title: Prognostic factors of metastatic renal cell carcinoma after failure of immunotherapy: new paradigm from a large phase III trial with shark cartilage extract AE 941.
abstract: OBJECTIVE
  We analyzed prognostic factors, described survival and generated a prognostic model in patients with metastatic renal cell carcinoma in whom immunotherapy failed and who were potentially eligible for novel agents.
  
  
  METHODS
  An analysis of the relationship between clinical features and survival was performed in 300 patients with advanced renal cell carcinoma in whom immunotherapy had failed and who were subsequently treated as part of a single, phase III clinical trial with the anti-angiogenic agent Neovastat (shark cartilage extract AE 941). Clinical features were first examined univariately and a stepwise modeling approach based on Cox proportional hazard regression was then performed to generate a multivariate model.
  
  
  RESULTS
  Median and progression-free survival (prognostic factors) for the whole cohort was 12.6 and 2 months, respectively. Prognostic features associated with shorter survival on multivariate analysis were the number of metastatic sites (greater than 1), time from nephrectomy to metastatic disease (less than 2 years), high alkaline phosphatase, abnormal corrected serum Ca and high lactate dehydrogenase (greater than 1.5 x the upper limit of normal). Four prognostic subgroups were identified by counting the number of adverse prognostic factors. Median survival in patients with zero adverse prognostic factors was 15.6 months compared to 11.7 months in patients with 1, 8.5 months in patients with 2 and 3.5 months in patients with 3 or more.
  
  
  CONCLUSIONS
  We identified 4 risk groups to predict survival in previously treated patients with renal cell carcinoma. This model was based on data from what is to our knowledge the largest experience in this population. It should be used in clinical trial design, risk stratification and patient counseling.
authors.affiliation: Institut Gustave Roussy, Villejuif, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.forename: Stéphane
authors.initials: S
authors.lastname: Oudard
authors.forename: Cezary
authors.initials: C
authors.lastname: Szczylik
authors.forename: Sylvie
authors.initials: S
authors.lastname: Négrier
authors.forename: Alain
authors.initials: A
authors.lastname: Ravaud
authors.forename: Christine
authors.initials: C
authors.lastname: Chevreau
authors.forename: Peter
authors.initials: P
authors.lastname: Venner
authors.forename: Pierre
authors.initials: P
authors.lastname: Champagne
authors.forename: Daniel
authors.initials: D
authors.lastname: Croteau
authors.forename: Eric
authors.initials: E
authors.lastname: Dupont
authors.forename: Claude
authors.initials: C
authors.lastname: Hariton
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Bukowski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000416:Alberta / Q000453:epidemiology; D001706:Biopsy; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D002356:Cartilage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009820:Ohio / Q000453:epidemiology; D011044:Poland / Q000453:epidemiology; D011379:Prognosis; D016016:Proportional Hazards Models; D011792:Quebec / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014020:Tissue Extracts / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D014020:Tissue Extracts; C111481:shark cartilage extract