title: Upper urinary tract disease: what we know today and unmet needs.
abstract: OBJECTIVE
  Upper tract urothelial carcinoma (UTUC) is a rare and poorly investigated disease. Intense collaborative efforts have increased our knowledge and improved the management of the disease. The objective of this review was to discuss recent advances and unmet needs in UTUC.
  
  
  METHODS
  A non-systematic Medline/PubMed literature search was performed on UTUC using the terms "upper tract urothelial carcinoma" with different combinations of keywords. Original articles, reviews and editorials in English language were selected based on their clinical relevance.
  
  
  RESULTS
  UTUC is a disease with specific epidemiologic and risk factors different to urothelial carcinoma of the bladder (UCB). Similarly to UCB, smoking increases the risk of UTUC and worsens its prognosis, whereas aristolochic acid (AA) exposure and mismatch repair genes abnormality are UTUC specific risk factors. A growing understanding of biological pathways involved in the tumorigenesis of UTUC has led to the identification of promising prognostic/predictive biomarkers. Risk stratification of UTUC is difficult due to limitations in staging and grading. Modern imaging and endoscopy have improved clinical decision-making, and allowed kidney-sparing management and surveillance in favorable-risk tumors. In high-risk tumors, radical nephroureterectomy (RNU) remains the standard. Complete removal of the intramural ureter is necessary with inferiority of endoscopic management. Post-RNU intravesical instillation has been shown to decrease bladder cancer recurrence rates. While the role of neoadjuvant cisplatin based combination chemotherapy and lymphadenectomy are not clearly established, the body of evidence suggests a survival benefit to these. There is currently no evidence for adjuvant chemotherapy (AC) in UTUC.
  
  
  CONCLUSIONS
  Despite growing interest and understanding of UTUC, its management remains challenging, requiring further high quality multicenter collaborations. Accurate risk estimation is necessary to avoid unnecessary RNUs while advances in technology are still required for optimal kidney-sparing approaches.
authors.affiliation: 1 Department of Urology, Rennes University Hospital, Rennes, France ; 2 Department of Urology, General Hospital, Medical University Vienna, Vienna, Austria ; 3 Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland ; 4 Academic Department of Urology, La Pitié-Salpetrière Hospital, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Pierre et Marie Curie, University Paris 6, Paris, France ; 5 Department of Urology, University of Texas Southwestern Medical Center, Dallas, USA ; 6 Department of Urology, Weill Cornell Medical College, New York, USA.
authors.forename: Romain
authors.initials: R
authors.lastname: Mathieu
authors.affiliation: 1 Department of Urology, Rennes University Hospital, Rennes, France ; 2 Department of Urology, General Hospital, Medical University Vienna, Vienna, Austria ; 3 Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland ; 4 Academic Department of Urology, La Pitié-Salpetrière Hospital, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Pierre et Marie Curie, University Paris 6, Paris, France ; 5 Department of Urology, University of Texas Southwestern Medical Center, Dallas, USA ; 6 Department of Urology, Weill Cornell Medical College, New York, USA.
authors.forename: Karim
authors.initials: K
authors.lastname: Bensalah
authors.affiliation: 1 Department of Urology, Rennes University Hospital, Rennes, France ; 2 Department of Urology, General Hospital, Medical University Vienna, Vienna, Austria ; 3 Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland ; 4 Academic Department of Urology, La Pitié-Salpetrière Hospital, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Pierre et Marie Curie, University Paris 6, Paris, France ; 5 Department of Urology, University of Texas Southwestern Medical Center, Dallas, USA ; 6 Department of Urology, Weill Cornell Medical College, New York, USA.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lucca
authors.affiliation: 1 Department of Urology, Rennes University Hospital, Rennes, France ; 2 Department of Urology, General Hospital, Medical University Vienna, Vienna, Austria ; 3 Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland ; 4 Academic Department of Urology, La Pitié-Salpetrière Hospital, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Pierre et Marie Curie, University Paris 6, Paris, France ; 5 Department of Urology, University of Texas Southwestern Medical Center, Dallas, USA ; 6 Department of Urology, Weill Cornell Medical College, New York, USA.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Mbeutcha
authors.affiliation: 1 Department of Urology, Rennes University Hospital, Rennes, France ; 2 Department of Urology, General Hospital, Medical University Vienna, Vienna, Austria ; 3 Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland ; 4 Academic Department of Urology, La Pitié-Salpetrière Hospital, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Pierre et Marie Curie, University Paris 6, Paris, France ; 5 Department of Urology, University of Texas Southwestern Medical Center, Dallas, USA ; 6 Department of Urology, Weill Cornell Medical College, New York, USA.
authors.forename: Morgan
authors.initials: M
authors.lastname: Rouprêt
authors.affiliation: 1 Department of Urology, Rennes University Hospital, Rennes, France ; 2 Department of Urology, General Hospital, Medical University Vienna, Vienna, Austria ; 3 Department of Urology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland ; 4 Academic Department of Urology, La Pitié-Salpetrière Hospital, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Pierre et Marie Curie, University Paris 6, Paris, France ; 5 Department of Urology, University of Texas Southwestern Medical Center, Dallas, USA ; 6 Department of Urology, Weill Cornell Medical College, New York, USA.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
keywords: Upper tract urothelial carcinoma (UTUC); chemotherapy; predictive tools; radical nephroureterectomy (RNU); risk factors; ureteroscopy
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