Background: Non-muscle-invasive bladder cancer (NMIBC) comprises about 75% of all bladder cancers. Although NMIBC is treatable, it poses significant costs and burdens to patients due to high recurrence rates. We conducted an updated meta-analysis of studies that evaluated the efficacy of and outcomes after treatment with mitomycin C (MMC), gemcitabine (GEM), and docetaxel (DOCE) for NMIBC recurrence and progression. Methods: We searched the PubMed and Cochrane databases for observational cohort studies and randomized clinical trials (RCT) conducted between 2009 and 2022 that assessed the efficacy of GEM, DOCE, or MMC, alone or in combination, regarding NMIBC outcomes. A total of 49 studies that met the inclusion criteria were reviewed for their quality, sample size, outcomes, and potential for bias, and relevant data were extracted for the meta-analysis. Separate meta-analyses were performed to assess the risks of recurrence or progression when comparing GEM/DOCE or MMC vs. other treatments. Study heterogeneity was assessed by I2 statistics. Results: Among 31 studies comparing GEM or MMC to other treatments for NMIBC recurrence, there were statistically significant risk reductions of 24% for GEM (pooled relative risk (RR) of 0.76; 95% confidence interval (CI) 0.64-0.87) and 37% for MMC (pooled RR = 0.63; 95% CI 0.58-0.68). Recurrence-free survival (RFS) for GEM or MMC alone was 69.5% (95% CI 66.6-72.3%) and 67.2% (95% CI 66.2-68.2%), respectively. Studies assessing the combination of treatments had a pooled RFS of 44.6% (95% CI 40.4-48.7%). Fewer studies examined the risk of NMIBC progression, with large variability and inconclusive results across them. Conclusions: Our findings corroborate recent guidelines indicating that both GEM and MMC are effective treatments that reduce tumor recurrence and improve survival of NMIBC, although with large variability across the studies. Fewer studies evaluated DOCE treatment, with inconclusive results. Women and minorities were generally underrepresented, raising concerns about the generalizability of the findings and highlighting the importance of including a broader patient population in future RCTs.
Keywords: docetaxel (DOCE); gemcitabine (GEM); meta-analysis; mitomycin C (MMC); non-muscle-invasive bladder cancer (NMIBC); progression; recurrence; systematic review.