The Role of Local Agents for the Treatment of Localized Upper Tract Urothelial Carcinoma: A Review of the Current Evidence.

Kidney-sparing surgery (KSS) for upper urinary tract urothelial carcinoma (UTUC) is a promising alternative to radical nephroureterectomy, especially for low-risk cases. However, due to the established risk of ipsilateral UTUC recurrence caused by the implantation of floating neoplastic cells after endoscopic resection, adjuvant endocavitary (endoureteral) instillations have been proposed. Instillation therapy may be also used as primary treatment for UTUC. The two most studied drugs that have been evaluated in both the adjuvant and primary setting of endocavitary instillation are mitomycin C and Bacillus Calmette-Guerin. The current paper provides an overview of the endocavitary treatments for UTUC, focusing on methods of administration, novel formulations, oncologic outcomes (in terms of endocavitary recurrence and progression), as well as on complications. In particular, the role of UGN-101 as a primary chemoablative treatment of primary noninvasive, endoscopically unresectable, low-grade, UTUC has been analysed. The drug achieved a complete response rate of 58% after the induction cycle, with a durable response independently of the maintenance cycle. The cumulative experience on the role of UUT instillation therapy appears encouraging; however, no definitive conclusions can be drawn about its therapeutic benefit. Given the current state of the art, any decision to administer adjuvant endoureteral therapy for UTUC should be carefully weighed against the potential adverse events. Nevertheless, newer investigations that improve visualization during ureteroscopy, genomic characterization, novel drugs and innovative strategies of improved drug delivery are under evaluation. The landscape of KSS for the treatment of the UTUC is evolving and seems promising.