title: Metastatic non-clear cell renal cell carcinoma treated with targeted therapy agents: characterization of survival outcome and application of the International mRCC Database Consortium criteria.
abstract: BACKGROUND
  This study aimed to apply the International mRCC Database Consortium (IMDC) prognostic model in metastatic non-clear cell renal cell carcinoma (nccRCC). In addition, the survival outcome of metastatic nccRCC patients was characterized.
  
  
  METHODS
  Data on 2215 patients (1963 with clear-cell RCC [ccRCC] and 252 with nccRCC) treated with first-line VEGF- and mTOR-targeted therapies were collected from the IMDC. Time to treatment failure (TTF) and overall survival (OS) were compared in groups with favorable, intermediate, and poor prognoses according to IMDC prognostic criteria
  
  
  RESULTS
  The median OS of the entire cohort was 20.9 months. nccRCC patients were younger (P < .0001) and more often presented with low hemoglobin (P = .014) and elevated neutrophils (P = .0001), but otherwise had clinicopathological features similar to those of ccRCC patients. OS (12.8 vs 22.3 months; P < .0001) and TTF (4.2 vs 7.8 months; P < .0001) were worse in nccRCC patients compared with ccRCC patients. The hazard ratio for death and TTF when adjusted for the prognostic factors was 1.41 (95% CI, 1.19-1.67; P < .0001) and 1.54 (95% CI, 1.33-1.79; P < .0001), respectively. The IMDC prognostic model reliably discriminated 3 risk groups to predict OS and TTF in nccRCC; the median OS of the favorable, intermediate, and poor prognosis groups was 31.4, 16.1, and 5.1 months, respectively (P < .0001), and the median TTF was 9.6, 4.9, and 2.1 months, respectively (P < .0001).
  
  
  CONCLUSIONS
  Although targeted agents have significantly improved the outcome of patients with nccRCC, for the majority survival is still inferior compared with patients with ccRCC. The IMDC prognostic model reliably predicts OS and TTF in nccRCC and ccRCC patients.
authors.affiliation: Tom Baker Cancer Center, Calgary, Alberta, Canada.
authors.forename: Nils
authors.initials: N
authors.lastname: Kroeger
authors.forename: Wanling
authors.initials: W
authors.lastname: Xie
authors.forename: Jae-Lyn
authors.initials: JL
authors.lastname: Lee
authors.forename: Georg A
authors.initials: GA
authors.lastname: Bjarnason
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Mackenzie
authors.forename: Lori
authors.initials: L
authors.lastname: Wood
authors.forename: Sandy
authors.initials: S
authors.lastname: Srinivas
authors.forename: Ulka N
authors.initials: UN
authors.lastname: Vaishamayan
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Rha
authors.forename: Sumanta K
authors.initials: SK
authors.lastname: Pal
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yuasa
authors.forename: Frede
authors.initials: F
authors.lastname: Donskov
authors.forename: Neeraj
authors.initials: N
authors.lastname: Agarwal
authors.forename: Christian K
authors.initials: CK
authors.lastname: Kollmannsberger
authors.forename: Min-Han
authors.initials: MH
authors.lastname: Tan
authors.forename: Scott A
authors.initials: SA
authors.lastname: North
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.forename: Daniel Y C
authors.initials: DY
authors.lastname: Heng
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002170:Canada / Q000453:epidemiology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality*; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D011379:Prognosis; D056910:Republic of Korea / Q000453:epidemiology; D012846:Singapore / Q000453:epidemiology; D016019:Survival Analysis; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D000970:Antineoplastic Agents
keywords: Heng risk criteria; IMDC risk model; non-clear cell renal cell carcinoma; overall survival; prognostication; targeted therapies