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

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.