Next generation drugs in urothelial cancer: adenoviruses in the treatment of BCG-unresponsive nonmuscle invasive bladder cancer

Treatment options for nonmuscle invasive urothelial carcinoma of the bladder (NMIBC) unresponsive to Bacillus Calmette-Guérin (BCG) instillations are currently limited and often total resection of the bladder is the only therapeutic option for these patients. Thus, novel treatment options that are safe and effective are needed to avoid the substantial treatment morbidity, impact on the quality of life and the significant surgical risk associated with radical cystectomies. Besides intravesical cytotoxic therapies, immune checkpoint inhibitors, cytokines or cancer vaccines, different approaches of intravesical application of adenoviruses are being evaluated in BCG-unresponsive NMIBC. Recently, intravesical nonreplicating adenovirus vector-based gene therapy with nadofaragene firadenovec, which induces intravesical interferon expression, was approved for the treatment of BCG-unresponsive NMIBC by the US Food and Drug Administration after a recently published phase III trial. In this short review, different adenoviruses that are currently being investigated in BCG-unresponsive NMIBC are discussed and the therapeutic potential of nadofaragene firadenovec is highlighted.