Top

Published in:

Open Access 01-12-2016 | Research article

Metabolic syndrome is associated with advanced prostate cancer in patients treated with radical retropubic prostatectomy: results from a multicentre prospective study

Authors: Cosimo De Nunzio, Giuseppe Simone, Aldo Brassetti, Riccardo Mastroianni, Devis Collura, Giovanni Muto, Michele Gallucci, Andrea Tubaro

Published in: BMC Cancer | Issue 1/2016

Abstract

Background

Prostate cancer (PCa) is the most common non-skin cancer in USA and the second leading cause of cancer death in Western Countries. Despite the high mortality associated with PCa, the only established risk factors are age, race and family history. A possible association between metabolic syndrome (MetS) and PCa was firstly described in 2004 and several subsequent studies in biopsy cohorts have shown conflicting results. Aim of our multicentre prospective study was to investigate the association between MetS and PCa in men undergoing radical prostatectomy (RP).

Methods

From January 2012 to June 2015, 349 consecutive men undergoing RP for PCa at three centres in Italy were enrolled into a prospective database. Body Mass Index (BMI) as well as waist circumference was measured before RP. Blood samples were also collected and tested for total PSA, fasting glucose, triglycerides and HDLs. Blood pressure was also recorded. We evaluated the association between MetS, defined according to Adult Treatment Panel III, PCa stage (advanced stage defined as pT ≥ 3 or N1) and grade (high grade defined as Gleason Score ≥ 4 + 3) using logistic regression analyses.

Results

Median age and preoperative PSA levels were 66 years (IQR: 61-69) and 7 ng/ml (IQR: 5-10), respectively. Median BMI was 26.12 kg/m² (IQR 24-29) with 56 (16 %) obese (BMI ≥ 30 kg/m²) patients and 87 (25 %) patients with MetS. At pathological evaluation, advanced PCa and high-grade disease were present in 126 (36 %) and 145 (41.5 %) patients, respectively. MetS was significantly associated with advanced PCa (45/87, 51 % vs 81/262, 31 %; p = 0.008) and high-grade disease (47/87, 54 % vs 98/262, 37 %; p = 0.001). On multivariable analysis, MetS was an independent predictor of pathological stage ≥ pT3a or N1 (OR: 2.227; CI: 1.273-3.893; p = 0.005) and Gleason score ≥ 4 + 3 (OR: 2.007, CI: 1.175-3.428; p = 0.011).

Conclusions

We firstly demonstrated in a European radical retropubic prostatectomy cohort study that MetS is associated with an increased risk of high-grade and advanced prostate cancer. Further studies with long term follow-up should evaluate the impact of Mets on PCa survival.

De Nunzio C, Freedland SJ, Miano R, Trucchi A, Cantiani A, Carluccini A, et al. Metabolic syndrome is associated with high grade gleason score when prostate cancer is diagnosed on biopsy. Prostate. 2011;71:1492–8. doi:10.1002/pros.21364.PubMed

Esposito K, Chiodini P, Capuano A, Bellastella G, Maiorino MI, Parretta E, et al. Effect of metabolic syndrome and its components on prostate cancer risk: meta-analysis. J Endocrinol Invest. 2013;36:132–9. doi:10.1007/BF03346748.CrossRefPubMed

Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37:1595–607.CrossRefPubMed

Ozbek E, Otunctemur A, Dursun M, Sahin S, Koklu I, Erkoc M, et al. The Metabolic Syndrome is Associated with More Aggressive Prostate Cancer. Asian Pac J Cancer Prev. 2014;15:4029–32.CrossRefPubMed

Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143–421.

De Nunzio C, Presicce F, Lombardo R, Cancrini F, Petta S, Trucchi A, et al. Physical activity as a risk factor for prostate cancer diagnosis: a prospective biopsy cohort analysis. BJU Int 2015. doi:10.1111/bju.13157.

De Nunzio C, Albisinni S, Freedland SJ, Miano L, Cindolo L, Finazzi Agrò E, et al. Abdominal obesity as risk factor for prostate cancer diagnosis and high grade disease: a prospective multicentre Italian cohort study. Urol Oncol. 2013;31:997–1002. doi:10.1016/j.urolonc.2011.08.007.CrossRefPubMed

De Nunzio C, Truscelli G, Trucchi A, Petta S, Tubaro M, Gacci M, et al. Metabolic abnormalities linked to an increased cardiovascular risk are associated with high-grade prostate cancer: a single biopsy cohort analysis. Prostate Cancer Prostatic Dis 2015. doi:10.1038/pcan.2015.45.

Laukkanen JA, Laaksonen DE, Niskanen L, Pukkala E, Hakkarainen A, Salonen JT. Metabolic syndrome and the risk of prostate cancer in Finnish men: a population-based study. Cancer Epidemiol Biomarkers Prev. 2004;13:1646–50.PubMed

10.

Bhindi B, Locke J, Alibhai SMH, Kulkarni GS, Margel DS, Hamilton RJ, et al. Dissecting the association between metabolic syndrome and prostate cancer risk: analysis of a large clinical cohort. Eur Urol. 2014;67:64–70. doi:10.1016/j.eururo.2014.01.040.CrossRefPubMed

11.

Grundmark B, Garmo H, Loda M, Busch C, Holmberg L, Zethelius B. The metabolic syndrome and the risk of prostate cancer under competing risks of death from other causes. Cancer Epidemiol Biomarkers Prev. 2010;19:2088–96. doi:10.1158/1055-9965.EPI-10-0112.CrossRefPubMedPubMedCentral

12.

Kayali M, Balci M, Aslan Y, Bilgin O, Guzel O, Tuncel A, et al. The relationship between prostate cancer and presence of metabolic syndrome and late-onset hypogonadism. Urology. 2014;84:1448–52. doi:10.1016/j.urology.2014.07.015.CrossRefPubMed

13.

Lund Håheim L, Wisløff TF, Holme I, Nafstad P. Metabolic syndrome predicts prostate cancer in a cohort of middle-aged Norwegian men followed for 27 years. Am J Epidemiol. 2006;164:769–74. doi:10.1093/aje/kwj284.CrossRefPubMed

14.

Morote J, Ropero J, Planas J, Bastarós JM, Delgado G, Placer J, et al. Metabolic syndrome increases the risk of aggressive prostate cancer detection. BJU Int. 2013;111:1031–6. doi:10.1111/j.1464-410X.2012.11406.x.CrossRefPubMed

15.

Sourbeer KN, Howard LE, Andriole GL, Moreira DM, Castro-Santamaria R, Freedland SJ, et al. Metabolic syndrome-like components and prostate cancer risk: results from the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study. BJU Int. 2015;115:736–43. doi:10.1111/bju.12843.CrossRefPubMed

16.

Tande AJ, Platz EA, Folsom AR. The metabolic syndrome is associated with reduced risk of prostate cancer. Am J Epidemiol. 2006;164:1094–102. doi:10.1093/aje/kwj320.CrossRefPubMed

17.

Wallner LP, Morgenstern H, McGree ME, Jacobson DJ, St Sauver JL, Jacobsen SJ, et al. The effects of metabolic conditions on prostate cancer incidence over 15 years of follow-up: results from the Olmsted County Study. BJU Int. 2011;107:929–35. doi:10.1111/j.1464-410X.2010.09703.x.CrossRefPubMed

18.

Xiang Y, Xiong H, Cui Z, Jiang S, Xia Q, Zhao Y, et al. The association between metabolic syndrome and the risk of prostate cancer, high-grade prostate cancer, advanced prostate cancer, prostate cancer-specific mortality and biochemical recurrence. J Exp Clin Cancer Res. 2013;32:9. doi:10.1186/1756-9966-32-9.CrossRefPubMedPubMedCentral

19.

Abdeen Z, Jildeh C, Dkeideek S, Qasrawi R, Ghannam I, Al Sabbah H. Overweight and obesity among Palestinian adults: analyses of the anthropometric data from the first national health and nutrition survey (1999-2000). J Obes. 2012;2012:213547. doi:10.1155/2012/213547.CrossRefPubMedPubMedCentral

20.

Frese EM, Fick A, Sadowsky HS. Blood pressure measurement guidelines for physical therapists. Cardiopulm Phys Ther J. 2011;22:5–12.PubMedPubMedCentral

21.

Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, 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. doi:10.1016/j.eururo.2013.09.046.CrossRefPubMed

22.

Epstein JI, Srigley J, Grignon D, Humphrey P. Recommendations for the reporting of prostate carcinoma. Hum Pathol. 2007;38:1305–9. doi:10.1016/j.humpath.2007.05.015.CrossRefPubMed

23.

Eble JN, Sauter G, Epstein JI, Sesterhenn IA. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. IARC Press 2004:1–353. doi:10.1016/j.urology.2004.09.048.

24.

Rodrigues G, Warde P, Pickles T, Crook J, Brundage M, Souhami L, et al. Pre-treatment risk stratification of prostate cancer patients: A critical review. Can Urol Assoc J. 2012;6:121–7. doi:10.5489/cuaj.11085.CrossRefPubMedPubMedCentral

25.

Freedland SJ, Isaacs WB, Platz EA, Terris MK, Aronson WJ, Amling CL, et al. Prostate size and risk of high-grade, advanced prostate cancer and biochemical progression after radical prostatectomy: a search database study. J Clin Oncol. 2005;23:7546–54. doi:10.1200/JCO.2005.05.025.CrossRefPubMed

26.

Freedland SJ, Wieder JA, Jack GS, Dorey F, DeKernion JB, Aronson WJ. Improved risk stratification for biochemical recurrence after radical prostatectomy using a novel risk group system based on prostate specific antigen density and biopsy Gleason score. J Urol. 2002;168:110–5. doi:10.1097/00005392-200207000-00025.CrossRefPubMed

27.

Oh JJ, Hong SK, Lee JK, Lee BK, Lee S, Kwon OS, et al. Prostate-specific antigen vs prostate-specific antigen density as a predictor of upgrading in men diagnosed with Gleason 6 prostate cancer by contemporary multicore prostate biopsy. BJU Int. 2012;110:494–9. doi:10.1111/j.1464-410X.2012.11182.x.CrossRef

28.

Kassouf W, Nakanishi H, Ochiai A, Babaian KN, Troncoso P, Babaian RJ. Effect of prostate volume on tumor grade in patients undergoing radical prostatectomy in the era of extended prostatic biopsies. J Urol. 2007;178:111–4. doi:10.1016/j.juro.2007.03.013.CrossRefPubMed

29.

Corcoran NM, Casey RG, Hong MKH, Pedersen J, Connolly S, Peters J, et al. The ability of prostate-specific antigen (PSA) density to predict an upgrade in Gleason score between initial prostate biopsy and prostatectomy diminishes with increasing tumour grade due to reduced PSA secretion per unit tumour volume. BJU Int. 2012;110:36–42. doi:10.1111/j.1464-410X.2011.10681.x.CrossRefPubMed

30.

Kundu SD, Roehl KA, Yu X, Antenor JA V, Suarez BK, Catalona WJ. Prostate specific antigen density correlates with features of prostate cancer aggressiveness. J Urol. 2007;177:505–9. doi:10.1016/j.juro.2006.09.039.CrossRefPubMed

31.

Beebe-Dimmer JL, Nock NL, Neslund-Dudas C, Rundle A, Bock CH, Tang D, et al. Racial differences in risk of prostate cancer associated with metabolic syndrome. Urology. 2009;74:185–90. doi:10.1016/j.urology.2009.03.013.CrossRefPubMedPubMedCentral

32.

Kheterpal E, Sammon JD, Diaz M, Bhandari A, Trinh Q-D, Pokala N, et al. Effect of metabolic syndrome on pathologic features of prostate cancer. Urol Oncol. 2013;31:1054–9. doi:10.1016/j.urolonc.2011.12.012.CrossRefPubMed

33.

Sfanos KS, De Marzo AM. Prostate cancer and inflammation: the evidence. Histopathology. 2012;60:199–215. doi:10.1111/j.1365-2559.2011.04033.x.CrossRefPubMedPubMedCentral

34.

Powell IJ, Bollig-Fischer A. Minireview: the molecular and genomic basis for prostate cancer health disparities. Mol Endocrinol. 2013;27:879–91. doi:10.1210/me.2013-1039.CrossRefPubMed

35.

De Marzo AM, Platz EA, Sutcliffe S, Xu J, Grönberg H, Drake CG, et al. Inflammation in prostate carcinogenesis. Nat Rev Cancer. 2007;7:256–69. doi:10.1038/nrc2090.CrossRefPubMedPubMedCentral

36.

De Nunzio C, Aronson W, Freedland SJ, Giovannucci E, Parsons JK. The correlation between metabolic syndrome and prostatic diseases. Eur Urol. 2012;61:560–70. doi:10.1016/j.eururo.2011.11.013.CrossRefPubMed

Title: Metabolic syndrome is associated with advanced prostate cancer in patients treated with radical retropubic prostatectomy: results from a multicentre prospective study
Authors: Cosimo De Nunzio
Giuseppe Simone
Aldo Brassetti
Riccardo Mastroianni
Devis Collura
Giovanni Muto
Michele Gallucci
Andrea Tubaro
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-016-2442-7

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2016

Deferasirox, a novel oral iron chelator, shows antiproliferative activity against pancreatic cancer in vitro and in vivo

A pilot study to compare the detection of HPV-16 biomarkers in salivary oral rinses with tumour p16INK4a expression in head and neck squamous cell carcinoma patients

Targeting Rad50 sensitizes human nasopharyngeal carcinoma cells to radiotherapy

Impact of Bevacizumab on parenchymal damage and functional recovery of the liver in patients with colorectal liver metastases

Comparing conVEntional RadioTherapy with stereotactIC body radiotherapy in patients with spinAL metastases: study protocol for an randomized controlled trial following the cohort multiple randomized controlled trial design

Benchmarking trial between France and Australia comparing management of primary rectal cancer beyond TME and locally recurrent rectal cancer (PelviCare Trial): rationale and design

Keynote webinar | Spotlight on antibody–drug conjugates in cancer