title: Early primary tumor size reduction is an independent predictor of improved overall survival in metastatic renal cell carcinoma patients treated with sunitinib.
abstract: BACKGROUND
  In metastatic renal cell carcinoma (mRCC) patients treated with targeted agents and their primary tumor (PT) in situ, early PT decrease in size correlates with improved overall PT response, but the effect on overall survival (OS) is unknown.
  
  
  OBJECTIVE
  To evaluate whether early PT size reduction is associated with improved OS in patients with mRCC undergoing treatment with sunitinib.
  
  
  METHODS
  We reviewed the clinical and radiographic data of all mRCC patients seen at our institution between January 2004 and December 2009 without prior systemic treatment who received sunitinib with their PT in situ.
  
  
  METHODS
  Two independent reviewers measured the diameter of the PT and metastatic disease at baseline and subsequent scans to assess response. Early minor response was defined as ≥10% decrease within 60 d of treatment initiation. Univariate and multivariate analyses were used to calculate a hazard ratio (HR) corresponding to the risk of death based on clinical and pathologic factors as well as PT response.
  
  
  CONCLUSIONS
  We identified 75 consecutive patients with a median follow-up of 15 mo. All patients were intermediate or poor risk by common risk stratification systems. Median initial PT diameter was 9.7cm. Median maximum PT size reduction was -10.2% overall and -36.4% in patients who had early minor PT response. Median OS for patients without minor PT response, with minor PT response after 60 d, and with early minor PT response was 10.3, 16.5, and 30.2 mo, respectively. On multivariate analysis, early minor response was an independent predictor of improved OS (HR: 0.26; p=0.031). Other significant predictors included venous thrombus, multiple bone metastases, lactate dehydrogenase above the upper limit of normal, symptoms at presentation, and more than two metastatic sites.
  
  
  CONCLUSIONS
  Early minor PT response is associated with improved OS. Future studies should evaluate this prognostic factor to identify patients with prolonged OS.
authors.affiliation: Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: E Jason
authors.initials: EJ
authors.lastname: Abel
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Culp
authors.forename: Nizar M
authors.initials: NM
authors.lastname: Tannir
authors.forename: Pheroze
authors.initials: P
authors.lastname: Tamboli
authors.forename: Surena F
authors.initials: SF
authors.lastname: Matin
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011758:Pyrroles / Q000627:therapeutic use*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D000077210:Sunitinib; D015996:Survival Rate; D013781:Texas; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib