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.

Although many patients with muscle-invasive bladder cancer (MIBC) achieve a pathologic complete response (CR) following neoadjuvant therapy (NAT), subsequent definitive bladder treatment (DBT) - radical cystectomy (RC) or trimodal therapy (TMT) remain standard treatments. Preliminary evidence suggests that a subset of patients may avoid DBT, but a definitive randomized comparison has not been conducted. NeoBLAST aims to evaluate the feasibility of randomizing patients with MIBC who achieve a clinical CR (cCR) following NAT to active surveillance (AS) versus DBT and to ultimately demonstrate the non-inferiority of AS. This study is an open-label phase 2/3 randomized controlled trial. Patients with resectable MIBC cT2-T4aN0M0 who achieve a cCR after receiving NAT are randomized 1:1 to AS or DBT. cCR determined by conventional imaging, circulating tumor DNA, bladder MRI, and template bladder biopsy. NeoBLAST phase 2 opened in August 2025 with the plan to enrol for 2 years and expand to a multicenter phase 3 trial in 2027. The phase 2 primary endpoint is feasibility to randomize, defined as ≥25% (≥18 of 72) acceptance of randomization in patients with cCR. The phase 3 primary endpoint is metastasis-free survival at 2 years. To determine a non-inferiority margin of 10%, the trial will need to randomize 172 patients with cCR. This study has the potential to be practice-changing by establishing the non-inferiority of AS in a randomized setting, but carries a risk of poor feasibility and unintended cross over after randomization. FUNDING: Canadian Institutes of Health Research and the Vancouver Prostate Centre. ETHICS AND TRIAL REGISTRATION: University of British Columbia H23-02447, NCT06537154.