Metformin does not affect risk of biochemical recurrence following radical prostatectomy: Results from the SEARCH database

E. H. Allott, M. R. Abern, L. Gerber, C. J. Keto, W. J. Aronson, M. K. Terris, C. J. Kane, C. L. Amling, M. R. Cooperberg, P. G. Moorman, S. J. Freedland

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Abstract

Background:While epidemiologic studies suggest that metformin use among diabetics may decrease prostate cancer (PC) incidence, the effect of metformin use on PC outcome is unclear. We investigated the association between pre-operative metformin use, dose and duration of use and biochemical recurrence (BCR) in PC patients with diabetes who underwent radical prostatectomy (RP).Methods:We conducted a retrospective cohort analysis within the Shared Equal Access Regional Cancer Hospital (SEARCH) database of 371 PC patients with diabetes who underwent RP. Time to BCR between metformin users and non-users, and by metformin dose and duration of use was assessed using multivariable Cox proportional analysis adjusted for demographic, clinical and/or pathologic features. Time to castrate-resistant PC (CRPC), metastases and PC-specific mortality were explored as secondary outcomes using unadjusted analyses.Results:Of 371 diabetic men, 156 (42%) were using metformin before RP. Metformin use was associated with more recent year of surgery (P<0.0001) but no clinical or pathologic characteristics. After adjustment for year of surgery, clinical and pathologic features, there were no associations between metformin use (hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.61-1.41), high metformin dose (HR 0.96; 95% CI 0.57-1.61) or duration of use (HR 1.00; 95% CI 0.99-1.02) and time to BCR. A total of 14 patients (3.8%) developed CRPC, 10 (2.7%) distant metastases and 8 (2.2%) died from PC. Unadjusted analysis suggested that high metformin dose vs non-use was associated with increased risk of CRPC (HR 5.1; 95% CI 1.6-16.5), metastases (HR 4.8; 95% CI 1.2-18.5) and PC-specific mortality (HR 5.0; 95% CI 1.1-22.5).Conclusions:Metformin use, dose or duration of use was not associated with BCR in this cohort of diabetic PC patients treated with RP. The suggestion that higher metformin dose was associated with increased risk of CRPC, metastases and PC-specific mortality merits testing in large prospective studies with longer follow-up.

Original languageEnglish (US)
Pages (from-to)391-397
Number of pages7
JournalProstate Cancer and Prostatic Diseases
Volume16
Issue number4
DOIs
StatePublished - Dec 1 2013

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Cancer Care Facilities
Metformin
Prostatectomy
Prostatic Neoplasms
Databases
Recurrence
Confidence Intervals
Neoplasm Metastasis
Mortality
Epidemiologic Studies
Cohort Studies

Keywords

  • Biochemical recurrence
  • Diabetes
  • Metformin
  • Outcomes

ASJC Scopus subject areas

  • Oncology
  • Urology
  • Cancer Research

Cite this

Metformin does not affect risk of biochemical recurrence following radical prostatectomy : Results from the SEARCH database. / Allott, E. H.; Abern, M. R.; Gerber, L.; Keto, C. J.; Aronson, W. J.; Terris, M. K.; Kane, C. J.; Amling, C. L.; Cooperberg, M. R.; Moorman, P. G.; Freedland, S. J.

In: Prostate Cancer and Prostatic Diseases, Vol. 16, No. 4, 01.12.2013, p. 391-397.

Research output: Contribution to journalArticle

Allott, EH, Abern, MR, Gerber, L, Keto, CJ, Aronson, WJ, Terris, MK, Kane, CJ, Amling, CL, Cooperberg, MR, Moorman, PG & Freedland, SJ 2013, 'Metformin does not affect risk of biochemical recurrence following radical prostatectomy: Results from the SEARCH database', Prostate Cancer and Prostatic Diseases, vol. 16, no. 4, pp. 391-397. https://doi.org/10.1038/pcan.2013.48
Allott, E. H. ; Abern, M. R. ; Gerber, L. ; Keto, C. J. ; Aronson, W. J. ; Terris, M. K. ; Kane, C. J. ; Amling, C. L. ; Cooperberg, M. R. ; Moorman, P. G. ; Freedland, S. J. / Metformin does not affect risk of biochemical recurrence following radical prostatectomy : Results from the SEARCH database. In: Prostate Cancer and Prostatic Diseases. 2013 ; Vol. 16, No. 4. pp. 391-397.
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abstract = "Background:While epidemiologic studies suggest that metformin use among diabetics may decrease prostate cancer (PC) incidence, the effect of metformin use on PC outcome is unclear. We investigated the association between pre-operative metformin use, dose and duration of use and biochemical recurrence (BCR) in PC patients with diabetes who underwent radical prostatectomy (RP).Methods:We conducted a retrospective cohort analysis within the Shared Equal Access Regional Cancer Hospital (SEARCH) database of 371 PC patients with diabetes who underwent RP. Time to BCR between metformin users and non-users, and by metformin dose and duration of use was assessed using multivariable Cox proportional analysis adjusted for demographic, clinical and/or pathologic features. Time to castrate-resistant PC (CRPC), metastases and PC-specific mortality were explored as secondary outcomes using unadjusted analyses.Results:Of 371 diabetic men, 156 (42{\%}) were using metformin before RP. Metformin use was associated with more recent year of surgery (P<0.0001) but no clinical or pathologic characteristics. After adjustment for year of surgery, clinical and pathologic features, there were no associations between metformin use (hazard ratio (HR) 0.93; 95{\%} confidence interval (CI) 0.61-1.41), high metformin dose (HR 0.96; 95{\%} CI 0.57-1.61) or duration of use (HR 1.00; 95{\%} CI 0.99-1.02) and time to BCR. A total of 14 patients (3.8{\%}) developed CRPC, 10 (2.7{\%}) distant metastases and 8 (2.2{\%}) died from PC. Unadjusted analysis suggested that high metformin dose vs non-use was associated with increased risk of CRPC (HR 5.1; 95{\%} CI 1.6-16.5), metastases (HR 4.8; 95{\%} CI 1.2-18.5) and PC-specific mortality (HR 5.0; 95{\%} CI 1.1-22.5).Conclusions:Metformin use, dose or duration of use was not associated with BCR in this cohort of diabetic PC patients treated with RP. The suggestion that higher metformin dose was associated with increased risk of CRPC, metastases and PC-specific mortality merits testing in large prospective studies with longer follow-up.",
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T1 - Metformin does not affect risk of biochemical recurrence following radical prostatectomy

T2 - Results from the SEARCH database

AU - Allott, E. H.

AU - Abern, M. R.

AU - Gerber, L.

AU - Keto, C. J.

AU - Aronson, W. J.

AU - Terris, M. K.

AU - Kane, C. J.

AU - Amling, C. L.

AU - Cooperberg, M. R.

AU - Moorman, P. G.

AU - Freedland, S. J.

PY - 2013/12/1

Y1 - 2013/12/1

N2 - Background:While epidemiologic studies suggest that metformin use among diabetics may decrease prostate cancer (PC) incidence, the effect of metformin use on PC outcome is unclear. We investigated the association between pre-operative metformin use, dose and duration of use and biochemical recurrence (BCR) in PC patients with diabetes who underwent radical prostatectomy (RP).Methods:We conducted a retrospective cohort analysis within the Shared Equal Access Regional Cancer Hospital (SEARCH) database of 371 PC patients with diabetes who underwent RP. Time to BCR between metformin users and non-users, and by metformin dose and duration of use was assessed using multivariable Cox proportional analysis adjusted for demographic, clinical and/or pathologic features. Time to castrate-resistant PC (CRPC), metastases and PC-specific mortality were explored as secondary outcomes using unadjusted analyses.Results:Of 371 diabetic men, 156 (42%) were using metformin before RP. Metformin use was associated with more recent year of surgery (P<0.0001) but no clinical or pathologic characteristics. After adjustment for year of surgery, clinical and pathologic features, there were no associations between metformin use (hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.61-1.41), high metformin dose (HR 0.96; 95% CI 0.57-1.61) or duration of use (HR 1.00; 95% CI 0.99-1.02) and time to BCR. A total of 14 patients (3.8%) developed CRPC, 10 (2.7%) distant metastases and 8 (2.2%) died from PC. Unadjusted analysis suggested that high metformin dose vs non-use was associated with increased risk of CRPC (HR 5.1; 95% CI 1.6-16.5), metastases (HR 4.8; 95% CI 1.2-18.5) and PC-specific mortality (HR 5.0; 95% CI 1.1-22.5).Conclusions:Metformin use, dose or duration of use was not associated with BCR in this cohort of diabetic PC patients treated with RP. The suggestion that higher metformin dose was associated with increased risk of CRPC, metastases and PC-specific mortality merits testing in large prospective studies with longer follow-up.

AB - Background:While epidemiologic studies suggest that metformin use among diabetics may decrease prostate cancer (PC) incidence, the effect of metformin use on PC outcome is unclear. We investigated the association between pre-operative metformin use, dose and duration of use and biochemical recurrence (BCR) in PC patients with diabetes who underwent radical prostatectomy (RP).Methods:We conducted a retrospective cohort analysis within the Shared Equal Access Regional Cancer Hospital (SEARCH) database of 371 PC patients with diabetes who underwent RP. Time to BCR between metformin users and non-users, and by metformin dose and duration of use was assessed using multivariable Cox proportional analysis adjusted for demographic, clinical and/or pathologic features. Time to castrate-resistant PC (CRPC), metastases and PC-specific mortality were explored as secondary outcomes using unadjusted analyses.Results:Of 371 diabetic men, 156 (42%) were using metformin before RP. Metformin use was associated with more recent year of surgery (P<0.0001) but no clinical or pathologic characteristics. After adjustment for year of surgery, clinical and pathologic features, there were no associations between metformin use (hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.61-1.41), high metformin dose (HR 0.96; 95% CI 0.57-1.61) or duration of use (HR 1.00; 95% CI 0.99-1.02) and time to BCR. A total of 14 patients (3.8%) developed CRPC, 10 (2.7%) distant metastases and 8 (2.2%) died from PC. Unadjusted analysis suggested that high metformin dose vs non-use was associated with increased risk of CRPC (HR 5.1; 95% CI 1.6-16.5), metastases (HR 4.8; 95% CI 1.2-18.5) and PC-specific mortality (HR 5.0; 95% CI 1.1-22.5).Conclusions:Metformin use, dose or duration of use was not associated with BCR in this cohort of diabetic PC patients treated with RP. The suggestion that higher metformin dose was associated with increased risk of CRPC, metastases and PC-specific mortality merits testing in large prospective studies with longer follow-up.

KW - Biochemical recurrence

KW - Diabetes

KW - Metformin

KW - Outcomes

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