Metformin and prostate cancer: Reduced development of castration-resistant disease and prostate cancer mortality Journal Article

Authors: Spratt, D. E.; Zhang, C.; Zumsteg, Z. S.; Pei, X.; Zhang, Z.; Zelefsky, M. J.
Article Title: Metformin and prostate cancer: Reduced development of castration-resistant disease and prostate cancer mortality
Abstract: Background: In vitro data and early clinical results suggest that metformin has desirable antineoplastic effects and has a theoretical benefit on castration-resistant prostate cancer (CRPC). Objective: To determine whether the use of metformin would be associated with improved clinical outcomes and a reduction in the development of CRPC. Design, setting, and participants: Data from 2901 consecutive patients (157 metformin, 162 diabetic non-metformin, and 2582 nondiabetic) with localized prostate cancer treated with external-beam radiation therapy from 1992 to 2008 were collected from a single institution in the United States. Intervention: Use of metformin in localized prostate cancer. Outcome measurements and statistical analysis: Univariate and multivariate regression models utilizing k-sample, Fine and Gray, Cox regression, log-rank, and Kaplan-Meier methods to assess prostate-specific antigen-recurrence-free survival (PSA-RFS), distant metastases-free survival (DMFS), prostate cancer-specific mortality (PCSM), overall survival (OS), and development of CRPC. Results and limitations: With a median follow-up of 8.7 yr, the 10-yr actuarial rates for metformin, diabetic non-metformin, and nondiabetic patients for PCSM were 2.7%, 21.9%, and 8.2% (log-rank p ≤ 0.001), respectively. Metformin use independently predicted (correcting for PSA, T stage, Gleason score, age, diabetic status, and androgen-deprivation therapy use) improvement in all outcomes compared with the diabetic non-metformin group; PSA-RFS (hazard ratio [HR]: 1.99 [1.24-3.18]; p = 0.004), DMFS (adjusted HR: 3.68 [1.78-7.62]; p < 0.001), and PCSM (HR: 5.15 [1.53-17.35]; p = 0.008). Metformin use was also independently associated with a decrease in the development of CRPC in patients experiencing biochemical failure compared with diabetic non-metformin patients (odds ratio: 14.81 [1.83-119.89]; p = 0.01). The retrospective study design was the primary limitation of the study. Conclusions: To our knowledge, our results are the first clinical data to indicate that metformin use may improve PSA-RFS, DMFS, PCSM, OS, and reduce the development of CRPC in prostate cancer patients. Further validation of metformin's potential benefits is warranted. © 2012 European Association of Urology.
Keywords: radiotherapy; prostate cancer; metformin; diabetes
Journal Title: European Urology
Volume: 63
Issue: 4
ISSN: 0302-2838
Publisher: Elsevier Science, Inc.  
Date Published: 2013-04-01
Start Page: 709
End Page: 716
Language: English
DOI: 10.1016/j.eururo.2012.12.004
PROVIDER: scopus
PUBMED: 23287698
PMCID: PMC4034673
Notes: --- - "Export Date: 1 April 2013" - "CODEN: EUURA" - "Source: Scopus"
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MSK Authors
  1. Zhigang Zhang
    240 Zhang
  2. Michael J Zelefsky
    616 Zelefsky
  3. Zachary Stephan Zumsteg
    34 Zumsteg
  4. Daniel Eidelberg Spratt
    83 Spratt
  5. Xin Pei
    98 Pei