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Published in: World Journal of Surgical Oncology 1/2017

Open Access 01-12-2017 | Research

Diabetes and beta-adrenergic blockage are risk factors for metastatic prostate cancer

Authors: Malte Krönig, Christian Haverkamp, Antonia Schulte, Laura Heinicke, Kathrin Schaal, Vanessa Drendel, Martin Werner, Ulrich Wetterauer, Wolfgang Schultze-Seemann, Cordula Annette Jilg

Published in: World Journal of Surgical Oncology | Issue 1/2017

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Abstract

Background

We evaluated the influence of comorbidity inferred risks for lymph node metastasis (pN1) and positive surgical margins (R1) after radical prostatectomy in order to optimize pretherapeutic risk classification.
We analyzed 454 patients after radical prostatectomy (RP) between 2009 and 2014. Comorbidities were defined by patients’ medication from our electronic patient chart and stratified according to the ATC WHO code. Endpoints were lymph node metastasis (pN1) and positive surgical margins (R1).

Results

Rates for pN1 and R1 were 21.4% (97/454) and 29.3% (133/454), respectively. In addition to CAPRA and Gleason score, we identified diabetes as a significant medication inferred risk factor for pN1 (OR 2.9, p = 0.004/OR 3.2, p = 0.001/OR 3.5, p = 0.001) and beta-blockers for R1 (OR 1.9, p = 0.020/OR 2.9, p = 0.004). Patients with diabetes showed no statistically significant difference in Gleason score, CAPRA Score, PSA, and age compared to non-diabetic patients.

Conclusions

We identified diabetes and beta1 adrenergic blockage as significant risk factors for lymph node metastasis and positive surgical margins in prostate cancer (PCa). Patients at risk will need intensive pretherapeutic staging for optimal therapeutic stratification.
Appendix
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Literature
1.
go back to reference Howlader N NA, Krapcho M, Miller D, Bishop K, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2013, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2013/, based on November 2015 SEER data submission, posted to the SEER web site, April 2016. 2016. Howlader N NA, Krapcho M, Miller D, Bishop K, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2013, National Cancer Institute. Bethesda, MD, http://​seer.​cancer.​gov/​csr/​1975_​2013/​, based on November 2015 SEER data submission, posted to the SEER web site, April 2016. 2016.
2.
go back to reference Shariat SF, Karakiewicz PI, Roehrborn CG, Kattan MW. An updated catalog of prostate cancer predictive tools. Cancer. 2008;113:3075–99.CrossRefPubMed Shariat SF, Karakiewicz PI, Roehrborn CG, Kattan MW. An updated catalog of prostate cancer predictive tools. Cancer. 2008;113:3075–99.CrossRefPubMed
3.
go back to reference Hernandez DJ, Nielsen ME, Han M, Partin AW. Contemporary evaluation of the Dʼamico risk classification of prostate cancer. Urology. 2007;70:931–5.CrossRefPubMed Hernandez DJ, Nielsen ME, Han M, Partin AW. Contemporary evaluation of the Dʼamico risk classification of prostate cancer. Urology. 2007;70:931–5.CrossRefPubMed
4.
go back to reference D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, Tomaszewski JE, Renshaw AA, Kaplan I, Beard CJ, Wein A. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998;280:969–74.CrossRefPubMed D'Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, Tomaszewski JE, Renshaw AA, Kaplan I, Beard CJ, Wein A. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998;280:969–74.CrossRefPubMed
5.
go back to reference Rodrigues G, Warde P, Pickles T, Crook J, Brundage M, Souhami L, Lukka H, Genitourinary Radiation Oncologists of C. Pre-treatment risk stratification of prostate cancer patients: a critical review. Can Urol Assoc J. 2012;6:121–7.CrossRefPubMedPubMedCentral Rodrigues G, Warde P, Pickles T, Crook J, Brundage M, Souhami L, Lukka H, Genitourinary Radiation Oncologists of C. Pre-treatment risk stratification of prostate cancer patients: a critical review. Can Urol Assoc J. 2012;6:121–7.CrossRefPubMedPubMedCentral
6.
go back to reference Cooperberg MR, Broering JM, Carroll PR. Risk assessment for prostate cancer metastasis and mortality at the time of diagnosis. J Natl Cancer Inst. 2009;101:878–87.CrossRefPubMedPubMedCentral Cooperberg MR, Broering JM, Carroll PR. Risk assessment for prostate cancer metastasis and mortality at the time of diagnosis. J Natl Cancer Inst. 2009;101:878–87.CrossRefPubMedPubMedCentral
7.
go back to reference Cooperberg MR, Pasta DJ, Elkin EP, Litwin MS, Latini DM, Du Chane J, Carroll PR. The University of California, San Francisco Cancer of the Prostate Risk Assessment score: a straightforward and reliable preoperative predictor of disease recurrence after radical prostatectomy. J Urol. 2005;173:1938–42.CrossRefPubMedPubMedCentral Cooperberg MR, Pasta DJ, Elkin EP, Litwin MS, Latini DM, Du Chane J, Carroll PR. The University of California, San Francisco Cancer of the Prostate Risk Assessment score: a straightforward and reliable preoperative predictor of disease recurrence after radical prostatectomy. J Urol. 2005;173:1938–42.CrossRefPubMedPubMedCentral
8.
go back to reference Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, Mason M, Matveev V, Wiegel T, Zattoni F, et al. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol. 2014;65:124–37.CrossRefPubMed Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, Mason M, Matveev V, Wiegel T, Zattoni F, et al. EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. Eur Urol. 2014;65:124–37.CrossRefPubMed
9.
go back to reference Hall WH, Jani AB, Ryu JK, Narayan S, Vijayakumar S. The impact of age and comorbidity on survival outcomes and treatment patterns in prostate cancer. Prostate Cancer Prostatic Dis. 2005;8:22–30.CrossRefPubMed Hall WH, Jani AB, Ryu JK, Narayan S, Vijayakumar S. The impact of age and comorbidity on survival outcomes and treatment patterns in prostate cancer. Prostate Cancer Prostatic Dis. 2005;8:22–30.CrossRefPubMed
11.
go back to reference Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, Pollak M, Regensteiner JG, Yee D. Diabetes and cancer: a consensus report. Diabetes Care. 2010;33:1674–85.CrossRefPubMedPubMedCentral Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, Pollak M, Regensteiner JG, Yee D. Diabetes and cancer: a consensus report. Diabetes Care. 2010;33:1674–85.CrossRefPubMedPubMedCentral
12.
go back to reference WHO. Anatomic therapeutic chemical code (ATC). 2011. WHO. Anatomic therapeutic chemical code (ATC). 2011.
13.
go back to reference Murray NP, Aedo S, Reyes E, Orellana N, Fuentealba C, Jacob O. A prediction model for early biochemical failure after radical prostatectomy based on the CAPRA-S score and the presence of secondary circulating prostate cells. BJU Int. 2015;118:556–62. Murray NP, Aedo S, Reyes E, Orellana N, Fuentealba C, Jacob O. A prediction model for early biochemical failure after radical prostatectomy based on the CAPRA-S score and the presence of secondary circulating prostate cells. BJU Int. 2015;118:556–62.
14.
go back to reference Cooperberg MR, Hilton JF, Carroll PR. The CAPRA-S score: a straightforward tool for improved prediction of outcomes after radical prostatectomy. Cancer. 2011;117:5039–46.CrossRefPubMedPubMedCentral Cooperberg MR, Hilton JF, Carroll PR. The CAPRA-S score: a straightforward tool for improved prediction of outcomes after radical prostatectomy. Cancer. 2011;117:5039–46.CrossRefPubMedPubMedCentral
15.
go back to reference Loeb S, Carvalhal GF, Kan D, Desai A, Catalona WJ. External validation of the cancer of the prostate risk assessment (CAPRA) score in a single-surgeon radical prostatectomy series. Urol Oncol. 2012;30:584–9.CrossRefPubMed Loeb S, Carvalhal GF, Kan D, Desai A, Catalona WJ. External validation of the cancer of the prostate risk assessment (CAPRA) score in a single-surgeon radical prostatectomy series. Urol Oncol. 2012;30:584–9.CrossRefPubMed
16.
go back to reference May M, Knoll N, Siegsmund M, Fahlenkamp D, Vogler H, Hoschke B, Gralla O. Validity of the CAPRA score to predict biochemical recurrence-free survival after radical prostatectomy. Results from a european multicenter survey of 1,296 patients. J Urol. 2007;178:1957–62. discussion 1962.CrossRefPubMed May M, Knoll N, Siegsmund M, Fahlenkamp D, Vogler H, Hoschke B, Gralla O. Validity of the CAPRA score to predict biochemical recurrence-free survival after radical prostatectomy. Results from a european multicenter survey of 1,296 patients. J Urol. 2007;178:1957–62. discussion 1962.CrossRefPubMed
17.
go back to reference Wojciechowska J, Krajewski W, Bolanowski M, Krecicki T, Zatonski T. Diabetes and cancer: a review of current knowledge. Exp Clin Endocrinol Diabetes. 2016;124:263–75.CrossRefPubMed Wojciechowska J, Krajewski W, Bolanowski M, Krecicki T, Zatonski T. Diabetes and cancer: a review of current knowledge. Exp Clin Endocrinol Diabetes. 2016;124:263–75.CrossRefPubMed
18.
go back to reference Lipscombe LL, Fischer HD, Austin PC, Fu L, Jaakkimainen RL, Ginsburg O, Rochon PA, Narod S, Paszat L. The association between diabetes and breast cancer stage at diagnosis: a population-based study. Breast Cancer Res Treat. 2015;150:613–20.CrossRefPubMed Lipscombe LL, Fischer HD, Austin PC, Fu L, Jaakkimainen RL, Ginsburg O, Rochon PA, Narod S, Paszat L. The association between diabetes and breast cancer stage at diagnosis: a population-based study. Breast Cancer Res Treat. 2015;150:613–20.CrossRefPubMed
19.
go back to reference Briganti A, Karakiewicz PI, Chun FK, Suardi N, Gallina A, Abdollah F, Freschi M, Doglioni C, Rigatti P, Montorsi F. Obesity does not increase the risk of lymph node metastases in patients with clinically localized prostate cancer undergoing radical prostatectomy and extended pelvic lymph node dissection. Int J Urol. 2009;16:676–81.CrossRefPubMed Briganti A, Karakiewicz PI, Chun FK, Suardi N, Gallina A, Abdollah F, Freschi M, Doglioni C, Rigatti P, Montorsi F. Obesity does not increase the risk of lymph node metastases in patients with clinically localized prostate cancer undergoing radical prostatectomy and extended pelvic lymph node dissection. Int J Urol. 2009;16:676–81.CrossRefPubMed
20.
go back to reference Margel D, Urbach D, Lipscombe LL, Bell CM, Kulkarni G, Austin PC, Fleshner N. Association between metformin use and risk of prostate cancer and its grade. J Natl Cancer Inst. 2013;105:1123–31.CrossRefPubMed Margel D, Urbach D, Lipscombe LL, Bell CM, Kulkarni G, Austin PC, Fleshner N. Association between metformin use and risk of prostate cancer and its grade. J Natl Cancer Inst. 2013;105:1123–31.CrossRefPubMed
21.
go back to reference Preston MA, Riis AH, Ehrenstein V, Breau RH, Batista JL, Olumi AF, Mucci LA, Adami HO, Sorensen HT. Metformin use and prostate cancer risk. Eur Urol. 2014;66:1012–20.CrossRefPubMed Preston MA, Riis AH, Ehrenstein V, Breau RH, Batista JL, Olumi AF, Mucci LA, Adami HO, Sorensen HT. Metformin use and prostate cancer risk. Eur Urol. 2014;66:1012–20.CrossRefPubMed
22.
go back to reference Bansal D, Bhansali A, Kapil G, Undela K, Tiwari P. Type 2 diabetes and risk of prostate cancer: a meta-analysis of observational studies. Prostate Cancer Prostatic Dis. 2013;16:151–8. S151.PubMed Bansal D, Bhansali A, Kapil G, Undela K, Tiwari P. Type 2 diabetes and risk of prostate cancer: a meta-analysis of observational studies. Prostate Cancer Prostatic Dis. 2013;16:151–8. S151.PubMed
23.
go back to reference Li Q, Kuriyama S, Kakizaki M, Yan H, Sone T, Nagai M, Sugawara Y, Ohmori-Matsuda K, Hozawa A, Nishino Y, Tsuji I. History of diabetes mellitus and the risk of prostate cancer: the Ohsaki Cohort Study. Cancer Causes Control. 2010;21:1025–32.CrossRefPubMed Li Q, Kuriyama S, Kakizaki M, Yan H, Sone T, Nagai M, Sugawara Y, Ohmori-Matsuda K, Hozawa A, Nishino Y, Tsuji I. History of diabetes mellitus and the risk of prostate cancer: the Ohsaki Cohort Study. Cancer Causes Control. 2010;21:1025–32.CrossRefPubMed
24.
go back to reference Scallan JP, Hill MA, Davis MJ. Lymphatic vascular integrity is disrupted in type 2 diabetes due to impaired nitric oxide signalling. Cardiovasc Res. 2015;107:89–97.CrossRefPubMedPubMedCentral Scallan JP, Hill MA, Davis MJ. Lymphatic vascular integrity is disrupted in type 2 diabetes due to impaired nitric oxide signalling. Cardiovasc Res. 2015;107:89–97.CrossRefPubMedPubMedCentral
25.
go back to reference Braadland PR, Ramberg H, Grytli HH, Tasken KA. β-adrenergic receptor signaling in prostate cancer. Front Oncol. 2014;4:375.PubMed Braadland PR, Ramberg H, Grytli HH, Tasken KA. β-adrenergic receptor signaling in prostate cancer. Front Oncol. 2014;4:375.PubMed
26.
go back to reference Goepel M, Wittmann A, Rubben H, Michel MC. Comparison of adrenoceptor subtype expression in porcine and human bladder and prostate. Urol Res. 1997;25:199–206.CrossRefPubMed Goepel M, Wittmann A, Rubben H, Michel MC. Comparison of adrenoceptor subtype expression in porcine and human bladder and prostate. Urol Res. 1997;25:199–206.CrossRefPubMed
27.
go back to reference Magnon C, Hall SJ, Lin J, Xue X, Gerber L, Freedland SJ, Frenette PS. Autonomic nerve development contributes to prostate cancer progression. Science. 2013;341:1236361.CrossRefPubMed Magnon C, Hall SJ, Lin J, Xue X, Gerber L, Freedland SJ, Frenette PS. Autonomic nerve development contributes to prostate cancer progression. Science. 2013;341:1236361.CrossRefPubMed
28.
go back to reference Andersen S, Richardsen E, Nordby Y, Ness N, Storkersen O, Al-Shibli K, Donnem T, Bertilsson H, Busund LT, Angelsen A, Bremnes RM. Disease-specific outcomes of radical prostatectomies in Northern Norway; a case for the impact of perineural infiltration and postoperative PSA-doubling time. BMC Urol. 2014;14:49.CrossRefPubMedPubMedCentral Andersen S, Richardsen E, Nordby Y, Ness N, Storkersen O, Al-Shibli K, Donnem T, Bertilsson H, Busund LT, Angelsen A, Bremnes RM. Disease-specific outcomes of radical prostatectomies in Northern Norway; a case for the impact of perineural infiltration and postoperative PSA-doubling time. BMC Urol. 2014;14:49.CrossRefPubMedPubMedCentral
29.
go back to reference Lu H, Liu X, Guo F, Tan S, Wang G, Liu H, Wang J, He X, Mo Y, Shi B. Impact of beta-blockers on prostate cancer mortality: a meta-analysis of 16,825 patients. Onco Targets Ther. 2015;8:985–90.CrossRefPubMedPubMedCentral Lu H, Liu X, Guo F, Tan S, Wang G, Liu H, Wang J, He X, Mo Y, Shi B. Impact of beta-blockers on prostate cancer mortality: a meta-analysis of 16,825 patients. Onco Targets Ther. 2015;8:985–90.CrossRefPubMedPubMedCentral
30.
go back to reference Morelli MB, Amantini C, Nabissi M, Liberati S, Cardinali C, Farfariello V, Tomassoni D, Quaglia W, Piergentili A, Bonifazi A, et al. Cross-talk between alpha1D-adrenoceptors and transient receptor potential vanilloid type 1 triggers prostate cancer cell proliferation. BMC Cancer. 2014;14:921.CrossRefPubMedPubMedCentral Morelli MB, Amantini C, Nabissi M, Liberati S, Cardinali C, Farfariello V, Tomassoni D, Quaglia W, Piergentili A, Bonifazi A, et al. Cross-talk between alpha1D-adrenoceptors and transient receptor potential vanilloid type 1 triggers prostate cancer cell proliferation. BMC Cancer. 2014;14:921.CrossRefPubMedPubMedCentral
31.
go back to reference Hui H, Fernando MA, Heaney AP. The alpha1-adrenergic receptor antagonist doxazosin inhibits EGFR and NF-kappaB signalling to induce breast cancer cell apoptosis. Eur J Cancer. 2008;44:160–6.CrossRefPubMed Hui H, Fernando MA, Heaney AP. The alpha1-adrenergic receptor antagonist doxazosin inhibits EGFR and NF-kappaB signalling to induce breast cancer cell apoptosis. Eur J Cancer. 2008;44:160–6.CrossRefPubMed
32.
go back to reference Partin JV, Anglin IE, Kyprianou N. Quinazoline-based alpha 1-adrenoceptor antagonists induce prostate cancer cell apoptosis via TGF-beta signalling and I kappa B alpha induction. Br J Cancer. 2003;88:1615–21.CrossRefPubMedPubMedCentral Partin JV, Anglin IE, Kyprianou N. Quinazoline-based alpha 1-adrenoceptor antagonists induce prostate cancer cell apoptosis via TGF-beta signalling and I kappa B alpha induction. Br J Cancer. 2003;88:1615–21.CrossRefPubMedPubMedCentral
Metadata
Title
Diabetes and beta-adrenergic blockage are risk factors for metastatic prostate cancer
Authors
Malte Krönig
Christian Haverkamp
Antonia Schulte
Laura Heinicke
Kathrin Schaal
Vanessa Drendel
Martin Werner
Ulrich Wetterauer
Wolfgang Schultze-Seemann
Cordula Annette Jilg
Publication date
01-12-2017
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2017
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/s12957-017-1117-4

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