Experimental Immunotherapy Could Help High-Risk Bladder Cancer Patients Skip Cystectomy

A Mayo Clinic–led international phase 3 trial reports that a new intravesical oncolytic immunotherapy, cretostimogene grenadenorepvec, may help many people with high-risk, BCG-unresponsive non-muscle-invasive bladder cancer avoid immediate bladder removal. Published in The Lancet Oncology, the study focused on patients whose disease returned or persisted after Bacillus Calmette-Guérin (BCG), the standard frontline approach for this risk category.

In most clinical pathways, surgery to remove the bladder is recommended after failure of BCG because durable cancer control is difficult to achieve with existing options. Here, investigators evaluated whether the experimental therapy could induce strong tumor regression within the bladder while maintaining an acceptable safety profile.

The trial enrolled 115 patients across 41 medical centers in North America, Asia, and Australia. Participants had high-risk disease, including carcinoma in situ, and were treated with cretostimogene grenadenorepvec administered directly into the bladder.

Results were striking for the primary outcome of complete response, defined by the absence of detectable cancer after treatment. Overall, 75% of patients achieved a complete response, and many of those responses remained durable for more than two years. Two years after starting treatment, an estimated 81% of patients had not required cystectomy.

Durability analyses suggested that among those with complete disappearance of cancer, about 60% remained cancer-free at the two-year mark. One patient reportedly remained free of recurrence for more than four years after completing therapy, indicating that prolonged remission is possible in a subset of patients.

Safety findings indicated that most treatment-related adverse effects were mild and temporary, largely involving bladder-related symptoms. Importantly, researchers reported no severe treatment-related side effects, supporting the tolerability of repeated intravesical dosing.

Investigators emphasize that these outcomes may shift management for BCG-unresponsive patients by adding a bladder-sparing alternative without compromising cancer control. They also caution that the therapy has not been directly compared with other bladder-preserving strategies in randomized trials.

The study was funded by CG Oncology, and the therapy remains investigational pending further evaluation.