A few bladder-sparing treatment options are available for BCG-unresponsive patients, including valrubicin and the recently FDA-approved pembrolizumab. However, additional treatment options that achieve a durable response are needed. A recent phase III open-label clinical trial by Boorjian et al., published in Lancet Oncology, investigated the efficacy of a novel strategy for intravesical interferon alfa gene delivery. The authors used nadofaragene firadenovec (rAd-IFNα/Syn3), a non-replicating recombinant adenovirus vector-based gene therapy that delivers a copy of the human interferon alfa-2b gene to urothelial cells. An earlier phase 2 study in 40 patients achieved a 12-month recurrence-free survival of 35%.