title: Stage migration and increasing proportion of favorable-prognosis metastatic renal cell carcinoma patients: implications for clinical trial design and interpretation.
abstract: BACKGROUND
  The Memorial Sloan-Kettering Cancer Center risk model classifies patients with metastatic renal cell carcinoma (RCC) by 5 pretreatment features as favorable, intermediate, and poor risk. The number of Memorial Sloan-Kettering Cancer Center patients in each risk group was examined by year of treatment to analyze stage migration.
  
  
  METHODS
  The distribution of risk groups was examined retrospectively in 789 Memorial Sloan-Kettering Cancer Center patients with metastatic RCC treated in a first-line therapy clinical trial from 1975 to 2007. Date of treatment onset was divided into 6 cohorts between 1975 and 2007 (1975-1980, 1981-1985, 1986-1990, 1991-1995, 1996-2001, and 2001-2007).
  
  
  RESULTS
  The median age of the first-line metastatic RCC clinical trial patients was 59 years (range, 20-82 years). Most patients received cytokine therapy (55%), 37% received chemotherapy/other, and 8% received vascular endothelial growth factor-targeted therapies. Overall survival increased with each consecutive cohort year group (P < .001). Median survival was 0.43 years (95% confidence interval [CI], 0.27-0.68) in the 1973-1980 cohort and 1.5 years in the 2001-2007 cohort (95% CI, 1.15-2.11). Memorial Sloan-Kettering Cancer Center risk-group distribution shifted between 1975 and 2007 (P < .0001). The poor-risk group proportion became smaller (from 44% in 1975-1980 to 13% in 2001-2007), whereas the favorable-risk group increased (from 0% in 1975-1980 to 49% in 2001-2007). The intermediate-risk group remained stable at 50%. After adjusting for type of therapy, the shifts continue to be significant (P < .0001).
  
  
  CONCLUSIONS
  The risk-group distribution for metastatic RCC patients in clinical trials shifted from 1975 to 2007. These shifts have direct implications for data analysis, interpretation of metastatic RCC trends, and drug development.
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Sujata
authors.initials: S
authors.lastname: Patil
authors.forename: Nicole
authors.initials: N
authors.lastname: Ishill
authors.forename: John
authors.initials: J
authors.lastname: Deluca
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D013997:Time Factors