Abstract
Purpose
To analyze the effect of the oral antidiabetic drug metformin on PSA level, free-to-total PSA ratio (f/t-ratio), PCa incidence and grade as well as mortality in men participating in a population-based screening trial.
Methods
Data from 4,314 men aged 55–70 years from a population-based PSA-screening trial (ERSPC Aarau) were analyzed. Information on metformin exposure was obtained by a self-administered questionnaire. Serum PSA threshold at ≥3 ng/ml triggered prostate biopsy. Data on PCa incidence and mortality were obtained through registry linkages.
Results
Median follow-up time was 7.6 years. Mean age at baseline was 65.5 years (±SD 4.4). In all, n = 150 (3.5 %) men used metformin [metf+]. Mean baseline PSA levels were comparable between both groups ([metf+] 1.6 ng/ml ± 2.4 vs. [metf−] 1.8ug/l ± 2.2, p = 0.4) while f/t-ratio was slightly higher in metformin users ([metf+] 30.7 % ± 10.9 vs. [metf−] 27.3 % ± 10.9, p = 0.01). Overall, n = 372 (8.6 %) PCa cases were detected. Neither cumulative PCa incidence (n = 11; 7.3 % [metf+] vs. n = 361 8.7 % [metf−]; p = 0.5) nor d`Amico risk groups were significantly different between both groups. One man in each group (metf+ 0.7 % and metf− 0.02 %) died from PCa (p < 0.0001), respectively. All-cause mortality was significantly higher among met + compared to met- (adjusted OR 2.50, 95 %CI 1.59–3.82; p = 0.0001).
Conclusion
No significant differences in PSA levels or PCa incidence and grade were observed. The slightly higher f/t-ratio did not result in lower PCa detection rate. Metformin users were at significantly higher risk of all-cause mortality. The relatively small number of men on metformin is a main limitation of the study.
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Acknowledgments
We thank Prof. Burkhard Seifert, Department of Biostatistics, University Zurich, Switzerland for statistical support. Furthermore, we thank Prof. Dr. Lukas Bubendorf, Pathology Committee of ERSPC, Institute for Pathology, Division of Cytology, University Hospital of Basel, Switzerland for reviewing all prostate cancer cases. Financial support ERSPC Switzerland: The Horten Foundation, Aargau Cancer League, Swiss Cancer League (Grant Nr KFS 787-2-1999 and 01112-02-2001), Health Department of Canton Aargau, Prostate Cancer Research Foundation, Baugarten Foundation and the Messerli Foundation.
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Randazzo, M., Beatrice, J., Huber, A. et al. Influence of metformin use on PSA values, free-to-total PSA, prostate cancer incidence and grade and overall survival in a prospective screening trial (ERSPC Aarau). World J Urol 33, 1189–1196 (2015). https://doi.org/10.1007/s00345-014-1426-y
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DOI: https://doi.org/10.1007/s00345-014-1426-y