Abstract
Background:
To evaluate the association between use of metformin and other antidiabetic drugs with tumor characteristics and survival in surgically managed prostate cancer (PCa) patients.
Methods:
The study population included 1314 men who underwent radical prostatectomy at the Tampere University Hospital during 1995–2009. Causes of deaths were collected from the Finnish Cancer Registry. Individual-level data on medication use during 1995–2009 was obtained from national prescription database. Fasting blood glucose and hemoglobin A1c values during the study period were gathered from hospital district database. Gleason grade and pathological stage were compared by drug use before surgery and separately by metformin usage. Risk of biochemical recurrence, all-cause death and PCa-specific death were calculated using Cox proportional hazard regression with adjustment for age, tumor characteristics, glycemic control and use of other drug groups.
Results:
High-grade tumors were more common among antidiabetic drug users (P=0.032), including metformin users (P=0.012). Despite this, no difference in PSA levels was observed. Men who had used antidiabetic drugs before surgery had an increased risk of Gleason 7–10 disease (odds ratio (OR) 1.83, 95% confidence interval (CI) 1.04–3.23). The risk of high-grade PCa was higher among metformin users compared with other antidiabetic drug users (OR 3.11, 95% CI 1.16–8.33). During the median follow-up of 8.6 years after surgery, 551 men had biochemical recurrence and 244 died, 32 owing to PCa. Generally, no association with risk of disease recurrence was observed. Risk of death was increased by preoperative use of antidiabetic drugs (hazard ratio 1.81 95% CI 1.03–3.19), but no survival associations for postoperative use of antidiabetic drugs or metformin were observed.
Conclusion:
Diabetic men have more high-grade PCa at lower PSA levels, but that does not have a clear impact on disease-specific survival in the short term even when glycemic control is being considered.
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References
Abdollah F, Briganti A, Suardi N, Gallina A, Capitanio U, Salonia A et al. Does diabetes mellitus increase the risk of high-grade prostate cancer in patients undergoing radical prostatectomy? Prostate Cancer Prostatic Dis 2011; 14: 74–78.
Ozbek E, Otunctemur A, Dursun M, Sahin S, Besiroglu H, Koklu I et al. Diabetes mellitus and hba1c levels associated with high grade prostate cancer. Asian Pac J Cancer Prev 2014; 15: 2555–2558.
Kim HS, Presti JC Jr, Aronson WJ, Terris MK, Kane CJ, Amling CL et al. Glycemic control and prostate cancer progression: results from the SEARCH database. Prostate 2010; 70: 1540–1546.
Lee H, Kuk H, Byun SS, Lee SE, Hong SK . Preoperative glycemic control status as a significant predictor of biochemical recurrence in prostate cancer patients after radical prostatectomy. PLoS ONE 2014; 9: e104789.
Onitilo AA, Stankowski RV, Berg RL, Engel JM, Glurich I, Williams GM et al. Type 2 diabetes mellitus, glycemic control and cancer risk. Eur J Cancer Prev 2014; 23: 134–140.
Margel D, Urbach DR, Lipscombe LL, Bell CM, Kulkarni G, Austin PC et al. Metformin use and all-cause and prostate cancer-specific mortality among men with diabetes. J Clin Oncol 2013; 31: 3069–3075.
Hitron A, Adams V, Talbert J, Steinke D . The influence of antidiabetic medications on the development and progression of prostate cancer. Cancer Epidemiol 2012; 36: 243–250.
Rieken M, Kluth LA, Xylinas E, Fajkovic H, Becker A, Karakiewicz PI et al. Association of diabete mellitus and metformin use with biochemical recurrence in patients treated with radical prostatectomy for prostate cancer. World J Urol 2014; 32: 999–1005.
Grinder-Hansen L, Ribel-Madsen R, Woitaszewski JF, Poulsen P, Grunnet LG, Vaag A . A common variation of the PTEN gene is associated with peripheral insulin resistance. Diabetes Metab 2016 (in press).
Epstein JI, Allsbrook WC, Amin MB, Egewad LL ; ISUP Grading Committee. The 2005 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am J Surg Pathol 2005; 29: 1228–1242.
Who Collaborating Centre for Drug Statistics Methodology, ATC/DDD Index 2013, 2013. Available from http://www.whocc.no/atc_ddd_index/.
Laitinen S, Martikainen PM, Tolonen T, Isola J, Tammela TL, Visakorpi T . EZH2, Ki-67 and MCM7 are prognostic markers in prostatectomy treated patients. Int J Cancer 2008; 122: 595–602.
Saramäki OR, Harjula AE, Martikainen PM, Vessella RL, Tammela TL, Visakorpi T . TMPRSS2:ERG fusion identifies a subgroup of prostate cancers with a favorable prognosis. Clin Cancer Res 2008; 14: 3395–3400.
Makkonen H, Jääskeläinen T, Pitkänen-Arsiola T, Rytinki M, Waltering KK, Mättö M et al. Identification of ETS-like transcription factor 4 as a novel androgen receptor target in prostate cancer cells. Oncogene 2008; 27: 4865–4876.
Leinonen KA, Saramäki OR, Furusato B, Kimura T, Takahashi H, Egawa S et al. Loss of PTEN is associated with aggressive behavior in ERG-positive prostate cancer. Cancer Epidemiol Biomarkers Prev 2013; 22: 2333–2344.
Pierce BL . Why are diabetics at reduced risk for prostate cancer? A review of the epidemiologic evidence. Urol Oncol 2012; 30: 735–743.
Allott EH, Abern MR, Gerber L, Keto CJ, Aronson WJ, Terris MK et al. Metformin does not affect risk of biochemical recurrence following radical prostatectomy: results from the SEARCH database. Prostate Cancer Prostatic Dis 2013; 16: 391–397.
Cai H, Xu Z, Xu T, Yu B, Zou Q . Diabetes mellitus and the risk of mortality among patients with prostate cancer: a meta-analysis of 11 cohort studies. Diabetes Metah Res Rev 2015; 31: 336–343.
Acknowledgements
We thank Ms Kirsi Rouhento for her work in updating the TaUH clinical database and for her help in retrieving the data.
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TLJ Tammela is a paid consultant for Astellas, GSK, Pfizer, Orion Pharma and Amgen; TJ Murtola receives lecture fees from Janssen-Cilag and MSD and is a paid consultant for Astellas. The other authors declare no conflict of interest.
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Joentausta, R., Kujala, P., Visakorpi, T. et al. Tumor features and survival after radical prostatectomy among antidiabetic drug users. Prostate Cancer Prostatic Dis 19, 367–373 (2016). https://doi.org/10.1038/pcan.2016.32
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DOI: https://doi.org/10.1038/pcan.2016.32
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