Single instillation intravesical chemotherapy after radical nephroureterectomy for upper tract urothelial carcinoma: current evidence and future directions

Upper urinary tract urothelial carcinoma (UTUC) accounts for 5% to 10% of urothelial carcinomas and two-thirds are high-grade at the time of diagnosis. The gold standard management of high-grade UTUC is radical nephroureterectomy (RNU). Despite primary treatment, disease recurrence involves the bladder in 22% to 47% of cases. Single dose, postoperative intravesical chemotherapy (pIVC) is an adjunct to RNU to decrease bladder recurrences that is currently recommended in guidelines from the European Association of Urology, National Cancer Center Network, and American Urological Association. Two clinical trials, using single dose, postoperative intravesical mitomycin C or pirarubicin, have provided level 1 evidence to support the formation of these guidelines. Despite this evidence, pIVC utilization is reportedly low among urologists, ranging from 12% to 55% among three studies, with non-utilizers citing lack of supporting evidence, safety concerns, and clinical infrastructure as leading rationale. In the past 10 years, no additional trials on single dose pIVC have been completed and validated in systematic reviews or meta-analyses. Utilization of pIVC still has room for improvement and further studies on this subject are warranted to overcome the barriers to implementation. Herein, we describe the critical literature that supports guideline recommendations for single dose pIVC after RNU to understand efficacy, safety, practice patterns, and discuss the future directions of this treatment adjunct.

Automated summary

Upper urinary tract urothelial carcinoma (UTUC) is a rare type of urothelial carcinoma, accounting for approximately 5% to 10% of cases. Radical nephroureterectomy (RNU) is currently considered the gold standard treatment for high-grade UTUC. However, despite treatment, bladder recurrence still occurs in 22% to 47% of cases. To decrease bladder recurrences, current guidelines recommend single dose, postoperative intravesical chemotherapy (pIVC) following RNU. Despite level 1 evidence supporting these guidelines, the utilization of pIVC remains low, with barriers to implementation.