Neoadjuvant Chemotherapy for Different Stages of Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-analysis

The purpose of this meta-analysis is to determine the survival benefits and pathological outcomes of neoadjuvant chemotherapy (NAC) combined with radical cystectomy (RC) administered to patients with cT2 or cT3-4N0M0 muscle-invasive bladder cancer (MIBC). PubMed, Embase, and the Cochrane Library were searched for comparing the use of NAC in combination with RC and RC alone in patients with different MIBC stages. A fixed effects model was used to calculate hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs), and the I-2 statistic was used to assess heterogeneity. Moreover, we determined possible sources of heterogeneity by subgroup and sensitivity analyses. Fifteen studies were finally selected. For cT2 bladder cancer, NAC combined with RC significantly increased the rates of pathological complete response (pCR) (OR=4.84, 95% CI: 1.18-19.92, p=0.029) but did not improve overall survival (OS) (HR=0.86, 95% CI: 0.72-1.02, p=0.078) across six studies. Regarding cT3-4 bladder cancer, NAC has a significantly improved effect on OS (HR=0.69; 95% CI: 0.59-0.81, p < 0.001, across seven studies and 5726 patients) and pCR (pooled OR=4.80; 95% CI: 2.06-11.23, p < 0.001, across two studies) than RC alone. Most studies were randomized prospective trials (level 1 evidence), and all the effects were irrespective of the type of study design and did not vary between subgroups of patients. In conclusion, NAC combined with RC is recommended for patients with T3-4aN0M0 but not for patients with T2N0M0.