Grant: Catalyst Grant: SPOR Innovative Clinical Trials (iCT)

Muscle invasive bladder cancer (MIBC) is typically treated with chemotherapy (CT) followed by surgical removal of the bladder or a combination of radiation and CT (TMT). However, these treatments can have significant side effects that affect patient quality of life. Studies have shown that approximately one third of patients who receive CT before surgical removal of their bladder experience a complete response (CR), meaning that there is no detectable cancer remaining in the bladder. These patients could theoretically avoid surgery or radiation, which would significantly improve their quality of life, but we currently lack the tools to identify these patients before bladder removal. Bladder preservation after CT is therefore associated with an unacceptably risk of recurrence and later metastatic spread of the cancer. We believe that combining state-of-the-art imaging (magnetic resonance imaging), repeat bladder biopsy, and novel molecular markers (cell-free DNA in blood and urine) will enhance residual cancer detection and make active surveillance without definitive bladder treatment safe after CT. We propose a phase II trial to assess the feasibility of randomizing MIBC patients with clinical CR following CT to active surveillance or treatment (surgery or TMT). The primary objective of the trial is to determine whether patients will accept randomization to the different treatment options. Secondary objectives include assessment of the accuracy of clinical restaging, patient quality of life, treatment acceptance rates, and survival outcomes. If randomization proves feasible, we will transition seamlessly to a larger randomized trial to address definitively whether active surveillance is as effective as local therapy in carefully selected patients with a clinical CR after CT. This would represent a paradigm shift in the management of patients with MIBC, representing a transition towards personalized treatment with improved quality of life for these patients.