Systematic Review and Meta-Analysis of Response Rates in BCG-unresponsive Non–Muscle-Invasive Bladder Cancer: a Consensus Statement From the International Bladder Cancer Group

There is a critical need to establish reference response rates following bladder-sparing therapies administered in the setting of bacillus Calmete-Guerin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC). We sought to determine the efficacy of different interventions in recent trials accruing patients fulfilling the strict BCGunresponsive definition established by the US Food and Drug Administration. We performed a systematic review and meta-analysis for clinical trials in the BCG-unresponsive disease space to include published and presented results. The primary endpoints were complete response rate for CIS±Ta/T1 tumors, recurrence-free rate for patients with papillary-only disease, and disease-free rate in studies enrolling both papillary CIS tumors (Ta/T1/CIS). I2 was used for assessing heterogeneity. Eleven studies using 9 different therapeutic agents in a total of 909 patients with BCG-unresponsive NMIBC were identified. The resulting outcomes at 3, 6, and 12 months were 44%, 38%, and 25% complete response rate in CIS±Ta/T1 tumors; 73%, 58%, and 48% recurrence-free rate in papillary-only; and 48%, 22%, and 43% disease-free rate in combined Ta/T1/CIS, respectively. Relatively low levels of heterogeneity were observed amongst studies restricted to papillary-only or CIS±Ta/T1 tumors. Future randomized controlled studies are needed and will likely require stratification between papillary-only and CIS±Ta/T1 tumors. Introduction