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Lee SF, Nikšić M, Luque-Fernandez MA. Understanding the role of metabolic syndrome in prostate cancer risk: A UK Biobank prospective cohort study. Sci Rep 2025; 15:2345. [PMID: 39824873 PMCID: PMC11748637 DOI: 10.1038/s41598-025-85501-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 01/03/2025] [Indexed: 01/20/2025] Open
Abstract
Predictive value of metabolic syndrome for prostate cancer risk is not clear. We aimed to assess the association between metabolic syndrome and its components with prostate cancer incidence. The primary outcome was prostate cancer incidence, i.e., incidence rate ratios and adjusted cumulative incidence curves derived from flexible parametric survival models. Adjusted cumulative incidence curves were derived using a flexible survival parametrical modeling framework. We analysed UK Biobank data including 242,349 adult males, recruited during 2006-2010 and followed up until 2021, during which 6,467 (2.7%) participants were diagnosed with prostate cancer. Our findings indicate that metabolic syndrome, as a whole, was not associated with prostate cancer risk (incidence rate ratios, 1.07; 95% confidence interval, 0.94-1.22). However, specific components such as hypertension and obesity increased the risk (incidence rate ratios, 1.22; 95% confidence interval, 1.03-1.44 and incidence rate ratios, 1.24; 95% confidence interval, 1.05-1.46, respectively). Other components, such as prediabetes/diabetes and low cholesterol, were associated with a reduced risk (incidence rate ratios, 0.80; 95% confidence interval, 0.67-0.94 and incidence rate ratios, 0.82; 95% confidence interval, 0.69-0.97, respectively), while hyperlipidaemia showed no significant effect (incidence rate ratios, 1.07; 95% confidence interval, 0.93-1.24). Further research is needed to understand the underlying mechanisms behind these relationships. Prostate cancer prevention strategies might benefit from targeting modifiable risk factors, particularly hypertension and obesity.
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Affiliation(s)
- Shing Fung Lee
- Department of Radiation Oncology, National University Cancer Institute, National University Hospital, Singapore, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Maja Nikšić
- Centre for Health Services Studies, University of Kent, Canterbury, UK
| | - Miguel Angel Luque-Fernandez
- Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK.
- Department of Statistics and Operations Research, University of Granada, Granada, Spain.
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Beitzen-Heineke A, Wise DR, Berger JS. Thrombo-inflammation linking androgen suppression with cardiovascular risk in patients with prostate cancer. CARDIO-ONCOLOGY (LONDON, ENGLAND) 2024; 10:87. [PMID: 39639392 PMCID: PMC11619638 DOI: 10.1186/s40959-024-00278-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 10/23/2024] [Indexed: 12/07/2024]
Abstract
Androgen deprivation therapy (ADT), a key element of prostate cancer treatment, is associated with increased risk for cardiovascular morbidity and mortality. The underlying mechanisms include adverse metabolic alterations, but further mechanisms are likely. Animal studies suggest increased progression of atherosclerosis in androgen deprived conditions. Based on in vitro studies, lack of androgens may modulate immune cells including monocytes, macrophages, and T-cells towards a pro-inflammatory phenotype and pro-atherogenic function. As a novel aspect, this review summarizes existing data on the effect of androgens and androgen deprivation on platelet activity, which play a major role in inflammation and in the initiation and progression of atherosclerotic lesions. Testosterone modulates platelet aggregation responses which are affected by dose level, source of androgen, and age. Data on the effects of ADT on platelet activity and aggregation are limited and conflicting, as both increased and decreased aggregation responses during ADT have been reported. Gaps in knowledge about the mechanisms leading to increased cardiovascular risk during ADT remain and further research is warranted. Improved understanding of pathogenic pathways linking ADT to cardiovascular risk may help identify clinically useful diagnostic and prognostic biomarkers, and accelerate finding novel therapeutic targets, and thus optimize prostate cancer treatment outcomes.
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Affiliation(s)
- Antonia Beitzen-Heineke
- Department of Medicine, New York University Grossman School of Medicine, 530 First Avenue, Skirball 9R, New York, NY, 10016, USA
- Department of Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - David R Wise
- Department of Medicine, Laura & Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA
| | - Jeffrey S Berger
- Department of Medicine, New York University Grossman School of Medicine, 530 First Avenue, Skirball 9R, New York, NY, 10016, USA.
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Zhang H, Yang W, Zhang B, Wu J, Zhang W, Wang Z, Cui J. Non-alcoholic fatty liver disease increases the risk of biochemical recurrence in high-grade metastatic prostate cancer patients. Asia Pac J Clin Oncol 2024; 20:707-713. [PMID: 38970310 DOI: 10.1111/ajco.14094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Revised: 02/21/2024] [Accepted: 05/22/2024] [Indexed: 07/08/2024]
Abstract
INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) has been reported to be helpful to identify high-risk individuals of developing prostate cancer. Our aim is to investigate the relationship between NAFLD and biochemical recurrence in metastatic prostate cancer patients. METHODS We retrospectively investigated 602 patients with metastatic prostate cancer receiving the androgen deprivation therapy. Liver fat was estimated with liver-to-spleen ratio by computed tomography (CT) scans. The relationship between NAFLD and biochemical recurrence was investigated with Cox models. The model for biochemical recurrence was adjusted for multiple variables. RESULTS NAFLD was significantly associated with biochemical recurrence in patients with Gleason score ≥4+3 when adjusting for each of body mass index (hazards ratio [HR] = 1.38; 95% confidence interval [CI] = 1.08-1.77; p = 0.01), visceral adipose tissue (HR = 1.36; 95% CI = 1.07-1.74; p = 0.01), hypertension (HR = 1.41; 95% CI = 1.10-1.80; p = 0.01), and diabetes mellitus (HR = 1.42; 95% CI = 1.11-1.82; p = 0.01), using age and prostate-specific antigen level as potential confounder. The 2-year biochemical recurrence rate in the Gleason score ≥4+3 patients with and without NAFLD was 84.0% (100/119) and 72.2% (130/180), respectively (p = 0.018). The median biochemical recurrence free survival of the Gleason score ≥4+3 patients with and without NAFLD were 17 and 21 months, respectively (p = 0.005). CONCLUSIONS NAFLD is an independent risk factor for biochemical recurrence in patients with high-grade metastatic prostate cancer. If validated in prospective studies, future research should test whether treatment of NAFLD can lead to better prognosis.
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Affiliation(s)
- Hongyi Zhang
- Department of Urology, The First Affiliated Hospital, Xi'an Medical University, Xi'an, Shaanxi, China
| | - Wenbo Yang
- Department of Oncology, The First Affiliated Hospital, Xi'an Medical University, Xi'an, Shaanxi, China
| | - Bin Zhang
- Department of Oncology, The First Affiliated Hospital, Xi'an Medical University, Xi'an, Shaanxi, China
| | - Jiahui Wu
- Department of Oncology, The First Affiliated Hospital, Xi'an Medical University, Xi'an, Shaanxi, China
| | - Wei Zhang
- Department of Urology, The Second Affiliated Hospital, Air Forth Medical University, Xi'an, Shaanxi, China
| | - Zhenlong Wang
- Department of Urology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Jie Cui
- Department of General Practice, The First Affiliated Hospital, Xi'an Medical University, Xi'an, Shaanxi, China
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Fichtel-Epstein C, Huang J, Rich BJ, Taswell CS, Isrow D, Jin W. Ultra-Processed Food and Prostate Cancer Risk: A Systemic Review and Meta-Analysis. Cancers (Basel) 2024; 16:3953. [PMID: 39682140 DOI: 10.3390/cancers16233953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 11/14/2024] [Accepted: 11/20/2024] [Indexed: 12/18/2024] Open
Abstract
Background/Objectives: Prostate cancer is the second leading cause of cancer death among American men, following lung cancer. While diet and exercise have been extensively studied in relation to prostate cancer prevention, the evidence remains inconclusive. Methods: A comprehensive literature search was performed to identify observational studies investigating the association between ultra-processed food (UPF) consumption and prostate cancer risk and mortality, determined by the NOVA classification system. In addition, we conducted subgroup analyses to assess the association based on study design, age, and data collection methods. Results: Six studies were identified, including four cohort studies and two case-control studies. No significant association was found between high UPF consumption and increased risk of prostate cancer [RR = 1.02, 95% confidence interval (CI) = 0.96-1.08, n = 5]. However, there was a slight increase in mortality (RR = 1.15, 95% CI = 0.99-1.35, n = 2). A subgroup analysis by the dietary assessment method revealed an RR of 1.01 (95% CI = 0.93-1.09) for studies using the food frequency questionnaire (FFQ) and 1.04 (95% CI = 0.93-1.16) for studies using 24-h recalls. There was no significant heterogeneity among the studies (I2 = 0, p = 0.82). Conclusions: This meta-analysis suggests no significant association between high UPF consumption and prostate cancer risk. Given the known associations with other chronic diseases, the potential public health implications of reducing UPF consumption remain important. Further research with the use of more robust food assignment systems and more precise dietary assessments is needed to clarify the role of UPF in prostate cancer development.
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Affiliation(s)
| | - Janice Huang
- Miller School of Medicine, University of Miami, Miami, FL 33136, USA
| | - Benjamin James Rich
- Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA
| | - Crystal Seldon Taswell
- Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA
| | - Derek Isrow
- Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA
| | - William Jin
- Department of Radiation Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA
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5
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Wang J, Apizi A, Tao N, An H. Association between the metabolic score for insulin resistance and prostate cancer: a cross-sectional study in Xinjiang. PeerJ 2024; 12:e17827. [PMID: 39076779 PMCID: PMC11285359 DOI: 10.7717/peerj.17827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 07/08/2024] [Indexed: 07/31/2024] Open
Abstract
Background Insulin resistance is associated with the development and progression of various cancers. However, the epidemiological evidence for the association between insulin resistance and prostate cancer is still limited. Objectives To investigate the associations between insulin resistance and prostate cancer prevalence. Methods A total of 451 patients who were pathologically diagnosed with prostate cancer in the First Affiliated Hospital of Xinjiang Medical University were selected as the case population; 1,863 participants who conducted physical examinations during the same period were selected as the control population. The metabolic score for insulin resistance (METS-IR) was calculated as a substitute indicator for evaluating insulin resistance. The Chi-square test and Mann-Whitney U test were performed to compare the basic information of the case population and control population. Univariate and multivariate logistic regression analyses to define factors that may influence prostate cancer prevalence. The generalized additive model (GAM) was applied to fit the relationship between METS-IR and prostate cancer. Interaction tests based on generalized additive model (GAM) and contour plots were also carried out to analyze the interaction effect of each factor with METS-IR on prostate cancer. Results METS-IR as both a continuous and categorical variable suggested that METS-IR was negatively associated with prostate cancer prevalence. Smoothed curves fitted by generalized additive model (GAM) displayed a nonlinear correlation between METS-IR and prostate cancer prevalence (P < 0.001), and presented that METS-IR was negatively associated with the odds ratio (OR) of prostate cancer. The interaction based on the generalized additive model (GAM) revealed that METS-IR interacted with low-density lipoprotein cholesterol (LDL-c) to influence the prostate cancer prevalence (P = 0.004). Contour plots showed that the highest prevalence probability of prostate cancer was achieved when METS-IR was minimal and low-density lipoprotein cholesterol (LDL-c) or total cholesterol (TC) was maximal. Conclusions METS-IR is nonlinearly and negatively associated with the prevalence of prostate cancer. The interaction between METS-IR and low-density lipoprotein cholesterol (LDL-c) has an impact on the prevalence of prostate cancer. The study suggests that the causal relationship between insulin resistance and prostate cancer still needs more research to confirm.
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Affiliation(s)
- Jinru Wang
- College of Public Health, Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Aireti Apizi
- Department of Urology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Ning Tao
- College of Public Health, Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Hengqing An
- Department of Urology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
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Alhajahjeh A, Al-Faouri R, Bahmad HF, Bader T, Dobbs RW, Abdulelah AA, Abou-Kheir W, Davicioni E, Lee DI, Shahait M. From Diabetes to Oncology: Glucagon-like Peptide-1 (GLP-1) Receptor Agonist's Dual Role in Prostate Cancer. Cancers (Basel) 2024; 16:1538. [PMID: 38672620 PMCID: PMC11048615 DOI: 10.3390/cancers16081538] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 04/09/2024] [Accepted: 04/16/2024] [Indexed: 04/28/2024] Open
Abstract
Glucagon-like peptide-1 (GLP-1), an incretin hormone renowned for its role in post-meal blood sugar regulation and glucose-dependent insulin secretion, has gained attention as a novel treatment for diabetes through GLP-1 receptor agonists (GLP-1-RA). Despite their efficacy, concerns have been raised regarding the potential associations between GLP-1-RA and certain malignancies, including medullary thyroid cancer. However, evidence of its association with prostate cancer (PCa) remains inconclusive. This review delves into the intricate relationship between GLP-1-RA and PCa, exploring the mechanisms through which GLP-1-Rs may impact PCa cells. We discuss the potential pathways involving cAMP, ERK, AMPK, mTOR, and P27. Furthermore, we underscore the imperative for additional research to elucidate the impact of GLP-1-RA treatment on PCa progression, patient outcomes, and potential interactions with existing therapies. Translational studies and clinical trials are crucial for a comprehensive understanding of the role of GLP-1-RA in PCa management.
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Affiliation(s)
- Abdulrahman Alhajahjeh
- School of Medicine, The University of Jordan, Amman 11190, Jordan;
- King Hussein Cancer Center (KHCC), Internal Medicine Department, Amman 11190, Jordan;
| | - Raad Al-Faouri
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02120, USA;
| | - Hisham F. Bahmad
- Arkadi M. Rywlin Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, FL 33140, USA;
| | - Taima’ Bader
- King Hussein Cancer Center (KHCC), Internal Medicine Department, Amman 11190, Jordan;
| | - Ryan W. Dobbs
- Cook County Health and Hospitals System, Chicago, IL 60612, USA;
| | - Ahmed A. Abdulelah
- Edinburgh Medical School, The University of Edinburgh, Edinburgh EH8 9YL, UK;
| | - Wassim Abou-Kheir
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut 1107, Lebanon;
| | | | - David I. Lee
- Department of Urology, University of California, Irvine, CA 92868, USA;
| | - Mohammed Shahait
- School of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates
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7
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Freeman JR, Saint-Maurice PF, Watts EL, Moore SC, Shams-White MM, Wolff-Hughes DL, Russ DE, Almeida JS, Caporaso NE, Hong HG, Loftfield E, Matthews CE. Actigraphy-derived measures of sleep and risk of prostate cancer in the UK Biobank. J Natl Cancer Inst 2024; 116:434-444. [PMID: 38013591 PMCID: PMC10919343 DOI: 10.1093/jnci/djad210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 08/02/2023] [Accepted: 10/08/2023] [Indexed: 11/29/2023] Open
Abstract
BACKGROUND Studies of sleep and prostate cancer are almost entirely based on self-report, with limited research using actigraphy. Our goal was to evaluate actigraphy-measured sleep and prostate cancer and to expand on findings from prior studies of self-reported sleep. METHODS We prospectively examined 34 260 men without a history of prostate cancer in the UK Biobank. Sleep characteristics were measured over 7 days using actigraphy. We calculated sleep duration, onset, midpoint, wake-up time, social jetlag (difference in weekend-weekday sleep midpoints), sleep efficiency (percentage of time spent asleep between onset and wake-up time), and wakefulness after sleep onset. Cox proportional hazards models were used to estimate covariate-adjusted hazards ratios (HRs) and 95% confidence intervals (CIs). RESULTS Over 7.6 years, 1152 men were diagnosed with prostate cancer. Sleep duration was not associated with prostate cancer risk. Sleep midpoint earlier than 4:00 am was not associated with prostate cancer risk, though sleep midpoint of 5:00 am or later was suggestively associated with lower prostate cancer risk but had limited precision (earlier than 4:00 am vs 4:00-4:59 am HR = 1.00, 95% CI = 0.87 to 1.16; 5:00 am or later vs 4:00-4:59 am HR = 0.79, 95% CI = 0.57 to 1.10). Social jetlag was not associated with greater prostate cancer risk (1 to <2 hours vs <1 hour HR = 1.06, 95% CI = 0.89 to 1.25; ≥2 hours vs <1 hour HR = 0.90, 95% CI = 0.65 to 1.26). Compared with men who averaged less than 30 minutes of wakefulness after sleep onset per day, men with 60 minutes or more had a higher risk of prostate cancer (HR = 1.20, 95% CI = 1.00 to 1.43). CONCLUSIONS Of the sleep characteristics studied, higher wakefulness after sleep onset-a measure of poor sleep quality-was associated with greater prostate cancer risk. Replication of our findings between wakefulness after sleep onset and prostate cancer are warranted.
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Affiliation(s)
- Joshua R Freeman
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Pedro F Saint-Maurice
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Eleanor L Watts
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Steven C Moore
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Marissa M Shams-White
- Risk Factor Assessment Branch, Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Dana L Wolff-Hughes
- Risk Factor Assessment Branch, Epidemiology and Genomics Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Daniel E Russ
- Trans-Divisional Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Jonas S Almeida
- Trans-Divisional Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Neil E Caporaso
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Hyokyoung G Hong
- Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Erikka Loftfield
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Charles E Matthews
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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8
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Kaneta K, Tanaka A, Nakai M, Sumita Y, Kaneko H, Noguchi M, Node K. Prevalence and temporal trends of prostate diseases among inpatients with cardiovascular disease: a nationwide real-world database survey in Japan. Front Cardiovasc Med 2023; 10:1236144. [PMID: 37928758 PMCID: PMC10620699 DOI: 10.3389/fcvm.2023.1236144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Accepted: 10/09/2023] [Indexed: 11/07/2023] Open
Abstract
Introduction Benign prostate hyperplasia (BPH) and prostate cancer (PCa) are major prostate diseases that potentially share cardiometabolic risk factors and an elevated risk for cardiovascular disease (CVD). However, the prevalence of prostate diseases among patients with established CVD remains unclear. Materials and methods This nationwide retrospective study assessed the prevalence and temporal trend of prostate diseases (i.e., BPH or PCa) among patients hospitalized for CVDs in Japan. We used a claims database (the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination), which included data on 6,078,487 male patients recorded from 1,058 hospitals between April 2012 and March 2020. We conducted the Cochran-Armitage trend test and calculated the adjusted odds ratio (aOR) with 95% confidence intervals (CIs). Results The prevalence of prostate diseases over the entire study period was 5.7% (BPH, 4.4%; PCa, 1.6%). When dividing the overall cohort into age categories (<65, 65-74, and ≥75 years old), the prevalence was 1.1%, 4.7%, and 9.9%, respectively (P for trend <0.05). In addition, the annual prevalence showed a modest increasing trend over time. Patients admitted for heart failure (HF) were significantly associated with a higher incidence of coexisting prostate diseases than those admitted for non-HF causes [aOR 1.02 (95% CI, 1.01-1.03)] or acute coronary syndrome [aOR 1.19 (95% CI, 1.17-1.22)]. Conclusions The nationwide real-world database revealed that the prevalence of prostate diseases is increasing among patients hospitalized for CVD, particularly HF. Attention to detailed causality and continued surveillance are needed to further clarify the clinical characteristics of prostate diseases among patients with CVD.
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Affiliation(s)
- Kohei Kaneta
- Department of Cardiovascular Medicine, Saga University, Saga, Japan
| | - Atsushi Tanaka
- Department of Cardiovascular Medicine, Saga University, Saga, Japan
| | - Michikazu Nakai
- Department of Medical and Health Information Management, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Yoko Sumita
- Department of Medical and Health Information Management, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
| | - Hidehiro Kaneko
- The Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan
- The Department of Advanced Cardiology, The University of Tokyo, Tokyo, Japan
| | | | - Koichi Node
- Department of Cardiovascular Medicine, Saga University, Saga, Japan
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9
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Kumasaka S, Seki Y, Takayama H, Kumasaka Y, Dineen RA, Tsushima Y. Predictive value of prostate calcification for future cancer occurrence: a retrospective long-term follow-up cohort study. Br J Radiol 2023; 96:20221110. [PMID: 37086073 PMCID: PMC10321267 DOI: 10.1259/bjr.20221110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 03/14/2023] [Accepted: 03/24/2023] [Indexed: 04/23/2023] Open
Abstract
OBJECTIVE Although prostate calcification is often identified on pelvic CT images, calcification itself is usually not considered clinically significant. A recent histological study proposed an association between prostate calcification and prostate cancer occurrence. Our aim was to determine the predictive value of prostate calcifications for future prostate cancer occurrence. METHODS We retrospectively analysed male patients (≥50 years old) without prior prostate cancer history, who underwent unenhanced pelvic CT between April 2010 and March 2011, and followed-up until December 2021. Cox proportional hazards models were used to assess prostate cancer risk with prostate calcification (defined as a high-density area larger than 3 mm with CT attenuation values ≥ 130 HU), controlling for age, body mass index (BMI), hypertension and diabetes mellitus. RESULTS A total of 636 male patients (mean age, 68 years ± 9 [standard deviation]) were evaluated. At the end of follow-up, prostate cancer had been more frequently diagnosed in patients with prostate calcification than those without prostate calcification (6.5% vs 2.6%). Multivariate analysis revealed that prostate calcification on CT was a significant predictor of future prostate cancer occurrence (hazard ratio [HR], 2.7; 95% CI: 1.20, 5.91; p = 0.016). No statistical differences were observed in any other factors. CONCLUSION Prostate calcification may be a significant predictor of future prostate cancer occurrence, and may be used for risk stratification and to guide screening protocols. ADVANCES IN KNOWLEDGE Presence of prostate calcification on unenhanced CT scan was associated with increased incidence of prostate cancer occurrence on long term follow-up.
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Affiliation(s)
| | - Yuko Seki
- Department of Radiology, Gunma University Hospital, Maebashi, Gunma, Japan
| | - Hiroaki Takayama
- Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
| | - Yuka Kumasaka
- Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
| | | | - Yoshito Tsushima
- Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan
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10
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Oderda M, Dematteis A, Calleris G, Conti A, D'Agate D, Falcone M, Marquis A, Montefusco G, Marra G, Gontero P. Predictors of Prostate Cancer at Fusion Biopsy: The Role of Positive Family History, Hypertension, Diabetes, and Body Mass Index. Curr Oncol 2023; 30:4957-4965. [PMID: 37232832 DOI: 10.3390/curroncol30050374] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Revised: 05/09/2023] [Accepted: 05/10/2023] [Indexed: 05/27/2023] Open
Abstract
BACKGROUND PSA density and an elevated PI-RADS score are among the strongest predictors of prostate cancer (PCa) in a fusion biopsy. Positive family history, hypertension, diabetes, and obesity have also been associated with the risk of developing PCa. We aim to identify predictors of the prostate cancer detection rate (CDR) in a series of patients undergoing a fusion biopsy. METHODS We retrospectively evaluated 736 consecutive patients who underwent an elastic fusion biopsy from 2020 to 2022. Targeted biopsies (2-4 cores per MRI target) were followed by systematic mapping (10-12 cores). Clinically significant PCa (csPCa) was defined as ISUP score ≥ 2. Uni- and multi-variable logistic regression analyses were performed to identify predictors of CDR among age, body mass index (BMI), hypertension, diabetes, positive family history, PSA, a positive digital rectal examination (DRE), PSA density ≥ 0.15, previous negative biopsy status, PI-RADS score, and size of MRI lesion. RESULTS The median patients' age was 71 years, and median PSA was 6.6 ng/mL. A total of 20% of patients had a positive digital rectal examination. Suspicious lesions in mpMRI were scored as 3, 4, and 5 in 14.9%, 55.0%, and 17.5% of cases, respectively. The CDR was 63.2% for all cancers and 58.7% for csPCa. Only age (OR 1.04, p < 0.001), a positive DRE (OR 1.75, p = 0.04), PSA density (OR 2.68, p < 0.001), and elevated PI-RADS score (OR 4.02, p = 0.003) were significant predictors of the CDR in the multivariable analysis for overall PCa. The same associations were found for csPCa. The size of an MRI lesion was associated with the CDR only in uni-variable analysis (OR 1.07, p < 0.001). BMI, hypertension, diabetes, and a positive family history were not predictors of PCa. CONCLUSIONS In a series of patients selected for a fusion biopsy, positive family history, hypertension, diabetes, or BMI are not predictors of PCa detection. PSA-density and PI-RADS score are confirmed to be strong predictors of the CDR.
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Affiliation(s)
- Marco Oderda
- Division of Urology, Department of Surgical Sciences, Molinette Hospital, University of Turin, 10126 Turin, Italy
| | - Alessandro Dematteis
- Division of Urology, Department of Surgical Sciences, Molinette Hospital, University of Turin, 10126 Turin, Italy
| | - Giorgio Calleris
- Division of Urology, Department of Surgical Sciences, Molinette Hospital, University of Turin, 10126 Turin, Italy
| | - Adriana Conti
- Division of Urology, Department of Surgical Sciences, Molinette Hospital, University of Turin, 10126 Turin, Italy
| | - Daniele D'Agate
- Division of Urology, Department of Surgical Sciences, Molinette Hospital, University of Turin, 10126 Turin, Italy
| | - Marco Falcone
- Division of Urology, Department of Surgical Sciences, Molinette Hospital, University of Turin, 10126 Turin, Italy
| | - Alessandro Marquis
- Division of Urology, Department of Surgical Sciences, Molinette Hospital, University of Turin, 10126 Turin, Italy
| | - Gabriele Montefusco
- Division of Urology, Department of Surgical Sciences, Molinette Hospital, University of Turin, 10126 Turin, Italy
| | - Giancarlo Marra
- Division of Urology, Department of Surgical Sciences, Molinette Hospital, University of Turin, 10126 Turin, Italy
| | - Paolo Gontero
- Division of Urology, Department of Surgical Sciences, Molinette Hospital, University of Turin, 10126 Turin, Italy
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11
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Guerrios-Rivera L, Howard LE, Wiggins EK, Hoyo C, Grant DJ, Erickson TR, Ithisuphalap J, Freedland AR, Vidal AC, Fowke JH, Freedland SJ. Metabolic syndrome is associated with aggressive prostate cancer regardless of race. Cancer Causes Control 2023; 34:213-221. [PMID: 36450931 PMCID: PMC11182659 DOI: 10.1007/s10552-022-01649-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 10/29/2022] [Indexed: 12/02/2022]
Abstract
PURPOSE Recent meta-analyses suggest the Metabolic Syndrome (MS) increases high-grade prostate cancer (PC), although studies are inconsistent and few black men were included. We investigated MS and PC diagnosis in black and white men undergoing prostate biopsy in an equal access healthcare system. We hypothesized MS would be linked with aggressive PC, regardless of race. METHODS Among men undergoing prostate biopsy at the Durham Veterans Affairs Hospital, medical record data abstraction of diagnosis or treatment for hypertension (≥ 130/85 mmHg), dyslipidemia (HDL < 40 mg/dL), hypertriglyceridemia (≥ 150 mg/dL), diabetes, hyperglycemia (fasting glucose ≥ 100 ml/dL), and central obesity (waist circumference ≥ 40 inches) were done. Biopsy grade group (GG) was categorized as low (GG1) or high (GG2-5). Multinomial logistic regression was used to examine MS (3-5 components) vs. no MS (0-2 components) and diagnosis of high grade and low grade vs. no PC, adjusting for potential confounders. Interactions between race and MS were also tested. RESULTS Of 1,051 men (57% black), 532 (51%) had MS. Men with MS were older, more likely to be non-black, and had a larger prostate volume (all p ≤ 0.011). On multivariable analysis, MS was associated with high-grade PC (OR = 1.73, 95% CI 1.21-2.48, p = 0.003), but not overall PC (OR = 1.17, 95% CI 0.88-1.57, p = 0.29) or low grade (OR = 0.87, 95% CI 0.62-1.21, p = 0.39). Results were similar in black and non-black men (all p-interactions > 0.25). CONCLUSION Our data suggest that metabolic dysregulation advances an aggressive PC diagnosis in both black and non-black men. If confirmed, prevention of MS could reduce the risk of developing aggressive PC, including black men at higher risk of PC mortality.
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Affiliation(s)
- Lourdes Guerrios-Rivera
- Urology Section, Surgery Department, Veterans Administration Caribbean Healthcare System, San Juan, Puerto Rico.
- University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico.
| | - Lauren E Howard
- Duke Cancer Institute, Duke University School of Medicine, Duke, USA
- Veterans Affairs Medical Center Durham, Urology Section, 508 Fulton St, Durham, NC, 27705, USA
| | - Emily K Wiggins
- Veterans Affairs Medical Center Durham, Urology Section, 508 Fulton St, Durham, NC, 27705, USA
| | - Cathrine Hoyo
- North Carolina State Department of Biology and Cancer Research Program, 2200 Hillsborough, Raleigh, NC, 27695, USA
| | - Delores J Grant
- Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, 1801 Fayetteville Street, Durham, NC, USA
| | - Tyler R Erickson
- Veterans Affairs Medical Center Durham, Urology Section, 508 Fulton St, Durham, NC, 27705, USA
| | - Jaruda Ithisuphalap
- Veterans Affairs Medical Center Durham, Urology Section, 508 Fulton St, Durham, NC, 27705, USA
| | - Alexis R Freedland
- Dept of Epidemiology, UCI School of Medicine, University of California, 1001 Health Sciences Rd, Irvine, CA, 92617, USA
| | - Adriana C Vidal
- Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, 8635 West 3rd Street Suite 1070W, Los Angeles, CA, 90048, USA
| | - Jay H Fowke
- Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Division of Epidemiology, Department of Preventive Medicine, University of Tennessee Health Science Center, Doctor's Office Building, 66 N. Pauline Street, Suite 600, Memphis, TN, 38163, USA
| | - Stephen J Freedland
- Veterans Affairs Medical Center Durham, Urology Section, 508 Fulton St, Durham, NC, 27705, USA
- Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute, 8635 West 3rd Street Suite 1070W, Los Angeles, CA, 90048, USA
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12
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Liu Z, Zhu X, He J, Lu J. Metabolic syndrome and its components predict the biochemical recurrence and adverse pathological features of patients following radical prostatectomy: a propensity score matching study. BMC Cancer 2023; 23:50. [PMID: 36641426 PMCID: PMC9840841 DOI: 10.1186/s12885-023-10507-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 01/02/2023] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND To investigate the predictive value of metabolic syndrome (MetS) and its components in biochemical recurrence (BCR) and adverse pathological features of patients with prostate cancer (PCa) after radical prostatectomy (RP). METHODS A total of 525 PCa patients who underwent RP between 2010 and 2019 at Peking University Third Hospital were analyzed retrospectively. The Kaplan-Meier method was performed to assess BCR-free survival (BCRFS). Univariate and multivariate Cox regression models and multivariate logistic regression models were conducted to identify the predictive factors of BCRFS and adverse pathological features respectively before and after propensity score matching (PSM). RESULTS Enrolled patients were allocated into MetS group (n = 136) and non-MetS group (n = 389) according to the presence or absence of MetS, and 127 new matched pairs were identified to balance the baseline characteristics after 1:1 PSM. In propensity matched patients, the Kaplan-Meier analysis revealed that MetS (P = 0.020), hyperglycemia (P = 0.015) and hypertriglyceridemia (P = 0.001) were significantly associated with worse BCRFS; the results of multivariate Cox analyses showed that hyperglycemia (P = 0.040), hypertriglyceridemia (P = 0.017), percentage of positive biopsy cores (P = 0.041) and prostate specific antigen (P = 0.019) were identified as independent prognostic factors for BCRFS. In addition, hypertriglyceridemia was independently associated with non-organ confined disease (NOCD) (P = 0.010), extra-capsular extension (ECE) (P = 0.010) and upgrading (P = 0.017) in the multivariate logistic analyses. CONCLUSIONS Hyperglycemia and hypertriglyceridemia are the two effective MetS components both identified as independent risk factors for worse BCRFS after RP, while hypertriglyceridemia was independently associated with NOCD, ECE and upgrading as well.
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Affiliation(s)
- Zenan Liu
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Xuehua Zhu
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Jide He
- Department of Urology, Peking University Third Hospital, Beijing, China
| | - Jian Lu
- Department of Urology, Peking University Third Hospital, Beijing, China.
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13
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Yang Y, Zhang W, Wan L, Tang Z, Zhang Q, Bai Y, Zhang D. Construction and validation of a clinical predictive nomogram for intraductal carcinoma of the prostate based on Chinese multicenter clinical data. Front Oncol 2022; 12:1074478. [PMID: 36591521 PMCID: PMC9798232 DOI: 10.3389/fonc.2022.1074478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 11/30/2022] [Indexed: 12/23/2022] Open
Abstract
Introduction Intraductal carcinoma of the prostate (IDC-P) is a special pathological type of prostate cancer that is highly aggressive with poor prognostic outcomes. Objective To establish an effective predictive model for predicting IDC-P. Methods Data for 3185 patients diagnosed with prostate cancer at three medical centers in China from October 2012 to April 2022 were retrospectively analyzed. One cohort (G cohort) consisting of 2384 patients from Zhejiang Provincial People's Hospital was selected for construction (Ga cohort) and internal validate (Gb cohort)of the model. Another cohort (I cohort) with 344 patients from Quzhou People's Hospital and 430 patients from Jiaxing Second People's Hospital was used for external validation. Univariate and multivariate binary logistic regression analyses were performed to identify the independent predictors. Then, the selected predictors were then used to establish the predictive nomogram. The apparent performance of the model was evaluated via externally validated. Decision curve analysis was also performed to assess the clinical utility of the developed model. Results Univariate and multivariate logistic regression analyses showed that alkaline phosphatase (ALP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), prostate specific antigen (PSA) and lactate dehydrogenase were independent predictors of IDC-P. Therefore, a predictive nomogram of IDC-P was constructed. The nomogram had a good discriminatory power (AUC = 0.794). Internal validation (AUC = 0.819)and external validation (AUC = 0.903) also revealed a good predictive ability. Calibration curves showed good agreement between the predicted and observed incidences of IDC-P. Conclusion We developed a clinical predictive model composed of alkaline phosphatase (ALP), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), prostate specific antigen (PSA) and lactate dehydrogenase (LDH) with a high precision and universality. This model provides a novel calculator for predicting the diagnosis of IDC-P and different treatment options for patients at an early stage.
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Affiliation(s)
- YunKai Yang
- Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, China,The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Wei Zhang
- Zhejiang Provincial People’s Hospital, Qingdao University, Shandong, Qingdao, China
| | - LiJun Wan
- Department of Urology, Quzhou People’s Hospital, Quzhou, Zhejiang, China
| | - ZhiLing Tang
- Department of Urology, Jiaxing Second People’s Hospital, Jiaxing, Zhejiang, China
| | - Qi Zhang
- Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, China
| | - YuChen Bai
- Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, China,*Correspondence: YuChen Bai, ; DaHong Zhang,
| | - DaHong Zhang
- Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang, China,The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China,*Correspondence: YuChen Bai, ; DaHong Zhang,
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14
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Lavalette C, Cordina-Duverger E, Rébillard X, Lamy PJ, Trétarre B, Cénée S, Menegaux F. Diabetes, metabolic syndrome and prostate cancer risk: Results from the EPICAP case-control study. Cancer Epidemiol 2022; 81:102281. [PMID: 36279644 DOI: 10.1016/j.canep.2022.102281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Revised: 08/30/2022] [Accepted: 10/17/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Diabetes may be associated with decreased prostate cancer (PCa) risk. However, previous studies have not always accounted for time since diabetes diagnosis or antidiabetic drug use. Futhermore, the role of metabolic syndrome (MetS) in PCa risk is still debated. We investigated the role of diabetes and MetS in PCa risk based on data from the Epidemiological study of PCa (EPICAP). METHODS EPICAP is a population-based case-control study that included 819 incident PCa cases in 2012-2013 and 879 controls frequency matched by age. MetS was characterized according to National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III). Logistic regression models adjusted for age, family history of PCa and ethnicity, were used to assess odds ratios (ORs) and their 95%conficence intervals (CIs) for the associations between diabetes, MetS and PCa risk. RESULTS Whereas we did not observed an association between diabetes and PCa, a decreased risk of PCa has been highlighted with an increasing treated diabetes duration (p-trend=0.008). No association has been observed between MetS, the number of MetS criteria and the risk of PCa. However, we suggested that NSAIDs use could modify the association between MetS and PCa risk. CONCLUSION Our results suggest an inverse association between the duration of diabetes and PCa risk. The role of metabolic factors, such as MetS and its components, in PCa risk remains unclear and requires further investigations.
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Affiliation(s)
- Céline Lavalette
- Université Paris-Saclay, UVSQ, Inserm, CESP, Exposome and Heredity Team, Villejuif, France
| | | | | | - Pierre-Jean Lamy
- Service Urologie, Clinique Beau Soleil, Montpellier, France; Institut médical d'Analyse Génomique-Imagenome, Labosud, Montpellier, France
| | - Brigitte Trétarre
- Registre des Tumeurs de l'Hérault, EA 2415, ICM, Montpellier, France
| | - Sylvie Cénée
- Université Paris-Saclay, UVSQ, Inserm, CESP, Exposome and Heredity Team, Villejuif, France
| | - Florence Menegaux
- Université Paris-Saclay, UVSQ, Inserm, CESP, Exposome and Heredity Team, Villejuif, France.
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15
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Li YD, Ren ZJ, Gao L, Ma JH, Gou YQ, Tan W, Liu C. Cholelithiasis increased prostate cancer risk: evidence from a case-control study and a meta-analysis. BMC Urol 2022; 22:160. [PMID: 36192737 PMCID: PMC9528176 DOI: 10.1186/s12894-022-01110-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 09/19/2022] [Indexed: 12/24/2022] Open
Abstract
Introduction Cholelithiasis represents a known risk factor for digestive system neoplasm. Few studies reported the association between cholelithiasis and the risk of prostate cancer (PCa), and the results were controversial. Methods We reviewed the medical records of the Second Affiliated Hospital of Chongqing Medical University Hospital to perform a retrospective matched case–control study, which included newly diagnosed 221 PCa patients and 219 matched controls. Logistic regression was applied to compare cholelithiasis exposure and adjusted for confounding factors. Additionally, we conducted a meta-analysis pooling this and published studies further to evaluate the association between cholelithiasis and PCa risk. Related ratio (RR) and 95% confidence interval (95%CI) were used to assess the strength of associations. Results Our case–control study showed that cholelithiasis was associated with a higher incidence of PCa (OR = 1.87, 95% CI: 1.06–3.31) after multivariable adjustment for covariates. The incidence of PCa was increased in patients with gallstones but not cholecystectomy. 7 studies involving 80,403 individuals were included in the meta-analysis. Similarly, the results demonstrated that cholelithiasis was associated with an increased risk of PCa (RR = 1.35, 95%CI: 1.17–1.56) with moderate-quality evidence. Cholelithiasis patients with low BMI increased the PCa incidence. Moreover, Subgroup analysis based on region showed that cholelithiasis was associated with PCa in Europe (RR = 1.24, 95%CI 1.03–1.51) and Asia (RR = 1.32, 95%CI 1.24–1.41). Conclusions The results suggested an association between cholelithiasis and the risk of PCa. There was no significant relationship between cholecystectomy therapy and PCa risk. Further cohort studies should be conducted to demonstrate the results better.
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Affiliation(s)
- Ya-Dong Li
- Department of Urology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Zheng-Ju Ren
- Department of Urology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Liang Gao
- Department of Urology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Jun-Hao Ma
- Department of Urology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Yuan-Qing Gou
- Department of Urology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Wei Tan
- Department of Urology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Chuan Liu
- Department of Urology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
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16
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Galvão DA, Taaffe DR, Hayne D, Lopez P, Lyons-Wall P, Tang CI, Chambers SK, Devine A, Spry N, Jeffery E, Kudiarasu C, Joseph D, Newton RU. Weight loss for overweight and obese patients with prostate cancer: a study protocol of a randomised trial comparing clinic-based versus Telehealth delivered EXercise and nutrition intervention (the TelEX trial). BMJ Open 2022; 12:e058899. [PMID: 35667725 PMCID: PMC9171278 DOI: 10.1136/bmjopen-2021-058899] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
INTRODUCTION Obese men with prostate cancer have an increased risk of biochemical recurrence, metastatic disease and mortality. For those undergoing androgen deprivation therapy (ADT), substantial increases in fat mass are observed in the first year of treatment. Recently, we showed that a targeted supervised clinic-based exercise and nutrition intervention can result in a substantial reduction in fat mass with muscle mass preserved in ADT-treated patients. However, the intervention needs to be accessible to all patients and not just those who can access a supervised clinic-based programme. The purpose of this study was to evaluate the efficacy of telehealth delivered compared with supervised clinic-based delivered exercise and nutrition intervention in overweight/obese patients with prostate cancer. METHODS AND ANALYSIS A single-blinded, two-arm parallel group, non-inferiority randomised trial will be undertaken with 104 overweight/obese men with prostate cancer (body fat percentage ≥25%) randomly allocated in a ratio of 1:1 to a telehealth-delivered, virtually supervised exercise and nutrition programme or a clinic-based, face-to-face supervised exercise and nutrition programme. Exercise will consist of supervised resistance and aerobic exercise performed three times a week plus additional self-directed aerobic exercise performed 4 days/week for the first 6 months. Thereafter, for months 7-12, the programmes will be self-managed. The primary endpoint will be fat mass. Secondary endpoints include lean mass and abdominal aortic calcification, anthropometric measures and blood pressure assessment, objective measures of physical function and physical activity levels, patient-reported outcomes and blood markers. Measurements will be undertaken at baseline, 6 months (post intervention), and at 12 months of follow-up. Data will be analysed using intention-to-treat and per protocol approaches. ETHICS AND DISSEMINATION Ethics approval has been obtained from the Edith Cowan University Human Research Ethics Committee (ID: 2021-02157-GALVAO). Outcomes from the study will be published in academic journals and presented in scientific and consumer meetings. TRIAL REGISTRATION NUMBER ACTRN12621001312831.
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Affiliation(s)
- Daniel A Galvão
- Exercise Medicine Research Institute, Edith Cowan University, Joondalup, Western Australia, Australia
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
| | - Dennis R Taaffe
- Exercise Medicine Research Institute, Edith Cowan University, Joondalup, Western Australia, Australia
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
| | - Dickon Hayne
- School of Surgery, The University of Western Australia, Perth, Western Australia, Australia
- Urology Department, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
| | - Pedro Lopez
- Exercise Medicine Research Institute, Edith Cowan University, Joondalup, Western Australia, Australia
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
| | - P Lyons-Wall
- Exercise Medicine Research Institute, Edith Cowan University, Joondalup, Western Australia, Australia
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
| | - Colin I Tang
- Exercise Medicine Research Institute, Edith Cowan University, Joondalup, Western Australia, Australia
- Department of Radiation Oncology, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
| | - Suzanne K Chambers
- Exercise Medicine Research Institute, Edith Cowan University, Joondalup, Western Australia, Australia
- Faculty of Health Sciences, Australian Catholic University, Brisbane, Queensland, Australia
| | - Amanda Devine
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
- Nutrition and Health Innovation Research Institute, Edith Cowan University, Joondalup, Western Australia, Australia
| | - Nigel Spry
- Exercise Medicine Research Institute, Edith Cowan University, Joondalup, Western Australia, Australia
| | - Emily Jeffery
- Exercise Medicine Research Institute, Edith Cowan University, Joondalup, Western Australia, Australia
- School of Public Health, Curtin University, Perth, Western Australia, Australia
| | - Christine Kudiarasu
- Exercise Medicine Research Institute, Edith Cowan University, Joondalup, Western Australia, Australia
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
| | - David Joseph
- Exercise Medicine Research Institute, Edith Cowan University, Joondalup, Western Australia, Australia
- Department of Radiation Oncology, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia
| | - Robert U Newton
- Exercise Medicine Research Institute, Edith Cowan University, Joondalup, Western Australia, Australia
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
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17
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Gan S, Liu J, Chen Z, Xiang S, Gu C, Li S, Wang S. Low serum total testosterone level as a predictor of upgrading in low-risk prostate cancer patients after radical prostatectomy: A systematic review and meta-analysis. Investig Clin Urol 2022; 63:407-414. [PMID: 35670005 PMCID: PMC9262493 DOI: 10.4111/icu.20210459] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 02/14/2022] [Accepted: 04/20/2022] [Indexed: 11/30/2022] Open
Abstract
Purpose To investigated the association between serum total testosterone and Gleason score upgrading of low-risk prostate cancer after radical prostatectomy (RP). Materials and Methods Medline, Web of Science, Embase, and Cochrane Library databases were searched to identify eligible studies published before October 2021. Multivariate adjusted odds ratios (ORs) and associated 95% confidence intervals (CIs) were calculated using random or fixed effects models. Results Five studies comprising 1,203 low-risk prostate cancer patients were included. The results showed that low serum total testosterone (<300 ng/dL) is associated with a high rate of Gleason score upgrading after RP (OR, 2.3; 95% CI, 1.38–3.83; p<0.001; I2, 92.2%). Notably, sensitivity and meta-regression analyses further strengthen the reliability of our results. Conclusions Our results support the idea that low serum total testosterone is associated with a high rate of Gleason score upgrading in prostate cancer patients after RP. It is beneficial for urologist to ensure close monitoring of prostate-specific antigen levels and imaging examination when choosing non-RP treatment for low-risk prostate cancer patients.
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Affiliation(s)
- Shu Gan
- Department of Urology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jian Liu
- Department of Urology, The Xinfeng County People's Hospital of Jiangxi Province, Jiangxi, China
| | - Zhiqiang Chen
- Department of Urology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Songtao Xiang
- Department of Urology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Chiming Gu
- Department of Urology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Siyi Li
- Department of Urology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Shusheng Wang
- Department of Urology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
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18
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Gao X, Li R, Jin T, Tang H. The Association Between Metabolic Syndrome and Prostate Cancer Risk: A Large-Scale Investigation and Study of Chinese. Front Endocrinol (Lausanne) 2022; 13:787268. [PMID: 35669684 PMCID: PMC9164813 DOI: 10.3389/fendo.2022.787268] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 04/05/2022] [Indexed: 11/13/2022] Open
Abstract
Background To investigate the association between metabolic syndrome (MetS) and its components and prostate cancer (PCa). Methods This study enrolled 482 943 consecutive men who underwent routine health checkups at the Health Management Center of West China Hospital Between 2010 and 2017. For patients with elevated prostate-specific antigen (PSA) levels or color Doppler ultrasound indicating abnormal prostates, we recommended prostate puncture and follow-up. We used the chi-square test and independent t-test for categorical variables and continuous variables, respectively. We used logistic regression analysis to evaluate the effects of MetS and its components on prostate cancer risk. Results We found that the incidence of PCa in Chinese men over 40 years of age was 0.1%. Among the 85882 participants, 31.5% (27016/85882) of the patients were diagnosed with MetS. PCa was associated with older age, higher PSA levels, lighter weight and shorter height, hypertension, elevated fasting blood glucose (FBG) and HDL cholesterol level, lower triglycerides. After excluded the interference of other factors in multivariate logistic analysis, we found that MetS, hypertension, hyperlipidemia, hyperglycemia, and obesity were not related to the risk of PCa. High age and PSA levels were risk factors for prostate cancer. Conclusions High age and PSA levels were risk factors for prostate cancer. MetS, hypertension, hyperlipidemia, hyperglycemia, and obesity were not related to the risk of PCa.
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Affiliation(s)
- Xiaoshuai Gao
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, China
| | - Ruicen Li
- Department of Health Management Center, West China Hospital, Sichuan University, Chengdu, China
| | - Tao Jin
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, China
| | - Huairong Tang
- Department of Health Management Center, West China Hospital, Sichuan University, Chengdu, China
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19
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Lopez P, Newton RU, Taaffe DR, Singh F, Lyons-Wall P, Buffart LM, Tang C, Hayne D, Galvão DA. Interventions for Improving Body Composition in Men with Prostate Cancer: A Systematic Review and Network Meta-analysis. Med Sci Sports Exerc 2022; 54:728-740. [PMID: 34935706 DOI: 10.1249/mss.0000000000002843] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
PURPOSE To perform a systematic review and network meta-analysis to investigate the most effective intervention for improving body composition outcomes in prostate cancer patients during or after treatment. METHODS A systematic search was undertaken in multiple databases from inception to December 2020. Randomized clinical trials examining the effects of exercise/physical activity and/or nutrition interventions on body composition and body weight measures in prostate cancer patients were included. The primary endpoints were both whole-body and regional fat mass and lean mass measures, with body weight and BMI as secondary outcomes. A frequentist random-effects network meta-analysis was undertaken to examine the clustering effect of intervention modalities or control groups on the outcomes of interest. The study protocol is publicly available on PROSPERO (CRD42020202339). RESULTS Fifty articles describing 47 trials (n = 3207) were included. Resistance training and combined resistance and aerobic exercise were the most effective interventions to reduce body fat percentage (-0.9%; 95% confidence interval [CI], -1.4% to -0.3%) and fat mass (-0.5 kg; 95% CI, -0.9 to -0.1 kg), respectively. For whole-body and regional lean mass, combined resistance and aerobic exercise + healthy diet (0.6 kg; 95% CI, 0.1 to 1.0 kg) and resistance training alone (0.7 kg, 95% CI: 0.4 to 1.0 kg) were the best intervention, respectively. A low-fat diet was the most effective for reducing body weight immediately after or at follow-up, while no intervention promoted significant reductions in BMI. CONCLUSIONS These results indicate that a resistance-based exercise program alone or combined with a general healthy diet are the most effective interventions for improving overall body composition in men with prostate cancer.
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Jiménez-Vacas JM, Montero-Hidalgo AJ, Gómez-Gómez E, Fuentes-Fayos AC, Ruiz-Pino F, Guler I, Camargo A, Anglada FJ, Carrasco-Valiente J, Tena-Sempere M, Sarmento-Cabral A, Castaño JP, Gahete MD, Luque RM. In1-Ghrelin Splicing Variant as a Key Element in the Pathophysiological Association Between Obesity and Prostate Cancer. J Clin Endocrinol Metab 2021; 106:e4956-e4968. [PMID: 34255835 DOI: 10.1210/clinem/dgab516] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
CONTEXT Recent studies emphasize the importance of considering the metabolic status to develop personalized medicine approaches. This is especially relevant in prostate cancer (PCa), wherein the diagnostic capability of prostate-specific antigen (PSA) dramatically drops when considering patients with PSA levels ranging from 3 to 10 ng/mL, the so-called grey zone. Hence, additional noninvasive diagnostic and/or prognostic PCa biomarkers are urgently needed, especially in the metabolic-status context. OBJECTIVE To assess the potential relation of urine In1-ghrelin (a ghrelin-splicing variant) levels with metabolic-related/pathological conditions (eg, obesity, diabetes, body mass index, insulin and glucose levels) and to define its potential clinical value in PCa (diagnostic/prognostic capacity) and relationship with PCa risk in patients with PSA in the grey zone. METHODS Urine In1-ghrelin levels were measured by radioimmunoassay in a clinically, metabolically, pathologically well-characterized cohort of patients without (n = 397) and with (n = 213) PCa with PSA in the grey zone. RESULTS Key obesity-related factors associated with PCa risk (BMI, diabetes, glucose and insulin levels) were strongly correlated to In1-ghrelin levels. Importantly, In1-ghrelin levels were higher in PCa patients compared to control patients with suspect of PCa but negative biopsy). Moreover, high In1-ghrelin levels were associated with increased PCa risk and linked to PCa aggressiveness (eg, tumor stage, lymphovascular invasion). In1-ghrelin levels added significant diagnostic value to a clinical model consisting of age, suspicious digital rectal exam, previous biopsy, and PSA levels. Furthermore, a multivariate model consisting of clinical and metabolic variables, including In1-ghrelin levels, showed high specificity and sensitivity to diagnose PCa (area under the receiver operating characteristic curve = 0.740). CONCLUSIONS Urine In1-ghrelin levels are associated with obesity-related factors and PCa risk and aggressiveness and could represent a novel and valuable noninvasive PCa biomarker, as well as a potential link in the pathophysiological relationship between obesity and PCa.
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Affiliation(s)
- Juan M Jiménez-Vacas
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain
- Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain
- Reina Sofia University Hospital (HURS), Cordoba, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain
| | - Antonio J Montero-Hidalgo
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain
- Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain
- Reina Sofia University Hospital (HURS), Cordoba, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain
| | - Enrique Gómez-Gómez
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain
- Reina Sofia University Hospital (HURS), Cordoba, Spain
- Urology Service, HURS/IMIBIC, Cordoba, Spain
| | - Antonio C Fuentes-Fayos
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain
- Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain
- Reina Sofia University Hospital (HURS), Cordoba, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain
| | - Francisco Ruiz-Pino
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain
- Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain
- Reina Sofia University Hospital (HURS), Cordoba, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain
| | - Ipek Guler
- Leuven Biostatistics and Statistical Bioinformatics Centre (L-BioStat), Katholiek Universiteit (KU) Leuven, University of Leuven, Leuven, Belgium
| | - Antonio Camargo
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain
- Reina Sofia University Hospital (HURS), Cordoba, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain
- Lipids and Atherosclerosis Unit, Internal Medicine Unit, Reina Sofia University Hospital, Cordoba, Spain
| | - Francisco J Anglada
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain
- Reina Sofia University Hospital (HURS), Cordoba, Spain
- Urology Service, HURS/IMIBIC, Cordoba, Spain
| | - Julia Carrasco-Valiente
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain
- Reina Sofia University Hospital (HURS), Cordoba, Spain
- Urology Service, HURS/IMIBIC, Cordoba, Spain
| | - Manuel Tena-Sempere
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain
- Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain
- Reina Sofia University Hospital (HURS), Cordoba, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain
| | - André Sarmento-Cabral
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain
- Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain
- Reina Sofia University Hospital (HURS), Cordoba, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain
| | - Justo P Castaño
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain
- Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain
- Reina Sofia University Hospital (HURS), Cordoba, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain
| | - Manuel D Gahete
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain
- Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain
- Reina Sofia University Hospital (HURS), Cordoba, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain
| | - Raúl M Luque
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain
- Department of Cell Biology, Physiology and Immunology, University of Cordoba, Cordoba, Spain
- Reina Sofia University Hospital (HURS), Cordoba, Spain
- CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Cordoba, Spain
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21
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Fragkoulis C, Glykas I, Tzelves L, Stasinopoulos K, Lazarou L, Kaoukis A, Dellis A, Stathouros G, Papadopoulos G, Ntoumas K. Association of metabolic syndrome with prostate cancer diagnosis and aggressiveness in patients undergoing transrectal prostate biopsy. Arch Ital Urol Androl 2021; 93:291-295. [PMID: 34839634 DOI: 10.4081/aiua.2021.3.291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 07/10/2021] [Indexed: 11/22/2022] Open
Abstract
INTRODUCTION AND OBJECTIVE Even though the only established risk factors for prostate cancer (PCa) are age, ethnic origin and family history, there are data suggesting that environmental factors, such as the presence of metabolic syndrome (MetS), may also play a role in the etiology of the disease. The aim of this study is to correlate MetS with PCa diagnosis and Gleason score (GS) in patients undergoing transrectal ultrasound guided prostate biopsy. MATERIALS AND METHODS This is a prospective, single-center study including 378 patients who underwent transrectal ultrasound guided prostate biopsy in our department during the years from 2018 to 2019. Patients were divided into two groups according to the presence of PCa. Group A included 197 patients diagnosed with PCa while Group B consisted of 181 patients without PCa in their biopsy result. Multiple variables such as the presence of MetS and its components were evaluated in correlation to the presence of PCa and PCa characteristics. Statistical analysis was performed using the IBM SPSS Statistics v.23 program. RESULTS Mean PSA value was 8.7 ng/dl in the PCa group and 7.1 ng/dl in the non PCa group, respectively. MetS was diagnosed in 108 patients (54.8%) with PCa and 80 patients (44.2%) without PCa and the difference was statistically significant. Hypertriglyceridemia was the MetS component with statistically higher frequency in PCa patients. Furthermore, the prevalence of MetS was higher in higher Gleason score PCa (GS ≥ 4+3) patients vs lower Gleason score PCa (GS ≤ 3+4) patients. More specifically, MetS, hypertriglyceridemia, and low HDL levels were independent factors associated with higher Gleason score PCa (GS ≥ 4+3). CONCLUSIONS Patients suffering from MetS who undergo prostate biopsy present with higher rates of PCa diagnosis and higher GS in comparison with patients with a normal metabolic profile.
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Affiliation(s)
| | - Ioannis Glykas
- Department of Urology, General Hospital of Athens ''G. Gennimatas'', Athens.
| | - Lazaros Tzelves
- 2nd Department of Urology, National and Kapodistrian University of Athens, School of Medicine, Sismanoglio Hospital, Athens.
| | | | - Lazaros Lazarou
- 2nd Department of Urology, National and Kapodistrian University of Athens, School of Medicine, Sismanoglio Hospital, Athens.
| | - Andreas Kaoukis
- Department of Cardiology, General Hospital of Athens ''G. Gennimatas'', Athens.
| | - Athanasios Dellis
- 2nd Department of Surgery, Aretaieion Hospital, School of Medicine, National and Kapodistrian University of Athens.
| | - Georgios Stathouros
- Department of Urology, General Hospital of Athens ''G. Gennimatas'', Athens.
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22
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Zhang Y, Zhang H, Rong S, Bian C, Yang Y, Pan H. NMR spectroscopy based metabolomics confirms the aggravation of metabolic disorder in metabolic syndrome combined with hyperuricemia. Nutr Metab Cardiovasc Dis 2021; 31:2449-2457. [PMID: 34154888 DOI: 10.1016/j.numecd.2021.05.015] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 04/16/2021] [Accepted: 05/14/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND AIMS Hyperuricemia (HUA) were associated with Metabolic syndrome (MetS) and its components. However, the molecular mechanism of uric acid in the development of MetS was not well elucidated. The aim of this study was developing a systemic metabolic profile by using metabolomics approach to explore the molecular mechanism of uric acid in the development of MetS. METHODS AND RESULTS Anthropometric, clinical biochemical data, and serum samples were collected from patients with MetS, MetS combined with HUA (MetS & HUA) and healthy controls. 1H nuclear magnetic resonance (NMR) spectroscopy was used to detect endogenous small molecule metabolites of serum samples, then multivariate statistical analysis was applied to distinguish samples of different groups. In addition, pathway analysis was performed to contribute to understanding the metabolic change. By serum metabolic profiling, a total of 20 identified metabolites including lipids, amino acids, and organic acids were significantly altered in MetS and MetS & HUA patients. MetS & HUA patients presented a more severe disorder in both identified metabolites and BMI and biochemical indexes. According to pathway analysis, there were 3 and 5 metabolic pathways remarkably perturbed in MetS and MetS & HUA group respectively. CONCLUSION Taken together, we identified disordered metabolites and related pathways for both MetS and MetS & HUA patients, and found a more severe metabolic disorder in MetS patients who has a higher serum uric acid. Our study provides biochemical insights into the metabolic alteration for the progress of MetS.
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Affiliation(s)
- Yannan Zhang
- Department of Nutrition and Food Hygiene, School of Public Health and Management, Ningxia Medical University, Yinchuan, 750004, China; Ningxia Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, 750004, China
| | - Huanzhen Zhang
- Department of Obstetrics and Gynecology, Tai'an Hospital of Traditional Chinese Medicine, Tai'an, 271000, China
| | - Shengzhong Rong
- Public Health School, Mudanjiang Medical University, Mudanjiang, Heilongjiang, 157011, China
| | - Cailing Bian
- Tai'an City Central Hospital, Tai'an, 271000, China
| | - Yuexin Yang
- National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing, 100050, China.
| | - Hongzhi Pan
- Collaborative Research Center, Shanghai University of Medicine and Health Sciences, Pudong, Shanghai, 201318, China.
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23
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Zhou L, Zhang C, Yang X, Liu L, Hu J, Hou Y, Tao H, Sugimura H, Chen Z, Wang L, Chen K. Melatonin inhibits lipid accumulation to repress prostate cancer progression by mediating the epigenetic modification of CES1. Clin Transl Med 2021; 11:e449. [PMID: 34185414 PMCID: PMC8181204 DOI: 10.1002/ctm2.449] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 05/16/2021] [Accepted: 05/20/2021] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Androgen deprivation therapy (ADT) is the main clinical treatment for patients with advanced prostate cancer (PCa). However, PCa eventually progresses to castration-resistant prostate cancer (CRPC), largely because of androgen receptor variation and increased intratumoral androgen synthesis. Several studies have reported that one abnormal lipid accumulation is significantly related to the development of PCa. Melatonin (MLT) is a functionally pleiotropic indoleamine molecule and a key regulator of energy metabolism. The aim of our study is finding the links between CRPC and MLT and providing the basis for MLT treatment for CRPC. METHODS We used animal CRPC models with a circadian rhythm disorder, and PCa cell lines to assess the role of melatonin in PCa. RESULTS We demonstrated that MLT treatment inhibited tumor growth and reversed enzalutamide resistance in animal CRPC models with a circadian rhythm disorder. A systematic review and meta-analysis demonstrated that MLT is positively associated with an increased risk of developing advanced PCa. Restoration of carboxylesterase 1 (CES1) expression by MLT treatment significantly reduced lipid droplet (LD) accumulation, thereby inducing apoptosis by increasing endoplasmic reticulum stress, reducing de novo intratumoral androgen synthesis, repressing CRPC progression and reversing the resistance to new endocrine therapy. Mechanistic investigations demonstrated that MLT regulates the epigenetic modification of CES1. Ces1-knockout (Ces-/- ) mice verified the important role of endogenous Ces1 in PCa. CONCLUSIONS Our findings provide novel preclinical and clinical information about the role of melatonin in advanced PCa and characterize the importance of enzalutamide combined with MLT administration as a therapy for advanced PCa.
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MESH Headings
- Acetylation
- Androgen Antagonists/pharmacology
- Animals
- Antioxidants/pharmacology
- Apoptosis
- Benzamides/pharmacology
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Carboxylic Ester Hydrolases/genetics
- Carboxylic Ester Hydrolases/metabolism
- Cell Proliferation
- DNA (Cytosine-5-)-Methyltransferase 1/genetics
- DNA (Cytosine-5-)-Methyltransferase 1/metabolism
- Drug Resistance, Neoplasm
- Epigenesis, Genetic
- Gene Expression Regulation, Neoplastic
- Humans
- Lipids/analysis
- Male
- Melatonin/pharmacology
- Mice
- Mice, Inbred C57BL
- Nitriles/pharmacology
- Phenylthiohydantoin/pharmacology
- Prognosis
- Prostatic Neoplasms, Castration-Resistant/genetics
- Prostatic Neoplasms, Castration-Resistant/metabolism
- Prostatic Neoplasms, Castration-Resistant/pathology
- Prostatic Neoplasms, Castration-Resistant/prevention & control
- Receptors, Androgen/chemistry
- Sirtuin 1/genetics
- Sirtuin 1/metabolism
- Survival Rate
- Tumor Cells, Cultured
- Xenograft Model Antitumor Assays
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Affiliation(s)
- Lijie Zhou
- Department of Urology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
- Shenzhen Huazhong University of Science and Technology Research InstituteShenzhenChina
| | - Cai Zhang
- Department of Clinical Laboratorythe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Xiong Yang
- Department of Urology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Lilong Liu
- Department of Urology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
- Shenzhen Huazhong University of Science and Technology Research InstituteShenzhenChina
| | - Junyi Hu
- Department of Urology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
- Shenzhen Huazhong University of Science and Technology Research InstituteShenzhenChina
| | - Yaxin Hou
- Department of Urology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
- Shenzhen Huazhong University of Science and Technology Research InstituteShenzhenChina
| | - Hong Tao
- Department of Tumor PathologyHamamatsu University School of MedicineHamamatsuShizuokaJapan
| | - Haruhiko Sugimura
- Department of Tumor PathologyHamamatsu University School of MedicineHamamatsuShizuokaJapan
| | - Zhaohui Chen
- Department of Urology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Liang Wang
- Department of Urology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Ke Chen
- Department of Urology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
- Shenzhen Huazhong University of Science and Technology Research InstituteShenzhenChina
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24
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Monroy-Iglesias MJ, Russell B, Crawley D, Allen NE, Travis RC, Perez-Cornago A, Van Hemelrijck M, Beckmann K. Metabolic syndrome biomarkers and prostate cancer risk in the UK Biobank. Int J Cancer 2021; 148:825-834. [PMID: 33405276 DOI: 10.1002/ijc.33255] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 07/10/2020] [Accepted: 07/14/2020] [Indexed: 01/08/2023]
Abstract
We investigated the association between metabolic syndrome (MetS) and its components and risk of prostate cancer (PCa) in a cohort of men enrolled in the UK Biobank. Our study cohort included 220 622 PCa-free men with baseline measurements of triglycerides (TGs), HDL-cholesterol (HDL), glycated hemoglobin (HbA1c), blood pressure (BP), and waist circumference (WC). Multivariable Cox proportional hazards regression was used to analyze associations with PCa for: individual metabolic components (TG, HDL, HbA1c, BP, WC), combinations of two and three components, and MetS overall (three or more components). We conducted mediation analyses to examine potential hormonal and inflammatory pathways (total testosterone [TT], C-reactive protein [CRP], insulin-like growth factor 1 [IGF-1]) through which MetS components may influence PCa risk. A total of 5409 men in the study developed PCa during a median follow-up of 6.9 years. We found no significant association between MetS and PCa risk (hazard ratio [HR] = 0.99, 95% confidence interval [CI] = 0.92-1.06). No associations were found with PCa risk and individual measurements of TG, HDL, BP, or WC. However, an inverse association was observed with elevated HbA1c (≥42 mmol/mol) (HR = 0.89, 95% CI = 0.79-0.98). Consistent inverse associations were observed between HbA1c and risk of PCa. Mediation analysis revealed TT, CRP, and IGF-1 as potential mediating factors for this association contributing 10.2%, 7.1%, and 7.9% to the total effect, respectively. Overall MetS had no association with PCa risk. However, a consistent inverse association with PCa risk was found for HbA1c. This association may be explained in part through hormonal and inflammatory pathways.
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Affiliation(s)
- Maria J Monroy-Iglesias
- Translational Oncology and Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, UK
| | - Beth Russell
- Translational Oncology and Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, UK
| | - Danielle Crawley
- Translational Oncology and Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, UK
| | - Naomi E Allen
- Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, Big Data Institute, University of Oxford, Oxford, UK
| | - Ruth C Travis
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Aurora Perez-Cornago
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Mieke Van Hemelrijck
- Translational Oncology and Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, UK
| | - Kerri Beckmann
- Translational Oncology and Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, UK
- Cancer Research Institute, University of South Australia, Adelaide, Australia
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25
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Lu Y, Zhang W, Fan S, Liang Z, Li Z, Tian J, Kang J, Song Y, Liu K, Zhou K, Wang X, Yang Y, Liu X. Metabolic Syndrome and Risk of Upper Tract Urothelial Carcinoma: A Case-Control Study From Surveillance, Epidemiology and End Results-Medicare-Linked Database. Front Oncol 2021; 10:613366. [PMID: 33552985 PMCID: PMC7859618 DOI: 10.3389/fonc.2020.613366] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 12/07/2020] [Indexed: 01/10/2023] Open
Abstract
Background Metabolic syndrome (MetS) and its components are associated with increased risks of several cancers. However, the relationship between MetS and upper tract urothelial carcinoma (UTUC) has never been investigated before. Methods We identified 3,785 UTUC cases aged over 65 years old within the Surveillance, Epidemiology and End Results-Medicare database between 2007 and 2016. For comparison, non-cancer controls (n = 189,953) were selected from the 5% random sample of individuals residing within regions of SEER registries and matched with cases through diagnosis date and pseudo-diagnosis date. MetS and its components were all defined by using ICD-9-CM codes. Multivariate logistic regression models were conducted to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Time trends for MetS and its components were reported and we also performed dose-response effect analysis to test the concomitant effect of these components. The study was presented following the STROBE reporting checklist. Results UTUC risk was associated with metabolic syndrome (NCEP-III: OR: 1.669, 95% CI: 1.550–1.792; IDF: OR: 1.924, 95% CI: 1.676–2.172) and its component factors: elevated waist circumference/central adiposity (OR: 1.872, 95% CI: 1.693–2.055), impaired fasting glucose (OR: 1.306, 95% CI: 1.133–1.480), high blood pressure (OR: 1.295, 95% CI: 1.239–1.353), high triglycerides (OR: 1.280, 95% CI: 1.222–1.341), and low high-density lipoprotein cholesterol (OR: 1.354, 95% CI: 1.118–1.592). Consistent associations could also be observed in the subgroup analyses by tumor stages, grades, and tumor size. Additionally, the rates of MetS increased over time in both UTUC and control cohort (NCEP-III criterion; EAPC: +18.1%, P <0.001; EAPC: +16.1%, P <0.001, respectively). A significantly gradual increase in UTUC rates could be seen as the No. of the MetS components increase (χ² = 37.239, Ptrend = 0.000). Conclusions Among people aged over 65, MetS and its components were significant risk factors for UTUC with consistent associations in different tumor stages, grades, and tumor size. Even if a subject who did not meet the criteria for MetS had only one of the components, he (she) still had an elevated risk for UTUC. Strategies to control the epidemic of MetS and its components might contribute to a reduction in the UTUC burden. The findings should be considered tentative until ascertained by more researches.
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Affiliation(s)
- Yi Lu
- Department of Urology, Tianjin Medical University General Hospital, Tianjin, China
| | - Wei Zhang
- Department of Urology, Tianjin Medical University General Hospital, Tianjin, China
| | - Shujun Fan
- Division of Epidemiology, School of Medicine, University of California, Riverside, CA, United States
| | - Zhen Liang
- Department of Urology, Tianjin Medical University General Hospital, Tianjin, China
| | - Zhongjia Li
- Department of Urology, Tianjin Medical University General Hospital, Tianjin, China
| | - Jia Tian
- Department of Urology, Tianjin Medical University General Hospital, Tianjin, China
| | - Jiaqi Kang
- Department of Urology, Tianjin Medical University General Hospital, Tianjin, China
| | - Yuxuan Song
- Department of Urology, Tianjin Medical University General Hospital, Tianjin, China
| | - Kang Liu
- Department of Urology, Tianjin Medical University General Hospital, Tianjin, China
| | - Kechong Zhou
- Department of Urology, Tianjin Medical University General Hospital, Tianjin, China
| | - Xiao Wang
- Department of Urology, Tianjin Medical University General Hospital, Tianjin, China
| | - Yongjiao Yang
- Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Xiaoqiang Liu
- Department of Urology, Tianjin Medical University General Hospital, Tianjin, China
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26
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Rogers LR, Ostrom QT, Schroer J, Vengoechea J, Li L, Gerson S, Nock CJ, Machtay M, Selman W, Lo S, Sloan AE, Barnholtz-Sloan JS. Association of metabolic syndrome with glioblastoma: a retrospective cohort study and review. Neurooncol Pract 2020; 7:541-548. [PMID: 33014395 DOI: 10.1093/nop/npaa011] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Background Metabolic syndrome is identified as a risk factor for the development of several systemic cancers, but its frequency among patients with glioblastoma and its association with clinical outcomes have yet to be determined. The aim of this study was to investigate metabolic syndrome as a risk factor for and affecting survival in glioblastoma patients. Methods A retrospective cohort study, consisting of patients with diagnoses at a single institution between 2007 and 2013, was conducted. Clinical records were reviewed, and clinical and laboratory data pertaining to 5 metabolic criteria were extrapolated. Overall survival was determined by time from initial surgical diagnosis to date of death or last follow-up. Results The frequency of metabolic syndrome among patients diagnosed with glioblastoma was slightly greater than the frequency of metabolic syndrome among the general population. Within a subset of patients (n = 91) receiving the full schedule of concurrent radiation and temozolomide and adjuvant temozolomide, median overall survival was significantly shorter for patients with metabolic syndrome compared with those without. In addition, the presence of all 5 elements of the metabolic syndrome resulted in significantly decreased median survival in these patients. Conclusions We identified the metabolic syndrome at a slightly higher frequency in patients with diagnosed glioblastoma compared with the general population. In addition, metabolic syndrome with each of its individual components is associated with an overall worse prognosis in patients receiving the standard schedule of radiation and temozolomide after adjustment for age.
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Affiliation(s)
- Lisa R Rogers
- Neurological Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Quinn T Ostrom
- Department of Medicine, Section of Epidemiology and Population Health, Baylor College of Medicine, Houston, Texas
| | - Julia Schroer
- Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Jaime Vengoechea
- Division of Medical Genetics, Emory University School of Medicine, Atlanta, Georgia
| | - Li Li
- Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Stanton Gerson
- Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Charles J Nock
- Case Western Reserve University School of Medicine, Cleveland, Ohio.,Department of Hematology and Oncology, University Hospitals, Cleveland, Ohio
| | - Mitchell Machtay
- Case Western Reserve University School of Medicine, Cleveland, Ohio.,Department of Radiation Oncology, University Hospitals, Cleveland, Ohio
| | - Warren Selman
- Neurological Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio.,Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Simon Lo
- Department of Radiation Oncology, University of Washington Medical Center, Seattle, Washington
| | - Andrew E Sloan
- Neurological Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio.,Case Western Reserve University School of Medicine, Cleveland, Ohio.,Case Comprehensive Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Jill S Barnholtz-Sloan
- Case Western Reserve University School of Medicine, Cleveland, Ohio.,Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio
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Goldberg H, Mohsin FK, Berlin A, Chandrasekar T, Wallis CJD, Klaassen Z, Ahmad AE, Saskin R, Kenk M, Saarela O, Kulkarni GS, Alibhai SMH, Fleshner N. The suggested chemopreventive association of metformin with prostate cancer in diabetic patients. Urol Oncol 2020; 39:191.e17-191.e24. [PMID: 32951988 DOI: 10.1016/j.urolonc.2020.08.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 08/15/2020] [Accepted: 08/23/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE Metformin, an insulin sensitizer, is the most common first-line antidiabetic therapy. There is increasing evidence suggesting metformin can prevent the emergence of prostate cancer (CaP). We aimed to analyze the chemopreventive role of metformin, in conjunction with other putative chemopreventive medications (statins, proton-pump-inhibitors, alpha-blockers, 5-alpha-reductase inhibitors, diabetic medications) in a population-based cohort study. METHODS Data were incorporated from the Institute for Clinical and Evaluative Sciences to identify all diabetic men aged 66 and above with prior history of a negative prostate biopsy (PB) between 1994 and 2016, who were not on any of the medications prior to study inclusion. Multivariable Cox regression models with time-dependent covariates were used to assess the association of metformin to CaP diagnosis, subsequent PB, and use of androgen deprivation therapy (ADT). All models were adjusted for age, rurality, comorbidity, and year of study inclusion. RESULTS Overall, 2,332 diabetic men were included, with a median follow-up time of 9.4 years (interquartile range 5.4-13.4 years). A total of 2,036 patients (87.3%) received metformin. Compared to non-metformin users, metformin use was associated with decreased CaP diagnosis rate (HR 0.69, 95%CI 0.54-0.88, P = 0.003), lower hazard of undergoing an additional PB (HR 0.64, 95%CI 0.44-0.95, P = 0.03), and receiving ADT (HR 0.72, 95%CI 0.54-0.96, P = 0.003). CONCLUSION Men receiving metformin were less likely to have suspected or diagnosed CaP, and in those with CaP, the use of ADT was less common. Ongoing prospective randomized studies will determine if these findings correspond to the suggested associations of metformin in the emergence and/or progression of CaP.
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Affiliation(s)
- Hanan Goldberg
- Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Urology, SUNY Upstate Medical University, Syracuse, NY; Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.
| | - Faizan K Mohsin
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Alejandro Berlin
- Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network; Department of Radiation Oncology, University of Toronto; and Techna Institute, University Health Network, Toronto, Ontario, Canada
| | - Thenappan Chandrasekar
- Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia PA
| | - Christopher J D Wallis
- Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, Ontario, Canada; Department of Urology, Vanderbilt University Medical Center, Nashville, TN
| | - Zachary Klaassen
- Division of Urology, Department of Surgery, Medical College of Georgia, Augusta University, Augusta, GA; Georgia Cancer Center, GA
| | - Ardalan E Ahmad
- Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
| | - Refik Saskin
- Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
| | - Miran Kenk
- Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, Ontario, Canada
| | - Olli Saarela
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - Girish S Kulkarni
- Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, Ontario, Canada; Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
| | - Shabbir M H Alibhai
- Department of Medicine, University Health Network and University of Toronto, Toronto, Ontario, Canada
| | - Neil Fleshner
- Division of Urology, Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network and the University of Toronto, Toronto, Ontario, Canada
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De Nunzio C, Tema G, Lombardo R, Cicione A, Dell'''''Oglio P, Tubaro A. The role of metabolic syndrome in high grade prostate cancer: development of a clinical nomogram. MINERVA UROL NEFROL 2020; 72:729-736. [PMID: 32748618 DOI: 10.23736/s0393-2249.20.03797-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND The aim of our study is to develop a clinical nomogram including metabolic syndrome status for the prediction of high-grade prostate cancer (HG PCa). METHODS A series of men at increased risk of PCa undergoing prostate biopsies were enrolled in a single center. Demographic and clinical characteristics of the patients were recorded. Metabolic syndrome was defined according to the adult treatment panel III. A nomogram was generated based on the logistic regression model and used to predict high grade prostate cancer defined as grade group ≥3 (ISUP 2014). ROC curves, calibration plots and decision curve analysis were used to evaluate the performance of the nomogram. RESULTS Overall, 738 patients were enrolled. Greater than or equal to 294/738 (40%) of the patients presented PCa and of those patients, 84/294 (39%) presented high grade disease (Grade Group ≥3). On multivariate analysis, DRE (OR: 3.24, 95% CI: 1.80-5.84), PSA (OR: 1.10, 95% CI: 1.05-1.16), PV (OR: 0.98, 95% CI: 0.97-0.99) and MetS (OR: 2.02, 95% CI: 1.13-3.59) were predictors of HG PCa. The nomogram based on the model presented good discrimination (AUC: 0.76), good calibration (Hosmer-Lemeshow Test, P>0.05) and a net benefit in the range of probabilities between 10% and 70%. CONCLUSIONS Metabolic syndrome is highly prevalent in patients at risk of prostate cancer and is particularly associated with high-grade prostate cancer. Our nomogram offers the possibility to include metabolic status in the assessment of patients at risk of prostate cancer to identify men who may have a high-grade form of the disease. External validation is warranted before its clinical implementation.
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Affiliation(s)
- Cosimo De Nunzio
- Department of Urology, Sant'Andrea Hospital, Sapienza University, Rome, Italy -
| | - Giorgia Tema
- Department of Urology, Sant'Andrea Hospital, Sapienza University, Rome, Italy
| | - Riccardo Lombardo
- Department of Urology, Sant'Andrea Hospital, Sapienza University, Rome, Italy
| | - Antonio Cicione
- Department of Urology, Sant'Andrea Hospital, Sapienza University, Rome, Italy
| | - Paolo Dell'''''Oglio
- Division of Experimental Oncology, Department of Urology, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy
| | - Andrea Tubaro
- Department of Urology, Sant'Andrea Hospital, Sapienza University, Rome, Italy
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Kenk M, Grégoire JC, Coté MA, Connelly KA, Davis MK, Dresser G, Ghosh N, Goodman S, Johnson C, Fleshner N. Optimizing screening and management of cardiovascular health in prostate cancer: A review. Can Urol Assoc J 2020; 14:E458-E464. [PMID: 32569573 DOI: 10.5489/cuaj.6685] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
In clinical practice, cancer management does not consistently encompass screening and identification of cardiovascular (CV) risk. The use of androgen deprivation therapy (ADT) in prostate cancer has been associated with increased CV risk and development of metabolic syndrome, necessitating identification of patients at risk in this population (e.g., those with pre-existing CV disease). A multidisciplinary team of Canadian physicians was assembled to develop a series of recommendations intended to identify patients who may benefit from optimal management of their CV disease and/or modification of cardiac risk factors. A key goal was the development of a simple screening tool for identification of patients with pre-existing CV disease. This simple and inclusive set of recommendations are intended for use within urology clinics to facilitate holistic approaches and simplify the management of patients.
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Affiliation(s)
- Miran Kenk
- Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
| | | | - Marc-Andre Coté
- Centre hospitalier universitaire de Quebec, Québec City, QC, Canada
| | - Kim A Connelly
- St. Michael's Hospital Li Ka Shing Knowledge Institute, Toronto, ON, Canada
| | - Margot K Davis
- University of British Columbia Diamond Health Care Center, Vancouver, BC, Canada
| | - George Dresser
- Division of Clinical Pharmacology, Department of Medicine, Western University, London, ON, Canada
| | - Nina Ghosh
- Queensway Carleton Hospital, University of Ottawa Heart Institute, Ottawa, ON, Canada
| | - Shaun Goodman
- Division of Cardiology, St. Michael's Hospital, Toronto, ON, Canada
| | | | - Neil Fleshner
- Department of Surgical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
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The association of metabolic syndrome and its components with serum prostate-specific antigen levels. Eur J Cancer Prev 2020; 29:36-41. [DOI: 10.1097/cej.0000000000000508] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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31
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Tanaka A, Node K. The Emerging and Promising Role of Care for Cardiometabolic Syndrome in Prostate Cancer. JACC CardioOncol 2019; 1:307-309. [PMID: 34396197 PMCID: PMC8352240 DOI: 10.1016/j.jaccao.2019.09.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Affiliation(s)
- Atsushi Tanaka
- Department of Cardiovascular Medicine, Saga University, Saga, Japan
| | - Koichi Node
- Department of Cardiovascular Medicine, Saga University, Saga, Japan
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32
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Ahmad AE, Mohammed A, Bhindi B, Richard PO, Fadaak K, Leão R, Finelli A, Fleshner NE, Kulkarni GS. Serum Adipokines as Predictors for the Outcome of Prostate Biopsies at Early Stage Prostate Cancer Diagnosis. Cancer Manag Res 2019; 11:10043-10050. [PMID: 31819637 PMCID: PMC6890197 DOI: 10.2147/cmar.s226174] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Accepted: 10/26/2019] [Indexed: 11/23/2022] Open
Abstract
Purpose Elevated adipokines in patients with obesity and metabolic syndrome have been linked to increased risk of prostate cancer (PCa). The association between select serum adipokines and the outcome of prostate biopsies alone and in combination with clinical parameters at different early stages of PCa was investigated. Patients and methods Clinical data and serum adipokines were retrieved from three retrospective cohorts representing men at different points in PCa detection: 1. Subjects with no prior biopsies (n=1061), 2. subjects with a prior negative biopsy (REDUCE trial, control arm) (n=1209), 3. subjects with low-risk PCa on active surveillance (AS) (n=154). Adipokines were chosen based on an unpublished pilot study and included: Resistin, Tumor Necrosis Factor-α, Interleukin-6, Monocyte Chemoattractant Protein-1, Hepatocyte Growth Factor, and Nerve Growth Factor. The primary outcome was the absence of PCa on biopsy and the secondary outcome was diagnosis of low-risk PCa fitting the criteria for continuing AS. Logistic regression analysis was used to assess the association of adipokines and negative and/or low-risk PCa at prostate biopsy. Results In men with no prior prostate biopsy or with prior negative biopsy, adipokines were not predictors of prostate biopsy outcomes on multivariable regression analysis controlling for known clinical variables. In the AS cohort, MCP-1 and Resistin were significant predictors of biopsy outcome on multivariable analysis (OR 0.20, 95% CI: 0.05–0.85, p= 0.03 & OR 0.30, 95% CI: 0.10 −0.86, p= 0.03). Conclusion Our findings do not support a strong role for adipokines for predicting the outcome of prostate biopsies at any early stage in PCa diagnosis.
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Affiliation(s)
- Ardalan E Ahmad
- Division of Urology, Department of Surgery, University Health Network, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Aza Mohammed
- Department of Urology, Luton and Dunstable University Hospital, Luton, UK
| | - Bimal Bhindi
- Division of Urology, Department of Surgery, University Health Network, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.,Southern Alberta Institute of Urology, Calgary, Alberta, Canada
| | - Patrick O Richard
- Division of Urology, Department of Surgery, Centre Hospitalier Universitaire de Sherbrooke, Centre de Recherche du CHUS, Université de Sherbrooke, Sherbrooke, Quebec, Canada
| | - Kamel Fadaak
- Department of Urology, King Fahd Hospital of the University, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Ricardo Leão
- CUF Department of Urology, Hospital De Braga, Faculty of Medicine, University of Coimbra, Portugal
| | - Antonio Finelli
- Division of Urology, Department of Surgery, University Health Network, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Neil E Fleshner
- Division of Urology, Department of Surgery, University Health Network, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
| | - Girish S Kulkarni
- Division of Urology, Department of Surgery, University Health Network, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada
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Discovering genetic interactions bridging pathways in genome-wide association studies. Nat Commun 2019; 10:4274. [PMID: 31537791 PMCID: PMC6753138 DOI: 10.1038/s41467-019-12131-7] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 08/20/2019] [Indexed: 12/20/2022] Open
Abstract
Genetic interactions have been reported to underlie phenotypes in a variety of systems, but the extent to which they contribute to complex disease in humans remains unclear. In principle, genome-wide association studies (GWAS) provide a platform for detecting genetic interactions, but existing methods for identifying them from GWAS data tend to focus on testing individual locus pairs, which undermines statistical power. Importantly, a global genetic network mapped for a model eukaryotic organism revealed that genetic interactions often connect genes between compensatory functional modules in a highly coherent manner. Taking advantage of this expected structure, we developed a computational approach called BridGE that identifies pathways connected by genetic interactions from GWAS data. Applying BridGE broadly, we discover significant interactions in Parkinson's disease, schizophrenia, hypertension, prostate cancer, breast cancer, and type 2 diabetes. Our novel approach provides a general framework for mapping complex genetic networks underlying human disease from genome-wide genotype data.
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Seretis A, Cividini S, Markozannes G, Tseretopoulou X, Lopez DS, Ntzani EE, Tsilidis KK. Association between blood pressure and risk of cancer development: a systematic review and meta-analysis of observational studies. Sci Rep 2019; 9:8565. [PMID: 31189941 PMCID: PMC6561976 DOI: 10.1038/s41598-019-45014-4] [Citation(s) in RCA: 125] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 05/28/2019] [Indexed: 12/13/2022] Open
Abstract
With the exception of renal cell carcinoma, studies assessing the association between hypertension and other cancers are inconsistent. We conducted a meta-analysis to assess this evidence. We included observational studies investigating the association between any definition of hypertension or systolic and diastolic blood pressure and risk of any cancer, after searching PubMed until November 2017. We calculated summary relative risks (RR) and 95% confidence intervals (CI) using inverse-variance weighted random effects methods. A total of 148 eligible publications were identified out of 39,891 initially screened citations. Considering only evidence from 85 prospective studies, positive associations were observed between hypertension and kidney, colorectal and breast cancer. Positive associations between hypertension and risk of oesophageal adenocarcinoma and squamous cell carcinoma, liver and endometrial cancer were also observed, but the majority of studies did not perform comprehensive multivariable adjustments. Systolic and diastolic blood pressure were positively associated with risk of kidney cancer but not with other cancers. In addition to the previously well-described association between hypertension and risk of kidney cancer, the current meta-analysis suggested that hypertensive individuals may also be at higher risk of colorectal and breast cancer. However, careful interpretation is required as most meta-analyses included relatively small number of studies, several relative risks had weak or moderate magnitude and maybe affected by residual confounding.
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Affiliation(s)
- Aristeidis Seretis
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | | | - Georgios Markozannes
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Xanthippi Tseretopoulou
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - David S Lopez
- The University of Texas School of Public Health, Houston, TX, USA
| | - Evangelia E Ntzani
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.,Center for Evidence-Based Medicine, Department of Health Services, Policy and Practice, School of Public Health, Brown University, Providence, RI, USA
| | - Konstantinos K Tsilidis
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. .,Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College London, London, UK.
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Abstract
Prostate cancer is the second most frequent cancer diagnosis made in men and the fifth leading cause of death worldwide. Prostate cancer may be asymptomatic at the early stage and often has an indolent course that may require only active surveillance. Based on GLOBOCAN 2018 estimates, 1,276,106 new cases of prostate cancer were reported worldwide in 2018, with higher prevalence in the developed countries. Differences in the incidence rates worldwide reflect differences in the use of diagnostic testing. Prostate cancer incidence and mortality rates are strongly related to the age with the highest incidence being seen in elderly men (> 65 years of age). African-American men have the highest incidence rates and more aggressive type of prostate cancer compared to White men. There is no evidence yet on how to prevent prostate cancer; however, it is possible to lower the risk by limiting high-fat foods, increasing the intake of vegetables and fruits and performing more exercise. Screening is highly recommended at age 45 for men with familial history and African-American men. Up-to-date statistics on prostate cancer occurrence and outcomes along with a better understanding of the etiology and causative risk factors are essential for the primary prevention of this disease.
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Affiliation(s)
- Prashanth Rawla
- Hospitalist, Department of Internal Medicine, SOVAH Health, Martinsville, VA 24112, USA.
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36
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Xu H, Tan P, Zheng X, Ai J, Lin T, Jin X, Gong L, Lei H, Yang L, Wei Q. Metabolic syndrome and upper tract urothelial carcinoma: A retrospective analysis from a large Chinese cohort. Urol Oncol 2019; 37:291.e19-291.e28. [DOI: 10.1016/j.urolonc.2018.12.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Revised: 11/28/2018] [Accepted: 12/05/2018] [Indexed: 10/27/2022]
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Yoo S, Oh S, Park J, Cho SY, Cho MC, Son H, Jeong H. Effects of metabolic syndrome on the prevalence of prostate cancer: historical cohort study using the national health insurance service database. J Cancer Res Clin Oncol 2019; 145:775-780. [PMID: 30656408 DOI: 10.1007/s00432-019-02842-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Accepted: 01/03/2019] [Indexed: 01/01/2023]
Abstract
PURPOSE To estimate the effect of metabolic syndrome (MetS) on the prevalence of prostate cancer using a large retrospective cohort with a 5-year follow-up duration. METHODS National Health Insurance Service health checkup cohort was used for the study. In total, 130,342 men included in the health checkup cohort in 2009 were divided into two groups according to the presence of prostate cancer. The prevalence of prostate cancer from 2009 to 2013 was cumulatively calculated from 2003. A generalized estimating equation was used to assess the effect of MetS and its component on the prevalence of prostate cancer after adjusting for other variables. RESULTS Prostate cancer was present in 2369 men (1.8%) in 2009. The prevalence of prostate cancer was significantly higher in patients with MetS than in those without MetS throughout the entire follow-up duration. Multivariable analysis showed that in addition to year at evaluation and age, the presence of MetS was associated with an increased prevalence of prostate cancer. Alcohol consumption and smoking levels were negatively associated with the prevalence of prostate cancer. Among MetS components, decreased high density lipoprotein (HDL)-cholesterolemia and central obesity were associated with an increased prevalence of prostate cancer after adjusting for other variables. CONCLUSION MetS and its components, especially decreased HDL-cholesterol levels and central obesity, were related to the increased prevalence of prostate cancer. Preventing MetS, maintaining high HDL-cholesterol level, and maintaining low waist circumference might be useful ways for decreasing the prevalence of prostate cancer.
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Affiliation(s)
- Sangjun Yoo
- Department of Urology, Seoul National University Boramae Medical Center, Sindaebang 2(i)-dong, Dongjak-gu, Seoul, 07061, Republic of Korea
| | - Sohee Oh
- Department of Biostatistics, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Juhyun Park
- Department of Urology, Seoul National University Boramae Medical Center, Sindaebang 2(i)-dong, Dongjak-gu, Seoul, 07061, Republic of Korea
| | - Sung Yong Cho
- Department of Urology, Seoul National University Boramae Medical Center, Sindaebang 2(i)-dong, Dongjak-gu, Seoul, 07061, Republic of Korea
| | - Min Chul Cho
- Department of Urology, Seoul National University Boramae Medical Center, Sindaebang 2(i)-dong, Dongjak-gu, Seoul, 07061, Republic of Korea
| | - Hwancheol Son
- Department of Urology, Seoul National University Boramae Medical Center, Sindaebang 2(i)-dong, Dongjak-gu, Seoul, 07061, Republic of Korea
- Department of Urology, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyeon Jeong
- Department of Urology, Seoul National University Boramae Medical Center, Sindaebang 2(i)-dong, Dongjak-gu, Seoul, 07061, Republic of Korea.
- Department of Urology, Seoul National University Hospital, Seoul, Republic of Korea.
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Zheng X, Qiu S, Liao X, Han X, Jin K, Yang L, Wei Q. The accumulation of metabolic syndrome components is associated with higher risk of positive surgical margin among patients with localized prostate cancer after radical prostatectomy. Onco Targets Ther 2019; 12:1613-1620. [PMID: 30881016 PMCID: PMC6396662 DOI: 10.2147/ott.s195148] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Objective To evaluate the association between metabolic syndrome (MetS) and the accumulation of its components with prostate cancer (PCa). Patients and methods Patients undergoing radical prostatectomy were retrospectively included. Patients were grouped by low risk and intermediate-high risk according to International Society of Urological Pathology grade. Multivariable logistic regression and Cox hazard regression model were utilized to assess the association of MetS with overall survival, biochemical recurrence, upgrading, upstaging, and positive surgical margin (PSM) after prostatectomy. Besides, trend test was also performed to evaluate the impact of the accumulation of MetS components on postoperative pathological feature. Results A total of 1,083 patients were eventually enrolled. With a median follow-up of 40.45 months, 197 patients were diagnosed with MetS. No significant association between MetS and survival outcomes and pathological features was found. However, we did notice that the accumulation of the MetS components could lead to an elevated gradient of the PSM risk in the entire cohort (one component: OR=1.46; two components: OR=1.89; ≥3 components: OR=2.07; P for trend=0.0194) and intermediate-high risk group (one component: OR=1.4; two components: OR=1.85; ≥3 components: OR=2.05; P for trend=0.0127). Conclusion The accumulation of MetS components could lead to increasing risk of PSM on the entire PCa cohort and patients with intermediate-high risk PCa after prostatectomy, but not for the low-risk patients.
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Affiliation(s)
- Xiaonan Zheng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China, ;
| | - Shi Qiu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China, ; .,Center of Biomedical Big Data, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Xinyang Liao
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China, ;
| | - Xin Han
- West China Medical School, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Kun Jin
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China, ;
| | - Lu Yang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China, ;
| | - Qiang Wei
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China, ;
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The Optimal Indication for Testosterone Replacement Therapy in Late Onset Hypogonadism. J Clin Med 2019; 8:jcm8020209. [PMID: 30736442 PMCID: PMC6406807 DOI: 10.3390/jcm8020209] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Revised: 02/01/2019] [Accepted: 02/03/2019] [Indexed: 12/21/2022] Open
Abstract
The use of testosterone replacement therapy (TRT) for late-onset hypogonadism (LOH) is increasing every year; however, the literature shows that many men are using testosterone (T) without a clear indication. Previous studies have estimated that up to 25% of men who receive TRT do not have their T tested prior to initiation of the therapy. Given the growing concern and need for proper TRT, clinicians need evidence-based information that informs them on the optimal indication for TRT in LOH patients. The diagnosis of LOH requires the presence of characteristic signs and symptoms, in combination with decreased serum total testosterone (TT). Based on the recent guidelines by the International Society for the Study of Aging Male (ISSAM), the European Association of Urology (EAU), the European Society of Endocrinology (ESE), the European Academy of Andrology (EAA), and the American Association of Urology (AUA), a TT of 250–350 ng/dL is the proper threshold value to define low T. The optimal indication for TRT in LOH is the presence of signs and symptoms of hypogonadism, and low T without contraindications for TRT.
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40
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Li T, Sun X, Chen L. Free testosterone value before radical prostatectomy is related to oncologic outcomes and post-operative erectile function. BMC Cancer 2019; 19:87. [PMID: 30658612 PMCID: PMC6339281 DOI: 10.1186/s12885-018-5148-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Accepted: 11/28/2018] [Indexed: 01/27/2023] Open
Abstract
PURPOSE To investigate whether free testosterone (FT) prior to radical prostatectomy was related to post-operative oncologic outcomes, erectile function and continence. METHODS The data of 586 patients with available information underwent treatment in our center was retrospectively reviewed. Total testosterone (TT) was tested by chemiluminescence immunoassay, and FT value was calculated using Vermeulen's formula. Post-operative continence and erectile function were evaluated by the requirement of pad and the IIEF-5 score at 12 months. RESULTS The median TT and FT value was 344 ng/dL (interquartile, IQR 314-374) and 6.9 ng/dL (IQR 6.4-7.3), and 106 patients (18.1%) and 152 patients (25.9%) were evaluated as having low TT and low FT based on current guidelines. Low TT and FT value were both related to older age (both p < 0.001), concomitant diabetes (p = 0.018 & 0.049), higher possibility of pre-operative erectile dysfunction (ED, both p < 0.001), higher pre-operative PSA value (both p < 0.001), higher clinical stage (both p < 0.001) and higher Gleason score in biopsy (both p < 0.001). Low FT was related to higher risk for pT3 (p = 0.020) and high Gleason score (p = 0.011) in logistic regression. The median follow-up duration was 52 moths (IQR 29-67) and FT was found to be an independent risk factor for biochemical recurrence (p = 0.005). In logistic regression TT was related to pre-operative ED (p = 0.010) and FT was related to post-operative ED (p = 0.001). CONCLUSION Low FT value before radical prostatectomy was related to adverse pathological outcomes, biochemical recurrence and post-operative ED.
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Affiliation(s)
- Tian Li
- Department of Urology, the Fifth Affiliated Hospital of Guangzhou Medical University, 621 Gangwan RD, Huangpu district, Guangzhou, 510700 China
- Minimally Invasive Technique and Product Translational Center, Guangzhou Medical University, 621 Gangwan RD, Huangpu district, Guangzhou, 510700 China
| | - Xiangzhou Sun
- Department of Urology, the First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Second Rd, Yuexiu Dis, Guangzhou, 510080 China
| | - Liheng Chen
- Department of Biomedical Engineering, Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Jinan University, 601 Huangpu Rd, Tianhe Dis, Guangzhou, 510632 China
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41
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Hurley DL. Neoplasia in Patients with Excess Fat Mass. BARIATRIC ENDOCRINOLOGY 2019:293-323. [DOI: 10.1007/978-3-319-95655-8_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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42
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Gómez-Gómez E, Carrasco-Valiente J, Campos-Hernández JP, Blanca-Pedregosa AM, Jiménez-Vacas JM, Ruiz-García J, Valero-Rosa J, Luque RM, Requena-Tapia MJ. Clinical association of metabolic syndrome, C-reactive protein and testosterone levels with clinically significant prostate cancer. J Cell Mol Med 2018; 23:934-942. [PMID: 30450757 PMCID: PMC6349154 DOI: 10.1111/jcmm.13994] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 10/16/2018] [Accepted: 10/17/2018] [Indexed: 12/16/2022] Open
Abstract
Recently, the influence that metabolic syndrome (MetS), hormonal alterations and inflammation might have on prostate cancer (PCa) risk has been a subject of controversial debate. Herein, we aimed to investigate the association between MetS‐components, C‐reactive protein (CRP) and testosterone levels, and the risk of clinically significant PCa (Sig‐PCa) at the time of prostate biopsy. For that, men scheduled for transrectal ultrasound guided biopsy of the prostate were studied. Clinical, laboratory parameters and criteria for MetS characterization just before the biopsy were collected. A total of 524 patients were analysed, being 195 (37.2%) subsequently diagnosed with PCa and 240 (45.8%) meet the diagnostic criteria for MetS. Among patients with PCa, MetS‐diagnosis was present in 94 (48.2%). Remarkably, a higher risk of Sig‐PCa was associated to MetS, greater number of MetS‐components and higher CRP levels (odds‐ratio: 1.83, 1.30 and 2.00, respectively; P < 0.05). Moreover, higher circulating CRP levels were also associated with a more aggressive Gleason score in PCa patients. Altogether, our data reveal a clear association between the presence of MetS, a greater number of MetS‐components or CRP levels >2.5 mg/L with an increased Sig‐PCa diagnosis and/or with aggressive features, suggesting that MetS and/or CRP levels might influence PCa pathophysiology.
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Affiliation(s)
- Enrique Gómez-Gómez
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.,Department of Urology, Reina Sofia University Hospital, Cordoba, Spain.,Department of Cell Biology, Physiology and Immunology, University of Cordoba (UCO), Cordoba, Spain
| | - Julia Carrasco-Valiente
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.,Department of Urology, Reina Sofia University Hospital, Cordoba, Spain
| | - Juan Pablo Campos-Hernández
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.,Department of Urology, Reina Sofia University Hospital, Cordoba, Spain
| | | | - Juan Manuel Jiménez-Vacas
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.,Department of Cell Biology, Physiology and Immunology, University of Cordoba (UCO), Cordoba, Spain.,CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Madrid, Spain
| | - Jesus Ruiz-García
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.,Department of Urology, Reina Sofia University Hospital, Cordoba, Spain
| | - Jose Valero-Rosa
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.,Department of Urology, Reina Sofia University Hospital, Cordoba, Spain
| | - Raul Miguel Luque
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.,Department of Cell Biology, Physiology and Immunology, University of Cordoba (UCO), Cordoba, Spain.,CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Madrid, Spain
| | - María José Requena-Tapia
- Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain.,Department of Urology, Reina Sofia University Hospital, Cordoba, Spain
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43
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Lebdai S, Mathieu R, Leger J, Haillot O, Vincendeau S, Rioux-Leclercq N, Fournier G, Perrouin-Verbe MA, Doucet L, Azzouzi AR, Rigaud J, Renaudin K, Charles T, Bruyere F, Fromont G. Metabolic syndrome and low high-density lipoprotein cholesterol are associated with adverse pathological features in patients with prostate cancer treated by radical prostatectomy. Urol Oncol 2018; 36:80.e17-80.e24. [DOI: 10.1016/j.urolonc.2017.09.026] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2017] [Revised: 09/08/2017] [Accepted: 09/29/2017] [Indexed: 10/18/2022]
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44
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Serretta V, Abrate A, Siracusano S, Gesolfo CS, Vella M, Di Maida F, Cangemi A, Cicero G, Barresi E, Sanfilippo C. Clinical and biochemical markers of visceral adipose tissue activity: Body mass index, visceral adiposity index, leptin, adiponectin, and matrix metalloproteinase-3. Correlation with Gleason patterns 4 and 5 at prostate biopsy. Urol Ann 2018; 10:280-286. [PMID: 30089986 PMCID: PMC6060586 DOI: 10.4103/ua.ua_188_17] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Context: The correlation between aggressive prostate cancer and obesity mainly based on body mass index (BMI) and pathology after surgery remains controversial. Aims: The aim of the study was to correlate BMI, visceral adiposity index (VAI), and the plasmatic levels of leptin, adiponectin, and matrix metalloproteinase-3 (MMP-3), and biomarkers of adipose tissue function, with the detection of Gleason patterns 4 and 5 at biopsy. Subjects and Methods: Consecutive patients with prostate cancer at 12-core transrectal biopsy were enrolled. BMI, waist circumference (WC), blood samples to evaluate the plasmatic levels of triglycerides (TG) and high-density lipoproteins (HDL), adiponectin, leptin, and MMP-3 were obtained immediately before biopsy. The VAI was calculated according to the formula: WC/(39.68 + [1.88 × BMI]) × TG/1.03 × 1.31/HDL. Results: One hundred and forty-nine patients were entered. The median PSA, BMI, and VAI were 10.0 ng/ml, 27.6 kg/m2, and 4.6, respectively. Gleason patterns 4 or 5 were detected in 68 (45.6%) patients; in 15 (41.7%), 31 (44.9%), and 22 (50.0%) among normal weight, overweight, and obese patients, respectively (P = 0.55). The statistical analysis did not show any significant correlation between BMI, VAI, the plasmatic levels of leptin, adiponectin, MMP-3, and the detection of Gleason patterns 4 and 5 at biopsy. A statistically significant association emerged with older age (P = 0.017) and higher PSA values (P = 0.02). Conclusion: We did not find any association between BMI, VAI, the plasmatic levels of adiponectin, leptin, and MMP-3 and the detection of Gleason patterns 4 and 5 at prostate biopsy.
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Affiliation(s)
- Vincenzo Serretta
- Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
| | - Alberto Abrate
- Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
| | - Simone Siracusano
- Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
| | - Cristina Scalici Gesolfo
- Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
| | - Marco Vella
- Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
| | - Fabrizio Di Maida
- Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
| | - Antonina Cangemi
- Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
| | - Giuseppe Cicero
- Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy
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Abstract
Metabolic syndrome is one of today's most important health problems. Due to increased prevalence of metabolic syndrome in society, studies done on this topic have increased in number. Although metabolic syndrome was previously considered to be important only for cardiovascular health, it has been learned that with new data, human health is compromised more thoroughly by metabolic syndrome and is also a danger to malignancy. As a result, a new definition in the form of metabesity has been introduced. In this review, available information on metabesity and urological cancers is presented.
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Affiliation(s)
- Ali Atan
- Department of Urology, Gazi University School of Medicine, Ankara, Turkey
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46
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Dickerman BA, Torfadottir JE, Valdimarsdottir UA, Wilson KM, Steingrimsdottir L, Aspelund T, Batista JL, Fall K, Giovannucci E, Sigurdardottir LG, Tryggvadottir L, Gudnason V, Markt SC, Mucci LA. Midlife metabolic factors and prostate cancer risk in later life. Int J Cancer 2017; 142:1166-1173. [PMID: 29114858 DOI: 10.1002/ijc.31142] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Revised: 10/12/2017] [Accepted: 10/17/2017] [Indexed: 12/18/2022]
Abstract
Metabolic syndrome is associated with several cancers, but evidence for aggressive prostate cancer is sparse. We prospectively investigated the influence of metabolic syndrome and its components on risk of total prostate cancer and measures of aggressive disease in a cohort of Icelandic men. Men in the Reykjavik Study (n = 9,097, enrolled 1967-1987) were followed for incident (n = 1,084 total; n = 378 advanced; n = 148 high-grade) and fatal (n = 340) prostate cancer until 2014. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for (1) measured metabolic factors at cohort entry (body mass index (BMI), blood pressure, triglycerides, fasting blood glucose) and (2) a metabolic syndrome score (range 0-4) combining the risk factors: BMI ≥30 kg/m2 ; systolic blood pressure (SBP) ≥130 or diastolic blood pressure (DBP) ≥85 mm Hg or taking antihypertensives; triglycerides ≥150 mg/dl; fasting blood glucose ≥100 mg/dl or self-reported type 2 diabetes. Hypertension and type 2 diabetes were associated with a higher risk of total, advanced, high-grade, and fatal prostate cancer, independent of BMI. Neither BMI nor triglycerides were associated with prostate cancer risk. Higher metabolic syndrome score (3-4 vs 0) was associated with a higher risk of fatal prostate cancer (HR 1.55; 95% CI: 0.89, 2.69; p trend = 0.08), although this finding was not statistically significant. Our findings suggest a positive association between midlife hypertension and diabetes and risk of total and aggressive prostate cancer. Further, metabolic syndrome as a combination of factors was associated with an increased risk of fatal prostate cancer.
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Affiliation(s)
- Barbra A Dickerman
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
| | | | - Unnur A Valdimarsdottir
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.,Centre for Public Health Sciences, University of Iceland, Reykjavik, Iceland.,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Kathryn M Wilson
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - Laufey Steingrimsdottir
- Unit for Nutrition Research, University Hospital & the Faculty of Food Science and Nutrition, University of Iceland, Reykjavik, Iceland
| | - Thor Aspelund
- Centre for Public Health Sciences, University of Iceland, Reykjavik, Iceland.,The Icelandic Heart Association, Kopavogur, Iceland
| | - Julie L Batista
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Katja Fall
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.,Clinical Epidemiology and Biostatistics, Örebro University Hospital, Örebro, Sweden
| | - Edward Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.,Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Lara G Sigurdardottir
- Centre for Public Health Sciences, University of Iceland, Reykjavik, Iceland.,Faculty of Medicine, University of Iceland, Reykjavik, Iceland.,Department of Education and Prevention, The Icelandic Cancer Society, Reykjavik, Iceland
| | | | - Vilmundur Gudnason
- The Icelandic Heart Association, Kopavogur, Iceland.,Faculty of Medicine, University of Iceland, Reykjavik, Iceland
| | - Sarah C Markt
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
| | - Lorelei A Mucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
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47
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Lin PH, Aronson W, Freedland SJ. An update of research evidence on nutrition and prostate cancer. Urol Oncol 2017; 37:387-401. [PMID: 29103966 DOI: 10.1016/j.urolonc.2017.10.006] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Revised: 09/15/2017] [Accepted: 10/06/2017] [Indexed: 12/28/2022]
Abstract
BACKGROUND Prostate cancer (PCa) remains a leading cause of mortality in US and other countries. Preclinical and clinical studies have examined the role of nutrition and dietary intake on the incidence and progression of PCa with mixed results. OBJECTIVE The objective of this chapter is to provide an update of recent published literature and highlight progress in the field. MAIN FINDINGS Low carbohydrate intake, soy protein, ω3 fat, green teas, tomatoes and tomato products and the herbal mixture-zyflamend showed promise in reducing PCa risk or progression. On the contrary, a higher animal fat intake and a higher β-carotene status may increase risk. A "U" shape relationship may exist between folate, vitamin C, vitamin D and calcium with PCa risk. Conclusion Despite the inconclusive findings, the potential for a role of dietary intake for the prevention and treatment of PCa remains promising. Maintaining a healthy body weight and following a healthy dietary pattern including antioxidant rich fruits and vegetables, reduced animal fat and refined carbohydrates, should be encouraged. CONCLUSION Despite the inconclusive findings, the potential for a role of dietary intake for the prevention and treatment of PCa remains promising. Maintaining a healthy body weight and following a healthy dietary pattern including antioxidant rich fruits and vegetables, reduced animal fat and refined carbohydrates, should be encouraged.
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Affiliation(s)
- Pao-Hwa Lin
- Department of Medicine, Duke University Medical Center, Durham, NC.
| | - William Aronson
- Urology Section, Department of Surgery, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA; Department of Urology, UCLA School of Medicine, Los Angeles, CA
| | - Stephen J Freedland
- Department of Surgery, Center for Integrated Research on Cancer and Lifestyle, Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA; Section of Urology, Department of Surgery, Durham Veterans Affairs Medical Center, Durham, NC
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48
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Ferro M, Lucarelli G, Bruzzese D, Di Lorenzo G, Perdonà S, Autorino R, Cantiello F, La Rocca R, Busetto GM, Cimmino A, Buonerba C, Battaglia M, Damiano R, De Cobelli O, Mirone V, Terracciano D. Low serum total testosterone level as a predictor of upstaging and upgrading in low-risk prostate cancer patients meeting the inclusion criteria for active surveillance. Oncotarget 2017; 8:18424-18434. [PMID: 27793023 PMCID: PMC5392340 DOI: 10.18632/oncotarget.12906] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Accepted: 10/14/2016] [Indexed: 12/22/2022] Open
Abstract
Active surveillance (AS) is currently a widely accepted treatment option for men with clinically localized prostate cancer (PCa). Several reports have highlighted the association of low serum testosterone levels with high-grade, high-stage PCa. However, the impact of serum testosterone as a predictor of progression in men with low-risk PCa has been little assessed. In this study, we evaluated the association of circulating testosterone concentrations with a staging/grading reclassification in a cohort of low-risk PCa patients meeting the inclusion criteria for the AS protocol but opting for radical prostatectomy. Radical prostatectomy (RP) was performed in 338 patients, eligible for AS according to the following criteria: clinical stage T2a or less, PSA<10ng/ml, two or fewer cancer cores, Gleason score (GS)=6 and PSA density<0.2 ng/mL/cc. Reclassification was defined as upstaging (stage>pT2) and upgrading (GS=7; primary Gleason pattern 4) disease. Unfavorable disease was defined as the occurrence of pathological stage>pT2 and predominant Gleason score 4. Total testosterone was measured before surgery. Low serum testosterone levels (<300 ng/dL) were significantly associated with upgrading, upstaging, unfavorable disease and positive surgical margins. The addition of testosterone to a base model, including age, PSA, PSA density, clinical stage and positive cancer involvement in cores, showed a significant independent influence of this variable on upstaging, upgrading and unfavorable disease. In conclusion, our results support the idea that total testosterone should be a selection criterion for inclusion of low-risk PCa patients in AS programs and suggest that testosterone level less than 300 ng/dL should be considered a discouraging factor when a close AS program is considered as treatment option
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Affiliation(s)
- Matteo Ferro
- Department of Urology, European Institute of Oncology, Via Ripamonti, Milan, Italy
| | - Giuseppe Lucarelli
- Department of Emergency & Organ Transplantation - Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari, Italy
| | - Dario Bruzzese
- Department of Public Health, University of Naples 'Federico II', Naples, Italy
| | - Giuseppe Di Lorenzo
- Department of Clinical Medicine, Medical Oncology Unit, University of Naples 'Federico II', Naples, Italy
| | - Sisto Perdonà
- Department of Urology, "Istituto Nazionale Tumori Fondazione Giovanni Pascale - IRCCS", Naples, Italy
| | | | | | - Roberto La Rocca
- Department of Urology, University of Naples 'Federico II', Naples, Italy
| | | | - Amelia Cimmino
- Institute of Genetics and Biophysics "A. Buzzati Traverso", National Research Council, Naples, Italy
| | - Carlo Buonerba
- Department of Clinical Medicine, Medical Oncology Unit, University of Naples 'Federico II', Naples, Italy
| | - Michele Battaglia
- Department of Emergency & Organ Transplantation - Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari, Italy
| | - Rocco Damiano
- Division of Urology, Magna Graecia University, Catanzaro, Italy
| | - Ottavio De Cobelli
- Department of Urology, European Institute of Oncology, Via Ripamonti, Milan, Italy.,University of Milan, Milan, Italy.,University of Medicine Iuliu Hatieganu, Cluj-Napoca, Romania
| | - Vincenzo Mirone
- Department of Urology, University of Naples 'Federico II', Naples, Italy
| | - Daniela Terracciano
- Department of Translational Medical Sciences, University of Naples 'Federico II', Naples, Italy
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49
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Breen KJ, O'Neill A, Murphy L, Fan Y, Boyce S, Fitzgerald N, Dorris E, Brady L, Finn SP, Hayes BD, Treacy A, Barrett C, Aziz MA, Kay EW, Fitzpatrick JM, Watson RWG. Investigating the role of the IGF axis as a predictor of biochemical recurrence in prostate cancer patients post-surgery. Prostate 2017; 77:1288-1300. [PMID: 28726241 DOI: 10.1002/pros.23389] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 06/22/2017] [Indexed: 12/30/2022]
Abstract
BACKGROUND Between 20% and 35% of prostate cancer (PCa) patients who undergo treatment with curative intent (ie, surgery or radiation therapy) for localized disease will experience biochemical recurrence (BCR). Alterations in the insulin-like growth factor (IGF) axis and PTEN expression have been implicated in the development and progression of several human tumors including PCa. We examined the expression of the insulin receptor (INSR), IGF-1 receptor (IGF-1R), PTEN, and AKT in radical prostatectomy tissue of patients who developed BCR post-surgery. METHODS Tissue microarrays (TMA) of 130 patients post-radical prostatectomy (65 = BCR, 65 = non-BCR) were stained by immunohistochemistry for INSR, IGF-1R, PTEN, and AKT using optimized antibody protocols. INSR, IGF1-R, PTEN, and AKT expression between benign and cancerous tissue, and different Gleason grades was assessed. Kaplan-Meier survival curves were used to examine the relationship between proteins expression and BCR. RESULTS INSR (P < 0.001), IGF-1R (P < 0.001), and AKT (P < 0.05) expression was significantly increased and PTEN (P < 0.001) was significantly decreased in cancerous versus benign tissue. There was no significant difference in INSR, IGF-1R, or AKT expression in the cancerous tissue of non-BCR versus BCR patients (P = 0.149, P = 0.990, P = 0.399, respectively). There was a significant decrease in PTEN expression in the malignant tissue of BCR versus non-BCR patients (P = 0.011). Combinational analysis of the tissue proteins identified a combination of decreased PTEN and increased AKT or increased INSR was associated with worst outcome. We found that in each case, our hypothesized worst group was most likely to experience BCR and this was significant for combinations of PTEN+INSR and PTEN+AKT but not PTEN+IGF-1R (P = 0.023, P = 0.028, P = 0.078, respectively). CONCLUSIONS Low PTEN is associated with BCR and this association is strongly modified by high INSR and high AKT expression. Measurement of these proteins could help inform appropriate patient selection for postoperative adjuvant therapy and prevent BCR.
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Affiliation(s)
- Kieran J Breen
- UCD School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland
| | - Amanda O'Neill
- UCD School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland
| | - Lisa Murphy
- UCD School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland
| | - Yue Fan
- UCD School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland
| | - Susie Boyce
- UCD School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland
- UCD School of Mathematical Sciences, Dublin, Ireland
| | - Noel Fitzgerald
- UCD School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland
| | - Emma Dorris
- UCD School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland
| | - Lauren Brady
- Department of Histopathology and Morbid Anatomy, Trinity Translational Medicine Institute, Trinity College, Dublin, Ireland
- Department of Histopathology, St. James's Hospital, Dublin, Ireland
| | - Stephen P Finn
- Department of Histopathology and Morbid Anatomy, Trinity Translational Medicine Institute, Trinity College, Dublin, Ireland
- Department of Histopathology, St. James's Hospital, Dublin, Ireland
| | - Brian D Hayes
- Department of Histopathology and Morbid Anatomy, Trinity Translational Medicine Institute, Trinity College, Dublin, Ireland
- Department of Histopathology, St. James's Hospital, Dublin, Ireland
| | - Ann Treacy
- Department of Histopathology, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Ciara Barrett
- Department of Histopathology, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Mardiana Abdul Aziz
- Department of Histopathology, Mater Misericordiae University Hospital, Dublin, Ireland
| | - Elaine W Kay
- Department of Pathology, RCSI Education and Research Centre, Beaumont Hospital, Dublin, Ireland
| | - John M Fitzpatrick
- UCD School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland
| | - R William G Watson
- UCD School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland
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50
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Bhindi B, Jiang H, Poyet C, Hermanns T, Hamilton RJ, Li K, Toi A, Finelli A, Zlotta AR, van der Kwast TH, Evans A, Fleshner NE, Kulkarni GS. Creation and internal validation of a biopsy avoidance prediction tool to aid in the choice of diagnostic approach in patients with prostate cancer suspicion. Urol Oncol 2017; 35:604.e17-604.e24. [PMID: 28781111 DOI: 10.1016/j.urolonc.2017.06.044] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Revised: 06/03/2017] [Accepted: 06/12/2017] [Indexed: 10/19/2022]
Abstract
INTRODUCTION To reduce unnecessary prostate biopsies while using novel tests judiciously, we created a tool to predict the probability of clinically significant prostate cancer (CSPC) vs. low-risk prostate cancer or negative biopsy (i.e., when intervention is likely not needed) among men undergoing initial or repeat biopsy. METHODS Separate models were created for men undergoing initial and repeat biopsy, identified from our institutional biopsy database and the placebo arm of the REDUCE trial, respectively, to predict the presence of CSPC (Gleason≥7 or>33% of cores involved). Predictors considered included age, race, body mass index, family history of prostate cancer, digital rectal examination, prostate volume, prostate-specific antigen (PSA), free-to-total PSA, presence of high-grade prostatic intraepithelial neoplasia or atypical small acinar proliferation on prior biopsy, number of prior biopsies, and number of cores previously taken. Multivariable logistic regression models that minimized the Akaike Information Criterion and maximized out-of-sample area under the receiver operating characteristics curve (AUC) were selected. RESULTS Of 7,963 biopsies (initial = 2,042; repeat = 5,921), 1,138 had CSPC (initial = 870 [42.6%]; repeat = 268 [4.5%]). Age, race, body mass index, family history, digital rectal examination, and PSA were included in the initial biopsy model (out-of-sample AUC = 0.74). Age, prostate volume, PSA, free-to-total PSA, prior high-grade prostatic intraepithelial neoplasia, and number of prior biopsies were included in the repeat biopsy model (out-of-sample AUC = 0.81). CONCLUSION These prediction models may help guide clinicians in avoiding unnecessary initial and repeat biopsies in men unlikely to harbor CSPC. This tool may also allow for the more judicious use of novel tests only in patients in need of further risk stratification before deciding whether to biopsy.
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Affiliation(s)
- Bimal Bhindi
- Department of Surgery, University Health Network, University of Toronto, Toronto, Canada; Department of Urology, Mayo Clinic, Rochester, MN.
| | - Haiyan Jiang
- Department of Biostatistics, University Health Network, University of Toronto, Toronto, Canada
| | - Cedric Poyet
- Department of Urology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Thomas Hermanns
- Department of Urology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Robert J Hamilton
- Department of Surgery, University Health Network, University of Toronto, Toronto, Canada
| | - Kathy Li
- Department of Surgery, University Health Network, University of Toronto, Toronto, Canada
| | - Ants Toi
- Department of Medical Imaging, University Health Network, University of Toronto, Toronto, Canada
| | - Antonio Finelli
- Department of Surgery, University Health Network, University of Toronto, Toronto, Canada
| | - Alexandre R Zlotta
- Department of Surgery, University Health Network, University of Toronto, Toronto, Canada; Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, Canada
| | | | - Andrew Evans
- Institute for Clinical and Evaluative Sciences, University of Toronto, Toronto, Canada
| | - Neil E Fleshner
- Department of Surgery, University Health Network, University of Toronto, Toronto, Canada
| | - Girish S Kulkarni
- Department of Surgery, University Health Network, University of Toronto, Toronto, Canada; Department of Pathology, University Health Network, University of Toronto, Toronto, Canada
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