mochtar, C. A., Rahman, F."Intravesical gemcitabine vs. intravesical Bacillus‑Calmette-Guérin for non‑muscle invasive bladder cancer: A systematic review and meta‑analysis". World Academy of Sciences Journal 7.6 (2025): 108.
Chicago
Nasher, F. Z., Hamid, A. R., Mochtar, C. A., Rahman, F."Intravesical gemcitabine vs. intravesical Bacillus‑Calmette-Guérin for non‑muscle invasive bladder cancer: A systematic review and meta‑analysis". World Academy of Sciences Journal 7, no. 6 (2025): 108. https://doi.org/10.3892/wasj.2025.396
Copy and paste a formatted citation
x
Spandidos Publications style
Nasher FZ, Hamid AR, Mochtar CA and Rahman F: Intravesical gemcitabine vs. intravesical Bacillus‑Calmette-Guérin for non‑muscle invasive bladder cancer: A systematic review and meta‑analysis. World Acad Sci J 7: 108, 2025.
APA
Nasher, F.Z., Hamid, A.R., Mochtar, C.A., & Rahman, F. (2025). Intravesical gemcitabine vs. intravesical Bacillus‑Calmette-Guérin for non‑muscle invasive bladder cancer: A systematic review and meta‑analysis. World Academy of Sciences Journal, 7, 108. https://doi.org/10.3892/wasj.2025.396
MLA
Nasher, F. Z., Hamid, A. R., Mochtar, C. A., Rahman, F."Intravesical gemcitabine vs. intravesical Bacillus‑Calmette-Guérin for non‑muscle invasive bladder cancer: A systematic review and meta‑analysis". World Academy of Sciences Journal 7.6 (2025): 108.
Chicago
Nasher, F. Z., Hamid, A. R., Mochtar, C. A., Rahman, F."Intravesical gemcitabine vs. intravesical Bacillus‑Calmette-Guérin for non‑muscle invasive bladder cancer: A systematic review and meta‑analysis". World Academy of Sciences Journal 7, no. 6 (2025): 108. https://doi.org/10.3892/wasj.2025.396
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