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. 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.
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.
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