Efficacy and Toxicity in Scheduled Intravesical Gemcitabine Versus Bacillus Calmette–Guérin for Bladder Cancer: A Systematic Review and Meta-Analysis

TL;DR

This study compares gemcitabine and BCG for bladder cancer treatment, finding similar effectiveness but fewer side effects with gemcitabine.

Contribution

The study provides a meta-analysis showing gemcitabine is as effective as BCG with lower toxicity for non-muscle-invasive bladder cancer.

Findings

Gemcitabine and BCG showed similar recurrence-free and progression-free survival rates.

Gemcitabine caused significantly fewer adverse events compared to BCG.

Most studies had moderate to high risk of bias, affecting the strength of conclusions.

Abstract

Bladder cancer that has not invaded the muscle layer is usually treated with surgery followed by medication placed directly into the bladder to reduce the risk of cancer returning. The most commonly used treatment is Bacillus Calmette–Guérin (BCG), but it can cause side effects and is sometimes difficult to obtain due to supply shortages. Gemcitabine has been proposed as an alternative treatment, but it has been unclear whether it works as well as BCG. In this study, we combined results from multiple clinical studies to compare these two treatments. We found that gemcitabine was as effective as BCG in preventing cancer recurrence and progression, while causing fewer side effects. These findings may help doctors choose safer treatment options, especially for patients who cannot tolerate BCG or when BCG is unavailable.

Background/Objectives: The present study aimed to compare the efficacy and safety of intravesical gemcitabine versus Bacillus Calmette–Guérin administered after transurethral resection of bladder tumor in patients with non-muscle-invasive bladder cancer. Methods: A comprehensive literature search was conducted using PubMed, Embase, and the Cochrane Library databases up to September 2025. Studies were eligible for inclusion if they were comparative studies evaluating intravesical gemcitabine versus Bacillus Calmette–Guérin following transurethral resection of bladder tumor. The primary outcomes were recurrence-free survival, progression-free survival, and incidence of adverse events. Pooled hazard ratios were calculated using a random-effects model based on log hazard ratios and standard error values. Results: Seven studies comprising approximately 774 patients were included in this analysis. The pooled hazard ratio was 0.80 (95% confidence interval, 0.42–1.53) for recurrence-free survival and 0.76 (95% confidence interval, 0.46–1.26) for progression-free survival, indicating no significant difference between gemcitabine and Bacillus Calmette–Guérin. However, gemcitabine was associated with a significantly lower incidence of adverse events, with a pooled odds ratio of approximately 0.48 (95% confidence interval, 0.27–0.86). Risk-of-bias assessment revealed that most randomized trials had “some concerns” based on the Risk of Bias 2 tool, whereas non-randomized studies were rated as having “moderate to serious” risk of bias according to the Risk of Bias in Non-randomized Studies of Interventions tool. Conclusions: Gemcitabine demonstrated an oncologic efficacy comparable to that of Bacillus Calmette–Guérin in terms of recurrence and progression outcomes while showing a substantially lower incidence of treatment-related toxicities.

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