title: Outcome of patients with metastatic sarcomatoid renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium.
abstract: BACKGROUND
  Sarcomatoid renal cell carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH. Electronic address: ckyriakopou@gmail.com.
authors.forename: Christos E
authors.initials: CE
authors.lastname: Kyriakopoulos
authors.affiliation: Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
authors.forename: Namita
authors.initials: N
authors.lastname: Chittoria
authors.affiliation: Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Department of Urology, University Hospital of Greifswald, Greifswald, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Kroeger
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Jae-Lyun
authors.initials: JL
authors.lastname: Lee
authors.affiliation: Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA.
authors.forename: Sandy
authors.initials: S
authors.lastname: Srinivas
authors.affiliation: Department of Medicine, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.affiliation: Department of Medical Oncology, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Georg A
authors.initials: GA
authors.lastname: Bjarnason
authors.affiliation: Department of Medical Oncology, Western University, London, Ontario, Canada.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Ernst
authors.affiliation: Department of Medicine and Urology, Queen Elizabeth II Health Sciences Center, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Lori A
authors.initials: LA
authors.lastname: Wood
authors.affiliation: Department of Medical Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI.
authors.forename: Ulka N
authors.initials: UN
authors.lastname: Vaishampayan
authors.affiliation: Department of Medical Oncology, University of Utah Huntsman Cancer Institute, Salt Lake City, UT.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Agarwal
authors.affiliation: Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA.
authors.forename: Sumanta K
authors.initials: SK
authors.lastname: Pal
authors.affiliation: Department of Medical Oncology, National Cancer Centre Singapore, Singapore.
authors.forename: Ravindran
authors.initials: R
authors.lastname: Kanesvaran
authors.affiliation: Department of Internal Medicine, Yonsei Cancer Center, Yonsei University Health System, Institute for Cancer Research, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Rha
authors.affiliation: Departments of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yuasa
authors.affiliation: Department of Oncology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Frede
authors.initials: F
authors.lastname: Donskov
authors.affiliation: Department of Oncology, Cross Cancer Center, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Scott A
authors.initials: SA
authors.lastname: North
authors.affiliation: Department of Medical Oncology, Tom Baker Cancer Center, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Daniel Y
authors.initials: DY
authors.lastname: Heng
authors.affiliation: Department of Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH.
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D016208:Databases, Factual; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D012189:Retrospective Studies; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A
keywords: IMDC risk model; Kidney cancer; Overall survival; Prognostication; Targeted therapies