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Protective Effects of Metformin Against Biochemical Failure Following Radical Prostatectomy or Radiation Therapy in Localized Prostate Cancer

  • Author Footnotes
    ⁎ Authors contributed equally.
    Linda My Huynh
    Footnotes
    ⁎ Authors contributed equally.
    Affiliations
    School of Medicine, University of Nebraska Medical Center; Omaha, NE

    Department of Urology, University of California, Irvine Medical Center; Omaha, NE
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  • Author Footnotes
    ⁎ Authors contributed equally.
    Emily Keit
    Footnotes
    ⁎ Authors contributed equally.
    Affiliations
    School of Medicine, University of Nebraska Medical Center; Omaha, NE
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  • Erica Huang
    Affiliations
    Department of Urology, University of California, Irvine Medical Center; Omaha, NE

    Division of Urology, Department of Surgery, University of Nebraska Medical Center; Omaha, NE

    Department of Radiation Oncology, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center; Omaha, NE
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  • Raymond Ceja Carrillo
    Affiliations
    School of Medicine, University of Nebraska Medical Center; Omaha, NE

    Department of Urology, University of California, Irvine Medical Center; Omaha, NE

    Division of Urology, Department of Surgery, University of Nebraska Medical Center; Omaha, NE

    Department of Radiation Oncology, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center; Omaha, NE
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  • Thomas E. Ahlering
    Affiliations
    School of Medicine, University of Nebraska Medical Center; Omaha, NE

    Department of Urology, University of California, Irvine Medical Center; Omaha, NE

    Division of Urology, Department of Surgery, University of Nebraska Medical Center; Omaha, NE

    Department of Radiation Oncology, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center; Omaha, NE
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  • Shawna Boyle
    Affiliations
    School of Medicine, University of Nebraska Medical Center; Omaha, NE

    Department of Urology, University of California, Irvine Medical Center; Omaha, NE

    Division of Urology, Department of Surgery, University of Nebraska Medical Center; Omaha, NE

    Department of Radiation Oncology, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center; Omaha, NE
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  • Charles A. Enke
    Affiliations
    School of Medicine, University of Nebraska Medical Center; Omaha, NE

    Department of Urology, University of California, Irvine Medical Center; Omaha, NE

    Division of Urology, Department of Surgery, University of Nebraska Medical Center; Omaha, NE

    Department of Radiation Oncology, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center; Omaha, NE
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  • Michael Baine
    Correspondence
    Address correspondence to: Michael J. Baine, M.D., Ph.D., Department of Radiation Oncology, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, 987521 Nebraska Medical Center, Omaha, NE 68198-7521.
    Affiliations
    School of Medicine, University of Nebraska Medical Center; Omaha, NE

    Department of Urology, University of California, Irvine Medical Center; Omaha, NE

    Division of Urology, Department of Surgery, University of Nebraska Medical Center; Omaha, NE

    Department of Radiation Oncology, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center; Omaha, NE
    Search for articles by this author
  • Author Footnotes
    ⁎ Authors contributed equally.
Published:January 27, 2021DOI:https://doi.org/10.1016/j.urology.2021.01.030

      ABSTRACT

      Objective

      To assess the impact of metformin on biochemical failure (BF) in localized prostate cancers (PC) treated with radical prostatectomy or radiation therapy.

      Materials and Methods

      About 1449 patients undergoing radical prostatectomy (n = 1338, 92.3%) or radiation therapy (n = 108, 7.5%) for localized PC between July 2007 and January 2020 were evaluated for metformin use, demographic/oncologic characteristics, and biochemical outcomes. Androgen deprivation therapy was utilized per NCCN guidelines. BF rates were assessed overall and at 1, 3, and 5 years. Time to BF was estimated via Kaplan-Meier; logistic regression and Cox proportionate hazards models were generated to adjust for significant differences.

      Results

      Of 1449 patients, 148 (10.2%) utilized metformin at time of diagnosis, while 1,301 (89.8%) did not. Patients on metformin were significantly older, had higher body mass indexes, and more aggressive disease (Gleason score >7). At a mean ± SD follow-up of 3.6 ± 2.6 years, patients on metformin were less likely to experience BF at later timepoints; however, univariate analysis showed no differences at 1, 3, and 5 years. In multivariate analysis, patients on metformin were significantly less likely to experience BF at 5 years and overall in both treatment groups. In Cox regression, metformin was independently associated with a 40% relative risk reduction in BF.

      Conclusion

      In multivariate analysis, metformin use was associated with a significant risk reduction in BF overall and at 5 years following primary treatment; this trend was not witnessed in univariate analysis. This suggests the need for future investigations of metformin's role in disease-free survival in men with localized PC.
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