title: The impact of cytoreductive nephrectomy on survival of patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor targeted therapy.
abstract: OBJECTIVE
  Vascular endothelial growth factor targeted therapy is a standard of care in patients with metastatic renal cell carcinoma. The role of cytoreductive nephrectomy in the era of novel agents remains poorly defined.
  
  
  METHODS
  We retrospectively reviewed baseline characteristics and outcomes of 314 patients with anti-vascular endothelial growth factor therapy naïve, metastatic renal cell carcinoma from United States and Canadian cancer centers to study the impact of cytoreductive nephrectomy on overall survival.
  
  
  RESULTS
  Patients who underwent cytoreductive nephrectomy (201) were younger (p < 0.01), and more likely to have a better Karnofsky performance status (p < 0.01), more than 1 site of metastasis (p = 0.04) and lower corrected calcium levels (p < 0.01) compared to those who did not undergo cytoreductive nephrectomy (113). On univariable analysis cytoreductive nephrectomy was associated with a median overall survival of 19.8 months compared to 9.4 months for patients who did not undergo cytoreductive nephrectomy (HR 0.44; 95% CI 0.32, 0.59; p < 0.01). On multivariable analysis and adjusting for established prognostic risk factors the overall survival difference persisted (adjusted HR 0.68; 95% CI 0.46, 0.99; p = 0.04) in favor of the cytoreductive nephrectomy group. In subgroup analyses stratified for favorable/intermediate/poor risk criteria, patients in the poor risk group had a marginal benefit (p = 0.06). Similarly patients with Karnofsky performance status less than 80% also had a marginal survival benefit (p = 0.08).
  
  
  CONCLUSIONS
  In this retrospective study cytoreductive nephrectomy was independently associated with a prolonged overall survival of patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor targeted agents, although the benefit is marginal in those patients with poor risk features.
authors.affiliation: Kidney Cancer Center, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA. Toni_Choueiri@dfci.harvard.edu
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.forename: Wanling
authors.initials: W
authors.lastname: Xie
authors.forename: Christian
authors.initials: C
authors.lastname: Kollmannsberger
authors.forename: Scott
authors.initials: S
authors.lastname: North
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.forename: J Geoffrey
authors.initials: JG
authors.lastname: Lampard
authors.forename: David F
authors.initials: DF
authors.lastname: McDermott
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.forename: Daniel Y C
authors.initials: DY
authors.lastname: Heng
mesh_terms: 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 / Q000188:drug therapy / Q000401:mortality* / Q000556:secondary / Q000601:surgery*; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009392:Nephrectomy / Q000379:methods*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D012189:Retrospective Studies; D000077157:Sorafenib; D000077210:Sunitinib; D015996:Survival Rate; D042442:Vascular Endothelial Growth Factors / 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; D042442:Vascular Endothelial Growth Factors; D009536:Niacinamide; D000068258:Bevacizumab; D000077157:Sorafenib; D000077210:Sunitinib