title: Conditional survival of patients with metastatic renal-cell carcinoma treated with VEGF-targeted therapy: a population-based study.
abstract: BACKGROUND
  The advent of targeted therapies in the past 7 years has extended median survival for metastatic renal-cell carcinoma. This improvement in clinical outcome has created a need for new, more accurate prognostic measures. We assessed the use of conditional survival--a measure that accounts for elapsed time since treatment initiation--for prognostication in patients with metastatic renal-cell carcinoma treated with first-line VEGF-targeted therapies.
  
  
  METHODS
  We obtained data for patients with metastatic renal-cell carcinoma who were treated with a first-line VEGF-targeted therapy between April 7, 2003, and Oct 12, 2010, from our large multi-institutional International mRCC Database Consortium (centres in Canada, the USA, Singapore, Denmark, and South Korea). All histologies, performance statuses, and prognostic risk groups were included. The primary outcome was 2-year conditional survival, defined as the probability of surviving an additional 2 years from a given timepoint since the start of targeted therapy. Secondary analyses included 1-year and 3-year conditional survival, along with stratification of patients by Heng prognostic risk criteria and Karnofsky performance score, and conditional survival based on length of time on therapy. We used the Kaplan-Meier method and a landmark analysis to calculate conditional survival.
  
  
  RESULTS
  In the 1673 patients analysed, median follow-up for alive patients was 20·1 months (IQR 9·0-34·4). We recorded an increase in the 2-year conditional survival probability from 44% (95% CI 41-47) at 0 months to 51% (46-55) at 18 months since beginning targeted therapy. When stratified by the Heng prognostic risk criteria defined at therapy initiation, 2-year conditional survival changed little in the favourable and intermediate groups, but in the poor-risk group, 2-year conditional survival improved from 11% (8-15) at 0 months to 33% (18-48) after 18 months. When conditioned on time on targeted therapy from 0 months to 18 months, 2-year conditional survival improved from 44% (41-47) to 68% (60-75) in the overall population and from 74% (68-79) to 90% (77-96) in the favourable group, 49% (45-53) to 57% (45-67) in the intermediate group, and 11% (8-15) to 73% (43-89) in the poor risk group.
  
  
  CONCLUSIONS
  Conditional survival is a clinically useful prediction measure that adjusts prognosis of patients with metastatic renal-cell carcinoma on the basis of survival since treatment initiation or therapy duration. Conditional survival might be especially relevant to adjust prognosis for poor-risk patients.
  
  
  BACKGROUND
  The Trust Family Fund for Kidney Cancer Research.
authors.affiliation: Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Harshman
authors.forename: Wanling
authors.initials: W
authors.lastname: Xie
authors.forename: Georg A
authors.initials: GA
authors.lastname: Bjarnason
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.forename: Mary
authors.initials: M
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: Vaishampayan
authors.forename: Min-Han
authors.initials: MH
authors.lastname: Tan
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Rha
authors.forename: Frede
authors.initials: F
authors.lastname: Donskov
authors.forename: Neeraj
authors.initials: N
authors.lastname: Agarwal
authors.forename: Christian
authors.initials: C
authors.lastname: Kollmannsberger
authors.forename: Scott
authors.initials: S
authors.lastname: North
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.forename: Daniel Y C
authors.initials: DY
authors.lastname: Heng
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality* / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D015996:Survival Rate
chemical_list: D040262:Receptors, Vascular Endothelial Growth Factor