Original Study| Volume 15, ISSUE 6, e1089-e1094, December 2017

Upper Tract Urothelial Carcinomas: Prognostic Factors and Outcomes in Patients With Non–Lymph Node Distant Metastasis

Published:August 01, 2017DOI:



      Upper tract urothelial carcinomas (UTUCs) are increasingly recognized as separate malignancies. Additional insight into clinical outcomes and key prognostic factors are needed.


      To detail outcomes of patients with UTUCs recurring after radical nephroureterectomy (RNU) and to determine a risk score that predicts outcomes of patients with non–lymph node distant metastasis.

      Design, Setting, and Participants

      Chart review of all patients who had an extraurothelial recurrence after RNU for UTUC at Dana-Farber Cancer Institute between 2009 and 2014.

      Outcome Measurements and Statistical Analysis

      Median overall survival defined as time from chemotherapy for distant relapse to death. Prognostic relevance of performance status, hemoglobin, and receipt of cisplatin were assessed by Cox regression model.

      Results and Limitations

      A total of 102 patients were identified, 57 of whom had non–lymph node distant metastases at relapse; 45 received chemotherapy. Median follow-up was 29.8 months; median overall survival was 14.7 months. Objective response rate to any chemotherapy in the first-line setting was only 22%. Hemoglobin > 11 g/dL and receipt of cisplatin was associated with numerically longer median survival but did not reach statistical significance in univariate and multivariate analysis. Prognostic risk score scale including hemoglobin < 11 g/dL and receipt of cisplatin was inversely associated with survival, with scores of 0, 1, and 2 leading to median survival of 19.0, 14.9, and 7.2 months (P = .38), respectively.


      Advanced UTUC portends a poor prognosis, and most patients cannot receive cisplatin-based chemotherapy. A risk score that includes anemia and receipt of cisplatin helps stratify patients with distant metastasis for inclusion into eventual clinical trials. More studies are needed to validate these findings.

      Patient Summary

      Metastatic UTUC is an aggressive disease, where anemia and ineligibility to receive cisplatin are adverse features associated with shorter survival.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Clinical Genitourinary Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Siegel R.L.
        • Miller K.D.
        • Jemal A.
        Cancer statistics, 2017.
        CA Cancer J Clin. 2017; 67: 7-30
        • Roupret M.
        • Babjuk M.
        • Compérat E.
        • et al.
        European Association of urology guidelines on upper urinary tract urothelial cell carcinoma: 2015 update.
        Eur Urol. 2015; 68: 868-879
        • Margulis V.
        • Shariat S.F.
        • Matin S.F.
        • et al.
        Outcomes of radical nephroureterectomy: a series from the Upper Tract Urothelial Carcinoma Collaboration.
        Cancer. 2009; 115: 1224-1233
        • Raman J.D.
        • Messer J.
        • Sielatycki J.A.
        • Hollenbeak C.S.
        Incidence and survival of patients with carcinoma of the ureter and renal pelvis in the USA, 1973-2005.
        BJU Int. 2010; 107: 1059-1064
        • Green D.A.
        • Rink M.
        • Xylinas E.
        • et al.
        Urothelial carcinoma of the bladder and the upper tract: disparate twins.
        J Urol. 2013; 189: 1214-1221
        • Xylinas E.
        • Rink M.
        • Margulis V.
        • et al.
        Impact of renal function on eligibility for chemotherapy and survival in patients who have undergone radical nephro-ureterectomy.
        BJU Int. 2013; 112: 453-461
        • Roupret M.
        • Yates D.R.
        • Compérat E.
        • Cussenot O.
        Upper urinary tract urothelial cell carcinomas and other urological malignancies involved in the hereditary nonpolyposis colorectal cancer (Lynch syndrome) tumor spectrum.
        Eur Urol. 2008; 54: 1226-1236
        • Sfakianos J.P.
        • Cha E.K.
        • Iyer G.
        • et al.
        Genomic characterization of upper tract urothelial carcinoma.
        Eur Urol. 2015; 68: 970-977
        • Mullane S.
        • De Velasco G.
        • Choueiri T.K.
        • Kantoff P.W.
        • Bellmunt J.
        Genomic alterations in upper tract urothelial carcinoma (UTUC) versus urothelial carcinoma of the bladder (UBC).
        J Clin Oncol. 2016; 34 (abstract 431)
        • Leow J.J.
        • Orsola A.
        • Chang S.L.
        • Bellmunt J.
        A contemporary review of management and prognostic factors of upper tract urothelial carcinoma.
        Cancer Treat Rev. 2015; 41: 310-319
        • Bajorin D.F.
        • Dodd P.M.
        • Mazumdar M.
        • et al.
        Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy.
        J Clin Oncol. 1999; 17: 3173-3181
        • Bellmunt J.
        • Choueiri T.K.
        • Fougeray R.
        • et al.
        Prognostic factors in patients with advanced transitional cell carcinoma of the urothelial tract experiencing treatment failure with platinum-containing regimens.
        J Clin Oncol. 2010; 28: 1850-1855
        • de Vos F.
        • de Wit R.
        Choosing chemotherapy in patients with advanced urothelial cell cancer who are unfit to receive cisplatin-based chemotherapy.
        Ther Adv Med Oncol. 2010; 2: 381-388
        • Galsky M.D.
        • Chen G.J.
        • Oh W.K.
        • et al.
        Comparative effectiveness of cisplatin-based and carboplatin-based chemotherapy for treatment of advanced urothelial carcinoma.
        Ann Oncol. 2012; 23: 406-410
        • Galsky M.D.
        • Hahn N.M.
        • Rosenberg J.
        • et al.
        Treatment of patients with metastatic urothelial cancer “unfit” for cisplatin-based chemotherapy.
        J Clin Oncol. 2011; 29: 2432-2438
        • Bellmunt J.
        • Petrylak D.P.
        New therapeutic challenges in advanced bladder cancer.
        Semin Oncol. 2012; 39: 598-607
        • Kikuchi E.
        • Miyazaki J.
        • Yuge K.
        • et al.
        Do metastatic upper tract urothelial carcinoma and bladder carcinoma have similar clinical responses to systemic chemotherapy? A Japanese multi-institutional experience.
        Jpn J Clin Oncol. 2016; 46: 163-169
        • Balar A.V.
        • Galsky M.D.
        • Rosenberg J.E.
        • Powles T.
        Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial.
        Lancet Oncol. 2017; 389: 67-76
        • Bellmunt J.
        • de Wit R.
        • Vaughn D.J.
        • et al.
        31st annual meeting and associated programs of the Society for Immunotherapy of Cancer (SITC 2016): late breaking abstracts.
        J Immunother Cancer. 2016; 4 (O2)
        • Van Belle S.
        • Cocquyt V.
        Impact of haemoglobin levels on the outcome of cancers treated with chemotherapy.
        Crit Rev Oncol Hematol. 2003; 47: 1-11