Efficacy and Safety of Intravesical Gemcitabine and Docetaxel Combination Therapy in Patients With Intermediate- and High-Risk Non-Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-Analysis.

This meta-analysis evaluated the oncological outcomes and safety profile of intravesical gemcitabine and docetaxel (Gem/Doce) in patients with non-muscle-invasive bladder cancer (NMIBC). Additionally, efficacy comparison to Bacillus Calmette-Guérin (BCG) therapy was aimed only for BCG-naïve NMIBC. A systematic review and meta-analysis were conducted following PRISMA guidelines. Studies evaluating Gem/Doce for NMIBC were identified through PubMed, Web of Science, and Scopus databases. The primary outcome was recurrence-free survival (RFS). Secondary outcomes were high-grade RFS (HG-RFS), progression-free survival (PFS) and risk of adverse events (AEs). A subgroup analysis was performed according to the European Association of Urology (EAU) 2021 risk stratification and previous BCG exposure. A total of 14 studies, involving 1634 NMIBC patients (999 Gem/Doce and 635 BCG), were included. In high-risk BCG-naïve and BCG-treated (BCG-exposed/-unresponsive) NMIBC, Gem/Doce resulted in 24-month RFS of 78% (95% confidence intervals [CI] 70%-84%) and 41% (95% CI: 34%-47%), and 24-month PFS of 97% (95% CI: 69%-100%) and 85% (95% CI: 63%-95%), respectively. Five studies, including BCG-naïve intermediate to very-high-risk NMIBC, directly compared Gem/Doce and BCG, and demonstrated significant heterogeneity and no significant difference in RFS (Hazard ratio: 0.87, 95% CI: 0.51-1.50) and risk of AEs (odds ratio: 0.58, 95% CI: 0.21-1.60). Grade ≥ 3 AEs were found in 3.6% of Gem/Doce cohorts. Across Gem/Doce cohorts, higher maintenance utilization was associated with significantly improved RFS at 24 months (p = .004). However, maintenance effects were derived from between-study comparisons and should be interpreted cautiously due to heterogeneity in maintenance protocols and adherence. Gem/Doce provided acceptable RFS and PFS at 2 years among BCG-naïve patients and those who previously experienced recurrence after BCG. Gem/Doce demonstrated RFS and HG-RFS comparable to BCG in BCG-naïve NMIBC and had an acceptable safety profile.