A contemporary review of management and prognostic factors of upper tract urothelial carcinoma

• Gold-standard treatment for UTUC remains NU, increasingly performed using minimally invasive surgery, which still lacks long-term oncologic equivalency to open NU.
• Nomograms including pre- and post-operative variables can aid prognostication and guide further therapy.
• Peri-operative chemotherapy improves survival outcomes, and should be considered in eligible patients.
• Radiotherapy is of limited role, except for advanced pathologic stages with poor prognostic factors.
• Future therapies based on genomic alterations in urothelial cancers are on the horizon.

BackgroundUpper tract urothelial carcinoma (UTUC) accounts for <5% of all urothelial cancers. Although the main treatment is radical nephroureterectomy (NU), oncologic outcomes are not comparable to lower tract urothelial cancers. Identifying prognostic factors can help guide management and potentially improve outcomes. This article systematically reviews current literature on prognostic factors and management options for UTUC.MethodsA comprehensive literature search was performed to identify all studies examining prognostic factors and management options for UTUC. The search included the Medline, Embase, Cochrane Central Register of Controlled Trials databases, and abstracts from the American Society of Clinical Oncology meetings up to November 2014. An updated systematic review was performed.ResultsPreoperative prognostic factors for UTUC patients include age, race, performance status, obesity, smoking status, elevated fibrinogen levels, hydronephrosis, tumor size, multi-focality, location, clinical grade and previous/synchronous bladder cancer. Postoperative variables include tumor stage/grade, multifocality, nodal involvement, lympho-vascular invasion, initial ureteral location, necrosis, sessile architecture, variant histologies and presence of tissue ALDH1 and SOX2. Curative treatment of choice is NU, with lymphadenectomy conferring survival benefits. Minimally invasive surgery has equivalent oncologic and better peri-operative outcomes compared to open surgery. Conservative therapy includes adjuvant BCG and intravesical mitomycin C. Two randomized trials investigating postoperative instillation of mitomycin C suggest bladder recurrence benefits. Adjuvant chemo-radiotherapy may be useful for patients with advanced T3/4 and/or N+ disease.ConclusionGold-standard treatment for UTUC remains NU, increasingly performed using minimally invasive surgery. Nomograms including pre- and post-operative variables can aid prognostication and guide further therapy.