Perioperative chemotherapy in the management of high risk upper tract urothelial cancers

Radical nephroureterectomy (RNU) remains the gold-standard in the treatment of invasive urothelial cancers of the upper tract (>pT2). However, there are stage-related, postoperative recurrence and cancer-specific death rates that are unacceptably high. Multimodality treatment regimens including neoadjuvant and adjuvant cisplatin-based systemic chemotherapy have been studied. While there is a paucity of Level 1 evidence to support either regimen, both have advantages and disadvantages. The provision of chemotherapy in the neoadjuvant setting is supported by extensive bladder cancer literature, but randomized controlled trials in the upper tract have not been completed. Neoadjuvant chemotherapy also risks overtreatment of patients due to the lack of accurate pre-operative staging modalities. On the other hand, adjuvant chemotherapy is supported by the findings of one prospective randomized trial, and eliminates the need for patient selection based on imperfect pre-operative modalities. However, the rigors of surgery and the renal function loss related to nephrectomy, may preclude the provision of adjuvant chemotherapy in a significant subset of patients. One may conclude that multimodal therapy is desirable for oncologic control, but the best means of providing such therapy requires further study.