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- Androgen Deprivation Therapy for Prostate Cancer Is Associated with Cardiovascular Morbidity and Mortality: A Meta-Analysis of Population-Based Observational Studies. [JOURNAL ARTICLE]
- PLoS One 2014; 9(9):e107516.
There is no consensus regarding whether androgen deprivation therapy (ADT) is associated with cardiovascular disease (CVD) and cardiovascular mortality (CVM). The objective of this study was to determine the role of ADT for prostate cancer (PCa) in development of cardiovascular events (CVD and CVM).We performed a meta-analysis from population-based observational studies comparing ADT vs control aimed at treating PCa in patients with PCa, reporting either CVD or CVM as outcome. Publications were searched using Medline, Embase, Cochrane Library Central Register of observational studies database up to May 31th 2014, and supplementary searches in publications from potentially relevant journals. 6 studies were identified with a total of 129,802 ADT users and 165,605 controls investigating the relationship between ADT and CVD. The incidence of CVD was 10% higher in ADT groups, although no significant association was observed (HR = 1.10, 95%CIs: 1.00-1.21; P = 0.06). For different types of ADT, CVD was related with gonadotropin-releasing hormone (GnRH) (HR = 1.19, 95%CIs: 1.04-1.36; P<0.001) and GnRH plus oral antiandrogen (AA) (HR = 1.46, 95%CIs: 1.03-2.08; P = 0.04), but not with AA alone or orchiectomy. For CVM, 119,625 ADT users and 150,974 controls from 6 eligible studies were included, pooled results suggested that ADT was associated with CVM (HR = 1.17, 95%CIs: 1.04-1.32; P = 0.01). Significantly increased CVM was also detected in GnRH and GnRH plus AA groups. When patients received other treatments (e.g. prostatectomy and radiotherapy) were ruled out of consideration, more increased CVD (HR = 1.19, 95%CIs: 1.08-1.30; P<0.001) and CVM (HR = 1.30, 95%CIs: 1.13-1.50; P<0.001) were found in men treated with ADT monotherapy.ADT is associated with both CVD and CVM. Particularly, GnRH alone and GnRH plus AA can significantly increase the incidence of cardiovascular events in patients with PCa.
- Androgen deprivation therapy in castrate-resistant prostate cancer: how important is GnRH agonist backbone therapy? [JOURNAL ARTICLE]
- World J Urol 2014 Sep 27.
A growing number of treatment options exist to treat metastatic castrate-resistant prostate cancer (mCRPC), and with these newer options, many questions about optimising treatment remain unanswered. One recommendation that may potentially be overlooked by practitioners is that androgen deprivation therapy (ADT) should be maintained when CRPC develops and when treatment with any of the newer agents is initiated.However, to emphasise this recommendation, it is valuable to interrogate the evidence for maintaining ADT in different clinical situations.This statement, reflecting the views of the authors, provides a discussion of this evidence and the rationale behind the recommendation that ADT should be continued in CRPC.
- The Academic Diligence Task (ADT): Assessing Individual Differences in Effort on Tedious but Important Schoolwork. [JOURNAL ARTICLE]
- Contemp Educ Psychol 2014 Oct 1; 39(4):314-325.
The current study reports on the development and validation of the Academic Diligence Task (ADT), designed to assess the tendency to expend effort on academic tasks which are tedious in the moment but valued in the long-term. In this novel online task, students allocate their time between solving simple math problems (framed as beneficial for problem solving skills) and, alternatively, playing Tetris or watching entertaining videos. Using a large sample of high school seniors (N = 921), the ADT demonstrated convergent validity with self-report ratings of Big Five conscientiousness and its facets, self-control and grit, as well as discriminant validity from theoretically unrelated constructs, such as Big Five extraversion, openness, and emotional stability, test anxiety, life satisfaction, and positive and negative affect. The ADT also demonstrated incremental predictive validity for objectively measured GPA, standardized math and reading achievement test scores, high school graduation, and college enrollment, over and beyond demographics and intelligence. Collectively, findings suggest the feasibility of online behavioral measures to assess noncognitive individual differences that predict academic outcomes.
- Cytoreductive Radical Prostatectomy in Patients with prostate cancer and low volume skeletal metastases - results of a feasibility and case-control study. [JOURNAL ARTICLE]
- J Urol 2014 Sep 21.
Androgen deprivation (ADT) represents the standard treatment for PCA with osseous metastases. We explored the role of cytoreductive radical prostatectomy in PCA with low volume skeletal metastases in terms of a feasibility study.23 patients with biopsy proven PCA, minimal osseous metastases (≤ 3 hot spots on bone scan), absence of visceral or extensive lymph node metastases and PSA decrease to < 1.0 ng/ml after neoadjuvant ADT were included in the feasibility study. 38 men with metastatic PCA who were treated by ADT without local therapy served as control group (group B). Surgery-related complications, time to castration resiatence, symptomatic-free, cancer-specific and overall survival were analyzed using descriptive statistical analysis.Mean age was 61 (42-69) and 64 (47-83) years in group A and B, respectively, with similar patient characteristics in terms of initial PSA, biopsy Gleason score, clinical stage, extent of metastatic disease. The median follow-up was 34.5 (7-75) and 47 (28-96) months in group A and B, respectively. Median time to CRPC was 40 (9-65) and 29 (16-59) months in groups A and B, respectively (p=0.04)- Patients in group A experienced significantly better clinical PFS (38.6 versus 26.5 months, p=0.032) and cancer specific survival rate (95.6% versus 84.2%, p=0.043) whereas the overall survival was similar. 0% and 29% of men in group A and B, respectively, underwent palliative surgical procedures for locally progressing PCA.CRP is feasible in well selected men with metastatic PCA who respond well to neoadjuvant ADT. These men have a long life expectancy and CRP reduces the risk of locally recurrent PCA and local complications. CRP might be a treatment option in the multimodality management of PCA with minimal osseous metastases.
- External beam radiation therapy and a low-dose-rate brachytherapy boost without or with androgen deprivation therapy for prostate cancer. [JOURNAL ARTICLE]
- Int Braz J Urol 2014 july-august; 40(4):474-483.
Purpose: To assess outcomes with external beam radiation therapy (EBRT) and a low-dose-rate (LDR) brachytherapy boost without or with androgen deprivation therapy (ADT) for prostate cancer. Materials and Methods: From January 2001 through August 2011, 120 intermediate-risk or high-risk prostate cancer patients were treated with EBRT to a total dose of 4,500 cGy in 25 daily fractions and a palladium-103 LDR brachytherapy boost of 10,000 cGy (n = 90) or an iodine-125 LDR brachytherapy boost of 11,000 cGy (n = 30). ADT, consisting of a gonadotropin-releasing hormone agonist ± an anti-androgen, was administered to 29/92 (32%) intermediate-risk patients for a median duration of 4 months and 26/28 (93%) high-risk patients for a median duration of 28 months. Results: Median follow-up was 5.2 years (range, 1.1-12.8 years). There was no statistically-significant difference in biochemical disease-free survival (bDFS), distant metastasis-free survival (DMFS), or overall survival (OS) without or with ADT. Also, therewas no statistically-significant difference in bDFS, DMFS, or OS with a palladium-103 vs. an iodine-125 LDR brachytherapy boost. Conclusions: There was no statistically-significant difference in outcomes with the addition of ADT, though the power of the current study was limited. The Radiation Therapy Oncology Group 0815 and 0924 phase III trials, which have accrual targets of more than 1,500 men, will help to clarify the role ADT in locally-advanced prostate cancer patients treated with EBRT and a brachytherapy boost. Palladium-103 and iodine- 125 provide similar bDFS, DMFS, and OS.
- Positive and negative mood in men with advanced prostate cancer undergoing androgen deprivation therapy: considering the role of social support and stress. [JOURNAL ARTICLE]
- Psychooncology 2014 Sep 23.
Advanced prostate cancer patients often undergo androgen deprivation therapy (ADT). Advanced disease and adverse ADT side effects are often debilitating and negatively impact mood. Social support has been shown to mitigate detrimental effects of stress on mood.This study sought to characterize positive and negative mood in this select patient population and determine whether social support moderated relations between stress and mood.Participants (N = 80) completed the Interpersonal Support Evaluation List, Perceived Stress Scale, and Derogatis Affect Balance Scale at a single time point. Hierarchical regression models evaluated relations among social support, stress, and mood controlling for relevant covariates. Standard moderation analyses were performed.Participants reported higher levels of negative and positive mood compared with published means of localized prostate cancer patients. Overall, mood was more positive than negative. Stress levels were comparable to cancer populations with recurrent disease. Moderated regression analyses showed that social support partially buffered the effects of stress on positive mood; men with high stress and low support reported the lowest levels of positive mood. The model with negative mood as the dependent measure did not support moderation; that is, the relationship between stress and negative mood did not differ by level of social support.Among individuals living with advanced prostate cancer, social support may be an important factor that sustains positive mood in the presence of stress. Future work should examine the extent to which social support prospectively impacts health-related quality of life by promoting positive mood. Limitations include cross-sectional design, which precludes causal inferences. Copyright © 2014 John Wiley & Sons, Ltd.
- Androgen Receptor Roles in Insulin Resistance and Obesity in Males: The Linkage of Androgen-Deprivation Therapy to Metabolic Syndrome. [REVIEW]
- Diabetes 2014 Oct; 63(10):3180-3188.
Prostate cancer (PCa) is one of the most frequently diagnosed malignancies in men. Androgen-deprivation therapy (ADT) is the first-line treatment and fundamental management for men with advanced PCa to suppress functions of androgen/androgen receptor (AR) signaling. ADT is effective at improving cancer symptoms and prolonging survival. However, epidemiological and clinical studies support the notion that testosterone deficiency in men leads to the development of metabolic syndrome that increases cardiovascular disease risk. The underlying mechanisms by which androgen/AR signaling regulates metabolic homeostasis in men are complex, and in this review, we discuss molecular mechanisms mediated by AR signaling that link ADT to metabolic syndrome. Results derived from various AR knockout mouse models reveal tissue-specific AR signaling that is involved in regulation of metabolism. These data suggest that steps be taken early to manage metabolic complications associated with PCa patients receiving ADT, which could be accomplished using tissue-selective modulation of AR signaling and by treatment with insulin-sensitizing agents.
- Physical functioning for prostate health. [Journal Article, Review]
- Can Urol Assoc J 2014 Jul; 8(7-8 Suppl 5):S162-3.
Men who undergo long-term androgen deprivation therapy (ADT) may experience systemic side effects similar to the classical metabolic syndrome. Exercise is a potential strategy for offsetting the adverse effects of ADT among patients with prostate cancer, resulting in improved muscular resistance and positive outcomes on body size and composition. Fitness (aerobic capacity), fatigue and certain quality of life (QOL) outcomes may also improve in response to a regular exercise regimen. Caution and cardiovascular screening are merited given the elderly population with this disease.
- Osteoporosis: The connection to urologic health. [Journal Article, Review]
- Can Urol Assoc J 2014 Jul; 8(7-8 Suppl 5):S156-8.
Men with prostate cancer are often treated with androgen deprivation therapy (ADT), which is associated with reduced bone mineral density (BMD) and a higher risk for fractures. Maintenance of optimum bone health throughout the natural course of prostate cancer is an important aspect in the management of this patient population. Bone targeted therapies, such as bisphosphonates and the RANK ligand inhibitor denosumab, have been demonstrated to reduce skeletal-related events in patients with metastatic cancer, while denosumab has also been shown to reduce the risk of fracture in men undergoing ADT for prostate cancer.
- GnRH antagonist associates with less adiposity and reduced characteristics of metabolic syndrome and atherosclerosis compared with orchiectomy and GnRH agonist in a preclinical mouse model. [JOURNAL ARTICLE]
- Urol Oncol 2014 Sep 18.
Observational studies relate androgen deprivation therapy (ADT) to metabolic syndrome (MS) and cardiovascular disease, an association potentially subject to uncontrollable confounding factors, especially diet and genetic/metabolic risk factors. In the absence of prospective randomized clinical trials, causality remains unproven. We comparatively investigated the effects of different ADT modalities on the development of MS and atherosclerosis in a mouse model.Low-density lipoprotein receptor knockout mice underwent orchiectomy plus vehicle (2.5% mannitol), sham surgery plus vehicle (control), sham surgery plus gonadotropin-releasing hormone (GnRH) antagonist (degarelix), or sham surgery plus GnRH agonist (leuprolide) (n = 9-13/group) and were followed for 4 months. Visceral fat accumulation, lean body mass, adipocyte size, fasting blood glucose, glucose tolerance, serum levels of leptin, follicle-stimulating hormone, luteinizing hormone, and testosterone, along with atherosclerotic plaque size and characteristics were measured.All 3 modes of ADT decreased circulating testosterone levels in mice, although leuprolide treatment reached nadir levels of testosterone later. Orchiectomized and leuprolide-treated mice gained significantly more visceral fat compared with degarelix-treated mice. Improved glucose tolerance tests were recorded in degarelix-treated mice. The aortic atherosclerotic plaque area in leuprolide-treated and orchiectomized mice was larger than in control mice (P<0.005 and P = 0.002, respectively), but it was not significantly different from control in degarelix-treated mice. The necrotic core area in degarelix-treated mice was smaller compared with leuprolide-treated and orchiectomized mice (P = 0.011 and P = 0.002, respectively).Our results suggest that ADT induced MS and atherosclerosis in a preclinical mouse model to a mode-specific extent. GnRH antagonist generated the least atherosclerosis and characteristics of MS compared with orchiectomy and GnRH agonist.