NeoBLAST trial tests active surveillance after complete response in MIBC

A phase 2/3 randomized controlled trial¹ is now open in Canada to answer one of the most consequential unanswered questions in muscle-invasive bladder cancer: Can patients who achieve a clinical complete response after neoadjuvant therapy safely forgo definitive bladder treatment—radical cystectomy or trimodal therapy—and be managed with active surveillance instead?

"When you face someone who's been informed they have muscle-invasive bladder cancer and we need to remove their bladder, it always is a bit shocking for them," said Marie-Pier St-Laurent, MD, FRCSC, a urologic oncologist at the University of British Columbia and the NeoBLAST (NCT06537154) Principal Investigator. "All of the patients will be asking, ‘can I just keep my bladder?’ "

The rationale for NeoBLAST draws on a body of retrospective data showing that some patients who elected not to proceed with cystectomy have showing “clinical response” to neoadjuvant treatment experienced prolonged responses, as well as early phase 2 signals from trials including RETAIN (NCT02710734), RETAIN-2 (NCT04506554) or HCRN GU16-257 (NCT03558087) by Galsky et al. That preliminary evidence was not sufficient to change practice—but it was sufficient to motivate a randomized trial.

"As of today, we need to do the cystectomy if you're not in a clinical trial," Dr. St-Laurent said. "We've got to find the answer before we actually change our practice."

The barrier to conducting such a trial has historically been patient and investigator willingness to accept randomization between surgery and non-surgery. Prior bladder cancer trials comparing cystectomy to BCG or radiation failed to accrue and closed early. NeoBLAST addressed this barrier through design: The definitive bladder treatment arm includes trimodal therapy as an option, meaning patients with clinical complete response randomly assigned away from surveillance are not necessarily committed to cystectomy.

"We're not randomizing surgery vs no surgery—we can be randomizing surveillance vs radiation," Dr. St-Laurent said. "For this reason, I believe we made randomization in this disease possible."

The phase 2 primary end point is feasibility—specifically, whether at least 25% of enrolled patients are found to have a clinical complete response and accept random assignment. If that threshold is met, the seamlessly connected phase 3 will continue with the same trial design, with phase 2 patient data contributing to the phase 3 analysis. The phase 3 primary end point is metastasis-free survival, with a non-inferiority margin of 10% and a randomization target of 172 patients with confirmed clinical complete response randomized. The trial opened at the University of British Columbia in August 2025.

REFERENCE

1. St-Laurent M-P, Eigl BJ, Tyldesley S, et al. NeoBLAST: A pilot randomized controlled trial of active surveillance versus definitive bladder treatment following clinical complete response to neoadjuvant therapy in muscle-invasive bladder cancer - study protocol. Eur Urol Oncol. 2026 Aug 7:S2588-9311(26)00198-7. doi:10.1016/j.euo.2026.07.008