Christos E Kyriakopoulos1, Namita Chittoria2, Toni K Choueiri3, Nils Kroeger4, Jae-Lyun Lee5, Sandy Srinivas6, Jennifer J Knox7, Georg A Bjarnason8, Scott D Ernst9, Lori A Wood10, Ulka N Vaishampayan11, Neeraj Agarwal12, Sumanta K Pal13, Ravindran Kanesvaran14, Sun-Young Rha15, Takeshi Yuasa16, Frede Donskov17, Scott A North18, Daniel Y Heng19, Brian I Rini2. 1. Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH. Electronic address: ckyriakopou@gmail.com. 2. Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH. 3. Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA. 4. Department of Urology, University Hospital of Greifswald, Greifswald, Germany. 5. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. 6. Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA. 7. Department of Medicine, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada. 8. Department of Medical Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada. 9. Department of Medical Oncology, Western University, London, Ontario, Canada. 10. Department of Medicine and Urology, Queen Elizabeth II Health Sciences Center, Dalhousie University, Halifax, Nova Scotia, Canada. 11. Department of Medical Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI. 12. Department of Medical Oncology, University of Utah Huntsman Cancer Institute, Salt Lake City, UT. 13. Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA. 14. Department of Medical Oncology, National Cancer Centre Singapore, Singapore. 15. Department of Internal Medicine, Yonsei Cancer Center, Yonsei University Health System, Institute for Cancer Research, Yonsei University College of Medicine, Seoul, South Korea. 16. Departments of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan. 17. Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. 18. Department of Oncology, Cross Cancer Center, University of Alberta, Edmonton, Alberta, Canada. 19. Department of Medical Oncology, Tom Baker Cancer Center, University of Calgary, Calgary, Alberta, Canada.
Abstract
BACKGROUND: Sarcomatoid renal cell carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking. PATIENTS AND METHODS: Clinical, prognostic, and treatment parameters in metastatic renal cell carcinoma patients with and without sarcomatoid histology treated with targeted therapy were retrospectively analyzed. RESULTS: Two thousand two hundred eighty-six patients were identified (sRCC: n = 230 and non-sRCC: n = 2056). sRCC patients had significantly worse IMDC prognostic criteria compared with non-sRCC (11% vs. 19% favorable risk; 49% vs. 57% intermediate risk, and 40% vs. 24% poor risk; P < .0001). Time from original diagnosis to relapse (excluding synchronous metastatic disease) was shorter in the sRCC group (18.8 vs. 42.9 months; P < .0001). There was no significant difference in the incidence of central nervous system metastases (6%-8%) or underlying clear cell histology (87%-88%). More than 93% of patients received VEGF inhibitors as first-line therapy; objective response was less common in sRCC whereas primary refractory disease was more common (21% vs. 26% and 43% vs. 21%; P < .0001, for both). sRCC patients had significantly less use of second- (P = .018) and third-line (P < .0001) systemic therapy. The median progression-free survival (PFS)/overall survival (OS) was 4.5/10.4 months in sRCC patients and 7.8/22.5 months in non-sRCC patients (P < .0001 for both). Sarcomatoid histology was associated with a significantly worse PFS and OS after adjusting for individual IMDC risk factors in multivariable analysis (hazard ratio, 1.5; P < .0001 for both). CONCLUSION: Patients with sRCC have a shorter time to relapse, worse baseline prognostic criteria, and worse clinical outcome with targeted therapy. Additional insight into the biology of sRCC is needed to develop alternative therapeutics.
BACKGROUND:Sarcomatoid renal cell carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking. PATIENTS AND METHODS: Clinical, prognostic, and treatment parameters in metastatic renal cell carcinomapatients with and without sarcomatoid histology treated with targeted therapy were retrospectively analyzed. RESULTS: Two thousand two hundred eighty-six patients were identified (sRCC: n = 230 and non-sRCC: n = 2056). sRCC patients had significantly worse IMDC prognostic criteria compared with non-sRCC (11% vs. 19% favorable risk; 49% vs. 57% intermediate risk, and 40% vs. 24% poor risk; P < .0001). Time from original diagnosis to relapse (excluding synchronous metastatic disease) was shorter in the sRCC group (18.8 vs. 42.9 months; P < .0001). There was no significant difference in the incidence of central nervous system metastases (6%-8%) or underlying clear cell histology (87%-88%). More than 93% of patients received VEGF inhibitors as first-line therapy; objective response was less common in sRCC whereas primary refractory disease was more common (21% vs. 26% and 43% vs. 21%; P < .0001, for both). sRCC patients had significantly less use of second- (P = .018) and third-line (P < .0001) systemic therapy. The median progression-free survival (PFS)/overall survival (OS) was 4.5/10.4 months in sRCC patients and 7.8/22.5 months in non-sRCC patients (P < .0001 for both). Sarcomatoid histology was associated with a significantly worse PFS and OS after adjusting for individual IMDC risk factors in multivariable analysis (hazard ratio, 1.5; P < .0001 for both). CONCLUSION:Patients with sRCC have a shorter time to relapse, worse baseline prognostic criteria, and worse clinical outcome with targeted therapy. Additional insight into the biology of sRCC is needed to develop alternative therapeutics.
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Authors: Nizar M Tannir; Eric Jonasch; Laurence Albiges; Emre Altinmakas; Chaan S Ng; Surena F Matin; Xuemei Wang; Wei Qiao; Zita Dubauskas Lim; Pheroze Tamboli; Priya Rao; Kanishka Sircar; Jose A Karam; David F McDermott; Christopher G Wood; Toni K Choueiri Journal: Eur Urol Date: 2015-11-26 Impact factor: 20.096