Impact of bone and liver metastases on patients with renal cell carcinoma treated with targeted therapy

Rana R McKay; Nils Kroeger; Wanling Xie; Jae-Lyun Lee; Jennifer J Knox; Georg A Bjarnason; Mary J MacKenzie; Lori Wood; Sandy Srinivas; Ulka N Vaishampayan; Sun-Young Rha; Sumanta K Pal; Frede Donskov; Srinivas K Tantravahi; Brian I Rini; Daniel Y C Heng; Toni K Choueiri

doi:10.1016/j.eururo.2013.08.012

Impact of bone and liver metastases on patients with renal cell carcinoma treated with targeted therapy

Eur Urol. 2014 Mar;65(3):577-84. doi: 10.1016/j.eururo.2013.08.012. Epub 2013 Aug 15.

Authors

Rana R McKay¹, Nils Kroeger², Wanling Xie³, Jae-Lyun Lee⁴, Jennifer J Knox⁵, Georg A Bjarnason⁶, Mary J MacKenzie⁷, Lori Wood⁸, Sandy Srinivas⁹, Ulka N Vaishampayan¹⁰, Sun-Young Rha¹¹, Sumanta K Pal¹², Frede Donskov¹³, Srinivas K Tantravahi¹⁴, Brian I Rini¹⁵, Daniel Y C Heng¹⁶, Toni K Choueiri¹⁷

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
² Department of Oncology, Tom Baker Cancer Center/University of Calgary, Calgary, Canada; Department of Urology, University Medicine Greifswald, Greifswald, Germany.
³ Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
⁴ Department of Oncology, Asan Medical Center/University of Ulsan College of Medicine, Seoul, South Korea.
⁵ Departments of Hematology and Medical Oncology, Princess Margaret Hospital, Toronto, Canada.
⁶ Division of Medical Oncology/Hematology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Canada.
⁷ Department of Medical Oncology, London Regional Cancer Program, London, Canada.
⁸ Division of Medical Oncology, Queen Elizabeth II Health Sciences Centre, Halifax, Canada.
⁹ Division of Oncology, Stanford Medical Center, Stanford, CA, USA.
¹⁰ Division of Hematology/Oncology, Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA.
¹¹ Division of Medical Oncology, Yonsei Cancer Center/Yonsei University College of Medicine, Seoul, South Korea.
¹² Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
¹³ Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
¹⁴ Division of Medical Oncology/Hematology, University of Utah/Huntsman Cancer Institute, Salt Lake City, UT, USA.
¹⁵ Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
¹⁶ Department of Oncology, Tom Baker Cancer Center/University of Calgary, Calgary, Canada.
¹⁷ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: toni_choueiri@DFCI.harvard.edu.

Abstract

Background: The skeleton and liver are frequently involved sites of metastasis in patients with metastatic renal cell carcinoma (RCC).

Objective: To analyze outcomes based on the presence of bone metastases (BMs) and/or liver metastases (LMs) in patients with RCC treated with targeted therapy.

Design, setting, and participants: We conducted a review from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) of 2027 patients with metastatic RCC.

Outcome measurements and statistical analysis: We analyzed the impact of the site of metastasis on overall survival (OS) and time-to-treatment failure. Statistical analyses were performed using multivariable Cox regression.

Results and limitations: The presence of BMs was 34% overall, and when stratified by IMDC risk groups was 27%, 33%, and 43% in the favorable-, intermediate-, and poor-risk groups, respectively (p<0.001). The presence of LMs was 19% overall and higher in the poor-risk patients (23%) compared with the favorable- or intermediate-risk groups (17%) (p=0.003). When patients were classified into four groups based on the presence of BMs and/or LMs, the hazard ratio, adjusted for IMDC risk factors, was 1.4 (95% confidence interval [CI], 1.22-1.62) for BMs, 1.42 (95% CI, 1.17-1.73) for LMs, and 1.82 (95% CI, 1.47-2.26) for both BMs and LMs compared with other metastatic sites (p<0.0001). The prediction model performance for OS was significantly improved when BMs and LMs were added to the IMDC prognostic model (likelihood ratio test p<0.0001). Data in this analysis were collected retrospectively.

Conclusions: The presence of BMs and LMs in patients treated with targeted agents has a negative impact on survival. Patients with BMs and/or LMs may benefit from earlier inclusion on clinical trials of novel agents or combination-based therapies.

Keywords: Bone metastases; Liver metastases; Outcome; Renal cell carcinoma; VEGF therapy; mTOR inhibitors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bone Neoplasms / secondary*
Carcinoma, Renal Cell / drug therapy*
Carcinoma, Renal Cell / secondary*
Female
Humans
Kidney Neoplasms / drug therapy*
Kidney Neoplasms / pathology*
Liver Neoplasms / secondary*
Male
Molecular Targeted Therapy
Retrospective Studies

Abstract

Publication types

MeSH terms

Grants and funding