Androgen Deprivation Therapy Users Research Articles

Association between Androgen Deprivation Therapy and the Risk of Inflammatory Rheumatic Diseases in Men with Prostate Cancer: Nationwide Cohort Study in Lithuania.

Background: The aim of this study was to assess the association between androgen deprivation therapy (ADT) and the risk of inflammatory rheumatic diseases in men with prostate cancer. Methods: Patients with prostate cancer between 2012 and 2016 were identified from the Lithuanian Cancer Registry and the National Health Insurance Fund database, on the basis of rheumatic diseases diagnoses and information on prescriptions for androgen deprivation therapy. Cox proportional hazard models were used to estimate hazard ratios (HR) to compare the risks of rheumatic diseases caused by androgen deprivation therapy exposure in groups of prostate cancer patients. Results: A total of 12,505 prostate cancer patients were included in this study, out of whom 3070 were ADT users and 9390 were ADT non-users. We observed a higher risk of rheumatic diseases in the cohort of prostate cancer patients treated with ADT compared with ADT non-users (HR 1.55, 95% confidence interval (CI) 1.01–2.28). Detailed risk by cumulative use of ADT was performed for rheumatoid arthritis, and a statistically significant higher risk was found in the group with longest cumulative ADT exposure (>105 weeks) (HR 3.18, 95% CI 1.39–7.29). Conclusions: Our study suggests that ADT usage could be associated with increased risk of rheumatoid arthritis, adding to the many known side effects of ADT.

Androgen deprivation therapy for prostate cancer and the risk of thyroid diseases.

Androgen deprivation therapy (ADT) is the major treatment for metastatic prostate cancer (PCa), but few studies have investigated the effects of ADT on thyroid diseases. This population-based, nationwide cohort study utilizedthe Taiwan National Health Insurance Research Database (NHIRD) with 17,192 PCa patients between 1997 and 2013. We used the Cox proportional hazards models and propensity score-matched analysis to analyze the association between ADT and the development of thyroid diseases. A total of 17,192 newly diagnosed men with PCa were selected from the NHIRD. There were 6200 ADT users and 6200 non-ADT users after 1:1 propensity score matching. There was asignificantly decreased risk of thyroid diseases among ADT users compared with non-ADT users(adjusted hazard ratio (aHR): 0.79, 95% confidence interval (CI): 0.65-0.95, p < 0.001). Further analysis showed a significantly decreased risk of thyroid diseases with increasing ADT duration (p < 0.001). The result showed that ADT use in men with PCa was associated with a decreased risk of thyroid disease development.

Androgen deprivation therapy prescription, blood and bone-density testing in a French population-based study exploring adherence to the French prostate cancer guidelines

The safety profile of androgen deprivation therapy (ADT) is well known, and cardiovascular and osteoporosis risk factors should be assessed before ADT initiation. In order to examine whether the French Committee of Urologic Oncology Prostate Cancer (PCa) Guidelines were properly followed by clinicians, including urologists, oncologists and radiotherapists, we used a nationwide comprehensive cohort of prostate cancer patients, who were new ADT users in 2011 and were followed-up to 2013. Reimbursements for biological examinations and prescribers were identified, as well as PCa specialist consultations at drug initiation. Our results in this French cohort showed that the proportions of patients resorting to specialized care between one year and 3 months before ADT initiation and in the 6 months following was around 40% for fasting glucose and 30% for lipid assessments. Bone densitometry was performed in approximately 1% of patients. In the 12 months after ADT initiation, 75% of the patients were seen by a urologist and about 47% by an oncologist or a radiotherapist. Overall, there is still room for improvement in terms of ADT monitoring by clinicians and in the information provided to general practitioners and patients regarding the expected adverse effects of this treatment.

Changes in resting-state measures of prostate cancer patients exposed to androgen deprivation therapy

The aim of the present work is to describe the differences in rs-fMRI measures (Amplitude of low frequency fluctuations [ALFF], Regional Homogeneity [ReHo] and Functional Connectivity [FC]) between patients exposed to Androgen deprivation therapy (ADT) and a control group. Forty-nine ADT patients and fifteen PC-non-ADT patients (Controls) were included in the study. A neuropsychological evaluation and a resting-state fMRI was performed to evaluate differences in ALFF and ReHo. Region of interest (ROI) analysis was also performed. ROIs were selected among those whose androgen receptor expression (at RNA-level) was the highest. FC analysis was performed using the same ROIs. Higher ALFF in frontal regions and temporal regions was identified in Controls than in ADT patients. In the ROI analysis, higher activity for Controls than ADT patients was shown in the left inferior frontal gyrus and in the left precentral gyrus. Lower ALFF in the right hippocampus and the lateral geniculate nucleus of the right thalamus was identified for Controls than ADT patients. Higher ReHo was observed in Controls in the left parietal-occipital area. Finally, ADT patients presented an increase of FC in more regions than Controls. These differences may reflect an impairment in brain functioning in ADT users.

PD05-03 ANDROGEN DEPRIVATION THERAPY (ADT) FOR PROSTATE CANCER AND ITS EFFECTS ON BRAIN VOLUME 3D PLANIMETRY

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) I (PD05)1 Sep 2021PD05-03 ANDROGEN DEPRIVATION THERAPY (ADT) FOR PROSTATE CANCER AND ITS EFFECTS ON BRAIN VOLUME 3D PLANIMETRY Ruel Neupane, Megan Prunty, Danly Omil-Lima, Amr Mahran, Kirtishri Mishra, Lee Ponsky, Carvell Nguyen, Christopher Kondray, Adam Calaway, and Laura Bukavina Ruel NeupaneRuel Neupane More articles by this author , Megan PruntyMegan Prunty More articles by this author , Danly Omil-LimaDanly Omil-Lima More articles by this author , Amr MahranAmr Mahran More articles by this author , Kirtishri MishraKirtishri Mishra More articles by this author , Lee PonskyLee Ponsky More articles by this author , Carvell NguyenCarvell Nguyen More articles by this author , Christopher KondrayChristopher Kondray More articles by this author , Adam CalawayAdam Calaway More articles by this author , and Laura BukavinaLaura Bukavina More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001969.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Approximately 1 in 9 American men will be diagnosed with prostate cancer. Androgen Deprivation Therapy (ADT) is commonly given for advanced local and metastatic prostate cancer with evidence of prolonged survival. However, there is increasing concern for the negative side effects including cognitive decline in ADT users. Our study seeks to quantify radiographic changes on brain parenchyma following ADT. METHODS: A retrospective multi-institutional study was performed on baseline and follow-up computerized tomography (CT) head scans of 59 men prior to and after initiation of ADT. All CT imaging were reviewed using 3D planimetry software (3D Splicer, Version 4.10.2). Brain and ventricular volumes were assessed via segmentation protocol. Multivariate logistic regression (MVR) adjusting for socio-demographic variables and comorbidities were used to assess risk factors for cortical loss. Paired Wilcoxon test was utilized to assess change in brain volume prior to and after initiation of ADT. RESULTS: A total of 59 patients were analyzed. An average decline in cortical volume of 86.2 cm3 [pre-ADT 1156.0 cm3 (1035.0, 1231.5) and post-ADT 1073.0cm3 (930.5, 1136.5), p>0.001] was seen in our cohort. As expected, sequential increase of 30% in ventricular volume from baseline (66 cm3) to post-ADT (84 cm3) was also noted. On MVR, lower BMI (OR 1.13, 95%CI 1,01-1.27, p=0.042), history of dementia (OR 3.47, 95% CI 1.05-12.66, p=0.042) and alcohol abuse (OR 4.7, 95%, CI 1.1-21.01, p=0.037) were all significantly associated with increased the risk of cortical loss. History of metastatic prostate cancer was not associated with risk of cortical loss (Figure 1C). CONCLUSIONS: Androgen deprivation therapy is commonly used for the management of localized and metastatic prostate cancer. There is mounting evidence that ADT may be correlated with loss of brain volume and cognitive decline. In this study we quantify the loss of cortical brain volume and ventricular expansion in patients on ADT. Source of Funding: N/A © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e56-e56 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ruel Neupane More articles by this author Megan Prunty More articles by this author Danly Omil-Lima More articles by this author Amr Mahran More articles by this author Kirtishri Mishra More articles by this author Lee Ponsky More articles by this author Carvell Nguyen More articles by this author Christopher Kondray More articles by this author Adam Calaway More articles by this author Laura Bukavina More articles by this author Expand All Advertisement Loading ...

Risk of Fracture During Androgen Deprivation Therapy Among Patients With Prostate Cancer: A Systematic Review and Meta-Analysis of Cohort Studies

Background: Androgen deprivation therapy (ADT) suppresses the production of androgen, and ADT is broadly used for intermediate or higher risk disease including advanced and metastatic cancer. ADT is associated with numerous adverse effects derived from the pharmacological properties. Previous meta-analysis on fracture risk among ADT users possessed limited data without further subgroup analysis. Risk estimation of updated real-world evidence on ADT-related fracture remains unknown.Objectives: To assess the risk of fracture and fracture requiring hospitalization associated with ADT among prostate cancer population on different disease conditions, treatment regimen, dosage level, fracture sites.Methods: The Cochrane Library, PubMed, and Embase databases were systematically screened for eligible cohort studies published from inception to March 2020. Two authors independently reviewed all the included studies. The risks of any fracture and of fracture requiring hospitalization were assessed using a random-effects model, following by leave-one-out, stratified, and sensitivity analyses. The Grading of Recommendations Assessments, Development and Evaluations (GRADE) system was used to grade the certainty of evidence.Results: Sixteen eligible studies were included, and total population was 519,168 men. ADT use is associated with increasing fracture risk (OR, 1.39; 95% CI, 1.26–1.52) and fracture requiring hospitalization (OR, 1.55; 95% CI, 1.29–1.88). Stratified analysis revealed that high-dose ADT results in an elevated risk of fracture with little statistical heterogeneity, whereas sensitivity analysis restricted to adjust for additional factors indicated increased fracture risks for patients with unknown stage prostate cancer or with no restriction on age with minimal heterogeneity. The GRADE level of evidence was moderate for any fracture and low for fracture requiring hospitalization.Conclusion: Cumulative evidence supports the association of elevated fracture risk with ADT among patients with prostate cancer, including those with different disease conditions, treatment regimens, dose levels, and fracture sites. Further prospective trials with intact information on potential risk factors on fracture under ADT use are warranted to identify the risky population.

Retrospective cohort study of androgen deprivation therapy and the risk of diabetes in men with prostate cancer in Lithuania

ObjectivesTo examine the risk of type 2 diabetes in patients with prostate cancer and its association with androgen deprivation therapy (ADT).Design and participantsWe performed a retrospective cohort study of patients...

Is There An Association Between Use Of Androgen Deprivation Therapy And Acute Kidney Injury In Prostate Cancer Patients Treated With Definitive Radiotherapy?

Androgen Deprivation Therapy (ADT) has been demonstrated to improve survival in men with prostate cancer undergoing definitive radiotherapy. However, ADT may have deleterious effects on cardiovascular, metabolic, bone, and mental health. Little is known about possible effects of ADT on renal function. Recent observational studies have demonstrated an association between ADT use and Acute Kidney Injury (AKI). These studies have included heterogeneous populations undergoing a variety of treatments, which may predispose to selection bias, and do not reflect recent changes in the definition of AKI. We sought to investigate the incidence of AKI in a large cohort of US veterans receiving definitive radiotherapy +/- ADT for prostate cancer. We investigated the prevalence of AKI through the Veterans Affairs Informatics and Computing Infrastructure (VINCI) platform. Our cohort consists of 44,246 veterans diagnosed with nonmetastatic prostate cancer between January 1st 2001 and October 31st 2015. All were treated with definitive radiotherapy. Exposure was defined as initiation of ADT within one year of diagnosis. The primary outcome was the incidence of AKI, defined via ICD codes. Covariates included in the multivariable regression model were: Age, Charlson Comorbidity Index score, race, smoking status, region, income, education, marital status, and year of diagnosis. Within the study population, 16,275 patients (37%) received RT+ADT and 27,971 (62%) received RT alone. With a median follow up of 6.8 years, there were 3,853 patients diagnosed with an AKI during the study period including 1,753 ADT users (10.8%) and 2,100 non-ADT users (7.5%). The overall cumulative incidence of AKI at 10 years was 11.4% including 14.1% for ADT users and 9.8% for non-ADT users. In the multivariable competing risks model, there was a significant association between ADT and AKI (subdistribution hazard ratio (SHR) = 1.28, 95% CI = 1.20-1.37, p<0.01). The use of ADT was associated with an increased risk of AKI in a large, modern cohort of US veterans undergoing definitive radiotherapy for prostate cancer. These findings warrant prospective confirmation, but suggest that renal function may be an important consideration when assessing the risks and benefits of ADT use. Further study will be useful to investigate if particular subgroups of patients receiving ADT are more susceptible to AKI and if the increased rate of AKI is associated with any long-term effects on renal function.

The Risk of Cardiovascular Disease in Prostate Cancer Patients Receiving Androgen Deprivation Therapies.

Androgen deprivation therapy (ADT), with a proven role in prostate cancer management, has been associated with various cardiovascular diseases. However, few studies have investigated these associations by type of ADT, particularly for newer ADTs such as the gonadotropin-releasing hormone (GnRH) antagonist degarelix. We investigated the risk of cardiovascular disease by type of ADT in a real-world setting. We identified men newly diagnosed with prostate cancer, from 2009 to 2015, from the Scottish Cancer Registry and ADTs from the nationwide Prescribing Information System. Cardiovascular events were based upon hospitalization (from hospital records) or death from cardiovascular disease (from death records). We used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular events with time-varying ADT exposure, comparing ADT users with untreated patients, after adjusting for potential confounders, including prior cardiovascular disease. The cohort contained 20,216 prostate cancer patients, followed for 73,570 person-years, during which there were 3,853 cardiovascular events. ADT was associated with a 30% increase in cardiovascular events (adjusted HR = 1.3; 95% CI = 1.2, 1.4). This reflected increases in cardiovascular events associated with GnRH agonists (adjusted HR = 1.3; 95% CI = 1.2, 1.4), degarelix (adjusted HR = 1.5; 95% CI = 1.2, 1.9), but not bicalutamide monotherapy (adjusted HR = 1.0; 95% CI = 0.82, 1.3). There were increased risks of cardiovascular disease with the use of GnRH agonists and degarelix, but not with bicalutamide monotherapy. This is the first study to observe increased cardiovascular risks with degarelix, but the cause of this association is unclear and merits further investigation.

Androgen deprivation therapy for prostate cancer and the risk of autoimmune diseases.

Androgen deprivation therapy (ADT) has been a mainstay of treatment for advanced prostate cancer (PCa), but limited studies have been performed to investigate the association between ADT and autoimmune diseases. We conducted a population-based nationwide cohort study of 17,168 patients newly diagnosed with PCa between 1996 and 2013 using the National Health Insurance Research Database (NHIRD) of Taiwan. Cox proportional hazards models with 1:1 propensity score-matched analysis were used to investigate the association between ADT use and the risk of autoimmune diseases. The autoimmune diseases included Graves' disease, Crohn's disease, psoriasis, systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, Guillain-Barre syndrome, Sjogren's syndrome, myasthenia gravis, pernicious anemia, hereditary hemolytic anemia, polyarteritis nodosa, Celiac disease, uveitis, polymyalgia rheumatica, dermatomyositis, Hashimoto's thyroiditis, hypersensitivity vasculitis, Behcet's disease, polymyositis, alopecia areata, Wegener's granulomatosis, ulcerative colitis, autoimmune hemolytic anemia, pemphigus, multiple sclerosis, systemic sclerosis, Goodpasture syndrome, giant cell arteritis, thromboangitis obliterans, arteritis obliterans, and Kawasaki disease. The duration of ADT use as a time-dependent variable was also examined for its association with autoimmune diseases. We also performed six secondary analyses. Of the 17,168 selected PCa patients, 14,444 patients met all the inclusion and exclusion criteria. After propensity score matching, 5590 ADT users and 5590 non-ADT users were included in the study cohort. A propensity score-matched analysis (adjusted hazard ratio (aHR), 0.619, 95% confidence interval (CI), 0.51-0.75, P < 0.001) demonstrated a significantly decreased risk of autoimmune diseases in ADT users. A significant decrease in the risk of autoimmune diseases with increasing ADT duration was also demonstrated (P < 0.001). We observed that ADT use in patients with PCa was associated with a decreased risk of autoimmune diseases. These novel findings provide a potential role for androgen deprivation therapy in the modification of inflammation and autoimmunity in Asian patients with prostate cancer.

Androgen Deprivation Therapy Use Increases the Risk of Heart Failure in Patients With Prostate Cancer: A Population-Based Cohort Study.

The aim of this study was to investigate the relationship between androgen deprivation therapy and heart failure among prostate cancer patients. This cohort study used the data from the Taiwan Longitudinal Health Insurance Database 2005. In the full cohort study, we identified 1244 prostate cancer patients who had received androgen deprivation therapy as the study cohort and 1806 prostate cancer patients who did not receive androgen deprivation therapy as the comparison cohort. To eliminate potential bias, we performed a propensity score-matched cohort study. Each prostate cancer patient was tracked for 1 year from the index date to ascertain whether they were subsequently diagnosed with heart failure. In the full cohort study, incidence rates of heart failure per 100 person-years within the 1-year follow-up period were 4.00 (95%CI, 2.95-5.30) and 1.89 (95%CI, 1.30-2.66) for androgen deprivation therapy users and nonusers, respectively. In addition, the multivariable Cox regression indicated that the hazard ratio (HR) of heart failure among androgen deprivation therapy users was 1.72 (95%CI, 1.08-2.73) compared with those androgen deprivation therapy nonusers. In the propensity score-matched cohort study, the adjusted HR for heart failure among androgen deprivation therapy users was 1.92 (95%CI, 1.15-3.18) compared with propensity score-matched nonusers. In conclusion, this study found that androgen deprivation therapy users had a higher risk of heart failure than nonusers among prostate cancer patients in both the full cohort study and the propensity score-matched study.

Association of androgen deprivation therapy with thromboembolic events in patients with prostate cancer: a systematic review and meta-analysis.

Whether androgen deprivation therapy (ADT) causes excess thromboembolic events (TEs) in men with prostate cancer (PCa) remains controversial and is the subject of the US Food and Drug Administration safety warning. This study aims to perform a systematic review and meta-analysis on previous studies to determine whether ADT is associated with TEs in men with PCa. Medline, Embase, and Cochrane Library databases were searched for relevant studies. These studies comprised those that compared ADT versus control to treat PCa, reported TEs as outcome, and were published before January 2018. Multivariate adjusted hazard ratios (HRs) and associated 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. Five retrospective population-based cohort studies involving 170,851 ADT users and 256,704 non-ADT users were identified. Deep venous thrombosis (DVT) was found significantly associated with gonadotropin-releasing hormone (GnRH) agonists alone (HR = 1.47, 95% CI: 1.07-2.03; P = 0.017; I2 = 96.3%), GnRH agonists plus oral antiandrogen (AA) (HR = 2.55, 95% CI: 2.21-2.94; P < 0.001; I2 = 0.0%), and AA alone (HR = 1.49, 95% CI: 1.13-1.96; P = 0.004; I2 = 0.0%), but not with orchiectomy (HR = 1.80, 95% CI: 0.93-3.47; P = 0.079; I2 = 94.8%). In addition, pulmonary embolism (PE) was significantly associated with GnRH agonists alone (HR = 2.26, 95% CI: 1.78-2.86; P < 0.001; I2 was unavailable) and orchiectomy (HR = 2.12, 95% CI: 1.44-3.11; P < 0.001; I2 = 57.2%). This relationship was also supported with subgroup analyses based on different continents and races. GnRH agonists alone, GnRH plus AA, and AA alone cause excess DVT in men with PCa after controlling the demographic and disease characteristics and other confounding factors, although statistically significant difference was not observed in orchiectomy group. Additionally, GnRH agonists alone and orchiectomy can increase the incidence of PE.

MP52-15 ANDROGEN DEPRIVATION THERAPY AND SUBSEQUENT HEMATOLOGIC DISORDERS IN 17,168 PATIENTS WITH PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) III1 Apr 2018MP52-15 ANDROGEN DEPRIVATION THERAPY AND SUBSEQUENT HEMATOLOGIC DISORDERS IN 17,168 PATIENTS WITH PROSTATE CANCER Jui-Ming Liu, Heng-Chang Chuang, Chun-Te Wu, Yu-Li Su, and Ren-Jun Hsu Jui-Ming LiuJui-Ming Liu More articles by this author , Heng-Chang ChuangHeng-Chang Chuang More articles by this author , Chun-Te WuChun-Te Wu More articles by this author , Yu-Li SuYu-Li Su More articles by this author , and Ren-Jun HsuRen-Jun Hsu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1666AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Androgen deprivation therapy (ADT) has been the mainstay treatment for advanced prostate cancer (PCa). Various ADT adverse effects have been reported. However, studies in subsequent hematologic disorders of ADT were limited. METHODS A population-based nationwide cohort study of 17,168 patients newly diagnosed with PCa between 1996 and 2013 was identified from the Taiwan National Health Insurance Research Database. According to different therapeutic approaches, patients were classified as receiving ADT, radiotherapy(RT), and radical prostatectomy(RP). Study outcomes were hematologic disorders including anemia and hematologic malignancies. We used propensity score–matched analysis, Cox proportional hazards models, and Kaplan-Meier curves to investigate the risk of subsequent hematologic disorders of ADT. RESULTS Of the 17,168 selected patients with PCa, 13,318 patients were met all inclusion and exclusion criteria, with 8,122 receiving ADT, 1,797 receiving RT, and 3,399 receiving RP, respectively. After propensity score matching, there were 1,797 ADT users, 1,797 receiving RT, and 1,797 receiving RP in the study cohort with a mean follow-up period of 5.36 years. Compared to patients with RP, ADT group and RT group were statistically increased risk of subsequent hematologic disorders (ADT: adjusted hazard ratio (aHR) 1.71, 95%CI 1.41-2.08; RT: aHR 2.08,95%CI 1.71-2.51) after Cox proportional hazards models (Table 1). Kaplan-Meier curves with higher to lower cumulative probability of remaining hematologic disorders–free were RP , ADT without bone metastasis, RT, and ADT with bone metastasis (Figure 1). CONCLUSIONS ADT use in patients with PCa may increase the risk of subsequent hematologic disorders. Further studies are warranted to investigate between ADT and hematologic disorders. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e700-e701 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Jui-Ming Liu More articles by this author Heng-Chang Chuang More articles by this author Chun-Te Wu More articles by this author Yu-Li Su More articles by this author Ren-Jun Hsu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Androgen deprivation therapy in the treatment of prostate cancer and dementia risk: A systematic review and meta-analysis.

5044 Background: Androgen deprivation therapy (ADT) to treat prostate cancer may be associated with an increased risk of dementia, but existing studies have shown conflicting results. Here we conduct a systematic review and meta-analysis on the association of ADT in the treatment of prostate cancer with the risk of dementia. Methods: We conducted a systematic review of articles reporting the outcome of dementia among individuals with prostate cancer in those exposed to ADT versus a lesser-exposed comparison group (e.g. no ADT, intermittent ADT) using the PRISMA statement guidelines. Two authors independently carried out searches in PubMed (1966–present), Web of Science (1945–present), Embase (1966–present), and PsycINFO (1806–present). The search was undertaken December 4th, 2016. We assessed the validity of each study per the Newcastle-Ottawa Scale criteria. We meta-analyzed studies reporting an effect estimate and controlling for confounding.Random- or fixed-effects meta-analytic models were used in the presence or absence of heterogeneity, respectively, per the I2statistic. Small study effects were evaluated using Egger and Begg’s tests. Results: Nine studies were included in the systematic review. Seven studies reported an adjusted effect estimate for dementia risk. A random-effects meta-analysis of studies reporting any dementia outcome, which included 50,541 individuals, showed an increased risk of dementia among ADT users (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.08–2.00; p = 0.02). We separately meta-analyzed studies reporting all-cause dementia (HR, 1.46; 95% CI, 1.05–2.02; p &lt; 0.001) and Alzheimer’s disease (HR, 1.25; 95% CI, 0.99–1.57; p = 0.06). The I2statistic to evaluate the proportion of heterogeneity due to study variation was 76% (95% CI, 47–89; p &lt; 0.001) for the primary analysis. There was no evidence of bias from small study effects (Egger, p = 0.19; Begg, p = 1.00). Conclusions: The currently available combined evidence suggests that ADT in the treatment of prostate cancer may be associated with an increased risk of dementia. The potential for neurocognitive deficits secondary to ADT should be discussed with patients and evaluated prospectively.

Androgen deprivation therapy and cardiovascular risk: No meaningful difference between GnRH antagonist and agonists—a nationwide population-based cohort study based on 2010–2013 French Health Insurance data

BackgroundObservational studies suggested that androgen deprivation therapy (ADT) is associated with an increased cardiovascular (CV) risk. They all compared ADT-treated cancer patients to non-treated patients or non-cancer subjects. Our aim was to evaluate whether CV risk differs by type of ADT. MethodsThrough nationwide population-based claims reimbursement database linked to hospital discharge database, we identified adult men with prostate cancer who initiated ADT (gonadotrophin releasing hormone [GnRH] agonist or antagonist, antiandrogen [AA], combined androgen blockade [CAB]) or had orchiectomy (OT) between 1st July, 2010, and the 31st December, 2011, and followed them up to 31st December, 2013. The main analysis followed an ‘on-treatment’ approach that censored all patients at the time of first therapeutic modification; it used Cox regression analysis to estimate hazard ratios (HRs) for hospitalisations for ischaemic events (myocardial infarction or ischaemic stroke, whichever came first), adjusted on age, baseline co-morbidities and taking into account death as a competing risk. ResultsAmong the 35,118 new ADT users, 71% received GnRH agonist (reference group), 12% CAB, 13% AA, 3.6% GnRH antagonist and 0.6% had OT. CAB was associated with an increased risk (adjusted HR [95% confidence interval {CI}], 1.6 [1.3–2.0]) and AA with a decreased risk (adjusted HR [95% CI], 0.6 [0.4–0.9]) of ischaemic events when compared to GnRH agonist. No significant association was found with GnRH antagonist (adjusted HR [95% CI], 1.2 (0.7–2.1)). ConclusionCV risk appeared different across ADT modalities. The probability of a clinically meaningful difference when comparing GnRH antagonists to agonists appears rather low. In a context where better overall and cancer specific survival without worsening quality of life is a challenge for clinicians, a potential heterogeneity in CV morbidity becomes crucial when choosing an ADT.

PD37-03 ANDROGEN DEPRIVATION THERAPY AND THE INCIDENCE OF AUTOIMMUNE DISEASES IN 17,168 PATIENTS WITH PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) II1 Apr 2017PD37-03 ANDROGEN DEPRIVATION THERAPY AND THE INCIDENCE OF AUTOIMMUNE DISEASES IN 17,168 PATIENTS WITH PROSTATE CANCER Jui-Ming Liu, Heng-Chang Chuang, Chun-Te Wu, and Ren-Jun Hsu Jui-Ming LiuJui-Ming Liu More articles by this author , Heng-Chang ChuangHeng-Chang Chuang More articles by this author , Chun-Te WuChun-Te Wu More articles by this author , and Ren-Jun HsuRen-Jun Hsu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1565AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Androgen deprivation therapy (ADT) has been the mainstay treatment for advanced prostate cancer for more than seven decades. However, the relationship between ADT and the incidence of autoimmune diseases remains unclear. METHODS A population-based nationwide cohort study of 17,168 patients diagnosed with prostate cancer between 1996 and 2013 was identified from the Taiwan National Health Insurance Research Database (NHIRD). Incident autoimmune diseases were ascertained at least 180 days after prostate cancer diagnosis. We used 1:1 propensity score–matched analysis ,multivariable-adjusted Cox proportional hazards models to investigate the association between ADT use and the risk of autoimmune diseases RESULTS Of the 17,168 selected prostate cancer patients, 16,379 patients were met our inclusion and exclusion criteria, with 7,025 receiving ADT and 9,354 were no-ADT users. After 1:1 propensity score matching, there were 5,590 ADT users and 5,590 non-ADT users in the study cohort. During a mean follow-up period of 5.1 years, 457 patients were newly diagnosed with autoimmune diseases with 155 among ADT users and 302 among non-ADT users. Kaplan-Meier curves demonstrated a higher cumulative probability of remaining autoimmune diseases-free among ADT users (Figure 1). Compared to non-ADT users, ADT group was statistically associated with a decreased risk of autoimmune diseases (adjusted hazard ratio (HR) 0.63, 95%CI 0.52-0.76) after Cox proportional hazards models. More specially, ADT users had a decreased risk of Graves' disease (aHR 0.46, 95%CI 0.23-0.91), psoriasis (aHR 0.53, 95%CI 0.29-0.97), type 1 diabetes (aHR 0.33, 95%CI 0.17-0.63), and uveitis (aHR 0.51, 95%CI 0.26-0.97) (Table 1). CONCLUSIONS The result of this study indicated that ADT use in patients with prostate cancer may decrease the risk of autoimmune diseases, especially in Graves' disease, psoriasis, type 1 diabetes, and uveitis. Further studies are warranted to further investigation to obtain a better understanding between ADT and autoimmune diseases. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e674-e675 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Jui-Ming Liu More articles by this author Heng-Chang Chuang More articles by this author Chun-Te Wu More articles by this author Ren-Jun Hsu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP57-11 ANDROGEN-DEPRIVATION THERAPY AND CARDIOVASCULAR RISK (ADTCR): A NATIONWIDE POPULATION-BASED COHORT STUDY

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) IV1 Apr 2017MP57-11 ANDROGEN-DEPRIVATION THERAPY AND CARDIOVASCULAR RISK (ADTCR): A NATIONWIDE POPULATION-BASED COHORT STUDY Lucie-Marie SCAILTEUX, Sébastien VINCENDEAU, Frédéric BALUSSON, Christophe LECLERCQ, André HAPPE, Béranger LE NAUTOUT, Elisabeth POLARD, Emmanuel NOWAK, and Emmanuel OGER Lucie-Marie SCAILTEUXLucie-Marie SCAILTEUX More articles by this author , Sébastien VINCENDEAUSébastien VINCENDEAU More articles by this author , Frédéric BALUSSONFrédéric BALUSSON More articles by this author , Christophe LECLERCQChristophe LECLERCQ More articles by this author , André HAPPEAndré HAPPE More articles by this author , Béranger LE NAUTOUTBéranger LE NAUTOUT More articles by this author , Elisabeth POLARDElisabeth POLARD More articles by this author , Emmanuel NOWAKEmmanuel NOWAK More articles by this author , and Emmanuel OGEREmmanuel OGER More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1785AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Background. Observational studies suggested that androgen deprivation therapy (ADT) is associated with an increased cardiovascular (CV) risk. They all compared ADT-treated cancer patients to non-treated patients or non-cancer subjects and there has not been to date a single trial with CV harm as a primary end point. Objective. To evaluate whether CV risk differs by type of ADT. METHODS Design. Through nationwide population-based claims reimbursement database linked to hospital discharge database, we identified adult men with prostate cancer who initiated ADT (GnRH agonist or antagonist, antiandrogen [AA], combined androgen blockade [CAB]) or had orchiectomy (OT) between 1st July 2010 and the 31st December 2011, and followed them up to 31st December 2013. Outcome measurements and statistical analysis. The main analysis followed an ‘on-treatment’ approach that censored all patients at the time of first therapeutic modification; it used Cox regression analysis to estimate hazard ratios (HR) for hospitalizations for ischemic events (myocardial infarction or ischemic stroke, whichever came first), adjusted on age, baseline co-morbidities and taking into account death as a competing risk. RESULTS Among the 35 118 new ADT users, 70.8% received GnRH agonist (reference group), 12.1 % CAB, 13.0 % AA, 3.6 % GnRH antagonist and 0.6 % had OT. During a median follow-up of 972 days, we observed 5 258 (15.0 %) overall death in a median time of 525 days. Through the ‘on-treatment’ approach, 472 ischemic events were eligible: 213 MI and 259 strokes. CAB was associated with an increased risk (adjusted HR [95%CI], 1.60 [1.27-2.03]) and AA with a decreased risk (adjusted HR [95%CI], 0.61 [0.43-0.88]) of ischemic events when compared to GnRH agonist. No significant association was found with GnRH antagonist (adjusted HR [95%], 1.20 (0.67-2.14)). Residual confounding might exist as CV risk factors have been under-estimated though non-differentially. CONCLUSIONS CV risk appeared different across ADT modalities and had to be taking into account as regard oncologic benefit of each modality. The probability of a clinically meaningful difference when comparing GnRH antagonists to agonists appears rather low. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e767-e768 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Lucie-Marie SCAILTEUX More articles by this author Sébastien VINCENDEAU More articles by this author Frédéric BALUSSON More articles by this author Christophe LECLERCQ More articles by this author André HAPPE More articles by this author Béranger LE NAUTOUT More articles by this author Elisabeth POLARD More articles by this author Emmanuel NOWAK More articles by this author Emmanuel OGER More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Androgen deprivation therapy for prostate cancer and dementia risk: a systematic review and meta-analysis.

Androgen deprivation therapy (ADT) to treat prostate cancer may be associated with an increased risk of dementia, but existing studies have shown conflicting results. Here we synthesize the literature on the association of ADT for the treatment of prostate cancer with dementia risk. We conducted a systematic review of articles reporting the outcome of dementia among individuals with prostate cancer in those exposed to ADT versus a lesser-exposed comparison group (for example, ADT versus no-ADT; continuous versus intermittent ADT) using PubMed (1966-present), Web of Science (1945-present), Embase (1966-present) and PsycINFO (1806-present). The search was undertaken on 4 December 2016 by two authors. We meta-analyzed studies reporting an effect estimate and controlling for confounding. Random- or fixed-effects meta-analytic models were used in the presence or absence of heterogeneity per the I2 statistic, respectively. Small study effects were evaluated using Egger and Begg's tests. Nine studies were included in the systematic review. Seven studies reported an adjusted effect estimate for dementia risk. A random-effects meta-analysis of studies reporting any dementia outcome, which included 50 541 individuals, showed an increased risk of dementia among ADT users (hazard ratio (HR), 1.47; 95% confidence interval (CI), 1.08-2.00; P=0.02). We separately meta-analyzed studies reporting all-cause dementia (HR, 1.46; 95% CI, 1.05-2.02; P<0.001) and Alzheimer's disease (HR, 1.25; 95% CI, 0.99-1.57; P=0.06). There was no evidence of bias from small study effects (Egger, P=0.19; Begg, P=1.00). The currently available combined evidence suggests that ADT in the treatment of prostate cancer may be associated with an increased dementia risk. The potential for neurocognitive deficits secondary to ADT should be discussed with patients and evaluated prospectively.

Falls and Frailty in Prostate Cancer Survivors: Current, Past, and Never Users of Androgen Deprivation Therapy.

To compare the prevalence of and association between falls and frailty of prostate cancer survivors (PCSs) who were current, past or never users of androgen deprivation therapy (ADT). Cross-sectional. Mail and electronic survey. PCSs (N = 280; mean age 72 ± 8). Cancer history, falls, and frailty status (robust, prefrail, frail) using traditionally defined and obese phenotypes. Current (37%) or past (34%) ADT users were more than twice as likely to have fallen in the previous year as never users (15%) (P = .002). ADT users had twice as many recurrent falls (P < .001) and more fall-related injuries than unexposed men (P = .01). Current (43%) or past (40%) ADT users were more likely to be classified as prefrail or frail than never users (15%) (P < .001), and the prevalence of combined obese frailty + prefrailty was even greater in current (59%) or past (62%) ADT users than never users (25%) (P < .001). Traditional and obese frailty significantly increased the likelihood of reporting falls in the previous year (odds ratio (OR) = 2.15, 95% CI = 1.18-3.94 and OR = 2.97, 95% CI = 1.62-5.58, respectively) and was also associated with greater risk of recurrent falls (OR = 3.10, 95% CI = 1.48-6.5 and OR = 3.99, 95% CI = 1.79-8.89, respectively). Current and past exposure to ADT is linked to higher risk of falls and frailty than no treatment. PCSs should be appropriately counseled on fall prevention strategies, and approaches to reduce frailty should be considered.

Androgen deprivation therapy and the risk of parkinsonism in men with prostate cancer.

Case reports and anecdotal experiences suggest that some men develop parkinsonism after initiating androgen deprivation therapy (ADT) for the treatment of prostate cancer, possibly due to neurophysiological effects of changes in testosterone and/or estrogen. We hypothesized that ADT would increase the risk of parkinsonism. Using linked administrative databases in Ontario, Canada, men age 40 or older with prostate cancer on continuous ADT for at least 6months or who underwent bilateral orchiectomy (n = 38,931) were matched 1:1 with men with prostate cancer who had never received ADT. Treated and untreated groups were range-matched on age at index date and year of diagnosis, and propensity-matched on comorbidities, medications, cardiovascular risk factors, and socio-economic variables. A competing risk analysis was conducted where the primary outcome was time to a new diagnosis of parkinsonism. The cohort was followed for a mean of 5.76 years. Based on the results from the multivariable cause-specific hazard regression model, the adjusted relative rate of experiencing parkinsonism among ADT users compared to non-users was 0.74 (95% confidence interval (CI) 0.67-0.83, p < 0.0001). The adjusted relative rate of experiencing the competing event of death among ADT users compared to non-users was 1.33 (95% CI 1.30-1.36, p < 0.0001). The 5-year incidence of parkinsonism was 1.03% in ADT users versus 1.56% in non-users. Contrary to our hypothesis, continuous ADT use for at least 6 months in men with prostate cancer was not associated with an increased risk of parkinsonism after accounting for the substantial competing risk of death.