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Eur Urol. 2014 Jun;65(6):1086-92. doi: 10.1016/j.eururo.2013.07.031. Epub 2013 Jul 30.

Survival outcome and treatment response of patients with late relapse from renal cell carcinoma in the era of targeted therapy.

Author information

  • 1University of Calgary, Tom Baker Cancer Center, Calgary, AB, Canada; University Medicine Greifswald, Department of Urology, Greifswald, Germany.
  • 2Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • 3University of Ulsan College of Medicine, Asan, South Korea.
  • 4Sunnybrook Odette Cancer Centre, Toronto, ON, Canada.
  • 5Princess Margaret Hospital, University of Toronto, Toronto, ON, Canada.
  • 6London Health Sciences Center, London, ON, Canada.
  • 7Queen Elizabeth II Health Sciences Center, Halifax, NS, Canada.
  • 8Stanford Cancer Institute, Stanford University, School of Medicine, Stanford, CA, USA.
  • 9Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
  • 10Yonsei Cancer Centre, Yonsei University College of Medicine, Seoul, South Korea.
  • 11Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
  • 12Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
  • 13Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
  • 14University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA.
  • 15Department of Medical Oncology, National Cancer Centre and Institute of Bioengineering and Nanotechnology, Singapore.
  • 16Department of Clinical Therapeutics, University of Athens, Athens, Greece.
  • 17Vancouver Cancer Center, British Columbia Cancer Agency, Vancouver, BC, Canada.
  • 18Cross Cancer Center, University of Alberta, Edmonton, AB, Canada.
  • 19Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
  • 20University of Calgary, Tom Baker Cancer Center, Calgary, AB, Canada. Electronic address:



A subset of primarily localized renal cell carcinoma (RCC) patients will experience disease recurrence ≥5 yr after initial nephrectomy.


To characterize the clinical outcome of patients with late recurrence beyond 5 yr.


Patients with metastatic RCC (mRCC) treated with targeted therapy were retrospectively characterized according to time to relapse. Relapse was defined as the diagnosis of recurrent metastatic disease >3 mo after initial curative-intent nephrectomy. Patients with synchronous metastatic disease at presentation were excluded. Patients were classified as early relapsers (ERs) if they recurred within 5 yr; late relapsers (LRs) recurred after 5 yr.


Demographics were compared with the Student t test, the chi-square test, or the Fisher exact test. The survival time was estimated with the Kaplan-Meier method, and associations with survival outcome were assessed with univariable and multivariable Cox regression analyses.


Among 1210 mRCC patients treated with targeted therapy after surgery for localized disease, 897 (74%) relapsed within the first 5 yr and 313 (26%) (range: 5-35 yr) after 5 yr. LRs presented with younger age (p<0.0001), fewer with sarcomatoid features (p<0.0001), more clear cell histology (p=0.001), and lower Fuhrman grade (p<0.0001). Overall objective response rates to targeted therapy were better in LRs versus ERs (31.8% vs 26.5%; p=0.004). LRs had significantly longer progression-free survival (10.7 mo vs 8.5 mo; p=0.005) and overall survival (OS; 34.0 mo vs 27.4 mo; p=0.004). The study is limited by its retrospective design, noncentralized imaging and pathology review, missing information on metastatectomy, and nonstandardized follow-up protocols.


A quarter of patients who eventually developed metastatic disease and were treated with targeted therapy relapsed over 5 yr from initial nephrectomy. LRs have more favorable prognostic features and consequently better treatment response and OS.

Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.


Late recurrence; Renal cell carcinoma; Survival outcome; Targeted therapies; Treatment response

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