Innovative Immunological and Target Therapies for NMIBC: Recent Clinical Trial Data Shaping the Future

Panelists discuss how low-risk non–muscle-invasive bladder cancer (NMIBC) requires transurethral resection of bladder tumor (TURBT) with surveillance. Intermediate-risk disease needs adjuvant intravesical chemotherapy. High-risk cases receive BCG induction/maintenance therapy after TURBT, with close monitoring.

Panelists discuss how BCG-unresponsive bladder cancer is defined by disease persistence/recurrence within 6 to 12 months of adequate BCG therapy. Treatment options include cystectomy, intravesical chemotherapy, immunotherapy, or clinical trials.

Panelists discuss how FDA approvals have expanded options for BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC), with pembrolizumab, nogapendekin alfa inbakicept-pmln, and nadofaragene firadenovec-vncg offering new immunotherapy and gene therapy approaches.

Panelists discuss how for patients with BCG-unresponsive bladder cancer, treatment selection depends on key factors including tumor characteristics (carcinoma in situ vs papillary), patient fitness, and preferences. Standard options include radical cystectomy (the gold standard) or bladder-preserving approaches such as pembrolizumab, intravesical chemotherapy, or clinical trials. The decision requires careful individualization based on risk stratification, comorbidities, and shared decision-making.

Panelists discuss how cretostimogene grenadenorepvec is an intravesical oncolytic virus therapy targeting BCG-unresponsive bladder cancer through selective replication in tumor cells and immune stimulation via granulocyte-macrophage colony-stimulating factor expression.

Panelists discuss how both TAR-200 and UGN-102/103 represent innovative approaches to intravesical drug delivery for bladder conditions. TAR-200 uses a novel silicone-based system designed for controlled gemcitabine release, potentially offering extended drug exposure compared with conventional instillations. UGN-102 and UGN-103 employ a proprietary RTGel technology that transforms from liquid to gel form at body temperature, allowing for longer retention of mitomycin (UGN-102) and high-dose botulinum toxin (UGN-103), respectively, in the bladder.

Panelists discuss how PD-L1 inhibitors such as durvalumab and sasanlimab represent a promising frontier in non–muscle-invasive bladder cancer (NMIBC) treatment. These immunotherapies work by unleashing the body’s immune response against cancer cells, potentially offering new options for patients whose disease doesn’t respond to conventional therapies such as BCG. Their ongoing phase 3 trials could establish immunotherapy as a valuable addition to the NMIBC treatment landscape.

Panelists discuss how it would be preferred that BCG monotherapy not remain the first-line treatment for intermediate-risk and high-risk disease within the next 10 years. It is encouraged that the future of first-line treatment be a noninfectious agent that would be easier to develop and include more data.