|Year : 2019 | Volume
| Issue : 8 | Page : 47-50
The effect of metabolic syndrome on prostate cancer final pathology
Selahattin Caliskan, Selçuk Kaba, Emrah Özsoy, Muzaffer Oğuz Keleş, Orhan Koca, Mehmet Akyüz, Muhammet Ihsan Karaman
Department of Urology, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey
|Date of Web Publication||22-Mar-2019|
Dr. Selahattin Caliskan
Bahcelievler Mah, Camlik Cad, No. 2, Çorum
Source of Support: None, Conflict of Interest: None
Aim of Study: Metabolic syndrome (MetS) is an abnormality that increases the risk of cardiovascular disease and diabetes. In the recent years, studies showed that MetS is associated with increased risk of incidence, aggressiveness, and mortality of prostate cancer (PCa). We examined the influence of MetS at final pathology in Turkish patients with PCa.
Materials and Methods: MetS was defined according to the American Heart Association, National Heart, Lung, Blood Institute, and International Diabetes Federation and requires any three of five components. The patients without and with MetS were in Group 1 and 2, respectively. Data were compared with independent sample t-test and Chi-squared test.
Results: There were 117 patients in the study. The patients' age was between 51 and 77 years with a median of 64.87 ± 5.65 and 62.29 ± 5.57, and prostate-specific antigen (PSA) level of the patients was 8.19 ± 5.35 and 8.68 ± 2.22 ng/ml in Group 1 and 2. Of these patients; Group 1 and 2 had 86 and 31 patients. High-grade PCa (Gleason >7) and advanced PCa (T3, T4) at final pathology were reported in 44.18–18.60% and 38.70–32.25% in Group 1 and 2.
Conclusion: The patients with MetS are diagnosed significantly younger and had higher PSA levels than the other patients. Advanced disease of PCa is seen much more in patients with MetS.
Keywords: Metabolic syndrome, prostate cancer, radical prostatectomy
|How to cite this article:|
Caliskan S, Kaba S, Özsoy E, Keleş MO, Koca O, Akyüz M, Karaman MI. The effect of metabolic syndrome on prostate cancer final pathology. J Can Res Ther 2019;15, Suppl S1:47-50
|How to cite this URL:|
Caliskan S, Kaba S, Özsoy E, Keleş MO, Koca O, Akyüz M, Karaman MI. The effect of metabolic syndrome on prostate cancer final pathology. J Can Res Ther [serial online] 2019 [cited 2021 Sep 21];15:47-50. Available from: https://www.cancerjournal.net/text.asp?2019/15/8/47/187290
| > Introduction|| |
Prostate cancer (PCa) is the most common diagnosed malignancy in industrialized countries and sixth leading cause of cancer death among men in worldwide. Rates of PCa in Asian countries are 10–15 times lower than Western countries, but the incidence is increasing rapidly because of western diet (fat and meat intake) and sedentary lifestyles. Asian-American men have rates of PCa that are lower than Caucasian, and African-American men have rates of PCa that are higher than their native counterparts.
Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that includes elevated blood pressure, obesity (central), dysglycemia, elevated triglyceride levels, and low levels of high-density lipoprotein (HDL) cholesterol. MetS may be involved in the development and progression of some cancers such as breast, endometrial, colorectal, pancreatic, and prostate. The prevalence of MetS is >40% in over the age of 60 years in the US. The association between MetS and PCa is not clear. Previous studies that investigated the association between PCa and MetS have reported contradictory results.
In this study, we investigated the patients diagnosed of PCa with MetS and compare them to other patients without MetS, who underwent open radical prostatectomy (RP) at our institution.
| > Materials and Methods|| |
From January 2003 to December 2013, the patients with a diagnosis of PCa and treated with RP were listed retrospectively. Patients on finasteride, dutasteride therapy, androgen deprivation therapy, and radiotherapy were excluded from the study. Blood pressure, blood glucose, HDL cholesterol, triglyceride, prostate specific antigen (PSA) levels, height and weight data were recorded from the computer notes.
MetS was defined according to the American Heart Association, National Heart, Lung, Blood Institute, and International Diabetes Federation consensus statement and requires any three of five MetS components. The parameters of MetS are obesity (body mass index ≥30 kg/m2), elevated serum triglycerides (≥150mg/dl), reduced HDL (≥100 mg/dl or diagnosis of type 2 diabetes mellitus).
All biopsies and RP specimens were undertaken by genitourinary pathologists. Prostate glands were weighted after removal of the seminal vesicles. The prostate was sectioned at 3 mm increments perpendicular to the long axis from the apex to the bladder. Surgical margins were reported positive and negative. Periprostatic tissues and seminal vesicles were examined for tumor invasion. The tumors were graded according to the Gleason grading system and staged TNM system. High grade cancer was defined ≥Gleason 7 at final pathology and insignificant prostate cancer (IPCa) criteria were tumor volume <0.5 cm3, organ confined disease and Gleason ≤6.
Data were expressed as mean ± standard error and P < 0.05 as considered with statistical significance, and independent sample t-test and Chi-squared test were used for comparison of the groups (MedCalc Statistical Software version 16.2.0, Ostend, Belgium; https://www.medcalc.org; 2016).
| > Results|| |
The patients who underwent open RP were reviewed retrospectively. Preoperative PSA, biopsy results, blood pressure, HDL cholesterol, triglyceride, glucose levels, height and weight, and RP specimen results were recorded. The patients who have any missing data were excluded from the study. A total of 117 patients were included in the study. The patients were divided into two groups; the patients without MetS were in Group 1 (86 patients) and had MetS in Group 2 (31 patients). Clinical characteristics of the patients were shown in [Table 1]. Among the patients who had MetS, 83.87% had 4 and 16.12% had 3 of the 5 components of MetS.
The mean age and PSA level of the patients were 64.87 ± 5.65 years–8.19 ± 5.35 ng/ml and 62.29 ± 5.57 years–8.68 ± 2.22 ng/ml in Groups 1 and 2, respectively. Gleason score concordance was reported in 63 (53.84%) patients. Of these patients, 48 (55.81%) and 15 (48.38%) patients were in Group 1 and 2, respectively. High grade prostate cancer (Gleason≥7) at final pathology was reported in 38 patients (44.18%) and 12 patients (38.70%) in Group 1 and 2 [Table 2]. Proportion of advanced PCa (T3, T4) was 18.60% in Group 1 and 32.25% in Group 2. Surgical margin was positive in 11 patients. One of these patients was in Group 2 and the others were in Group 1.
| > Discussion|| |
The prevalence of MetS has been increasing, and it is a major public health problem in several countries over the past two decades. There is contradictory about the association between MetS and PCa results in the literature. In a study from the US, a prospective cohort of 6429 patients followed for 12.1 years, reported that MetS was inversely related to PCa risk. In 2009, Martin et al. reported on a prospective cohort of 29364 Norwegian men who were followed for a mean of 9.3 years, reported that there was no association between MetS and PCa incidence or mortality. In contrast, three cohort studies in healthy populations have found a positive association between MetS and overall PCa incidence; Laukkanen et al. reported the relative risk of 1.94, Lund Håheim et al. reported the relative risk of 1.56, and Grundmark et al. reported an odds ratio was 1.64.
The investigators from Korea reported that the patients with MetS were associated with a significantly decreased risk of high-grade PCa on biopsy. On the contrary, The authors from China, found that the biopsy Gleason score ≥7 was detected in 37.7% and 71.42% of the patients without and with MetS. Zhang et al. reported that 33.7–34.7% and 37.1–32.1% of the patients had Gleason score 7 and >8 with and without MetS retrospectively. In this study, 29.03% and 23.25% of the patients had Gleason score ≥7 on biopsy with and without MetS. We think that the study design and selected patients are the main cause of the difference results.
Kheterpal et al. reported that the patients with MetS were more likely to have significant Gleason score and locally advanced stage at final pathology. In a meta-analysis, the authors found that MetS was significantly associated with an increased risk of PCa with a high-Gleason score or advanced stage with biochemical recurrence after primary treatment and PCa specific mortality. Zhang et al. reported that men with MetS are associated with an increased risk of prostatectomy Gleason score ≥8, pT3–4 disease, and lymph node involvement. Similarly, the authors investigated the association between MetS and PCa diagnosis and found the relationship between MetS and risk of clinically significant disease and risk of intermediate-high grade disease. On the contrary, Han et al. found that there was no significant difference for pathologic stage and Gleason score between the patients with and without MetS. The present study showed that pT3-4 disease and Gleason score ≥7 were 32.25-38.70% in patients with MetS and 18.60-44.18% in group 1 at final pathology (p:0.39 and 0.59).
Gleason score upgrading and positive surgical margin are important prognostic parameters in the postoperative period. The authors reported that Gleason upgrading was detected in 43.36% of the patients with MetS. The Gleason upgrading of the patients without MetS at final pathology was 33.74%. There are several quantifiable factors for the incidence of upgrading that include serum PSA level, pathology weight, age, extent of cancer on biopsy, and needle biopsy sampling. Positive surgical margin was reported in 21.5% and 21.9% of the patients with and without MetS. Bhindi et al. investigated the patients with MetS and PCa and reported that the patients with MetS had a greater probability of positive surgical margin (p: 0.002) and no increased risk of Gleason upgrading (p: 0.77). In the current study, the Gleason upgrading and positive surgical margin were reported in 32.25% and 3.22% of the patients with MetS. In the patients without MetS, 32.55% of the patients were upgraded and 10 patients (11.62%) had positive surgical margin (p: 0.975 and p: 0.171). The difference from the groups failed to reach statistical significance.
The biological mechanism of linking MetS with PCa is not understood well. Several mechanisms may explain the association that are including hyperinsulinemia and insulin-like growth factor-1 (IGF-1) pathway, inflammatory pathways, and decreased serum testosterone levels. Hyperinsulinemia and IGF-1 have been implicated in cellular proliferation that may be cornerstone for progression of benign prostate hyperplasia and PCa. Obesity is associated with decreased testosterone levels, and there is an inverse relationship between total testosterone and body mass index. Adipose tissue has the activity of aromatase that results in peripheral conversion of testosterone to estradiol. Elevated estradiol levels inhibit pituitary-hypothalamic axis resulting in decreased testosterone levels. Reduced serum testosterone levels are associated with poorly differentiated and more advanced prostate tumors at presentation. De Nunzio et al. reported that MetS provokes a pro inflammatory condition that results in increased levels of C-reactive protein, tumor necrosis factor-α, interleukin (IL)-8, IL-6, and IL-16.
Other obesity-related cytokines are leptin and adiponectin that may act by modulating tumor growth and angiogenesis. These adipocytokines have a pro-inflammatory effect and can induce insulin resistance. Insulin resistance leads to hyperinsulinemia and IGF-1 production that is a mitogenic and apoptosis inhibitor factor for PCa. Leptin stimulates the in vitro growth of androgen insensitive PCa cells and adiponectin has antitumor activity via inhibition of angiogenesis. Although circulating leptin levels are elevated, adiponectin levels were reduced in obese patients.
Some components of MetS affect the serum PSA levels. Obesity is associated with decreased PSA levels and increased prostate volume that may decrease the sensitivity of prostate biopsy and lead to delay in the detection of PCa. Obesity-related hemodilution and or decreased androgen levels are the main reason of the low PSA levels.
There are some limitations in the current study. This study includes small number of patients with retrospective design. Second, information of the patients about family history and medication usage could not mentioned. Lymph node dissection was not performed in all patients, so this parameter was not evaluated. In addition, we used body mass index for obesity rather than waist circumference which may lead to misclassification. The men who have elevated muscle mass, resulting in increased body mass index may have normal or low waist circumference.
| > Conclusion|| |
The patients with MetS and PCa are younger than the other patients statistically significantly. Advanced disease of PCa is seen much more in patients with MetS. Other risk factors; positive surgical margin and high-grade PCa are favorable in patients with MetS when comparing the other patients. Further studies are needed to define the relationship between MetS and PCa.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Xiang YZ, Xiong H, Cui ZL, Jiang SB, Xia QH, 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.
Kheterpal E, Sammon JD, Diaz M, Bhandari A, Trinh QD, Pokala N, et al.
Effect of metabolic syndrome on pathologic features of prostate cancer. Urol Oncol 2013;31:1054-9.
Esposito K, Chiodini P, Colao A, Lenzi A, Giugliano D. Metabolic syndrome and risk of cancer: A systematic review and meta-analysis. Diabetes Care 2012;35:2402-11.
Jeon KP, Jeong TY, Lee SY, Hwang SW, Shin JH, Kim DS. Prostate cancer in patients with metabolic syndrome is associated with low grade Gleason score when diagnosed on biopsy. Korean J Urol 2012;53:593-7.
Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al.
Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009;120:1640-5.
McGrowder DA, Jackson LA, Crawford TV. Prostate cancer and metabolic syndrome: Is there a link? Asian Pac J Cancer Prev 2012;13:1-13.
Bhindi B, Locke J, Alibhai SM, 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 2015;67:64-70.
Tande AJ, Platz EA, Folsom AR. The metabolic syndrome is associated with reduced risk of prostate cancer. Am J Epidemiol 2006;164:1094-102.
Martin RM, Vatten L, Gunnell D, Romundstad P, Nilsen TI. Components of the metabolic syndrome and risk of prostate cancer: The HUNT 2 cohort, Norway. Cancer Causes Control 2009;20:1181-92.
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.
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.
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.
Zhang JQ, Geng H, Ma M, Nan XY, Sheng BW. Metabolic syndrome components are associated with ıncreased prostate cancer risk. Med Sci Monit 2015;21:2387-96.
Zhang GM, Zhu Y, Dong DH, Han CT, Gu CY, Gu WJ, et al.
The association between metabolic syndrome and advanced prostate cancer in Chinese patients receiving radical prostatectomy. Asian J Androl 2015;17:839-44.
] [Full text]
Han BK, Choi WS, Yu JH, Han JH, Chang IH, Jeong SJ, et al
. The characteristics of prostate cancer with metabolic syndrome in Korean men. Korean J Urol 2007;48:585-91.
Epstein JI, Feng Z, Trock BJ, Pierorazio PM. Upgrading and downgrading of prostate cancer from biopsy to radical prostatectomy: Incidence and predictive factors using the modified Gleason grading system and factoring in tertiary grades. Eur Urol 2012;61:1019-24.
Kwon YS, Leapman M, McBride RB, Hobbs AR, Collingwood SA, Stensland KD, et al.
Robotic-assisted laparoscopic prostatectomy in men with metabolic syndrome. Urol Oncol 2014;32:40.e9-16.
Bhindi B, Xie WY, Kulkarni GS, Hamilton RJ, Nesbitt M, Finelli A, et al.
Influence of metabolic syndrome on prostate cancer stage, grade, and overall recurrence risk in men undergoing radical prostatectomy. Urology 2016. pii: S0090-429500302-2.
Gonzalgo ML, Isaacs WB. Molecular pathways to prostate cancer. J Urol 2003;170 (6 Pt 1):2444-52.
Peehl DM, Cohen P, Rosenfeld RG. The role of insulin-like growth factors in prostate biology. J Androl 1996;17:2-4.
Zhang PL, Rosen S, Veeramachaneni R, Kao J, DeWolf WC, Bubley G. Association between prostate cancer and serum testosterone levels. Prostate 2002;53:179-82.
De Nunzio C, Kramer G, Marberger M, Montironi R, Nelson W, Schröder F, et al.
The controversial relationship between benign prostatic hyperplasia and prostate cancer: The role of inflammation. Eur Urol 2011;60:106-17.
Cicione A, Cantiello F, De Nunzio C, Tubaro A, Damiano R. Patients with metabolic syndrome and widespread high grade prostatic intraepithelial neoplasia are at a higher risk factor of prostate cancer on re-biopsy: A prospective single cohort study. Urol Oncol 2014;32:28.e27-31.
Clements A, Gao B, Yeap SH, Wong MK, Ali SS, Gurney H. Metformin in prostate cancer: Two for the price of one. Ann Oncol 2011;22:2556-60.
[Table 1], [Table 2]