title: The association between metformin use and oncologic outcomes among surgically treated diabetic patients with localized renal cell carcinoma.
abstract: BACKGROUND
  Metformin inhibits renal cell carcinoma (RCC) cell proliferation both in vitro and in vivo; however, clinical data regarding the effect of metformin in patients with RCC are lacking. We evaluated the association of metformin use with outcomes among patients with surgically treated localized RCC.
  
  
  METHODS
  We identified 283 consecutive diabetic patients treated surgically for localized RCC between January 1, 1994 and December 31, 2008. Clinicopathologic features were compared between patients exposed to metformin (n = 83, 29%) and those who were not (n = 200, 71%). Progression-free, cancer-specific, and overall survival rates were estimated with the Kaplan-Meier analysis, and Cox models were used to evaluate the association of metformin use with outcomes.
  
  
  CONCLUSIONS
  Patients receiving metformin had a better renal function (median estimated glomerular filtration rate = 65 vs. 55 ml/min/1.73 m(2), P<0.001), performance status (Eastern Cooperative Oncology Group<1: 89% vs. 71%, P = 0.001), and lower Charlson comorbidity index (median = 2 vs. 3, P = 0.02) compared with those who did not, but were otherwise similar across other clinicopathologic features (P>0.05 for all). At a median postoperative follow-up of 8.1 years, patients exposed to metformin had similar 5-year progression-free (80% vs. 75%, P = 0.6) and cancer-specific survival rates (91% vs. 81%, P = 0.16), but significantly improved overall survival rate (79% vs. 62%, P = 0.01). However, metformin was not independently associated with the risks of progression, RCC-specific mortality, or all-cause mortality on multivariable analyses. In this surgical cohort of diabetic patients with M0 RCC, preoperative metformin exposure was associated with improved overall survival on unadjusted analysis. Although metformin was not independently associated with oncologic or survival outcomes, future studies appear warranted.
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN.
authors.forename: Sarah P
authors.initials: SP
authors.lastname: Psutka
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Boorjian
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Lohse
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN.
authors.forename: Suzanne B
authors.initials: SB
authors.lastname: Stewart
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Tollefson
authors.affiliation: Department of Pathology, Mayo Clinic, Rochester, MN.
authors.forename: John C
authors.initials: JC
authors.lastname: Cheville
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN.
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Leibovich
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN. Electronic address: thompson.robert@mayo.edu.
authors.forename: R Houston
authors.initials: RH
authors.lastname: Thompson
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Diabetes; Metformin; Mortality; Recurrence; Renal cell carcinoma