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Molecular and genomic characterization studies on UTUC have shown changes occurring at differing frequencies from bladder cancer, with unique molecular and clinical subtypes, potentially with different responses to treatment. Systemic chemotherapy is the standard approach for patients with inoperable locally advanced or metastatic UCs. Although initial response rates are high, the median survival with combination chemotherapy is about 15\u2009months. In first-line chemotherapy several cisplatin-based regimens have been proposed. For patients with advanced UC who progress to first-line treatment, the only product licensed in Europe is vinflunine, a third-generation, semisynthetic, vinca alkaloid. Better response rates (15\u201360%), with higher toxicity rates and no overall survival (OS) benefit, are generally achieved in multidrug combinations, which often include taxanes and gemcitabine. The US FDA has recently approved five agents targeting the programmed death-1 and programmed death ligand-1 pathway as a second-line therapy in patients with locally advanced or metastatic UC with disease progression during or following platinum-containing chemotherapy. Potential therapeutic targets are present in 69% of tumours analyzed. Specific molecular alterations include those involved in the RTK\/Ras\/PI(3)K, cell-cycle regulation and chromatin-remodeling pathways, many of them have either targeted therapies approved or under investigation. Angiogenic agents, anti-epidermal growth factor receptor therapy, phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) pathway inhibitors and immunotherapeutic drugs are being successfully investigated. <\/jats:p>","DOI":"10.1177\/1756287218815372","type":"journal-article","created":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T19:43:19Z","timestamp":1547062999000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":10,"title":["Contemporary best practice in the management of urothelial carcinomas of the renal pelvis and ureter"],"prefix":"10.1177","volume":"11","author":[{"given":"Maristella","family":"Bianconi","sequence":"first","affiliation":[{"name":"Medical Oncology Unit, \u2018Madonna del Soccorso\u2019 Hospital, ASUR Marche AV5, San Benedetto del Tronto, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Cimadamore","sequence":"additional","affiliation":[{"name":"Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Faloppi","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Macerata General Hospital, ASUR Marche AV3, Macerata, Italy Department of Medical Oncology, \u2018Duilio Casula\u2019 Polyclinic, Cagliari State University, Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Scartozzi","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, \u2018Duilio Casula\u2019 Polyclinic, Cagliari State University, Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Santoni","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Macerata General Hospital, ASUR Marche AV3, Macerata, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Lopez-Beltran","sequence":"additional","affiliation":[{"name":"Department of Surgery, Cordoba University Medical School, Cordoba, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Scarpelli","sequence":"additional","affiliation":[{"name":"Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3938-610X","authenticated-orcid":false,"given":"Rodolfo","family":"Montironi","sequence":"additional","affiliation":[{"name":"Section of Pathological Anatomy, Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Via Conca 71, Ancona, Marche, I\u221260126, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,1,8]]},"reference":[{"key":"bibr1-1756287218815372","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21332"},{"key":"bibr2-1756287218815372","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2017.07.036"},{"key":"bibr3-1756287218815372","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800559"},{"key":"bibr4-1756287218815372","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2012.04.009"},{"key":"bibr5-1756287218815372","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2013.02.001"},{"key":"bibr6-1756287218815372","doi-asserted-by":"publisher","DOI":"10.5858\/2007-131-1244-HVOIUC"},{"volume-title":"Histological typing of urinary bladder tumours","year":"1973","author":"Mostofi FK","key":"bibr7-1756287218815372"},{"key":"bibr8-1756287218815372","unstructured":"Eble JN, Sauter G, Epstein JI, et al. 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