title: Epidemiologic trends in renal cell carcinoma in the cytokine and post-cytokine eras: a registry analysis of 28,252 patients.
abstract: Advances in the targeted treatment of renal cell cancer (RCC) have shown improvements in survival in clinical trials and have largely replaced cytokine therapies as the standard of care. However it is unclear if these advances have translated to the general RCC population. We present a retrospective study of a large clinical cancer registry that demonstrates statistically significant improvements in survival in cancer patients, but the causes of this improvement are difficult to determine because of many confounders.
  
  
  BACKGROUND
  Before 2004, advanced renal cell cancer (RCC) therapy consisted primarily of cytokines such as interferon and/or interleukin-2. Subsequently, randomized trials of targeted therapies have shown a survival benefit, leading to the approval of several new agents since 2004. Whether the survival benefit seen in highly selected patients accrued to these trials has already translated to the general RCC patient population is unclear. To explore this, a large RCC patient registry was evaluated for changes in outcome between the cytokine (1998-2003) and post-cytokine (2004-2007) eras.
  
  
  METHODS
  Data from the California Cancer Registry (CCR), a population-based cancer surveillance system, was used to retrospectively analyze 28,252 patients with RCC diagnosed between 1998 and 2007. Inter-era differences in clinical variables-including year of diagnosis, histologic characteristics, age, sex, race, stage, nephrectomy status, overall survival (OS), and cause-specific survival (CSS)-were assessed. Univariate and multivariate Cox models were used.
  
  
  RESULTS
  Crude 3-year OS (68.2% vs. 74.6%; 2P < .001) and CSS (78.1% vs. 82.3%; 2P < .001) were significantly higher in the post-cytokine era. In multivariate analysis, the 3 strongest predictors for improved survival were localized disease (hazard ratio [HR], 18.1; 95% confidence interval [CI], 16.6-19.6), nephrectomy (HR, 2.87; 95% CI, 2.68-3.08), and clear cell histologic type (HR, 1.33; 95% CI, 1.22-1.44).
  
  
  CONCLUSIONS
  In this analysis of a large RCC registry, there was an apparent increase in crude OS and CSS in the post-cytokine era compared with the cytokine era. Insufficient follow-up time in the post-cytokine era and a higher proportion of localized disease in that era confound the possibility of benefit derived from targeted therapies. Longer follow-up for patients treated in the post-cytokine era is necessary for a more robust comparison of long-term OS.
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, University of California, Davis School of Medicine, Sacramento, CA 95817, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Shek
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tomlinson
authors.forename: Monica
authors.initials: M
authors.lastname: Brown
authors.forename: Ann
authors.initials: A
authors.lastname: Brunson
authors.forename: Chong-Xian
authors.initials: CX
authors.lastname: Pan
authors.forename: Primo N
authors.initials: PN
authors.lastname: Lara
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002140:California / Q000453:epidemiology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000401:mortality*; D016207:Cytokines / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D015999:Multivariate Analysis; D012042:Registries; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines