Active Surveillance Versus Intravesical Bacillus Calmette-Guérin for High-grade T1 Bladder Cancer with Negative Second Transurethral Resection: The Randomized Noninferiority Phase 3 JCOG1019 Trial.

Abstract

We evaluated the noninferiority of active surveillance (AS) in comparison to intravesical bacillus Calmette-Guérin (BCG) in terms of recurrence and progression for patients with high-grade T1 (HG T1) bladder cancer at initial transurethral resection of the bladder (TURB) and no residual tumor at second TURB. After initial evaluation, participants diagnosed with HG T1 bladder cancer who had undergone complete eradication of visible tumors underwent a second TURB. Those with specimens showing T0 were randomized to either AS or to intravesical BCG for 8 wk without maintenance therapy. The primary endpoint was invasive relapse-free survival (iRFS). In total, 513 participants were enrolled in the initial evaluation. After second TURB, 263 participants were enrolled and randomized. AS was noninferior to BCG in terms of iRFS (hazard ratio 0.69, 90% confidence interval 0.44-1.08; p = 0.001). Rates of adverse events were 50% and 90% for any grade, and in 3.1% and 3.8% for grade ≥3 events in the AS and BCG arms, respectively. The protocol treatment in the control arm was not the current standard. In this highly selected patient population, AS was noninferior to eight-dose intravesical BCG induction therapy in terms of iRFS for T1 disease or deeper intravesical and/or extravesical recurrence. The safety profile of AS was better than that of BCG. These findings indicate that AS represents a potentially viable therapeutic strategy for selected patients with HG T1 bladder cancer for whom second TURB demonstrates the absence of residual disease.