Androgen Deprivation Therapy For Prostate Cancer Research Articles

Changes in plasma metabolomic profiles during the first 3 months of androgen-deprivation therapy for prostate cancer.

116 Background: Androgen-deprivation therapy (ADT) with a GnRH agonist is the foundational systemic therapy for prostate cancer but causes gain of fat mass, loss of muscle mass, adverse changes in serum lipid profile, and a decline in insulin sensitivity. It is unknown whether ADT causes a broader pattern of metabolic alterations. In order to better characterize the metabolic effects of ADT, we measured changes in plasma metabolomic profile during the first 3 months of ADT. Methods: Fasting plasma samples were drawn from 36 subjects at baseline and after 3 months (range: 71-112 days) of GnRH agonist therapy. Metabolomic analyses were performed by Metabolon, Inc (Durham, NC). Extracted samples were split into equal parts for analysis on the gas chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry platforms. Matched pairs t-test was used to identify biochemicals that differed between baseline and month 3. Results: Of the 504 identified metabolites, 88 changed significantly (p<0.05) from baseline to 3 months. Consistent changes in biochemicals were grouped as follows: (a) Multiple steroids were lower at 3 months, consistent with the effect of therapy on gonadal androgen synthesis. (b) Markers of lipid beta-oxidation (acetyl-carnitines and ketone bodies) and omega-oxidation were lower at 3 months. (c) Two previously-identified biomarkers of insulin resistance (2-hydroxybutyrate and branch chain keto-acid dehydrogenase complex products) were lower at 3 months. (d) Most bile acids and their metabolites were higher during treatment. Cholesterol levels changed very little (1.06 fold change, P = 0.029). Conclusions: Unbiased metabolomic analyses on fasting plasma samples from men receiving GnRH agonist therapy revealed expected, unexpected, and novel results. Steroid levels fell, consistent with the effects of ADT. Biomarkers of lipid metabolism and insulin resistance also fell, unexpected results given that ADT has previously been shown to decrease insulin sensitivity. Finally, we observed evidence of increased levels of bile acids and bile acid metabolites. Further investigation of this novel finding is warranted.

Androgen-Deprivation Therapy for Nonmetastatic Prostate Cancer Is Associated With an Increased Risk of Peripheral Arterial Disease and Venous Thromboembolism

BackgroundPrevious studies demonstrate that androgen-deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists and orchiectomy for prostate cancer (PCa) is associated with cardiovascular disease. However, few studies have examined its effect on the peripheral vascular system. ObjectiveTo study the risk of peripheral artery disease (PAD) and venous thromboembolism associated with ADT for PCa. Design, settings, and participantsThis was a population-based observational study of 182 757 US men ≥66 yr of age who were diagnosed with nonmetastatic PCa from 1992 to 2007, with a median follow-up of 5.1 yr, of whom 47.8% received GnRH agonists and 2.2% orchiectomy. MeasurementsWe used Cox proportional hazards models with time-varying treatment variables to adjust for demographic and tumor characteristics in assessing whether treatment with GnRH agonists or orchiectomy were associated with PAD and/or venous thromboembolism. Results and limitationsGnRH agonist use was associated with an increased risk of incident PAD (adjusted hazard ratio [HR]: 1.16; 95% confidence interval [CI], 1.12–1.21) and incident venous thromboembolism (adjusted HR: 1.10; 95% CI, 1.04–1.15). In addition, orchiectomy was associated with an increased risk of peripheral arterial disease (adjusted HR: 1.13; 95% CI, 1.02–1.26) and venous thromboembolism (adjusted HR: 1.27; 95% CI, 1.11–1.45). Limitations include the observational study design and the inability to assess the use of oral antiandrogens. ConclusionsADT for nonmetastatic PCa is associated with an increased risk of PAD and venous thromboembolism. Additional research is needed to better understand the potential risks and benefits of ADT, so that this treatment can be targeted to patients for whom the benefits are clearest.

Vitamin D receptor gene variants and clinical outcomes after androgen-deprivation therapy for prostate cancer

Molecular epidemiology studies have shown that vitamin D receptor (VDR) gene polymorphisms are associated with prostate cancer risk. However, the prognostic value of these polymorphisms on clinical outcomes in prostate cancer patients receiving androgen-deprivation therapy (ADT) has not been determined. We evaluated the association of five common VDR polymorphisms, ApaI, Tru9I, BsmI, FokI, and Cdx2, with clinicopathologic characteristics and clinical outcomes, including disease progression, prostate cancer-specific mortality, and all-cause mortality, in a cohort of 601 prostate cancer patients treated with ADT. Of the five VDR polymorphisms, FokI rs2228570 and BsmI rs1544410 were associated with Gleason score at diagnosis (P=0.043) and prostate-specific antigen nadir following ADT (P=0.023), respectively. The haplotype analysis revealed that the A-A-G (ApaI-Tru9I-BsmI) compared with C-G-G individuals were more likely to have high Gleason score (P=0.050). However, none of these polymorphisms were significantly associated with disease progression and mortality after ADT. This is the largest study to date investigating the association of VDR polymorphisms and clinical outcomes in prostate cancer patients receiving ADT. Polymorphisms in the VDR gene might be associated with Gleason score, but these polymorphisms had no main effect on predicting response to ADT.

Early prediction of response to radiotherapy and androgen-deprivation therapy in prostate cancer by repeated functional MRI: a preclinical study

BackgroundIn modern cancer medicine, morphological magnetic resonance imaging (MRI) is routinely used in diagnostics, treatment planning and assessment of therapeutic efficacy. During the past decade, functional imaging techniques like diffusion-weighted (DW) MRI and dynamic contrast-enhanced (DCE) MRI have increasingly been included into imaging protocols, allowing extraction of intratumoral information of underlying vascular, molecular and physiological mechanisms, not available in morphological images. Separately, pre-treatment and early changes in functional parameters obtained from DWMRI and DCEMRI have shown potential in predicting therapy response. We hypothesized that the combination of several functional parameters increased the predictive power.MethodsWe challenged this hypothesis by using an artificial neural network (ANN) approach, exploiting nonlinear relationships between individual variables, which is particularly suitable in treatment response prediction involving complex cancer data. A clinical scenario was elicited by using 32 mice with human prostate carcinoma xenografts receiving combinations of androgen-deprivation therapy and/or radiotherapy. Pre-radiation and on days 1 and 9 following radiation three repeated DWMRI and DCEMRI acquisitions enabled derivation of the apparent diffusion coefficient (ADC) and the vascular biomarker Ktrans, which together with tumor volumes and the established biomarker prostate-specific antigen (PSA), were used as inputs to a back propagation neural network, independently and combined, in order to explore their feasibility of predicting individual treatment response measured as 30 days post-RT tumor volumes.ResultsADC, volumes and PSA as inputs to the model revealed a correlation coefficient of 0.54 (p < 0.001) between predicted and measured treatment response, while Ktrans, volumes and PSA gave a correlation coefficient of 0.66 (p < 0.001). The combination of all parameters (ADC, Ktrans, volumes, PSA) successfully predicted treatment response with a correlation coefficient of 0.85 (p < 0.001).ConclusionsWe have in a preclinical investigation showed that the combination of early changes in several functional MRI parameters provides additional information about therapy response. If such an approach could be clinically validated, it may become a tool to help identifying non-responding patients early in treatment, allowing these patients to be considered for alternative treatment strategies, and, thus, providing a contribution to the development of individualized cancer therapy.

SLCO2B1 and SLCO1B3 May Determine Time to Progression for Patients Receiving Androgen Deprivation Therapy for Prostate Cancer

Androgen deprivation therapy (ADT), an important treatment for advanced prostate cancer, is highly variable in its effectiveness. We hypothesized that genetic variants of androgen transporter genes, SLCO2B1 and SLCO1B3, may determine time to progression on ADT. A cohort of 538 patients with prostate cancer treated with ADT was genotyped for SLCO2B1 and SLCO1B3 single nucleotide polymorphisms (SNP). The biologic function of a SLCO2B1 coding SNP in transporting androgen was examined through biochemical assays. Three SNPs in SLCO2B1 were associated with time to progression (TTP) on ADT (P < .05). The differences in median TTP for each of these polymorphisms were about 10 months. The SLCO2B1 genotype, which allows more efficient import of androgen, enhances cell growth and is associated with a shorter TTP on ADT. Patients carrying both SLCO2B1 and SLCO1B3 genotypes, which import androgens more efficiently, exhibited a median 2-year shorter TTP on ADT, demonstrating a gene-gene interaction (P(interaction) = .041). Genetic variants of SLCO2B1 and SLCO1B3 may function as pharmacogenomic determinants of resistance to ADT in prostate cancer.

Health professional awareness of treatment-related bone loss in prostate cancer.

e15099 Background: Prostate cancer is the most common male cancer. Androgen deprivation therapy (ADT) is the mainstay of treatment for metastatic disease, and is increasingly used in radical therapy. Treatment with ADT causes bone mineral density (BMD) loss, and is a significant contributor to fracture risk. Therapy with bisphosphonates, raloxifen or denosumab can impact on BMD loss. Imaging with dual energy X-ray absorptiometry (DEXA) scanning is the gold standard for the quantification of BMD. Despite the growing body of evidence supporting BMD loss secondary to ADT a screening and management consensus has not been reached in the United Kingdom. Methods: A questionnaire based study was undertaken. The aims were to investigate current practice around bone health among health professionals treating men with ADT for prostate cancer. Results: Responses from 76 urologists, 49 clinical nurse specialists (CNS) and 48 medical oncologists (of which only 12 regularly treat prostate cancer) have been evaluated to date. Of all 137 treating clinicians 127 (93%) are treating at least 20% of their patients with ADT. In total 114 (83%) do not have local guidelines for the screening and management of BMD loss. Whilst 115 (84%) do have access to DEXA scanning, 95 (69%) have not ordered a DEXA scan in the past 6 months, and 95 (69%) are ‘not confident at all’ of interpreting DEXA scan results. When asked if responders would repeat an abnormal DEXA scan at a later date only 45 (33%) responded yes, 86 (63%) did not know. Understanding of the role of lifestyle advice and therapeutic intervention was poor. When asked whether national guidelines would benefit practice 119 (87%) responded yes. Conclusions: This study shows that understanding of the importance of screening for, and management of BMD loss was poor. Further education about this important complication of treatment is required.

Dietary modification to reduce cardiovascular risk factors in patients receiving androgen-deprivation therapy for prostate cancer.

e15053 Background: Androgen-deprivation therapy (ADT) is associated with the metabolic syndrome and cardiovascular disease (unfavorable lipid profile, obesity and insulin resistance). The Mediterrean Diet (MedD), a diet high in olive oil, fruits, vegetables, nuts and whole grains, may reduce the risk of the metabolic syndrome. An 8-week MedD program was administered to assess the feasibility of intensive dietary modification in patients with prostate cancer on ADT. Methods: Men receiving androgen therapy for prostate cancer were eligible. Only men receiving ADT as adjuvant therapy, for biochemical relapse or for stable metastatic disease were eligible. Patients were instructed to increase daily consumption of extra virgin olive oil to 90mls and > 4 servings of vegetables. Poultry and seafood were limited to 8oz a day. Dietary records were maintained by patients and reviewed during week 4 and 8. Anthropometric measures and blood work was performed pre and post diet. Weight-loss goal was 5% of pre-program weight. Outcome Measures: percent weight loss (PWL), waist circumference (WC), HDL, LDL, insulin levels, fasting triglyceride level (FTG) and blood glucose (FBG). Results: 20 patients were enrolled of which 16 completed the study (2 diet noncompliant, 2 consented but did not start). No patient had symptomatic disease progression while on study. The median age was 70.9 years. PWL was 5.9%. Treatment results are summarized below (Table). Conclusions: An 8-week MedD program is associated with a reduction in central obesity and triglycerides. Increased emphasis should be placed on dietary modification to reduce cardiovascular mortality in men receiving ADT for prostate cancer. This pilot trial suggests that an eight week MedD may be able to modify dyslipidemia and abdominal obesity. Further evaluation is indicated. Baseline Post diet P value BMI (kg/m2) 32.5+/-4.2 30.5+/-3.6 <0.01 Waist (cm) 106.7+/-9.4 102.4+/-8.9 <0.01 LDL (mg/dl) 113+/-19 113+/-26 0.94 HDL (mg/dl) 46+/-11 44+/-9 0.25 FTG (mg/dl) 109+/-46 86+/-38 <0.01 Insulin (uIU/ml) 11.8+/-7.5 9.9+/-9.2 0.12 FBS (mg/dl) 108+/-11 105+/-7 0.12

Strength Training as an Intervention against the Musculoskeletal Side Effects of Prostate Cancer Treatment

Androgen deprivation therapy (ADT) is effective for slowing tumor growth in prostate cancer (PCa) patients, but results in fatigue and a reduction in muscle power, strength, and functional abilities. Black men have the highest incidence and mortality rates of PCa compared to any other racial or ethnic group, yet they are under represented in previous PCa and exercise studies. Strength training (ST) has been used previously in PCa patients to attenuate some of the side effects of ADT, however, it is unclear whether ADT prevents ST-induced gains in muscle power, a strong predictor of physical function. PURPOSE: To determine the effects of ST on muscle power, strength, fatigue resistance and physical function in black men on ADT for PCa. METHODS: 16 black men (age 58-80) with PCa on ADT were assessed at baseline for upper and lower body strength (1RM). Fatigue resistance was determined by the number of repetitions performed during the chest and leg press at 70% of 1RM before fatigue ensued. Knee extensor peak power was measured as the highest power reached at 50, 60, and 70% of 1 RM. Physical function was estimated using 3 separate walking tests, a stair climb test, and the number of chair stands completed in 30 sec. All assessments were repeated after a 12 wk full-body ST program. Changes with ST were determined using paired T-tests. Associations between improvements in muscle function (strength, power, and fatigue resistance) and physical function were analyzed via a correlation matrix. RESULTS: Knee extensor, chest, and leg press 1RM increased significantly (range 14.5 - 23.8%; all P < 0.01), as did chest and leg press endurance (65% and 149% respectively; all P < 0.001) with ST. All indices of physical function also improved significantly with ST (range 6.5 - 17.4%; all P < 0.05). Peak power significantly increased at all intensities for the right leg and at 50 and 60% for the left leg (range 8.4 - 16.5%, P < 0.05). The strongest correlations were between the changes in power and those in the 6m rapid walk (r = 0.55 - 0.70; P < 0.05). CONCLUSIONS: Despite ablation of testosterone from ADT, ST increases muscle power, strength, fatigue resistance, and physical function in black men on ADT. ST-induced improvements in muscle function are associated with faster walking times in these patients. Supported by NIH grants R21CA127784 and AG000268.

Germline CAG repeat length of the androgen receptor and time to progression in patients with prostate cancer treated with androgen deprivation therapy

• Germline CAG repeat polymorphisms in the androgen receptor (AR-CAG) have been shown to influence the activity of the AR. • The purpose of the present study was to determine if AR-CAG repeat length correlates with time to progression on androgen deprivation therapy (ADT). • Germline AR-CAG repeat lengths were determined in a cohort of 480 patients with recurrent or metastatic prostate cancer treated at a single tertiary care institution and correlated to time to progression (TTP) and overall survival. • There was no significant correlation between differences in the AR-CAG repeat lengths and TTP or overall survival in patients with prostate cancer receiving ADT. • AR-CAG repeat lengths did not significantly correlate with age, prostate-specific antigen (PSA), Gleason score or clinical stage at diagnosis. • In patients with metastatic disease, longer AR-CAG repeat lengths (>23 vs ≤23) were associated with a longer TTP on ADT, but this finding was of borderline significance (median TTP 18.3 vs 15.5 months, P = 0.09; adjusted HR = 0.76, 95% confidence interval = 0.54-1.09). • This is the largest published study to date investigating the association of germline AR-CAG repeat lengths and efficacy of ADT in prostate cancer. • Germline AR-CAG repeat lengths do not predict response to ADT.

Reimbursement Policy and Androgen-Deprivation Therapy for Prostate Cancer

Reimbursement Policy and Androgen-Deprivation Therapy for Prostate Cancer

Reimbursement policy and androgen-deprivation therapy for prostate cancer.

Reimbursement policy and androgen-deprivation therapy for prostate cancer.

Reimbursement Policy and Androgen-Deprivation Therapy for Prostate Cancer

Reimbursement Policy and Androgen-Deprivation Therapy for Prostate Cancer

Reimbursement Policy and Androgen-Deprivation Therapy for Prostate Cancer

The Medicare Modernization Act led to moderate reductions in reimbursement for androgen-deprivation therapy (ADT) for prostate cancer, starting in 2004 and followed by substantial changes in 2005. We hypothesized that these reductions would lead to decreases in the use of ADT for indications that were not evidence based. Using the Surveillance, Epidemiology, and End Results (SEER) Medicare database, we identified 54,925 men who received a diagnosis of incident prostate cancer from 2003 through 2005. We divided these men into groups according to the strength of the indication for ADT use. The use of ADT was deemed to be inappropriate as primary therapy for men with localized cancers of a low-to-moderate grade (for whom a survival benefit of such therapy was improbable), appropriate as adjuvant therapy with radiation therapy for men with locally advanced cancers (for whom a survival benefit was established), and discretionary for men receiving either primary or adjuvant therapy for localized but high-grade tumors. The proportion of men receiving ADT was calculated according to the year of diagnosis for each group. We used modified Poisson regression models to calculate the effect of the year of diagnosis on the use of ADT. The rate of inappropriate use of ADT declined substantially during the study period, from 38.7% in 2003 to 30.6% in 2004 to 25.7% in 2005 (odds ratio for ADT use in 2005 vs. 2003, 0.72; 95% confidence interval [CI], 0.65 to 0.79). There was no decrease in the appropriate use of adjuvant ADT (odds ratio, 1.01; 95% CI, 0.86 to 1.19). In cases involving discretionary use, there was a significant decline in use in 2005 but not in 2004. Changes in the Medicare reimbursement policy in 2004 and 2005 were associated with reductions in ADT use, particularly among men for whom the benefits of such therapy were unclear. (Funded by the American Cancer Society.).

Osteoprotegerin: A Biomarker With Many Faces

Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor superfamily, is a soluble decoy receptor for the osteoclast differentiation factor receptor-activator of nuclear factor κB ligand (RANKL) that inhibits interaction between RANKL and its membrane-bound receptor RANK (Figure).1 The RANKL/OPG/RANK axis has been shown to regulate bone remodeling2,3 and was more recently found to be involved in carcinogenesis as well as central thermoregulation.4,5 This system has also been linked to the development of atherosclerosis and plaque destabilization.6,7 RANKL exhibits several properties with relevance to atherogenesis, such as promotion of inflammatory responses in T cells and dendritic cells, induction of chemotactic properties in monocytes, induction of matrix metalloproteinase (MMP) activity in vascular smooth muscle cells (SMC), and RANKL has also been found to have prothrombotic properties.2,8 In observational studies, elevated circulating OPG levels have been associated with prevalence and severity of coronary artery disease, cerebrovascular disease, and peripheral vascular disease.2,8 Circulating OPG levels are increased in patients with acute coronary syndrome,9 and enhanced expression has been found within symptomatic carotid plaques.10 Elevated OPG levels have also been associated with the degree of coronary calcification in the general population as a marker of coronary atherosclerosis.11 OPG has been reported to predict survival in patients with heart failure after acute myocardial infarction,12 to predict heart failure hospitalization and mortality in patients with acute coronary syndrome,9 and to be associated with long-term mortality in patients with ischemic stroke.13 There are also a few …

Metabolic and cardiovascular risks of androgen-deprivation therapy for prostate cancer

Androgen-deprivation therapy is frequently used to treat metastatic prostate cancer and is increasingly used to treat local and regional prostate cancer. Androgen deprivation has been shown to increase central obesity and insulin resistance, and it can alter serum lipid profiles. Recent data suggest that androgen-deprivation therapy is also associated with incident diabetes and cardiovascular disease and cardiac-related mortality. Patients and physicians making decisions regarding the use of androgen-deprivation therapy should weigh the benefits and possible risks, particularly when androgen-deprivation therapy is being used for indications where benefits have not been clearly defined. They may also want to consider monitoring for possible side effects related to cardiovascular and metabolic outcomes.

Differential androgen receptor signals in different cells explain why androgen-deprivation therapy of prostate cancer fails

Prostate cancer is one of the major causes of cancer-related death in the western world. Androgen-deprivation therapy (ADT) for the suppression of androgens binding to the androgen receptor (AR) has been the norm of prostate cancer treatment. Despite early success to suppress prostate tumor growth, ADT eventually fails leading to recurrent tumor growth in a hormone-refractory manner, even though AR remains to function in hormone-refractory prostate cancer. Interestingly, some prostate cancer survivors who received androgen replacement therapy had improved quality of life without adverse effect on their cancer progression. These contrasting clinical data suggest that differential androgen/AR signals in individual cells of prostate tumors can exist in the same or different patients, and may be used to explain why ADT of prostate cancer fails. Such a hypothesis is supported by the results obtained from transgenic mice with selective knockout of AR in prostatic stromal vs epithelial cells and orthotopic transplants of various human prostate cancer cell lines with AR over-expression or knockout. These studies concluded that AR functions as a stimulator for prostate cancer proliferation and metastasis in stromal cells, as a survival factor of prostatic cancer epithelial luminal cells, and as a suppressor for prostate cancer basal intermediate cell growth and metastasis. These dual yet opposite functions of the stromal and epithelial AR may challenge the current ADT to battle prostate cancer and should be taken into consideration when developing new AR-targeting therapies in selective prostate cancer cells.

Editorial Comment

Osteoporosis or osteopenia is a potential significant and debilitating problem for patients with prostate cancer (CaP) receiving androgen deprivation therapy (ADT). The increasing use of ADT in patients with locally advanced disease in combination with radiation, patients with node positive CaP after prostatectomy, and patients with biochemical recurrence have significantly contributed to a higher incidence of osteoporosis in this population. 1 Saylor P.J. Keating N.L. Smith M.R. Prostate cancer survivorship prevention and treatment of the adverse effects of androgen deprivation therapy. J Gen Intern Med. 2009; 24: 389-394 Crossref Scopus (49) Google Scholar Osteoporosis puts patients at risk for fracture, and with a fracture the mortality rate is 12%-20% after the first year of the event. 2 Mincey B.A. Tan W.W. The management of bone loss in patients with breast or prostate cancer. Support Cancer Ther. 2004; 1: 150-156 Crossref PubMed Google Scholar Over the past few years, urologist, radiation oncologist, medical oncologist have began to recognize this problem and had screened for this side effect. Bisphosphonates had been shown in several studies to improve bone mineral density in patients who are being started on ADT; however, there are limited studies to show any direct effect on the risk of fractures. 3 Smith M.R. McGovern F.J. Zietman A.L. et al. Pamidronate to prevent bone loss during androgen deprivation therapy for prostate cancer. N Engl Med. 2001; 345: 948-955 Crossref PubMed Scopus (655) Google Scholar , 4 Smith M.R. Eastham J. Gleason D.M. et al. Randomized controlled trial of zolendronic acid to prevent bone loss in men receiving androgen deprivation for nonmetastatic prostate cancer. J Urol. 2003; 169: 2008-2012 Abstract Full Text Full Text PDF PubMed Scopus (591) Google Scholar This article highlights the most common problem: patients already on ADT who had severe osteopenia (bone mineral density [BMD]> −2) or osteoporosis and the outcome of these patients when they are treated. These are the highest risk patients who are more prone to develop skeletal events. Several studies have shown that bisphosphonates prevent decline in BMD, and more recently, Rank ligand inhibitors (denosumab) are able to decrease the incidence of fracture in CaP that are on ADT for biochemical recurrence. 5 Smith M.R. Egerdie B. Toriz N.H. et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. North Engl Edn Med. 2009; 361: 745-755 Crossref PubMed Scopus (909) Google Scholar Several issues that are brought to the forefront with ADT use include the need to screen for osteoporosis before starting any patient on ADT, need to be monitored for decrease bone loss while on treatment, necessity to treat appropriately when diagnosed with osteoporosis, and the importance of proactively prescribing physical activity and calcium with vitamin D to patients high risk of osteoporosis. The Use of Zoledronic Acid in Men Receiving Androgen Deprivation Therapy for Prostate Cancer With Severe Osteopenia or OsteoporosisUrologyVol. 75Issue 5PreviewTo study the effect of zoledronic acid on patients with pre-existing osteoporosis on androgen deprivation therapy (ADT), who are at highest risk for fracture. Zoledronic acid is a potent bisphosphonate that can prevent osteoporosis in patients with nonmetastatic (M0), prostate cancer (CaP) who are initiating ADT. The effect of zoledronic acid on patients with pre-existing osteoporosis on ADT, who are highest risk for fracture, has not been adequately studied. Full-Text PDF

The Effect Of Strength Training On Body Composition In Prostate Cancer Survivors On Adt: Preliminary Findings From A One-year Randomized, Controlled Trial

Androgen deprivation therapy (ADT) is a common treatment for prostate cancer survivors with advanced disease. Side effects of ADT are rapid bone and muscle loss and fat gain that can compromise physical function and increase the risk of comorbid conditions. PURPOSE: To present preliminary data from a recently completed randomized controlled trial of one-year of strength training (STR) versus a control program of flexibility training (FLEX) in prostate cancer survivors on ADT. METHODS: To date, 37 men completed baseline and 12 month testing and were randomized to one year of STR (N=26) or FLEX (N=11). Select measures include: Total body fat mass, total body lean mass, % body fat (%BF) and bone mineral density (BMD) at the lumbar L1-L4 spine, total hip, femoral neck, and greater trochanter. Separate 2 (group) × 2 (time) RM-ANOVAs for each outcome measure were run to examine significant group × time interactions (p<.05). RESULTS: After one year, there was a significant group × time interaction for total fat mass (p=.03; Table 1). There were no other significant differences over time between groups for remaining variables (Table 1.).TABLE 1: Changes in body composition over 12 months for STR and FLEX groups. Soft tissue changes are reported as difference in mean scores and BMD as % changeCONCLUSION: These preliminary data suggest that one year of strength training can prevent an increase in fat mass in men on ADT for prostate cancer. Definitive conclusions are precluded until the final analyses are complete. Supported by the Lance Armstrong Foundation

Androgen-Deprivation Therapy in Prostate Cancer: Clinical Evidence and Future Perspectives

Androgens are involved in the development and progression of prostate cancer even if the mechanism is not well-recognized. For this reason androgen-deprivation therapy remains a milestone for the treatment of patients with advanced and metastatic disease and, in the last years, in conjunction with radiotherapy and surgery in locally advanced tumors. Alternative options, such as intermittent deprivation suppression, seem to be promising in terms of clinical benefits and toxicity profile. However, current therapies present side effects, such as testosterone surge with consequent clinical flare-up, metabolic syndrome and hormone-resistance, which develops after a variable number of years. Novel therapies such as LH-RH antagonists and prolonged depot LH-RH analogues have been developed in order to avoid clinical flare-up and testosterone microsurges. Novel androgen synthesis inhibitors, such as abiraterone acetate and MDV3100, have been recently discovered and tested as promising hormonal second-line agents in patients with castration-resistant prostate cancer. Finally, long-term side effects from androgen deprivation, such as osteoporosis, sarcopenic obesity and cardiovascular morbidity should be carefully monitored and properly treated.

Androgen-Deprivation Therapy in Prostate Cancer and Cardiovascular Risk

Androgen-deprivation therapy (ADT) is a widely used treatment for prostate cancer. Recently, several studies have reported an association between ADT and an increased risk of cardiovascular events, including myocardial infarction and cardiovascular mortality.1–5 These reports have led to increased interest and discussion regarding the metabolic effects of ADT and its possible association with increased cardiovascular risk. In addition, likely as a result of these reports, internists, endocrinologists, and cardiologists are now being consulted regarding the evaluation and management of patients in whom ADT is being initiated. Most of these physicians are not aware of the possible effects of ADT on cardiovascular risk factors or the issues regarding ADT and cardiovascular disease. Therefore, this multidisciplinary writing group has been commissioned to review and summarize the metabolic effects of ADT, to evaluate the data regarding a possible relationship between ADT and cardiovascular events in patients with prostate cancer, and to generate suggestions regarding the evaluation and management of patients, both with and without known cardiac disease, in whom ADT is being initiated. The writing group emphasizes that the purpose of this advisory is strictly informative. This advisory should thus not be construed as dictating clinical practice or superseding the clinical judgment of physicians, and it should not be used for medicolegal purposes. Androgens, produced mainly in the testicles, stimulate prostate cancer cells to grow. Lowering androgen levels can eliminate prostate cancer cells that require androgens to survive.6 ADT reduces levels of androgens in circulation, with the goal of improving outcomes in men with prostate cancer. Gonadotropin-releasing hormone (GnRH) agonists (eg, leuprolide, goserelin, and triptorelin) currently are the most common form of ADT and have largely supplanted the use of bilateral orchiectomy. Antiandrogens (eg, flutamide and bicalutamide) are a form of prostate cancer therapy that blocks the binding of androgen to …