Role Of Androgen Deprivation Therapy Research Articles

Utility of PSMA PET Guided Metastasis-Directed Radiotherapy

Metastasis-directed radiotherapy (MDT) is becoming a mainstay in the management of oligometastatic prostate cancer (PCa), and PSMA-PET is currently the most sensitive imaging modality for PCa metastasis screening. The efficacy of MDT guided by PSMA-PET imaging has not yet been well characterized. Moreover, the optimal role of androgen deprivation therapy (ADT) in the context of MDT is not known. We sought to assess the efficacy of PSMA PET-guided MDT in patients with metastatic PCa treated with and without ADT. This is a single institutional retrospective study of patients diagnosed with metastatic prostate cancer by PSMA-PET imaging who were treated with MDT. Biochemical progression was defined as a PSA increase of ≥ 25% and ≥ 2 ng/mL if PSA was ≥ 2 ng/mL at time of initiating salvage treatment, or a PSA increase of ≥ 25% if PSA was < 2 ng/mL at time of salvage treatment. Survival analyses were performed using the Kaplan-Meier method with log-rank testing for significance. Cumulative incidence analyses were performed with Gray's testing for significance. Adverse event data were assessed per CTCAE v5 guidelines. A total of 196 PSMA PET-avid lesions from 101 patients were irradiated with stereotactic body radiotherapy (SBRT). Median time from prior definitive locoregional therapy to MDT was 6.2 years. 79 patients had hormone-sensitive PCa (HSPC) and 22 patients had castration-resistant PCa (CRPC) at time of MDT. 47 of 79 (59%) patients with HSPC received ADT along with MDT, and 20 of the 47 patients received augmented ADT. 25 of the 32 (78%) HSPC patients receiving MDT without ADT had undergone at least one prior course of ADT, and none had castrate levels of testosterone at time of MDT with a median testosterone level of 341 ng/dl. With a median follow-up of 22.4 months, 5 of 196 lesions (2.6%) demonstrated radiographic progression. 2-year cumulative incidence of progression from HSPC to CRPC was 11% in patients who received ADT at time of MDT and 35% in those who did not (P = 0.027). Median biochemical progression free survival of patients with CRPC, HSPC treated without ADT, and HSPC treated with ADT following MDT was 5.4, 7.6, and 43.9 months respectively (P<0.0001). 2-year overall survival of the abovementioned groups was 72.2%, 100%, and 97.5% respectively (P<0.001). No Grade 3-5 adverse effects were observed. MDT guided by PSMA-PET imaging is well-tolerated and delays biochemical progression in patients with CRPC and HSPC, with a greater effect observed in patients also receiving ADT.

Stereotactic Body Radiation Therapy: A Radiosurgery Society Guide to the Treatment of Localized Prostate Cancer Illustrated by Challenging Cases

Traditionally, external beam radiotherapy (EBRT) for localized prostate cancer (PCa) involved lengthy courses with low daily doses. However, advancements in radiation delivery and a better understanding of prostate radiobiology have enabled the development of shorter courses of EBRT. Ultrahypofractionated radiotherapy, administering doses greater than 5 Gy per fraction, is now considered a standard of care regimen for localized PCa, particularly for intermediate-risk disease. Stereotactic body radiotherapy (SBRT), a specific type of ultrahypofractionated radiotherapy employing advanced planning, imaging, and treatment technology to deliver in five or fewer fractions, is gaining prominence as a cost-effective, convenient, and safe alternative to longer radiotherapy courses. It is crucial to address practical considerations related to patient selection, fractionation scheme, target delineation, and planning objectives. This is especially important in challenging clinical situations where clear evidence for guidance may be lacking. The Radiosurgery Society endorses this case-based guide with the aim of providing a practical framework for delivering SBRT to the intact prostate, exemplified by two case studies. The article will explore common SBRT dose/fractionation schemes and dose constraints for organs-at-risk. Additionally, it will review existing evidence and expert opinions on topics such as SBRT dose escalation, the use of rectal spacers, the role of androgen deprivation therapy in the context of SBRT, SBRT in special patient populations (e.g., high-risk disease, large prostate, high baseline urinary symptom burdens, and inflammatory bowel disease), as well as new imaging-guidance techniques like Magnetic Resonance Imaging for SBRT delivery.

Effect of COVID-19 pandemic on vaccination and treatment pattern of prostate cancer: a comprehensive literature review, phase 2

During the COVID-19 pandemic, overall screening, diagnostics, and treatment have faced a downtrend, especially during the first wave and lockdown. Statistics showed improvements starting from the late era of the pandemic and the end of 2020. To improvise, the risk of delayed curative treatment was measured and treatment plans were amended accordingly in order to lower the number of hospital visits needed while the results were still contradictory. The protective role of androgen deprivation therapy on COVID-19 triggered many debates, but the majority of clinical studies found no significant association. Concerns about a reduced immune response to vaccination in patients with prostate cancer occurred, but additional research is needed. The pandemic added additional burdens to patients with prostate cancer and different aspects of the quality of life of patients were assessed. While we anticipate that we are reaching the end of the pandemic, it is essential to re-examine how the pandemic has changed the overall care of patients with prostate cancer and how to proceed even further.

Effect of COVID-19 pandemic on diagnosis and treatment pattern of prostate cancer: a comprehensive literature review, phase 1

Since its outbreak in late 2019, the COVID-19 pandemic has brought many changes to medical practice, including the care and management methods regarding prostate cancer. Patients with prostate cancer are exposed to high risk of infection, hospitalization, and death due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while other elements including male gender, old age, and pre-existing comorbidities increased the possibility of infection. Although patients with prostate cancer need intensive support and care, high concerns of infection resulted in delay or avoidance of medical care, especially during the initial phase of the pandemic, which led to needs of revisions in diagnostic procedures and treatment plans. Our review illustrates the changes that have occurred in prostate cancer diagnosis, treatment, and prognosis since the emergence of the COVID-19 pandemic. We further conducted a review on topics recently being highlighted which include the protective role of androgen deprivation therapy on SARS-CoV-2 infection, vaccination and immune response in patients with prostate cancer, and the outcomes of altered treatment plans. As with the many efforts in treating cancer since the outbreak of COVID-19, identifying the changes in research and clinical practice of patients with prostate cancer worldwide is essential in providing appropriate patient care in rapidly changing circumstances.

Immunosuppressive environment in response to androgen deprivation treatment in prostate cancer.

To invest the role of androgen deprivation therapy (ADT) on the tumor immune microenvironment of prostate cancer. Here we have profiled the transcriptomes of 19,227 single cells from 4 prostate tumors, including two cases who received ADT. To validated the single-cell analysis we use another group of patients receiving neoadjuvant ADT. After receiving ADT treatment, the killing effect of prostate cancer immune cells on tumors is weakened, the interaction between immune cells and tumor cells is weakened, and the proportion of immunosuppressive cells Myeloid-derived suppressor cell (MDSC) and Regulatory T cells (Treg) cells increases. Our results highlight that ADT induces immunosuppressive in the prostate tumor microenvironment. These data have important implications for combining ADT with immunotherapy.

Cardiovascular Effects of Androgen Deprivation Therapy in Prostate Cancer Patients: A Systematic Review

The purpose of this study was to investigate the relationship between androgen deprivation therapy (ADT) and cardiovascular events in men with prostate cancer. Cardiovascular disease (CVD) is a primary cause of noncancer mortality in men with prostate cancer. Surveillance, Epidemiology, and End Results (SEER) Medicare-linked data revealed that CVD was responsible for about a quarter of deaths among men with prostate cancer, with a focus on the role of ADT as a contributing cause.We performed a literature search in November 2021 utilizing search engines such as PubMed, Scopus, Science Direct, and Google Scholar. Original publications with data published between 2006 and 2020 were used in the investigation of men with prostate cancer undergoing ADT treatment with a CVD outcome. Two reviewers independently examined the content of the studies and extracted data from the final papers after they had been validated for quality using quality assessment tools. A total of 14 observational studies and two randomized controlled trials are included in this systematic review. Sample sizes in the examined publications varied from 79 to 201,797 individuals. ADT was the intervention in all of the investigations. Seven of the included studies did not identify the type of ADT utilized; instead, they compared the outcomes of individuals who got ADT against those who did not. The specific type of ADT used is mentioned in the remaining nine studies included in the systematic review. Patients who got ADT, such as gonadotropin-releasing hormone (GnRH) agonists, combination androgen blockade, surgical castration, and oral anti-androgen, are compared to those who did not receive ADT to discover who had a better prognosis.In conclusion, even though ADT has several negative metabolic side effects that increase the risk of cardiovascular toxicity, published research utilizing a variety of designs has demonstrated inconsistency in the impact of ADT on cardiovascular outcomes. While the risk of CVD should be considered when prescribing ADT, the findings suggest that it should not be considered a contraindication if the expected benefit is substantial.

Low Serum Testosterone in Men with Newly Diagnosed Androgen-Deprivation Therapy-Naïve Prostate Cancer and Its Relationship to Cardiovascular Risk Factors: A RADICAL-PC Substudy

Cardiovascular disease is a common cause of death in prostate cancer patients. Low testosterone is associated with increased cardiovascular risk in the general male population. We investigated the relationship between serum testosterone, cardiovascular disease and risk factors in androgen-deprivation therapy-naïve prostate cancer patients. We performed a cross-sectional analysis of a subgroup of 1,326 androgen-deprivation therapy-naïve men from RADICAL-PC (Role of Androgen-Deprivation Therapy In CArdiovascular Disease-A Longitudinal Prostate Cancer study) in whom serum testosterone was measured at baseline. RADICAL-PC is a prospective multicenter cohort study of men (2,565) enrolled within 1 year of prostate cancer diagnosis, or within 6 months of commencing androgen-deprivation therapy for the first time. Cardiovascular risk factors, cancer characteristics and total serum testosterone were collected at baseline. Low testosterone was defined as total serum testosterone <11 nmol/L (<320 ng/dL). A Framingham cardiovascular risk score ≥15 was considered high risk for future cardiovascular events. We performed logistic regression to calculate odds ratios for the association between testosterone and cardiovascular risk. Among 1,326 participants (median age 67 years, range 45-93), 553 (42%) had low testosterone. Low testosterone was associated with existing cardiovascular disease, diabetes, elevated hemoglobin A1c, obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension and Framingham score >15. Among patients with low testosterone, the odds ratio for high cardiovascular risk was 1.33 (1.02-1.73) after adjusting for ethnicity, education, alcohol use, cancer characteristics, physical activity and body mass index. Among androgen-deprivation therapy-naïve prostate cancer patients, low testosterone is common and associated with increased cardiovascular risk factors.

Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19

Androgen deprivation therapy (ADT) has been theorized to decrease the severity of SARS-CoV-2 infection in patients with prostate cancer owing to a potential decrease in the tissue-based expression of the SARS-CoV-2 coreceptor transmembrane protease, serine 2 (TMPRSS2). To examine whether ADT is associated with a decreased rate of 30-day mortality from SARS-CoV-2 infection among patients with prostate cancer. This cohort study analyzed patient data recorded in the COVID-19 and Cancer Consortium registry between March 17, 2020, and February 11, 2021. The consortium maintains a centralized multi-institution registry of patients with a current or past diagnosis of cancer who developed COVID-19. Data were collected and managed using REDCap software hosted at Vanderbilt University Medical Center in Nashville, Tennessee. Initially, 1228 patients aged 18 years or older with prostate cancer listed as their primary malignant neoplasm were included; 122 patients with a second malignant neoplasm, insufficient follow-up, or low-quality data were excluded. Propensity matching was performed using the nearest-neighbor method with a 1:3 ratio of treated units to control units, adjusted for age, body mass index, race and ethnicity, Eastern Cooperative Oncology Group performance status score, smoking status, comorbidities (cardiovascular, pulmonary, kidney disease, and diabetes), cancer status, baseline steroid use, COVID-19 treatment, and presence of metastatic disease. Androgen deprivation therapy use was defined as prior bilateral orchiectomy or pharmacologic ADT administered within the prior 3 months of presentation with COVID-19. The primary outcome was the rate of all-cause 30-day mortality after COVID-19 diagnosis for patients receiving ADT compared with patients not receiving ADT after propensity matching. After exclusions, 1106 patients with prostate cancer (before propensity score matching: median age, 73 years [IQR, 65-79 years]; 561 (51%) self-identified as non-Hispanic White) were included for analysis. Of these patients, 477 were included for propensity score matching (169 who received ADT and 308 who did not receive ADT). After propensity matching, there was no significant difference in the primary end point of the rate of all-cause 30-day mortality (OR, 0.77; 95% CI, 0.42-1.42). Findings from this cohort study suggest that ADT use was not associated with decreased mortality from SARS-CoV-2 infection. However, large ongoing clinical trials will provide further evidence on the role of ADT or other androgen-targeted therapies in reducing COVID-19 infection severity.

Severe acute respiratory syndrome coronavirus 2 infection in patients with prostate cancer: A critical review.

Real-world data suggest a possible interplay between androgen deprivation therapy (ADT) and susceptibility to and the severity of SARS-CoV-2 infection. As ADT is the backbone of prostate cancer treatment, various authors have evaluated different patient cohorts but the evidence provided is conflicting. The aim of this review is to assess the available publications concerning the role of ADT in preventing or reducing the severity of SARS-CoV-2 infection. After a literature search we identified four full papers, five letters, and four meeting abstracts, but these used different search methods and the quality of the evidence varied. They frequently had different endpoints, did not report the status of the prostate cancer patients and evaluated heterogeneous populations. The available data do not support the view that ADT protects against SARS-CoV-2 infection. Larger and more precise studies are warranted, considering variables that affect infection outcomes as these significantly influence the reliability of the findings.

Development and Comparability of a Short Food-Frequency Questionnaire to Assess Diet in Prostate Cancer Patients: The Role of Androgen Deprivation Therapy in CArdiovascular Disease - A Longitudinal Prostate Cancer Study (RADICAL PC) Substudy.

ABSTRACTBackgroundThere are few concise tools to evaluate dietary habits in men with prostate cancer in Canada.ObjectiveThe aim was to develop a short food-frequency questionnaire (SFFQ) in a cohort of prostate cancer patients.MethodsA total of 130 men with prostate cancer completed the SFFQ and a validated comprehensive food-frequency questionnaire (CFFQ). Both questionnaires were administered at baseline and 6 mo later.ResultsWe found good correlation between the SFFQ and the CFFQ for seafood, dairy, egg, fruits, potatoes, grains, soft drinks, and processed meat (Spearman rank correlation >0.5). Moderate correlation was found for meat, sweets, vegetables, protein, and carbohydrates (Spearman rank correlation: 0.3–0.5). We found a weaker correlation for total fat measured by SFFQ and CFFQ (Spearman rank correlation <0.3). There was adequate reproducibility during the 6-mo follow-up among all food groups and nutrients, with the exception of meat.ConclusionsOur SFFQ can be considered an appropriate tool to be used for measuring the habitual dietary intake of prostate cancer patients. This trial was registered at www.clinicaltrials.gov as NCT03127631.

Does Exist a Differential Impact of Degarelix Versus LHRH Agonists on Cardiovascular Safety? Evidences From Randomized and Real-World Studies.

The main systemic therapy for the management of hormone-sensitive prostate cancer (PC) is androgen deprivation therapy (ADT), with the use of long-acting luteinizing hormone releasing-hormone (LHRH) agonists considered the main form of ADT used in clinical practice to obtain castration in PC. The concomitant administration of antiandrogens for the first weeks could reduce the incidence of clinical effects related to the testosterone flare-up in the first injection of LHRH. On the contrary, Gonadotropin Rh (GnRH) antagonists produce a rapid decrease of testosterone levels without the initial flare-up, with degarelix commonly used in clinical practice to induce castration in PC patients. Even if no long-term data are reported in terms of survival to define a superiority of GnRH or LHRH, for oncological efficacy and PC control, data from randomized clinical trials and from real-life experiences, suggest a difference in cardiovascular risk of patients starting ADT. The age-related decline in testosterone levels may represent a factor connected to the increase of cardiovascular disease risk, however, the role of ADT in increasing CV events remains controversial. For these reasons, the aim of the paper is to synthesize the difference in cardiovascular risk between LHRH and degarelix in patients undergoing ADT. A difference in cardiovascular risk could be indeed an important parameter in the evaluation of these two forms of castration therapy. The Randomized trials analyzed in this paper sustain a possible protective role for degarelix versus LHRH agonists in reducing the rate of new CV events and interventions in the short-term period. On the contrary, real-word data are contradictory in different national experiences and are strongly conditioned by huge differences between the LHRH agonists group and the degarelix group.

The role of androgen deprivation therapy on the clinical course of COVID-19 infection in men with prostate cancer.

41 Background: TMPRSS2, a cell surface protease which is commonly upregulated in prostate cancer (PC) and regulated by androgens, is a necessary component for SARS-CoV2 cellular entry into respiratory epithelial cells. PC patients receiving ADT were reported to have a lower risk of SARS-CoV-2 infection. However, whether ADT may have an impact on the severity of COVID-19 illness in this population is poorly understood. Methods: In this study performed across 7 US medical centers, we retrospectively evaluated patients with active PC and SARS-COV-2 viral detection by PCR between 03/01/20 and 05/31/20. We collected information on demographics; medical comorbidities; medications; PC Gleason score at initial diagnosis; presence of active disease, metastases, and castration resistance; ADT use as defined by GnRH analog or antagonist within 3 months or castration levels of testosterone &lt; 50 ng/dL within 6 months of COVID-19 diagnosis, or history of bilateral orchiectomy; active non-ADT systemic therapies including, but not limited to, androgen-receptor-targeted therapies and chemotherapy; and COVID-19-related outcomes including hospitalization, supplemental oxygen use, mechanical ventilation requirement, WHO COVID-19 ordinal scale for clinical improvement, follow-up duration, and vital status. Multivariable mixed-effect logistic regression was performed to evaluate any difference in COVID-19 clinical outcomes between patients on and not on ADT. Survival analysis was done using adjusted Cox proportion-hazards regression model. All tests were two-sided at 0.05 significance level. Results: We identified 465 evaluable patients with median age of 71 (61-81) years. Median duration of follow-up was 60 (12-114.2) days. In this follow up period, there were 195 (41.9%) hospitalizations and 111 (23.9%) deaths. When adjusted for age, BMI, and PC clinical disease state, overall survival (HR 1.28 [95%CI 0.79-2.08], P = 0.32), hospitalization status (HR 1.07 [0.61-1.87], P = 0.82), supplemental oxygen use (HR 1.29 [0.77-2.17], P = 0.34), and use of mechanical ventilation (HR 1.07 [0.51-2.23], P = 0.87) were not statistically different between ADT and non-ADT cohorts. Similarly, in subgroup analysis, no statistical difference in overall survival was found between ADT and non-ADT cohorts for hospitalized patients (HR 1.42 [0.82-2.47], P = 0.21) and those receiving supplemental oxygen (HR 1.10 [0.65-1.85], P = 0.73). Conclusions: In this retrospective cohort of PC patients, use of ADT prior to COVID-19 diagnosis does not protect against severe COVID-19 illness as defined by hospitalization, supplemental oxygen use, or death. Further preclinical work in understanding TMPRSS2 expression and androgen regulation in respiratory epithelial cells is needed. As well, longer clinical follow-up and additional clinical studies inclusive of prospective data are warranted to fully address this question.

Radical prostate radiotherapy and the use of androgen deprivation in the era of risk stratification: Does real-world practice follow the evidence?

216 Background: Prostate cancer is a common condition with varied pathologies based on stage, grade and presenting PSA allowing non-metastatic cases to be risk stratified at presentation. There is an evidence base for the use of Androgen Deprivation Therapy (ADT) combined with radical radiation showing a survival benefit but with an increase in patient morbidity. Prostate cancer risk stratification can be used to guide ADT therapy duration to reduce toxicity but it is unknown how closely these guidelines are followed internationally. Methods: A cross sectional survey collecting data on 15,255 patients with prostate cancer was conducted across 5 European countries and Japan. Data was interrogated to provide real-world evidence for ADT prescribing in combination with radical radiotherapy treatment and compared against the available evidence base and international best practice guidelines. Results: 3,393 patients were included in data analysis; 53% were high risk, 35% intermediate, and 12% low risk cases. 48% of patients were ages 71-80yrs with 10% being aged over 80. Data, including proposed length of hormone treatment was available for 2,832 patients. Concordance to the evidence base was good for high- and low-risk prostate cancer patients (64% and 96% respectively) but there was more disparity in the intermediate risk group with a concordance rate of only 28%. Conclusions: The data was robust enough to be interrogated and produce meaningful results. Concordance to the evidence base was high in both high and low risk disease although there was a tendency towards over-treatment in both these groups in some of the countries included. There was significant disparity in the intermediate risk group with evidence of both over- and potential under-treatment across all countries. Any potential over treatment with ADT needs to take account of the known evidence base and the potential for bone and metabolic toxicities. The data suggests that guidelines offering greater clarity on the role of ADT in intermediate risk prostate cancer may be beneficial.

635P ARCHES - The role of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): Post hoc analyses of efficacy by baseline prostate-specific antigen (PSA) levels

635P ARCHES - The role of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): Post hoc analyses of efficacy by baseline prostate-specific antigen (PSA) levels

Does ADT benefit unfavourable intermediate risk prostate cancer patients treated with brachytherapy boost and external beam radiotherapy? A propensity-score matched analysis

PurposeTo investigate the role of androgen deprivation therapy (ADT) in unfavorable intermediate risk (UIR) prostate cancer patients treated with high-dose rate (HDR) brachytherapy (BT) boost. Material and methodsData from 326 consecutive NCCN UIR prostate cancer patients treated in a single institution from 2009 to 2016 with 15 Gy HDR-BT boost plus 37.5 Gy external beam radiotherapy (EBRT) in 15 fractions to prostate and proximal seminal vesicles were retrospectively collected. Baseline information was collected and patients receiving vs. not receiving ADT were matched using a propensity-score model. Primary endpoint was biochemical-failure-free survival (BFFS). Kaplan–Meier estimates and stratified log-rank tests (adjusting for matched design) were used to compare BFFS, castration-resistance (CRFS) and metastasis free survival (MFS) outcomes between both groups. ResultsA total of 326 patients were included in the analysis of which 52 ADT patients were matched to 104 non-ADT patients in a 1:2 ratio. Median follow-up was 3.4 years and 5.5 years for ADT and non-ADT respectively. No significant baseline differences were observed. ADT was used for a median total time of 6 months (interquartile range [IQR]: 4–6) and delivered a median time of 2.7 months (IQR: 1.7–4.3) prior to HDR-BT. BFFS was significantly improved in the ADT group (stratified log-rank: p = 0.043) with 3-year and 6-year BFFS of 98% and 90% for the ADT group and 92% and 82% for the non-ADT group, respectively. No significant differences were detected for CRFS or MFS. ConclusionShort-term ADT increased BFFS in UIR prostate cancer patients treated with HDR-BT boost plus EBRT.

PD13-10 THE PREVALENCE OF CARDIOVASCULAR DISEASE AND ITS RISK FACTORS AMONG PROSTATE CANCER PATIENTS TREATED WITH AND WITHOUT ANDROGEN DEPRIVATION

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History I (PD13)1 Apr 2020PD13-10 THE PREVALENCE OF CARDIOVASCULAR DISEASE AND ITS RISK FACTORS AMONG PROSTATE CANCER PATIENTS TREATED WITH AND WITHOUT ANDROGEN DEPRIVATION Jehonathan Pinthus*, Bobby Shayegan, Robert Siemens, Laurence Klotz, Patrick Luke, Tamim Niazi, Vincent Fradet, Yves Fradet, Emmanuelle Duceppe, Luke Lavallee, Negareh Mousavi, Robert Hamilton, Ian Brown, Joseph Chin, Darin Gopaul, Darin Gopaul, Philippe Violette, Margot Davis, Sarah Karampatos, Rajibul Mian, and Darryl Leong Jehonathan Pinthus*Jehonathan Pinthus* More articles by this author , Bobby ShayeganBobby Shayegan More articles by this author , Robert SiemensRobert Siemens More articles by this author , Laurence KlotzLaurence Klotz More articles by this author , Patrick LukePatrick Luke More articles by this author , Tamim NiaziTamim Niazi More articles by this author , Vincent FradetVincent Fradet More articles by this author , Yves FradetYves Fradet More articles by this author , Emmanuelle DuceppeEmmanuelle Duceppe More articles by this author , Luke LavalleeLuke Lavallee More articles by this author , Negareh MousaviNegareh Mousavi More articles by this author , Robert HamiltonRobert Hamilton More articles by this author , Ian BrownIan Brown More articles by this author , Joseph ChinJoseph Chin More articles by this author , Darin GopaulDarin Gopaul More articles by this author , Darin GopaulDarin Gopaul More articles by this author , Philippe ViolettePhilippe Violette More articles by this author , Margot DavisMargot Davis More articles by this author , Sarah KarampatosSarah Karampatos More articles by this author , Rajibul MianRajibul Mian More articles by this author , and Darryl LeongDarryl Leong More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000847.010AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cardiovascular disease (CVD) is the second most common cause of death in prostate cancer (PC) patients, yet the prevalence of CVD and its risk factors have been incompletely described in this population. Androgen deprivation therapy (ADT) is a risk factor for CVD. The objectives of this study were to describe the CVD characteristics and risk factors in PC patients and the relationship between CVD risk and how ADT is used in real-world practice. METHODS: RADICAL-PC (Role of Androgen Deprivation Therapy in CArdiovascular Disease – A Longitudinal Prostate Cancer Study) is an ongoing prospective cohort study. We recruited 2395 consecutive men (mean age 68 years) with newly diagnosed PC or with a plan to prescribe ADT for the first time. Cardiovascular risk was estimated by calculating Framingham risk scores. A Framingham score >17 (corresponding with a predicted 10-year CVD risk of >30%) was considered high-risk. Multivariable logistic regression was performed with ADT use as the outcome variable and CVD risk factors as the exposures of interest. RESULTS: The prevalence of known CVD for the entire cohort was 22% and 35% had a Framingham risk score >17. Most participants (58%) were current or former smokers; 16% had diabetes; 45% had hypertension and 23% had high blood pressure but had not received a diagnosis of hypertension; 31% were obese (BMI ≥30kg/m2); 24% had low levels of physical activity. There was a positive relationship between each major cardiovascular risk factor and the use of ADT. However, after adjustment for age, education, alcohol use, BMI and time from PC diagnosis to eligibility assessment, these associations were significantly attenuated. Participants in whom ADT was planned had higher Framingham risk scores than those not intending to receive ADT. This risk was abolished after adjustment for confounders. CONCLUSIONS: One in three men with PC is at high cardiovascular risk. Men receiving ADT are a priori at higher CVD risk than PC patients whose treatment strategy does not include ADT. These differences are explained by confounding factors. Source of Funding: Prostate Cancer CanadaHamilton Health Sciences Strategic Research Initiative Heart and Stroke Foundation of Canada © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e270-e270 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jehonathan Pinthus* More articles by this author Bobby Shayegan More articles by this author Robert Siemens More articles by this author Laurence Klotz More articles by this author Patrick Luke More articles by this author Tamim Niazi More articles by this author Vincent Fradet More articles by this author Yves Fradet More articles by this author Emmanuelle Duceppe More articles by this author Luke Lavallee More articles by this author Negareh Mousavi More articles by this author Robert Hamilton More articles by this author Ian Brown More articles by this author Joseph Chin More articles by this author Darin Gopaul More articles by this author Darin Gopaul More articles by this author Philippe Violette More articles by this author Margot Davis More articles by this author Sarah Karampatos More articles by this author Rajibul Mian More articles by this author Darryl Leong More articles by this author Expand All Advertisement PDF downloadLoading ...

Optimizing the role of androgen deprivation therapy in advanced prostate cancer: Challenges beyond the guidelines.

BackgroundFor specific clinical indications, androgen deprivation therapy (ADT) will induce disease prostate cancer (PC) regression, relieve symptoms and prolong survival; however, ADT has a well‐described range of side effects, which may have a detrimental effect on the patient's quality of life, necessitating additional interventions or changes in PC treatment. The risk‐benefit analysis for initiating ADT in PC patients throughout the PC disease continuum warrants review.MethodsA 14‐member panel comprised of urologic and medical oncologists were chosen for an expert review panel, to provide guidance on a more judicious use of ADT in advanced PC patients. Panel members were chosen based upon their academic and community experience and expertise in the management of PC patients. Four academic members of the panel served as group leaders; the remaining eight panel members were from Large Urology Group Practice Association practices with proven experience in leading their advanced PC clinics. The panel members were assigned to four separate working groups, and were tasked with addressing the role of ADT in specific PC settings.ResultsThis article describes the practical recommendations of an expert panel for the use of ADT throughout the PC disease continuum, as well as an algorithm summarizing the key recommendations. The target for this publication is all providers (urologists, medical oncologists, radiation oncologists, or advanced practice providers) who evaluate and manage advanced PC patients, regardless of their practice setting.ConclusionThe panel has provided recommendations for monitoring PC patients while on ADT, recognizing that PC patients will progress despite testosterone suppression and, therefore, early identification of conversion from castrate‐sensitive to castration resistance is critical. Also, the requirement to both identify and mitigate side effects of ADT as well as the importance of quality of life maintenance are essential to the optimization of patient care, especially as more combinatorial therapeutic strategies with ADT continue to emerge.

The prevalence of cardiovascular disease and its risk factors among prostate cancer patients treated with and without androgen deprivation.

364 Background: Cardiovascular disease (CVD) is the second most common cause of death in prostate cancer (PC) patients, yet the prevalence of CVD and its risk factors have been incompletely described in this population. Androgen deprivation therapy (ADT) is a risk factor for CVD. The objective of this study were to describe the CVD characteristics and risk factors in PC patients and the relationship between CVD risk and how ADT is used in real-world practice. Methods: RADICAL-PC (Role of Androgen Deprivation Therapy in CArdiovascular Disease – A Longitudinal Prostate Cancer Study) is an ongoing prospective cohort study. We recruited 2395 consecutive men (mean age 68 years) with newly diagnosed PC or with a plan to prescribe ADT for the first time. Cardiovascular risk was estimated by calculating Framingham risk scores. A Framingham score &gt;17 (corresponding with a predicted 10-year CVD risk of &gt;30%) was considered high-risk. Multivariable logistic regression was performed with ADT use as the outcome variable and CVD risk factors as the exposures of interest. Results: The prevalence of known CVD for the entire cohort was 22% and 35% had a Framingham risk score &gt;17. Most participants (58%) were current or former smokers; 16% had diabetes; 45% had hypertension and 23% had high blood pressure but had not received a diagnosis of hypertension; 31% were obese (BMI ≥30kg/m2); 24% had low levels of physical activity. There was a positive relationship between each major cardiovascular risk factor and the use of ADT. However, after adjustment for age, education, alcohol use, BMI and time from PC diagnosis to eligibility assessment, these associations were significantly attenuated. Participants in whom ADT was planned had higher Framingham risk scores than those not intending to receive ADT. This risk was abolished after adjustment for confounders. Conclusions: One in three men with PC is at high cardiovascular risk. Men receiving ADT are a priori at higher CVD risk than PC patients whose treatment strategy does not include ADT. These differences are explained by confounding factors. Clinical trial information: NCT03127631.

The Cost of Bottling It Up: Emotion Suppression as a Mediator in the Relationship Between Anger and Depression Among Men with Prostate Cancer.

BackgroundProstate cancer is a risk factor for major depressive disorder. Recent psycho-oncology research suggests a potential role for male-specific mood-related symptoms in this relationship. Gender socialisation experiences may reinforce men’s anger and emotion suppression responses in times of distress, and anger and emotion suppression may be implicated in pathways to, and maintenance of depression in prostate cancer.Patients and MethodsData were collected online from men with a self-reported diagnosis of prostate cancer (N=100; mean age 64.8 years). Respondents provided information regarding diagnosis and treatment, in addition to current experience of major depression and male-specific externalising symptoms.ResultsProstate cancer diagnosis in the last 12 months occurred for 35.4% of the sample. Elevated major depression symptoms were observed for 49% of respondents, with 14% endorsing past 2-week suicide ideation. Parallel mediation analysis (99% CIs) controlling for prostatectomy and active surveillance indicated men’s emotion suppression mediated the relationship between anger and depression symptoms (R2=0.580). Trichotimised emotion suppression scores with control variables yielded a large multivariate effect (p<0.001, partial η2=0.199). Univariate moderate-sized effects were observed for emotion suppression comparisons for symptoms of depressed mood and sleep disturbance, and a large effect observed for guilt-proneness.ConclusionFindings highlight the salience of anger in the experience of depression symptoms for men with prostate cancer. The mediating role of emotion suppression, which in turn was strongly linked to men’s feelings of guilt, suggests potential assessment and intervention targets. Future work should examine the role of androgen deprivation therapy and other treatments including active surveillance on the relationship between anger and depression in men with prostate cancer. Consideration of interventions focused on emotion processing skills in psycho-oncology settings may help reduce men’s reliance on emotion suppression as a strategy for coping with feelings of anger or guilt in the context of prostate cancer.

853P - ARCHES - The role of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): Post hoc analyses of high and low disease volume and risk groups

BackgroundENZA, a potent androgen receptor inhibitor, provides benefit in men with castration-resistant prostate cancer (CRPC). In post hoc analyses, the role of ENZA + ADT in mHSPC patients (pts) randomized within the multinational, double-blind, PBO-controlled, Phase 3 ARCHES study (NCT02677896) was determined by disease volume and risk group stratification. MethodsmHSPC pts were randomized 1:1 to ENZA (160mg/day) + ADT or PBO + ADT. The primary endpoint was radiographic progression-free survival (rPFS). Secondary endpoints included prostate-specific antigen (PSA) progression and radiographic responses, overall survival (OS), and quality of life (QoL). Analyses were completed by CHAARTED-defined disease volume and LATITUDE-defined risk groups. Results1150 pts were randomized (ENZA + ADT, n=574; PBO + ADT, n=576). Median follow-up was 14.4 months. ENZA + ADT significantly improved rPFS (hazard ratio [95% CI] 0.39 [0.30, 0.50]; p<0.0001). ENZA + ADT pts significantly benefited from prolonged rPFS in all subgroups (Table). Significant treatment benefits were observed with ENZA + ADT in several secondary clinical endpoints in the overall population and in both high and low disease volume and risk groups (Table). High QoL at baseline was maintained over time. OS data are immature. Adverse events (AEs) were reported in 85.1% of ENZA + ADT vs. 85.9% of PBO + ADT pts, with no unexpected AEs.Table853PTableOverall (n=1150)Low-volume diseasea (n=423)High-volume diseasea (n=727)Low riskb (n=556)High riskb (n=511)HR (95% CI)cPrimary endpointrPFSd0.39 (0.30, 0.50)0.25 (0.14, 0.46)0.43 (0.33, 0.57)0.42 (0.28, 0.62)0.34 (0.25, 0.47)Secondary endpointsTime to PSA progression0.19 (0.13, 0.26)0.08 (0.03, 0.20)0.22 (0.16, 0.32)0.14 (0.08, 0.25)0.21 (0.14, 0.31)Time to castration resistance0.28 (0.22, 0.36)0.18 (0.10, 0.32)0.32 (0.24, 0.41)0.27 (0.18, 0.39)0.27 (0.20, 0.37)Time to first SSE0.52 (0.33, 0.80)0.25 (0.07, 0.91)0.59 (0.37, 0.95)0.39 (0.19, 0.81)0.56 (0.32, 0.98)Time to new antineoplastic therapy0.28 (0.20, 0.40)0.39 (0.18, 0.82)0.27 (0.18, 0.40)0.28 (0.16, 0.50)0.28 (0.18, 0.43)Rate difference (95% CI)ePSA undetectable (<0.2ng/mL) rate,f %50.5 (45.3, 55.7)48.4 (39.3, 57.4)50.7 (44.5, 57.0)54.7 (47.2, 62.1)46.0 (38.5, 53.5)ORR,f %19.3 (10.4, 28.2)21.1 (5.0, 37.3)18.6 (7.9, 29.3)16.4 (2.9, 29.9)21.7 (9.8, 33.5)aDefined as per CHAARTED trial criteria; high volume is defined as the presence of visceral metastases or≥4 bone lesions with ≥1 beyond the vertebral bodies and pelvis (Sweeney et al, New Engl J Med 2014);bDefined as per LATITUDE trial criteria; high-risk patients had ≥2 of the following: Gleason score of≥8 (scale of 2–10), ≥3 bone lesions and/or the presence of measurable visceral metastasis (Fizazi et al, New Engl J Med 2017);cHR<1 favors ENZA + ADT; HR>1 favors PBO + ADT;dAssessed by ICR or death within 24 weeks of treatment discontinuation;eDifference >0 favors ENZA + ADT; difference <0 favors PBO + ADT;fOf those with detectable PSA or measurable disease at baseline, respectively. ADT=androgen deprivation therapy; CI=confidence interval; ENZA=enzalutamide; HR=hazard ratio; ICR=independent central review; PBO=placebo; PSA=prostate-specific antigen; ORR=objective response rate; OS=overall survival; QoL=quality of life; rPFS=radiographic progression free survival; SSE=symptomatic skeletal event. ConclusionsENZA + ADT treatment showed efficacy benefit across all mHSPC pts, irrespective of disease volume and risk group. Similar delays in rPFS, symptomatic skeletal events, PSA progression, castration resistance, and improvements in radiographic responses and PSA declines, with maintenance of high QoL over time, were observed. Preliminary safety analysis appears consistent with the safety profile of ENZA in previous CRPC clinical trials. Clinical trial identificationNCT02677896. Editorial acknowledgementBeatrice Vetter-Ceriotti and Lauren Smith from Complete HealthVizion, funded by the study sponsors. Legal entity responsible for the studyAstellas Pharma Inc. and Medivation LLC, a Pfizer Company, the co-developers of enzalutamide. FundingAstellas Pharma Inc. and Medivation LLC, a Pfizer Company, the co-developers of enzalutamide. DisclosureA. Stenzl: Advisory / Consultancy: Bipsen Pharma; Advisory / Consultancy: Roche; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: Alere; Advisory / Consultancy: BMS; Advisory / Consultancy: Stebatiotechnology; Research grant / Funding (self): Karl Storz AG; Research grant / Funding (self): Astellas Pharma; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Medivation; Travel / Accommodation / Expenses: Ipsen Pharma; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Aventis; Travel / Accommodation / Expenses: Curevac; Travel / Accommodation / Expenses: Ferring. R.Z. Szmulewitz: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): AbbVie; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Merck; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (self): Janssen Oncology; Advisory / Consultancy: Sanofi; Advisory / Consultancy, Research grant / Funding (self): Astellas Pharma; Advisory / Consultancy: Pfizer; Research grant / Funding (self): Incyte; Research grant / Funding (self): Macrogenics; Travel / Accommodation / Expenses: Concept Therapeutics. D.P. Petrylak: Advisory / Consultancy, Shareholder / Stockholder / Stock options: Bellicum; Shareholder / Stockholder / Stock options: Tyme; Advisory / Consultancy: Astellas Pharma; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Merck; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Ferring; Advisory / Consultancy, Research grant / Funding (institution): Johnson & Johnson; Speaker Bureau / Expert testimony: Celgene; Advisory / Consultancy, Research grant / Funding (institution): Medivation, Lilly; Advisory / Consultancy, Research grant / Funding (institution): Millineum, Dendreon, Aventis; Research grant / Funding (institution): Progenics; Advisory / Consultancy, Research grant / Funding (institution): Roche Laboratories; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Innocrin; Research grant / Funding (institution): Agensys; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Endocyte; Advisory / Consultancy, Research grant / Funding (institution): Pfizer. J. Holzbeierlein: Research grant / Funding (self): Astellas Pharma; Research grant / Funding (self): MDX Health. A. Villers: Advisory / Consultancy: Astellas France; Research grant / Funding (institution): Astellas Pharma. A.A. Azad: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas Pharma; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: Sanofi; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: Tolmar; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis. A. Alcaraz: Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Olympus; Travel / Accommodation / Expenses: Ipsen. B.Y. Alekseev: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Astellas Pharma; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ferring; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Sanofi. T. Iguchi: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Astellas Pharma; Speaker Bureau / Expert testimony: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bayer. N.D. Shore: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen Scientific Affairs; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Dendreon; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Tolmar; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Ferring; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Medivation/Astellas; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Myovant Sciences; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer. B. Rosbrook: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. B. Baron: Advisory / Consultancy, Full / Part-time employment: Astellas. G.P. Haas: Full / Part-time employment: Astellas Pharma. R. Morlock: Advisory / Consultancy: Abbott Medical Optics; Advisory / Consultancy: Ironwood; Advisory / Consultancy: Genentech; Full / Part-time employment: Astellas Pharma. K. Ramaswamy: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. A.J. Armstrong: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Dendreon; Honoraria (institution): Janssen Oncology; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Medivation; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen Biotech; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas Scientific & Medical Affairs Inc; Research grant / Funding (institution): Gilead Sciences; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Active Biotech; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Janssen.