title: Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study.
abstract: OBJECTIVE
  There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) treated with vascular endothelial growth factor (VEGF) -targeted therapy.
  
  
  METHODS
  Baseline characteristics and outcomes on 645 patients with anti-VEGF therapy-naïve metastatic RCC were collected from three US and four Canadian cancer centers. Cox proportional hazards regression, followed by bootstrap validation, was used to identify independent prognostic factors for OS.
  
  
  RESULTS
  The median OS for the whole cohort was 22 months (95% CI, 20.2 to 26.5 months), and the median follow-up was 24.5 months. Overall, 396, 200, and 49 patients were treated with sunitinib, sorafenib, and bevacizumab, respectively. Four of the five adverse prognostic factors according to the Memorial Sloan-Kettering Cancer Center (MSKCC) were independent predictors of short survival: hemoglobin less than the lower limit of normal (P < .0001), corrected calcium greater than the upper limit of normal (ULN; P = .0006), Karnofsky performance status less than 80% (P < .0001), and time from diagnosis to treatment of less than 1 year (P = .01). In addition, neutrophils greater than the ULN (P < .0001) and platelets greater than the ULN (P = .01) were independent adverse prognostic factors. Patients were segregated into three risk categories: the favorable-risk group (no prognostic factors; n = 133), in which median OS (mOS) was not reached and 2-year OS (2y OS) was 75%; the intermediate-risk group (one or two prognostic factors; n = 301), in which mOS was 27 months and 2y OS was 53%; and the poor-risk group (three to six prognostic factors; n = 152), in which mOS was 8.8 months and 2y OS was 7% (log-rank P < .0001). The C-index was 0.73.
  
  
  CONCLUSIONS
  This model validates components of the MSKCC model with the addition of platelet and neutrophil counts and can be incorporated into patient care and into clinical trials that use VEGF-targeted agents.
authors.affiliation: FRCPC, Department of Medical Oncology, Tom Baker Cancer Center, University of Calgary, Calgary, Alberta, Canada. daniel.heng@cancerboard.ab.ca
authors.forename: Daniel Y C
authors.initials: DY
authors.lastname: Heng
authors.forename: Wanling
authors.initials: W
authors.lastname: Xie
authors.forename: Meredith M
authors.initials: MM
authors.lastname: Regan
authors.forename: Mark A
authors.initials: MA
authors.lastname: Warren
authors.forename: Ali Reza
authors.initials: AR
authors.lastname: Golshayan
authors.forename: Chakshu
authors.initials: C
authors.lastname: Sahi
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Eigl
authors.forename: J Dean
authors.initials: JD
authors.lastname: Ruether
authors.forename: Tina
authors.initials: T
authors.lastname: Cheng
authors.forename: Scott
authors.initials: S
authors.lastname: North
authors.forename: Peter
authors.initials: P
authors.lastname: Venner
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.forename: Kim N
authors.initials: KN
authors.lastname: Chi
authors.forename: Christian
authors.initials: C
authors.lastname: Kollmannsberger
authors.forename: David F
authors.initials: DF
authors.lastname: McDermott
authors.forename: William K
authors.initials: WK
authors.lastname: Oh
authors.forename: Michael B
authors.initials: MB
authors.lastname: Atkins
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Bukowski
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000627:therapeutic use; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000401:mortality* / Q000556:secondary*; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011379:Prognosis; D011725:Pyridines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D000077157:Sorafenib; D000077210:Sunitinib; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000068258:Bevacizumab; D000077157:Sorafenib; D000077210:Sunitinib