Androgen Deprivation Therapy In Patients Research Articles

Long-Term Outcomes of a Phase I Trial of Weekly Docetaxel, Total Androgen Blockade, and Image Guided Intensity Modulated Radiation Therapy for Localized High-Risk Prostate Adenocarcinoma

PurposeOur purpose was to describe the long-term outcomes seen with the addition of concurrent weekly docetaxel to high-dose intensity modulated radiation (IMRT) to the prostate and androgen deprivation therapy in patients with high-risk nonmetastatic adenocarcinoma of the prostate. Methods and MaterialsNineteen patients with high-risk, localized prostate cancer were treated in a phase I trial with concurrent docetaxel at doses of 10 to 30 mg/m2, in a dose-escalated scheme, in addition to IMRT (77.4 Gy/43 fx) and neoadjuvant and concurrent combined androgen blockade (gonadotropin-releasing hormone agonist and antiandrogen). A gonadotropin-releasing hormone agonist was continued for an additional 24 months post radiation. Kaplan-Meier analysis was used to estimate the survival probabilities. ResultsAt a median follow-up of 10.5 years, 5-year and 10-year overall survival were found to be 89.5% and 68.4%, respectively. The median metastasis-free survival and progression-free survival were determined to be 11.3 years and 9.0 years, respectively. ConclusionsThis regimen produced a 10-year overall survival of 68% with a 10-year metastasis-free survival of 58%. Grade >2 toxicity was minimal. These limited data suggest that the addition of concurrent weekly docetaxel to high-dose IMRT for high-risk prostate cancer warrants further investigation.

Impact of Three-Month Androgen Deprivation Therapy on [68Ga]Ga-PSMA-11 PET/CT Indices in Men with Advanced Prostate Cancer-Results from a Pilot Prospective Study.

Simple SummaryPositron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA)-specific tracers is gaining traction for prostate cancer imaging. The aim of this pilot study was to evaluate PSMA PET/CT imaging response in 30 patients who had undergone three months of androgen deprivation therapy (ADT). Different imaging indices and the modified PET response criteria in solid tumors 1.0 served as outcome measures. Most patients showed a consistent reduction of PSMA PET/CT indices over three months. A total of 24 (80%) participants were partial responders. Patients in the International Society of Urological Pathology grade group 5 (n = 16) showed a less prominent reduction of the imaging indices, and none of them reached a complete response. Collectively, our data support the clinical usefulness of PSMA PET/CT imaging for monitoring treatment response after the first three months of ADT.Purpose: The purpose of this pilot prospective study is to examine the gallium-68-prostate-specific membrane antigen-11 ([68Ga]Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) imaging response in patients with advanced or metastatic hormone-naïve prostate cancer (PC) after 3 months of androgen deprivation therapy (ADT). Methods: We prospectively included men with untreated, clinical stage III or IV PC scheduled to receive ADT for at least 6 months. [68Ga]Ga-PSMA-11 PET/CT images were obtained before the start of ADT and 10–14 weeks thereafter. The following indices were examined: maximum standardized uptake value (SUVmax), mean SUV, PSMA total volume, and PSMA total lesion values of the prostate, nodes, bones, and whole-body. The therapeutic response was assessed using the modified PET response criteria in solid tumors 1.0. A subgroup analysis of patients with the International Society of Urological Pathology (ISUP) grade group 5 versus <5 was also performed. Results: A total of 30 patients were eligible. All PSMA PET/CT indices were significantly reduced (p < 0.001) after 3 months of ADT. Twenty-four (80%) patients showed partial response. Complete response, stable disease, and disease progression were observed in two patients each. Sixteen patients with ISUP grade group 5 showed a less prominent SUVmax reduction (p = 0.006), and none of them reached complete response. Conclusions: Three months of ADT in patients with untreated, advanced PC significantly reduced PSMA PET/CT indices. While most participants partially responded to ADT, patients with ISUP grade group 5 showed a less prominent SUVmax reduction. Collectively, our pilot results indicate that [68Ga]Ga-PSMA-11 PET/CT imaging holds promise to monitor treatment response after the first three months of ADT.

A randomized, controlled, phase 3 study of darolutamide in addition to androgen deprivation therapy (ADT) versus ADT alone in metastatic hormone-sensitive prostate cancer (ARANOTE).

TPS200 Background: Previous randomized, phase 3 trials have shown the efficacy of adding docetaxel, abiraterone acetate, enzalutamide, or apalutamide to ADT in improving overall survival and/or radiologic progression-free survival (rPFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). However, these combinations are associated with an increased risk of adverse events (eg, fatigue, rash, and cardiovascular events). Darolutamide is a structurally distinct and highly potent androgen receptor inhibitor. In the ARAMIS study, darolutamide has been shown to significantly reduce the risk of death by 31% and have a favorable safety profile in men with nonmetastatic castration-resistant prostate cancer. It has a low incidence of central nervous system−related adverse events, which may be explained by its distinct low blood−brain barrier penetration. Darolutamide has also been shown to have a low potential for drug−drug interactions, allowing flexibility with concomitant medications. ARANOTE will evaluate the efficacy and safety of darolutamide plus ADT in patients with mHSPC (NCT04736199). Methods: ARANOTE is an international, multicenter (ex-US), randomized, double-blind, placebo-controlled, phase 3 study in patients with histologically or cytologically confirmed adenocarcinoma of the prostate and documented metastatic disease by conventional imaging (eg, computed tomography or magnetic resonance imaging) who started ADT ≤12 weeks before randomization. In total, 555 patients will be randomized 2:1 to darolutamide 600 mg twice daily or placebo, plus ADT. Patients will be stratified by the presence of visceral metastases, assessed by central review, and prior local therapy. Patients will be evaluated every 12 weeks for efficacy, safety, and quality of life (using the FACT-P questionnaire) during treatment and active follow-up post treatment. For long-term follow-up, patients will be contacted by telephone every 12 weeks. The primary endpoint is rPFS; secondary endpoints include overall survival, time to castration-resistant prostate cancer, time to prostate-specific antigen progression, and safety. Recruitment is ongoing, and the first patient first visit was on February 23, 2021. The estimated study completion date is September 2025. Clinical trial information: NCT04736199.

Prognostic Significance of 3-Month Prostate-specific Antigen Level Following Androgen-deprivation Therapy in Metastatic Hormone-sensitive Prostate Cancer.

We examined the prognostic use of the 3-month prostate-specific antigen (PSA3m) level after androgen-deprivation therapy in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). The present study included 145 patients with mHSPC who received primary androgen-deprivation therapy. The optimal cutoff PSA3m value for prediction of 5-year overall survival was 2.56 ng/ml (area under the receiver operating characteristics curve=0.67) using a time-dependent receiver operating characteristic (survival ROC) curve. In patients with CHAARTED low-volume and LATITUDE low-risk disease, the median overall survival was longer for patients with low PSA3m than that for those with high PSA3m. Multivariate analysis revealed PSA3m (hazard ratio=1.99; p=0.006) and age ≥80 years as independent risk factors for overall survival in patients with mHSPC. PSA3m can be a useful prognostic biomarker to avoid excessive upfront combination therapy, particularly in elderly patients with low-volume and low-risk mHSPC.

Changes in Magnetic Resonance Imaging Radiomic Features in Response to Androgen Deprivation Therapy in Patients with Intermediate- and High-risk Prostate Cancer

AimsThe benefits of neoadjuvant androgen deprivation therapy (nADT) in the management of intermediate- and high-risk prostate cancer patients have been well-established. The aim of this study was to identify radiomic prognostic features derived from routine anatomic magnetic resonance imaging (MRI) sequences that can predict the response of the prostate cancer to nADT. Materials and methodsPatients with intermediate- and high-risk prostate cancer (with one of clinical stage ≥ T2c, Gleason score ≥7 or presenting prostate-specific antigen ≥10) who received 3 months of ADT prior to radical external beam radiotherapy were enrolled into this study. The relative blood volume and the relative blood flow were used as dynamic MRI kinetic parameters to quantify vascular changes as responses to nADT. For all pre- and post-nADT data sets, a combination of T2-weighted and contrast-enhanced T1-weighted anatomic images were used to define regions of interest (ROI) as the dominant malignant nodules (DMNs) and the benign prostate (the entire prostate with the summed DMNs being subtracted). MRI textural radiomic features associated with prostate cancer response in the literature of energy and homogeneity were selected. Pyradiomics was used to extract textural features of the ROIs. A Wilcoxon signed-rank test was carried out to investigate if there were statistically significant differences in values of radiomic features between: (i) benign prostate ROI and DMN pre-nADT; (ii) pre- and post-nADT of benign prostate ROI; (iii) pre- and post-nADT of DMN. Changes in radiomic features and dynamic MRI kinetic parameters were correlated using the Spearman correlation test. ResultsTwenty prostate cancer patients were recruited into the study. The median time between the first baseline scan and the first on-treatment scan was 91.5 days (range 82–105). One patient had no discernible tumour visible, leaving 19 patients with evaluable data for the analysis. Baseline homogeneity and energy values differed significantly between benign and malignant tissue (P < 0.01). In response to nADT, homogeneity and energy showed reciprocal changes, significantly increased in benign prostate while decreasing in the DMN. The reduction in tumour homogeneity and energy feature values showed a positive association with the decline in tumour blood flow and tumour blood volume induced by androgen deprivation as derived from dynamic MRI parameters. ConclusionEnergy and homogeneity radiomic features derived from MRI of benign and malignant prostate showed significant reciprocal changes in response to nADT. This study confirms the potential of these radiomic features to act as surrogate markers of tumour androgen sensitivity due to their strong association with ADT-induced physiological effects in prostate tumours.

Risk of cardiovascular intervention after androgen deprivation therapy in prostate cancer patients with a prior history of ischemic cardiovascular and cerebrovascular disease: A nationwide population-based cohort study.

Androgen deprivation therapy for prostate cancer is known to increase the risk of cardiovascular disease, but there is controversy regarding the cardiovascular risk in patients with preexisting cardiovascular disease. This study assessed the risk of cardiovascular intervention after androgen deprivation therapy in patients with a history of cardiovascular disease, cerebrovascular disease, and cardiovascular intervention. Between 2008 and 2017, 195,308 men with newly diagnosed prostate cancer were identified from the nationwide claims database in South Korea. Among them, 49,090 men with a history of ischemic cardiovascular and cerebrovascular diseases were analyzed. The patients were divided into the androgen deprivation therapy (n = 14,092) and non-androgen deprivation therapy (n = 34,988) groups. The primary outcome was cardiovascular interventions (percutaneous transluminal angioplasty and coronary bypass surgery). Cox proportional hazard regression models were used to estimate the adjusted hazard ratios and 95% confidence intervals of the events. After balancing the covariates with 1:1 exact matching, the two groups had 10,514 subjects each. Multivariable analysis demonstrated that androgen deprivation therapy was not significantly associated with an increased risk of cardiovascular interventions (hazard ratio, 1.060; 95% confidence interval, 0.923-1.217; P = 0.4104), regardless of the duration of therapy. A history of cardiovascular intervention, diabetes mellitus, antithrombotic medication use, and cardiovascular events significantly increased the risk of cardiovascular intervention. Androgen deprivation therapy was not associated with cardiovascular intervention in patients with a previous history of cardiovascular disease, regardless of the duration of therapy. Therefore, the cardiovascular risk of androgen deprivation therapy should be reassessed in this population.

A prospective phase-II trial of biweekly docetaxel plus androgen deprivation therapy in patients with previously-untreated metastatic castration-na\xefve prostate cancer

IntroductionThe aim of this prospective phase II study was to evaluate the efficacy and safety of biweekly docetaxel plus androgen-deprivation therapy (ADT) in patients with metastatic castration-naïve prostate cancer (mCNPC).Patients and methodsPatients with histologically-proven, previously-untreated mCNPC received ADT plus docetaxel, 40 mg/m2. Docetaxel was repeated every 2 weeks, up to 12 cycles. Endpoints included castration-resistant prostate cancer (CRPC)-free survival, prostate-specific antigen (PSA) response, and safety.ResultsA total of 42 patients were registered and analyzed for final outcomes. Of the 42 patients, 36 (86%) completed the 12 planned cycles of docetaxel plus ADT. During a median follow up of 25 months, all but two patients (95%) achieved a PSA response with a nadir PSA level of 0.42 ng/ml (range 0.01–1280.87). The median CRPC-free survival was 26.4 months (95% confidence interval [CI] 20.9–32.0) with a one-year CRPC-free rate of 79% (33 patients, 95% CI 66–91). Multivariable analysis revealed that the performance status of the Eastern Cooperative Oncology Group 0 was independently associated with longer CRPC-free survival (hazard ratio [HR] 0.27, 95% CI 0.07–0.99). The most common adverse events of any grade were anemia (95%), followed by nail changes (33%), fatigue (29%), and oral mucositis (26%). Severe (grade 3 or higher) adverse events were infrequent: pneumonitis (n = 2), diarrhea (n = 1), and neutropenia (n = 1).ConclusionOur results suggest that biweekly docetaxel plus ADT is feasible, and clinical efficacy does not seem to be compromised compared to a standard triweekly docetaxel 75 mg/m2 plus ADT regimen.

The Relationship Between Androgen Deprivation Therapy Duration and External Beam Radiotherapy With or Without a Brachytherapy Boost in High-Risk Prostate Cancer

The use/prolongation of androgen deprivation therapy (ADT) with external beam radiotherapy (EBRT) improves distant metastasis outcomes in patients with high-risk prostate cancer. The optimal duration of ADT when adding a brachytherapy boost (EBRT+BT) remains unknown.A total of 2935 patients who received treatment across 15 institutions between 2000-2014 were identified (1827 treated with EBRT and 1108 with EBRT+BT). Three broad ADT strata were defined: no ADT, 1-18 months ADT, and 18-36 months ADT. Fine-Gray competing risk regression models evaluating the association between differing ADT duration strata and time to distant metastasis (DM) were developed. Models were adjusted for ln (initial PSA), clinical T stage, Gleason grade group, age at treatment, treatment type, and interaction between ADT duration and treatment. A continuous, non-linear relationship between ADT duration and DM was investigated in the overall cohort and within the EBRT and EBRT+BT cohorts using a restricted cubic spline transformation with 4 knots. Splines were adjusted for the same covariates.Median follow-up was 8 years (IQR, 5-11.3 years). ADT duration was significantly greater in patients treated with EBRT (median 18 months vs. 8 months, P < 0.001). A substantial proportion of patients did not receive any ADT (26.2% and 14.9% of those undergoing EBRT and EBRT+BT, respectively). Overall, DM rates were improved with adding 1-18 months of ADT or 18-36 months of ADT versus no ADT (sHR 0.66 and 0.43, respectively). DM rates were also lower after 18-36 months vs. 1-18 months (sHR 0.64). No significant interaction between treatment type and ADT duration was seen. Based on spline analysis, the optimal durations of ADT were 26 months for the total cohort and patients receiving EBRT and 22.5 months for patients receiving EBRT+BT. However, the incremental benefit of prolonged time to DM per month ADT added appears to be more pronounced in patients receiving EBRT than in those undergoing combined EBRT+BT treatment.A clear relationship between ADT duration and DM risk following definitive radiotherapy in patients with HRPCa was seen, with durations of 18-36 months being associated with the lowest risk of DM. The lack of a significant interaction between ADT duration and treatment type implies this relationship persists even in patients receiving EBRT+BT. However, the magnitude of this benefit may differ, and prospective evidence seems warranted to determine the optimal duration of ADT in patients receiving of EBRT+BT.

Influence of androgen deprivation therapy on the severity of COVID-19 in prostate cancer patients.

BackgroundThe TMPRSS2 protein has been involved in severe acute respiratory syndrome caused by coronavirus 2 (SARS‐CoV‐2). The production is regulated by the androgen receptor (AR). It is speculated that androgen deprivation therapy (ADT) may protect patients affected by prostate cancer (PC) from SARS‐CoV‐2 infection.MethodsThis is a retrospective study of patients treated for COVID‐19 in our institution who had a previous diagnosis of PC. We analyzed the influence of exposure of ADT on the presence of severe course of COVID‐19.ResultsA total of 2280 patients were treated in our center for COVID‐19 with a worse course of disease in males (higher rates of hospitalization, intense care unit [ICU] admission, and death). Out of 1349 subjects registered in our PC database, 156 were on ADT and 1193 were not. Out of those, 61 (4.52%) PC patients suffered from COVID‐19, 11 (18.0%) belonged to the ADT group, and 50 (82.0%) to the non‐ADT group. Regarding the influence of ADT on the course of the disease, statistically significant differences were found neither in the death rate (27.3% vs. 34%; p = 0.481), nor in the presence of severe COVID‐19: need for intubation or ICU admission (0% vs. 6.3%; p = 0.561) and need for corticoid treatment, interferon beta, or tocilizumab (60% vs. 34.7%; p = 0.128). Multivariate analysis adjusted for clinically relevant comorbidities did not find that ADT was a protective factor for worse clinical evolution (risk ratio [RR] 1.08; 95% confidence interval [CI], 0.64–1.83; p = 0.77) or death (RR, 0.67; 95% CI, 0.26–1.74; p = 0.41).ConclusionsOur study confirms that COVID‐19 is more severe in men. However, the use of ADT in patients with PC was not shown to prevent the risk of severe COVID‐19.

Supervised exercise therapy compared with no exercise therapy to reverse debilitating effects of androgen deprivation therapy in patients with prostate cancer: a systematic review and meta-analysis

BackgroundAndrogen deprivation therapy (ADT) in patients with prostate cancer can have several debilitating side effects. Supervised exercise is recommended to ameliorate these negative effects.ObjectiveTo systematically evaluate the effect of supervised exercise therapy compared to no exercise therapy in patients with prostate cancer undergoing ADT, primarily according to the patient critical outcomes, ‘disease-specific quality of life’ and ‘walking performance’ measured at end of treatment.MethodsWe searched PubMed/Medline, Embase, Cochrane Library, Cinahl and Pedro, to identify randomised controlled trials (RCTs), which investigated the effect of supervised exercise therapy compared to no exercise therapy in patients with prostate cancer receiving ADT, last search: June 2021. Two independent reviewers extracted data, and assessed risk of bias using Cochrane Risk of Bias Tool and evaluated the certainty of evidence using the GRADE-method.ResultsEigthteen RCTs (n = 1477) comprised patients with prostate cancer stages T1-T4 were included in the meta-analyses. Compared to no exercise therapy, supervised exercise therapy showed clinically relevant improvements in ‘disease-specific quality of life’ and ‘walking performance’. The standardised mean differences were 0.43 (95% confidence interval (CI): 0.29, 0.58) and −0.41 (95% CI: −0.60, −0.22), respectively. The overall certainty of evidence was moderate due to serious risk of bias.ConclusionsEvidence of moderate quality shows that supervised exercise therapy probably is superior to no exercise therapy in improving ‘disease-specific quality of life’ and ‘walking performance’ in patients with prostate cancer undergoing ADT. The results apply to all patients receiving androgen deprivation therapy regardless of cancer stage. The results support a strong recommendation for supervised exercise therapy for managing side effects in this population.Protocol registrationNKR-38-Focused-questions-PICOs-for-updating1.ashx (sst.dk)

1632P At home androgen deprivation therapy for patients with prostate cancer during the COVID-19 pandemic. One center experience

COVID-19 pandemic created major challenges in cancer care. Studies have shown increased risk for COVID-19 infectivity, severe disease and death in patients with cancer. Cancer centers worldwide adapted by modifying and often delaying treatment to minimize contact with patients. To provide safe and uninterrupted care for patients, a home care program was created for patients with prostate cancer at Acad. F. Todua Medical center. Men with locally advanced or metastatic prostate cancer (MPC) receiving androgen deprivation therapy (ADT) were enrolled. Patients and their caretakers were instructed on gonadotropin-releasing hormone (GnRH) subcutaneous injections (SQ) for home administration. Monthly at home laboratory testing and virtual consultations with medical oncologists every 1-3 months were arranged. A total of 52 patients were enrolled during the period of March 2020 – March 2021. All men were White and had ECOG 0/1. The mean age was 71 [±6.3 y] years. Sixteen (31%) patients had stage IIIB PC and 36 (69%) patients had stage IV disease. Stage IIIB patients were receiving adjuvant ADT with SQ Goserelin Acetate 10,8mg every 8 weeks and bicalutamide 50mg daily for two weeks after definitive local treatment. Thirty-one (86%) patients had hormone sensitive metastatic PC and were receiving SQ Goserelin Acetate 10.8mg (28) every 8 weeks or SQ Leuprolide Acetate 22,5mg every 8 weeks (3) with 2 weeks of Bicalutamide 50mg daily. Five (14%) patients had castration resistant (CR) PC and were receiving SQ Goserelin Acetate 10,8mg every 8 weeks with Enzalutamide 160mg daily. Thirty-three (63%) patients had Gleason’s score of 8/9. All patients were compliant with home injections, laboratory tests and virtual physician visits. Thirty-nine (75%) patients administered injections by themselves. Forty-two (80%) patients had PSA reduction >50%. Ten (20%) patients had disease progression and required clinic visits for investigations. Median time to progression was 12 months. Only 1 (2%) patient acquired COVID-19 infection, was hospitalized and died of respiratory failure. At home ADT with appropriate patient/caregiver education and close follow up may be safe for patients with PC during the COVID-19 pandemic.

PD34-08 ASSOCIATION BETWEEN DISEASE INDICATION AND STEROID USE AND MINERALOCORTICOID-RELATED TOXICITY OF ABIRATERONE ACETATE IN PATIENTS WITH ADVANCED PROSTATE CANCER: A META-ANALYSIS OF RANDOMIZED CONTROL TRIALS

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) III (PD34)1 Sep 2021PD34-08 ASSOCIATION BETWEEN DISEASE INDICATION AND STEROID USE AND MINERALOCORTICOID-RELATED TOXICITY OF ABIRATERONE ACETATE IN PATIENTS WITH ADVANCED PROSTATE CANCER: A META-ANALYSIS OF RANDOMIZED CONTROL TRIALS Mary Hall, Whitney Padgett, Zachary Klaassen, Diana Magee, Aaron Laviana, Amy Luckenbaugh, Raj Satkunasivam, and Christopher Wallis Mary HallMary Hall More articles by this author , Whitney PadgettWhitney Padgett More articles by this author , Zachary KlaassenZachary Klaassen More articles by this author , Diana MageeDiana Magee More articles by this author , Aaron LavianaAaron Laviana More articles by this author , Amy LuckenbaughAmy Luckenbaugh More articles by this author , Raj SatkunasivamRaj Satkunasivam More articles by this author , and Christopher WallisChristopher Wallis More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002038.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Abiraterone acetate (AA) has proven survival benefit for patients with metastatic hormone sensitive prostate cancer (mHSPC) and metastatic castrate resistant prostate cancer (mCRPC) either before or after docetaxel chemotherapy. Due to its mechanism of action, AA requires co-administration with an oral corticosteroid. Previous randomized control trials (RCTs) have shown increased cardiac risk with AA+ androgen deprivation therapy (ADT). We compiled available evidence regarding the cardiotoxicity of AA via meta-analysis, focusing on mechanistically related side-effects and differences based on disease indication and trial design. METHODS: We performed a systematic review and meta-analysis for phase II and III RTCs of AA+ADT vs ADT for patients with prostate cancer published as of 8/11/2020. Primary outcomes were hypokalemia and fluid retention, and secondary outcomes were cardiac disorders and hypertension. We performed a meta-analysis comparing intervention and control, stratifying according to disease state (HSPC, pre-chemo mCRPC, vs post-chemo mCRPC) and trial design (steroids in the control arm). RESULTS: Among 2739 search results, 6 studies of 5,901 patients with HSPC (including mHSPC and advanced localized disease) or mCRPC were included. Treatment groups received AA 1000mg, ADT, and steroid, and controls received ADT, placebo, +/- steroid. Patients receiving AA were more likely to experience hypokalemia (17.3% vs 6.0%, p <0.001), fluid retention (24.1% vs 17.6%, p <0.001), hypertension (25.3% vs 15.1%, p <0.001), and cardiac events (25.4% vs 15.9%, p=0.002). The apparent effect of AA on these outcomes was significantly modified on the basis of whether patients in the control arm received steroid with placebo (hypokalemia: p <0.001, hypertension: p=0.01, and cardiac disorders: p <0.001) and on the basis of disease state/indication (hypokalemia: p <0.001, hypertension: p=0.03, and cardiac disorders: p=0.01). CONCLUSIONS: The magnitude of cardiovascular effects attributable to AA vary significantly by trial design and disease indication; studies in which steroids were not given to the control group demonstrate an increased attributable risk while patients receiving AA earlier in the disease process appear to have a greater magnitude of risk of several adverse events, including hypokalemia and hypertension. These hypothesis-generating data may be helpful in understanding AA toxicity and offering individualized counseling. Source of Funding: none © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e585-e586 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mary Hall More articles by this author Whitney Padgett More articles by this author Zachary Klaassen More articles by this author Diana Magee More articles by this author Aaron Laviana More articles by this author Amy Luckenbaugh More articles by this author Raj Satkunasivam More articles by this author Christopher Wallis More articles by this author Expand All Advertisement Loading ...

Factors influencing the choice of androgen deprivation therapy for patients with hormone-sensitive prostate cancer : Results of the ProComD study

HintergrundDie Androgendeprivationstherapie (ADT) mit einem GnRH-Agonisten (Gonadotropin-releasing-Hormon) oder -Antagonisten stellt einen zentralen Bestandteil der Behandlung des Prostatakarzinoms (PCa) dar. Über die Faktoren, welche die Wahl der ADT beeinflussen, ist bis jetzt wenig bekannt.Ziele der ArbeitFaktoren, welche die Wahl der ADT bei Patienten mit hormonsensitivem PCa beeinflussen, werden identifiziert. Vom Urologen zur Identifizierung von Begleiterkrankungen genutzte Informationsquellen sowie deren Prävalenzen werden bestimmt.MethodenDie zweiarmige, prospektive, nicht-interventionelle Studie „ProComD“ wurde von Sept. 2014 bis Juni 2019 an 80 Studienzentren in Deutschland durchgeführt. Patienten mit hormonnaivem PCa und Notwendigkeit einer ADT wurden nach erfolgter Therapieentscheidung in die Studie eingeschlossen. Fragen bezüglich Informationsquelle und Therapieentscheidung wurden vom Arzt direkt im elektronischen Datenerfassungssystem (eCRF) beantwortet.ErgebnisseEs wurden Daten von 413 Patienten ausgewertet (Degarelix n = 268; GnRH-Agonisten n = 145). Ausschlaggebend für die Therapieentscheidung waren für beide Behandlungsgruppen u. a. die Faktoren Komorbiditäten (bei 42 % aller Patienten), Compliance (64 %) und Alter (81 %).Die häufigste konsultierte Informationsquelle bzgl. vorhandener Komorbiditäten ist die Anamnese durch den behandelnden Urologen selbst (68,5 % in beiden Gruppen). Bei Patienten mit kardiovaskulären Vorerkrankungen wurde zusätzlich der Arztbrief (45,8 % Degarelix vs. 38,9 % GnRH-Agonisten) oder der Anamnese-Fragebogen (38,9 % Degarelix vs. 20 % GnRH-Agonisten) herangezogen.SchlussfolgerungenKomorbiditäten zählen neben dem Alter und der Compliance zu den wichtigen Faktoren, die die Wahl der ADT beeinflussen.

Abstract 677: Immune biomarkers of response to Ra223 dichloride and stereotactic body radiation therapy in patients with oligometastatic prostate cancers

Abstract Prostate cancer is the second leading cause of death in men in the developed countries. Androgen deprivation therapy (ADT) is commonly used to treat prostate tumors at earlier stages due to hormone-dependence of cancer cells. However, the onset of androgen-resistance with tumor progression and the negative impact of ADT on the quality of life are significant challenges. To address these issues, we have initiated a novel clinical trial combining radium Ra223 dichloride with stereotactic body radiation treatment (SBRT) and short course of ADT in patients with oligometastatic, castration-sensitive prostate cancer (NCT03351735). Patients with one to four oligometastatic prostate cancer lesions have been receiving ADT for nine months, together with SBRT to all metastatic sites and six cycles of Ra223 to target micrometastatic bone lesions. Eight out of the planned 24 patients have already completed the full treatment course, with five patients currently on surveillance (not requiring any further treatment) and three patients receiving next cycle of therapy. As part of this investigator-initiated study, we have performed a comprehensive immune characterization of peripheral immune cells and serum immune biomarkers in all treated patients. Based on flow cytometric analysis, we found a significant decrease in the percentage of CD4+ T cells befoe and after SBRT (cycle 1) but no changes in the elevated levels of programmed cell death-1 (PD-1), a marker of T-cell exhaustion, on the circulating CD4+ and CD8+ T cells. In addition, we observed high levels of the activated STAT3 (pSTAT3) in myeloid-derived suppressor cells (MDSCs), together with its downstream target Arginase-I. Finally, IL-8 stood out as a cytokine strongly elevated in plasma of patients who received the complete Ra223 treatment but not directly after SBRT. Overall, these preliminary results suggest that this combinatorial radiotherapy patients with oligometastatic prostate cancers impacts immune cell activity but rather than leading to T cell activation it may promote tolerogenic activity of MDSCs. Citation Format: Marice Alcantara, Tanya Dorff, Jessica Liu, Paul Frankel, Przemyslaw Twardowski, Savita Dandapani, Marcin Kortylewski. Immune biomarkers of response to Ra223 dichloride and stereotactic body radiation therapy in patients with oligometastatic prostate cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 677.

LRPPRC regulates metastasis and glycolysis by modulating autophagy and the ROS/HIF1-α pathway in retinoblastoma

Retinoblastoma (RB) is the most common intraocular tumor among children. Leucine-rich pentatricopeptide repeat (PPR)-motif-containing protein (LRPPRC), a suppressor gene of autophagy, has been proven to play a regulatory role in tumor progression. However, little is known about functional roles and mechanisms of LRPPRC in RB progression. First, we performed a detailed analysis for RB and normal control. The expression of LRPPRC in the RB tissues was significantly higher than that in normal tissues. Moreover, LRPPRC suppression could repress tumor cell migration, invasion, glycolysis, and reactive oxygen species (ROS)/hypoxia-inducible factor-1α (HIF1-α) pathway activation by mediating autophagy. Furthermore, overexpression of HIF1-α partially reversed the above changes induced by LRPPRC knockdown. The regulation of LRPPRC on tumor metastasis and glycolysis was also validated by a xenograft tumor assay. In summary, LRPPRC could regulate metastasis and glycolysis of RB by mediating autophagy suppression and further activating the ROS/HIF1-α pathway, and LRPPRC could be a promising prognostic biomarker for RB.

Effect of androgen deprivation therapy on cognitive functioning in men with prostate cancer: A systematic review.

The objective of this study was to review publications assessing cognitive functioning in patients with prostate cancer treated with androgen deprivation therapy. We conducted a systematic review of the literature published in PubMed, Embase, Web of Science, Cochrane Library, and PsycINFO up to February 2020. A total of 31 studies were included. Half of the studies (n = 16) demonstrated that androgen deprivation therapy in patients with prostate carcinoma did not result in a negative effect on cognitive functioning, however, still a substantial proportion of the studies (n = 11) reported a negative effect on cognitive functioning. In four studies the results were inconclusive. In the three studies using additional functional magnetic resonance imaging, no significant effect on neuropsychological tests was found, but grey matter volume, brain activity, and brain connectivity were affected. Given the substantial number of studies showing a significant negative effect of androgen deprivation therapy on cognitive functioning, clinicians should be aware of this side effect. Furthermore, future research should focus on the further examination of brain characteristics using functional magnetic resonance imaging, since these techniques might be more sensitive in detecting brain abnormalities as a result of androgen deprivation therapy.

P1224 - Androgen deprivation therapy in patients with prostate cancer is associated with the risk of subsequent Alzheimer’s disease but not with vascular dementia

P1224 - Androgen deprivation therapy in patients with prostate cancer is associated with the risk of subsequent Alzheimer’s disease but not with vascular dementia

The efficacy of enzalutamide (ENZA) plus androgen deprivation therapy (ADT) on bone oligometastatic hormone-sensitive prostate cancer: A post hoc analysis of ARCHES.

5071 Background: In ARCHES (NCT02677896), ENZA + ADT reduced the risk of radiographic progression and improved secondary clinical outcomes in patients with metastatic hormone-sensitive prostate cancer (mHSPC) with variable patterns of disease spread over placebo (PBO) + ADT. This post hoc analysis aimed to evaluate the efficacy of ENZA + ADT in patients with bone oligometastatic mHSPC compared to polymetastatic mHSPC in ARCHES. Methods: Patients with mHSPC (n = 1150) were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume and prior docetaxel chemotherapy. This post hoc analysis included patients with bone metastases only, categorized as oligometastatic (1–≤5 metastases) or as polymetastatic (≥6 metastases) based on central review at screening. Efficacy outcomes were compared across treatment arms. Results: Of the ARCHES population with bone metastases (n = 512), the largest subgroup included patients with ≤5 metastases (ENZA + ADT, n = 160; PBO + ADT, n = 136). Baseline characteristics were generally comparable between treatment arms and across subgroups. When compared to PBO + ADT, ENZA + ADT improved rPFS and secondary endpoints in patients with ≤5 metastases (Table). Similar results were observed across other oligometastatic subgroups (1–≤4) as well as in polymetastatic disease (≥6). The safety profile of ENZA + ADT versus PBO + ADT was similar across subgroups and consistent with previous findings. Conclusions: This post hoc analysis demonstrates that ENZA + ADT provides clinical benefit across bone oligometastatic as well as polymetastatic mHSPC, supporting the utility of ENZA irrespective of metastatic burden in the ARCHES study. Clinical trial information: NCT02677896. [Table: see text]

Phase 3 Randomized Controlled Trial of Androgen Deprivation Therapy with or Without Docetaxel in High-risk Biochemically Recurrent Prostate Cancer After Surgery (TAX3503)

BackgroundNo standard of care exists for patients with high-risk biochemical recurrence (BCR) after prostatectomy. ObjectiveTo evaluate whether addition of docetaxel to androgen deprivation therapy (ADT) improved progression-free survival (PFS) in high-risk BCR patients. Design, setting, and participantsTAX3503 was a multicenter phase 3 trial that randomized patients with high-risk BCR to ADT for 18 mo ± docetaxel (75 mg/m2 q3w for ten cycles). Eligibility included prostate-specific antigen (PSA) ≥1.0 ng/ml after prostatectomy alone or after postoperative radiation therapy, PSA doubling time ≤9 mo, and absence of metastases on computed tomography and bone scintigraphy. Outcome measurements and statistical analysisThe primary endpoint was PFS following testosterone recovery to noncastrate levels (testosterone >50 ng/dl). Secondary endpoints included time to testosterone recovery, overall survival (OS), quality of life, and safety. Results and limitationsBetween September 2007 and May 2011, 413 patients were assigned to ADT ± docetaxel. In 2012, following completion of accrual and treatment, the sponsor withdrew support of the study, and in 2013, a registry was created to secure the primary endpoint. The final analysis included data from the original trial and registry. At a median follow-up of 33.6 mo, 260 patients demonstrated testosterone recovery, which occurred similarly between groups. ADT plus docetaxel trended toward a nonclinically meaningful improvement in PFS (median 26.2 vs 24.7 mo) for the testosterone-recovered population (218 events, hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.61–1.04) and in OS for the intention-to-treat population (medians not reached, HR 0.51, 95% CI 0.23–1.10). Grade ≥3 adverse events occurred more frequently in the ADT plus docetaxel group (48.0% vs 10.8%). ConclusionsTAX3503 did not demonstrate a meaningful benefit of adding docetaxel to ADT in patients with high-risk BCR. Testosterone recovery was unaffected by addition of docetaxel to ADT. Patient summaryAddition of docetaxel to androgen deprivation therapy did not meaningfully improve outcomes for men with high-risk biochemically recurrent prostate cancer.

Influence of androgen deprivation therapy on glucose metabolism and ambulatory glucose profile

Introduction. Androgen deprivation, used to treat prostate cancer, leads to metabolic disorders, including glucose metabolism disorders. The timing of development and the characteristics of these changes have not been sufficiently studied. The expansion of the possibilities for assessing glycemia makes it possible to obtain changes in glucose.Objective. To study the dynamics of the effect of long-term androgen-deprivation therapy with gonadotropin-releasing hormone agonists (GnRH agonists) on the parameters of glucose metabolism and ambulatory glucose profile in patients with locally advanced prostate cancer (La PCa).Materials and methods. The study included 99 patients with La PCa receiving androgendeprivation therapy (ADT) with (GnRH agonists) for at least 12 months. The study of fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) levels was performed at baseline, after 3, 6 and 12 months of ADT, and constant self-monitoring of glycemia was recommended using portable glucometers. Flash glucose monitoring systems (FreeStyle Libre) were installed in ten patients with a detected increase in glycemia on the background of ADT, allowing them to obtain data on the ambulatory glucose profile (AGP).Results and discussion. Long-term ADT in patients with La PCa, regardless of baseline age, BMI, WC, was accompanied by an early, progressive deterioration in parameters of glucose metabolism. The proportion of patients with prediabetic FPG values after 12 months becames 66% according ADA criteria. We found that 12-month ADT changes the AGP: an increase area under the curve and postprandial glycemic levels, an increase in blood glucose variability with an increase in the CONGA index to 6.817 (p &lt; 0.001).Conclusion. ADT by GnRH agonists in patients with La PCa is accompanied by a predisposition to early disorders of glucose metabolism with a high risk of rapid development of prediabetes regardless of baseline age, BMI, and WC. The AGP of patients is characterized by an increase in the total glycemic load, and glycemic variability.