Upper urinary tract urothelial carcinoma (UUTUC) is relatively rare, occurring in only 5% of all urothelial cancers. It has not been as extensively studied and reviewed as carcinoma of the bladder. UUTUC has a propensity for multifocality, local recurrence, and development of metastases, which argues for an aggressive treatment approach. Open radical nephroureterectomy (ORNU) with removal of an ipsilateral bladder cuff still remains the gold standard treatment for patients with UUTUC and a normal contralateral kidney, which, however, is being challenged by minimally invasive approaches, such as endoscopic and laparoscopic approaches. They are rapidly evolving as reasonable alternatives of care depending on grade and stage of disease. Adjuvant therapy seems to be safe, although its efficacy is debatable. Immunotherapy appears to be most effective in patients with upper-tract carcinoma in situ. Chemotherapy and radiotherapy also show some improvement in recurrence rates, but there have been no randomized, prospective trials. Gene and molecular-targeted therapy is expected. Several controversies remain in our management, including a selection of endoscopic versus laparoscopic approaches, management strategies on the distal ureter, the role of lymphadenectomy, and the value of immunotherapy, chemotherapy, radiotherapy and genetics and molecular markers in UUTUC. Aims of this paper are to critically review the treatment of UUTUC.
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