Androgen Deprivation Therapy Patients Research Articles

Development of depression in patients using androgen deprivation therapy: A systemic review and meta-analysis.

Androgen deprivation therapy (ADT) is an effective treatment for advanced prostate cancer (PCa). Multiple studies have highlighted serious consequences this therapy poses to mental health, particularly depression. We aimed to review the incidence and association between ADT in men with PCa and the risk of depression. We systematically searched multiple databases, including MEDLINE, Scopus till August 2023 for studies that compared ADT versus control for treating PCa reporting depression as outcome. Meta-analysis was performed using random-effects models and results presented as odds ratios (ORs) with 95% confidence interval (CI). Quality assessment of the included studies was conducted using Joanna Briggs Institute critical appraisal checklists. A total of 38 studies (17 retrospective studies, 16 prospective studies, two cross-sectional studies and two randomized trials) with 360,650 subjects met the inclusion criteria and were included in this meta-analysis. The estimated pooled incidence of depression among ADT patients is 209.5 (95% CI = 122.3; 312.2) per 1000 patients. There is statistically significant relationship between ADT treatment and depression (OR = 1.46, 95% CI = 1.28, 1.67; p = 0, I2 = 86.4%). The results remained consistent across various subgroups. No risk of publication bias was detected by funnel plot and Eggers's test (p > 0.05). There is a higher risk of depression for men receiving ADT. Further studies evaluating optimal treatments for depression in men on ADT are warranted.

Examining the impact of androgen deprivation therapy, masculine self-esteem, and psychological flexibility on distress and quality of life in men with prostate cancer.

Studies suggest that androgen deprivation therapy (ADT) exacerbates psychological and quality of life (QoL) issues associated with prostate cancer (PCa). However, quantitative research examining underlying psychosocial mechanisms for this is limited. We examined the association of PCa symptoms with distress and QoL in ADT-treated and ADT-naïve patients, and the influence of masculine self-esteem and psychological flexibility (PF) on these relationships. Secondary analysis of a quantitative, cross-sectional survey of 286 PCa patients. Independent samples t-tests, moderation, and conditional process analysis were used to assess relationships between predictor, mediator, moderator, and outcome variables. ADT was associated with greater PCa symptomology, lower masculine self-esteem, and lower QoL. Moderation analysis showed that ADT potentiated adverse impacts of PCa symptomology on distress and QoL. High PF attenuated these relationships, though less so for ADT-treated participants. Conditional process analysis showed that masculine self-esteem mediated the predictive effect of symptoms on distress across treatments. However, ADT did not moderate this indirect effect, nor was moderation conditional on PF. PF appears to: (1) attenuate psychological distress in ADT patients; and (2) improve distress, QoL, and masculine self-esteem in ADT-naïve patients. Interventions targeting PF may thus be a viable adjunct to established approaches. However, their effects may be comparatively limited in ADT patients, who may benefit from more intensive and tailored treatment.

Androgen Deprivation Therapy for Prostate Cancer: Focus on Cognitive Function and Mood.

Prostate cancer is the second leading cause of cancer death in men in the United States. Androgen deprivation therapy (ADT) is currently the primary treatment for metastatic prostate cancer, and some studies have shown that the use of anti-androgen drugs is related to a reduction in cognitive function, mood changes, diminished quality of life, dementia, and possibly Alzheimer's disease. ADT has potential physiological effects such as a reduction in white matter integrity and a negative impact on hypothalamic functions due to the lowering of testosterone levels or the blockade of downstream androgen receptor signaling by first- and second-generation anti-androgen drugs. A comparative analysis of prostate cancer patients undergoing ADT and Alzheimer patients identified over 30 shared genes, illustrating common ground for the mechanistic underpinning of the symptomatology. The purpose of this review was to investigate the effects of ADT on cognitive function, mood, and quality of life, as well as to analyze the relationship between ADT and Alzheimer's disease. The evaluation of prostate cancer patient cognitive ability via neurocognitive testing is described. Future studies should further explore the connection among cognitive deficits, mood disturbances, and the physiological changes that occur when hormonal balance is altered.

Major adverse cardiovascular event risk following androgen deprivation therapy initiation by personal history of cardiovascular events.

351 Background: Associations between androgen deprivation therapy (ADT) and increased cardiovascular (CV) risk in prostate cancer (PCa) patients have been reported; however, how many of these major adverse CV events (MACE) are caused by ADT itself has been debated. One risk factor for increased CV risk is a prior history of CV events; an analysis found that each new CV event increased the probability of a future event. This study aims to evaluate the incidence of MACE after ADT initiation for patients with and without a prior medical history of MACE. Methods: Analyses of US electronic medical records (2010 to 2020) of PCa patients (n=45,059) receiving LHRH agonist and antagonist injections were conducted to evaluate MACE incidence after ADT initiation in patients with and without MACE history. Exclusion criteria included lack of ADT initiation date or myocardial infarction (MI)/stroke within 6 months prior to ADT initiation. MACE was defined as MI, stroke, and death from any cause. Kaplan-Meier event-free survival curves were constructed, and Cox regression was used to compare the MACE hazard rates between patients with and without a personal history of MACE. Multivariate Cox regression adjusted for agonists vs antagonist, increasing age per year, BMI (<18.5 vs ≥18.5 kg/m2), race (White vs Black), family MACE history, ethnicity (Hispanic vs non-Hispanic), urology vs oncology setting, history of hypertension, and history of hypercholesterolemia. Results: Overall, MACE incidence was 3.9% and 19.6% for the cohort at one year and four years after ADT initiation, respectively. MACE risk following ADT initiation was higher for patients with history of prior MACE (unadjusted: (HR=2.76, 95% CI [2.49, 3.06], p<0.001); adjusted: HR=2.29, 95% CI [1.93, 2.71], p<0.001). When MACE was divided into component events, the risks of myocardial infarction and stroke were higher for patients with a prior MACE history compared to those without (8 vs. 1% and 8 vs. 2%, respectively), and the risk of any-cause death was similar (13 vs. 14%). Conclusions: MACE incidence in PCa patients in the first year of ADT was consistent with previous publications.(3). When MACE risk was analyzed in detail, ADT patients with a personal history of stroke or myocardial infarction (MI) had a 4- and 8-fold greater risk of a subsequent stroke and MI, respectively, compared to those without a history of stroke or MI. Given the large sample size (~45,000 PCa patients) of this data set over the recent past decade, these results likely reasonably reflect the real world. Urologists and oncologists should work with cardiologists, cardio-oncologists, and primary care practitioners to ensure the highest quality CV care is delivered.

Real-world combination therapy patterns in patients receiving leuprolide or relugolix for androgen deprivation therapy in 2021 (The REAL-ADT COMBO Study): Analysis from a US EMR database.

74 Background: Relugolix, an oral gonadotropin releasing hormone (GnRH) receptor antagonist, was FDA approved for the treatment of adults with advanced prostate cancer (PC) in December 2020 and became commercially available in January 2021. Data from a subgroup of patients from the Phase 3 HERO study showed patients combining relugolix with enzalutamide or docetaxel had similar efficacy and safety as other cohorts in the study. However, due to limited data, some guidelines do not recommend relugolix in combination with other therapies. We evaluated real world utilization of leuprolide and relugolix in combination with other PC medications. Methods: An observational retrospective analysis was conducted using Electronic Medical Record (EMR) data. PPS Analytics data from 89 urology practices with patients represented across all 50 states in the US were analyzed. Patients with at least one record of androgen deprivation therapy (ADT) in 2021 were included. Patients whose date of ADT initiation could not be determined were excluded from this analysis. This analysis focused on the occurrence of patients with ADT as well as in combination with other PC medications. Data are reported for all patients treated with leuprolide or relugolix and stratified by new and continuing ADT use. Combination PC medications were reported for these two ADT groups. Results: In 2021, 51,735 patients were treated with ADT; 45,599 (88.1%) were treated with leuprolide and 3,096 (6.0%) patients had at least 1 prescription for relugolix. Combination PC medications (ComboPCRx) were proportionately higher in relugolix patients than in leuprolide patients (698 [22.5%] vs 8,897 [19.5%] respectively; p < 0.0001). ComboPCRx in users new to ADT was more frequent for relugolix users (342/2,169 [15.8%]) than for leuprolide users (1934/17,737 [10.9%]). In both groups, novel anti-androgens were the most frequent type of ComboPCRx. Conclusions: In this real-world EMR analysis, relugolix use in combination with other PC medication was frequently observed, for both new to ADT and continuing ADT patients. The percentage of combination therapy with PC medications was higher for relugolix users than it was for leuprolide users. These results provide insight into the real-world use of relugolix in combination with other PC medications. Further analyses are needed to make informed treatment decisions. [Table: see text]

Abstract 12761: Association of Androgen Deprivation Therapy With Metabolic Disease in Prostate Cancer Patients: An Updated Meta-Analysis

Introduction: Androgen deprivation therapy (ADT), a backbone treatment for advanced prostate cancer (PC) is known to have a variety of metabolic side effects. We conducted an updated meta-analysis to quantify metabolic risks of ADT. Hypothesis: We hypothesized that ADT would increase the risk for metabolic diseases compared to PC patients not on ADT. Methods: We searched PubMed, Web of Science, and Scopus in May of 2022 for studies that investigated the risk of metabolic syndrome (MetS), diabetes, and hypertension from ADT in PC patients using keywords. 4 blinded reviewers screened studies. Only studies that had a comparison group of PC patients not on ADT were included. For included studies, relative risk (RR) was pooled using a random effects model. Results: 1846 records were screened, of which 19 were found suitable for data extraction (Figure 1). 5 studies including 831 patients had MetS as an outcome, with the random effects model showing a pooled RR of 1.49 ([95% Confidence Interval (CI), 1.01-2.21]; I 2 =59%: p=0.04) for patients on ADT. 12 studies including 409,490 patients examined diabetes as an outcome, and the random effects model showed a RR of 1.40 (95% CI, 1.28-1.54), while 4 studies including 7,051 patients examined hypertension as an outcome, and the random effects model showed a RR of 1.30 (95% CI, 1.08-1.55) in ADT patients. Conclusions: ADT was shown to increase the risk of MetS, diabetes, and hypertension in patients with PC undergoing ADT compared to PC patients not on ADT. These results should be understood in the context of collaboration between a patient’s oncologist and primary care provider to optimize care.

Changes in Renal Function of Patients With Prostate Cancer: Focus on Androgen Deprivation Therapy.

To investigate the association between androgen deprivation therapy (ADT) and changes in the estimated glomerular filtration rate (eGFR) in male Japanese patients with prostate cancer, based on post-hoc analysis of data from a previous prospective study. Among 103 patients with prostate cancer in whom renal function changes were tracked over 5 years, 88 were divided into a group who completed ADT within 3 years (short ADT group; n=47) and a group who continued with ADT for more than 5 years (continuous ADT group; n=41). We compared the groups in terms of the eGFR, calculated based on age and serum creatinine (mg/dl) before ADT initiation and every other year over the next 5 years. The eGFR decreased by 4.91 and 2.89 ml/min in the short and continuous ADT groups, respectively, over the 5-year period following ADT initiation. The respective decreases in the eGFR were 0.98 and 0.58 ml/min/year. No significant difference in the eGFR was observed between the two groups at any measurement point. Patients treated with ADT showed a decrease in the eGFR of 0.58-0.98 ml/min/year over a 5-year period, which is about twice as high as that of normal Japanese males. No significant difference in the eGFR by ADT duration was observed. The eGFR decreased by 0.58-0.98 ml/min/year in our ADT patients, which was about twice as high as the rate of decrease in normal Japanese males, and approximately the same as in urine protein-positive male patients. We suggest that a large decrease in the eGFR may not play a role in the development of acute kidney injury. In addition, the duration of ADT does not appear to have a significant effect on the eGFR.

Significant financial differences of chemical and surgical androgen deprivation in a contemporary cohort.

BackgroundAndrogen deprivation therapy (ADT) remains a cornerstone of treatment for advanced prostate cancer. Few men elect for surgical castration via bilateral orchiectomy. We sought to compare the relative difference in financial charges between chemical and surgical ADT in men.MethodsBilling data was obtained for patients with metastatic prostate cancer receiving chemical ADT and who had bilateral orchiectomy from 2014–2019. Men had chosen intervention based on personal preference. We compared charges of ADT administration for chemical ADT and overall charges for bilateral orchiectomy. We determined the time chemical ADT patient charges surpassed those of surgical charges, as well as the net present value (NPV) of hypothetical savings for electing surgery over various ADT agents.ResultsOne hundred and thirty-seven patients receiving chemical ADT and 7 patients who had undergone bilateral orchiectomy were analyzed. Median and mean surgical charges were $13,000. By 38 weeks following treatment initiation, 50% of chemical ADT patients had surpassed surgical charges, with 95% at 2 years. The NPV in savings for a median patient varied between ADT agent and was highest at $167,000 for leuprolide.ConclusionsIn less than a year, the median chemical ADT patient charges were greater than surgical castration. The NPV of electing surgery over ADT was the highest with leuprolide. Despite under-utilization, surgical castration remains a medically appropriate and cost-effective option for permanent ADT.

Abstract 1742: Molecular characterization of CRPC pathogenesis and development of a novel anti-PSMA-drug conjugated hybrid nanoparticle therapy with reduced cellular toxicity

Abstract Background: Metastatic castration-resistant prostate cancer (mCRPC) is responsible for most of PCa deaths. Androgen deprivation therapy (ADT), taxanes and enzalutamide are the standard care for CRPC and mCRPC. Unfortunately, these approaches often fail to prevent tumor relapse due to at least in part, the inherently low oxygen levels within the prostate tumor environment. In addition to this, lower drug stability and fast drug clearance among ADT patients are the major therapeutic limitations in drug delivery and drug efficacy. Therefore, it is clinically warranted to develop an increased drug stability system to enhance the drug efficacy. Recent developments in drug delivery system including our earlier report, nanoparticle loaded drugs shows greater stability and better drug efficacy with sub-optimal drug concentrations in vitro. It is an essential to develop an ideal CRPC preclinical model system to test the anti-PSMA-drug conjugated hybrid nanoparticle efficacy with high drug stability with limited cellular toxicity. Materials and Methods: CRPC lines were developed from PSMA proficient LNCaP, LAPC4, C4-2, 22Rv1, and PSMA deficient PC3-ML cells with intermittent hypoxia. CRPC cells were analyzed for proliferation, RB status, AR signaling, migration invasion and drug resistance in both in vitro and in vivo. Further, CRPC bone metastases clinical samples from Thomas Jefferson University Hospital were compared with preclinical CRPC model. Efficient anti-PSMA-drug conjugated hybrid nanoparticle therapy was established. Results: Hypoxia resistance models show CRPC, RB loss, hormone therapy resistance in vitro and in vivo. Anti-PSMA-drug conjugated hybrid nanoparticle shows enhanced drug stability and drug efficacy in vitro and in vivo. Interestingly we observed fibrosis, immune impairment and inactive RB in bone metastatic CRPC samples correlated with our preclinical studies. Further, our clinical bone metastases samples present osteoblastic, osteolytic and osteoblastic & osteolytic nature. Anti-PSMA conjugated-drug loaded hybrid nanoparticles localized to PSMA specific cells in vitro & in vivo, causing cell cycle arrest. Drug loaded anti-PSMA conjugated hybrid nanoparticles did not cause major toxicities in mice. Conclusion: Hypoxia resistant mCRPC models are ideal and are comparable with CRPC induced bone metastases in patient’s samples. Drug-loaded anti-PSMA conjugated hybrid nanoparticles targets PSMA specific prostate cancer cells and show enhanced drug stability and drug efficacy in CRPC preclinical model. Citation Format: Thangavel Chellappagounder. Molecular characterization of CRPC pathogenesis and development of a novel anti-PSMA-drug conjugated hybrid nanoparticle therapy with reduced cellular toxicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1742.

Oligometastatic Prostate Cancer: A Comparison between Multimodality Treatment vs. Androgen Deprivation Therapy Alone.

Simple SummaryData regarding the survival effect of radical prostatectomy in patients with oligometastatic PC (OPC) are sparse and based on small series. Moreover, few studies compared radical prostatectomy with systemic treatment in an OPC setting. We compared multimodality treatment (MMT, defined as robot-assisted radical prostatectomy (RARP) with androgen deprivation therapy (ADT), with or without adjuvant radiotherapy (RT)) vs. ADT alone in oligometastatic prostate cancer (OPC) patients. MMT was associated with lower CSM, mCRPC and second-line therapy rates. A lower rate of treatment-related adverse events was recorded for the MMT group.Background: We compared multimodality treatment (MMT, defined as robot-assisted radical prostatectomy (RARP) with androgen deprivation therapy (ADT), with or without adjuvant radiotherapy (RT)) vs. ADT alone in oligometastatic prostate cancer (OPC) patients. Methods: From 2010 to 2018, we identified 74 patients affected by cM1a-b OPC (≤5 metastases). Kaplan–Meier (KM) plots depicted cancer-specific mortality (CSM), disease progression, metastatic castration-resistant PC (mCRPC), and time to second-line systemic therapy rates. Multivariable Cox regression models (MCRMs) focused on disease progression and mCRPC. Results: Forty (54.0%) MMT and thirty-four (46.0%) ADT patients were identified. On KM plots, higher CSM (5.9 vs. 37.1%; p = 0.02), mCRPC (24.0 vs. 62.5%; p < 0.01), and second-line systemic therapy (33.3 vs. 62.5%; p < 0.01) rates were recorded in the ADT group. No statistically significant difference was recorded for disease progression. ForMCRMs adjusted for the metastatic site and PSA, a higher mCRPC rate was recorded in the ADT group. No statistically significant difference was recorded for disease progression. Treatment-related adverse events occurred in 5 (12.5%) MMT vs. 15 (44.1%) ADT patients (p < 0.01). Conclusions: MMT was associated with lower CSM, mCRPC, and second-line therapy rates. A lower rate of treatment-related adverse events was recorded for the MMT group.

A Population-Level Analysis of the Protective Effects of Androgen Deprivation Therapy Against COVID-19 Disease Incidence and Severity.

BackgroundThe incidence and severity of coronavirus disease 19 (COVID-19) is substantially higher in men. Sex hormones may be a potential mechanism for differences in COVID-19 outcome in men and women. We hypothesized that men treated with androgen deprivation therapy (ADT) have lower incidence and severity of COVID-19.MethodsWe conducted an observational study of male Veterans treated in the Veterans Health Administration from February 15th to July 15th, 2020. We developed a propensity score model to predict the likelihood to undergo Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing. We performed multivariable logistic regression modeling adjusted with inverse probability weighting to examine the relationship between ADT and COVID-19 incidence. We conducted logistic regression analysis among COVID-19 patients to test the association between ADT and COVID-19 severity.ResultsWe identified a large cohort of 246,087 VA male patients who had been tested for SARS-CoV-2, of whom 3,057 men were exposed to ADT, and 36,096 men with cancer without ADT. Of these, 295 ADT patients and 2,427 cancer patients not on ADT had severe COVID-19 illness. In the primary, propensity-weighted comparison of ADT patients to cancer patients not on ADT, ADT was associated with decreased likelihood of testing positive for SARS-CoV-2 (adjusted OR, 0.88 [95% CI, 0.81–0.95]; p = 0.001). Furthermore, ADT was associated with fewer severe COVID-19 outcomes (OR 0.72 [95% CI 0.53–0.96]; p = 0.03).ConclusionADT is associated with reduced incidence and severity of COVID-19 amongst male Veterans. Testosterone and androgen receptor signaling may confer increased risk for SARS-CoV-2 infection and contribute to severe COVID-19 pathophysiology in men.

Evaluating Patterns and Factors Related to Sleep Disturbances in Prostate Cancer Patients.

Prostate cancer patients may experience disturbed sleep as a result of their diagnosis or treatment. This study sought to evaluate disturbed sleep and excessive daytime sleepiness in newly diagnosed patients and those receiving androgen deprivation therapy (ADT). This study was conducted with 74 patients. Subjective data using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) and actigraphy data on ADT/ADT-naïve patients were collected. The prevalence of poor sleep quality, determined from PSQI and ESS scores, was 50% and 16.7% respectively. Those on ADT (n = 20) had poorer sleep quality as determined by significantly higher PSQI scores (70 vs. 40% scoring > 5) and were more likely to have poor sleep quality, sleep latency, and sleep efficiency than ADT-naïve patients (n = 40). Actigraphy data showed that ADT patients slept significantly longer (7.7 vs. 6.8 h), experienced a higher Fragmentation Index (48.3 vs. 37.4%), and had longer daytime nap duration (64.1 vs. 45.2 min) than ADT-naïve patients. The use of objective measures such as actigraphy in the clinical arena is recommended and may be used as a valuable tool for research into sleep assessment in prostate cancer patients.

Risks of metabolic diseases and androgen deprivation therapy for prostate cancer in a Chinese population: a prospective multi-centre cohort study.

Androgen deprivation therapy (ADT) use in prostate cancer (PCa) has seen a rising trend. We are looking into the relationship between ADT and development of metabolic diseases in Chinese patients. This is a prospective multi-centre cohort yielded from the READT database (Real-life experience of ADT in Asia), in which patients diagnosed of PCa and offered ADT were prospectively recruited since 2016. Chinese patients recruited from Hong Kong were selected and compared to another cohort of newly diagnosed PCa patients in Hong Kong (HK-Cap database), which was collected prospectively and retrieved retrospectively for this study. Patient outcomes are followed through for 2years. We compared between the groups the new diagnoses of hypertension, diabetes and hyper-lipidaemia, as well as the initiation of related medication for these conditions. Baseline characteristics including pre-treatment comorbidities, medications and tumour characteristics are documented. 151 patients receiving ADT (from READT database) and 447 patients not receiving ADT (from HK-Cap database) were analysed. ADT is related to higher risks of developing any of concerned medical co-morbidities (23.8% vs 13.0*, p = 0.001) and new-onset DM (16.6% vs 4.4%, p < 0.001). Initiation of new medications is also more common in ADT patients. New anti-hypertensives (37.8% vs 12.5%, p < 0.001), oral hypoglycemic agents (12.6% vs 4.9%, p = 0.001), insulin (4.0% vs 0.05%, p = 0.001) and statin (23.7% vs 12.8%, p = 0.023) are more commonly added in ADT cohort. Chinese receiving ADT are exposed to increased risks of new-onset hypertension, diabetes and hyper-lipidaemia, and a higher likelihood of stepping up pharmaceutical control for pre-existing comorbidities. This highlights physicians' role to monitor metabolic profiles in at-risk men upon offering ADT.

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

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

Effects of Androgen Deprivation Therapy on COVID-19 in Patients with Prostate Cancer: A Systematic Review and Meta-Analysis.

Transmembrane serine protease 2 (TMPRSS2) facilitates SARS-CoV-2 cellular entry. Androgens regulate this protein and may increase the risk of COVID-19. Therefore, androgen deprivation therapy (ADT) may protect patients with prostate cancer from SARS-CoV-2 infection or decrease the severity of the disease. Therefore, we conducted a meta-analysis to study the effect of androgen deprivation therapy (ADT) on COVID-19 in patients with prostate cancer. We systematically searched PubMed, Embase, Scopus, and Cochrane databases. All records underwent a two-step screening process to identify the eligible studies. The registered PROSPERO number of this study was CRD42021228398. We evaluated the effect of ADT on the risk of infection, hospitalization, ICU admission, and mortality. Six studies met inclusion criteria and were evaluated in this study. We performed meta-analysis on four eligible studies. The overall incidence of COVID-19 was 2.65% among patients with prostate cancer receiving ADT. COVID-19 mortality rate was about 22.7% in ADT (+) patients. ADT did not decrease the risk of any of the major outcomes; infection risk (OR= 0.63, 95% CI= 0.27- 1.48, P = 0.29), hospitalization rate (OR= 0.51, 95% CI= 0.10- 2.53, P = 0.41), ICU admission (OR= 1.11, 95% CI= 0.43- 2.90, P = 0.82), and mortality risk (OR= 1.21, 95% CI= 0.34- 4.32, P = 0.77). We did not observe a protective effect on the risk of infection, hospitalization, ICU admission, and mortality in patients receiving ADT; therefore, it should not be considered as a prophylactic or treatment for COVID-19. On the other hand, ADT did not increase the mortality and morbidity of COVID-19 and should be considered a safe treatment for patients with prostate cancer during the pandemic. Further studies are necessary to confirm our findings.

Impact of Hypertension on Early Renal Dysfunction in Japanese Prostate Cancer Patients Treated With Androgen Deprivation Therapy.

Recently, it was reported that the use of androgen deprivation therapy (ADT) is significantly associated with an increased risk of acute kidney injury (AKI) in patients with newly diagnosed non-metastatic prostate cancer. This study aimed to investigate the incidence of early renal dysfunction in Japanese prostate cancer patients receiving ADT and the factors associated with it. A total of 135 patients who had been pathologically diagnosed with prostate cancer and had received ADT for at least 6 months were eligible for study inclusion. The estimated glomerular filtration rate (eGFR) before treatment, and at 1, 3, and 6 months of ADT were evaluated retrospectively. We assessed renal function using eGFR and investigated the rate of change in the eGFR (ΔeGFR) during ADT. Univariate and multivariate logistic analyses were carried out to identify clinical factors that were significantly associated with renal dysfunction after 6 months ADT. A total of 110 cases were evaluated in this study. The incidence of renal dysfunction after 6 months ADT was 63% (69/110). The mean ΔeGFR after 1, 3, and 6 months of ADT were -0.6%, -3.1% and -1.7%, respectively (p<0.001). Multivariate analysis showed that renal dysfunction after 3 months of ADT and hypertension were independent risk factors for renal dysfunction after 6 months ADT. Renal dysfunction occurs from 1 month of ADT and hypertensive prostate cancer patients receiving ADT are at high risk of developing renal dysfunction, and that such patients should be treated very carefully. Therefore, patients that are started on ADT should undergo periodic prostate-specific antigen, renal function, and urinary salt intake examinations.

The Effects of Androgen-Deprivation Therapy on MRI Delta Radiomics Features in a Prospective Radiotherapy Treatment Trial for Prostate Cancer

The aim of this study is to evaluate the effects of androgen-deprivation therapy (ADT) on the variation of multiparametric (mp)MRI-radiomics features, defined as "delta radiomics", in patients from a prospective radiotherapy trial in which 48% of men received short term androgen deprivation therapy (STADT). Twenty-five patients with favorable to high-risk prostate cancer were enrolled on a Phase I trial of MRI-guided radiotherapy treatment trial. Median follow up is 63 mo, range 17 to 90. mpMRI was carried out pre-RT, 3 and 9 months after completion of RT and at 2.0-2.5 years after completion of all treatment. A high dose (12-14 Gy) was given on day 1 to a portion near the center of the mpMRI delineated GTV(s). The mpMRI exam consisted of T2 weighted, T1 non-contrast, T1 dynamic contrast-enhanced (DCE)-MRI, and diffusion weighted imaging (DWI) with the generation of an Apparent Diffusion Coefficient (ADC) map. Prostate, peripheral zone (PZ) and transition zone (TZ) were contoured in MIM. GTV(s) were translated from the planning CT to all 4 mpMRI. Thirty variables (mean±SD) were extracted from GTV, normal appearing (NA)-PZ and NA-TZ on T2w and ADC, as well as the perfusion parameters Ktrans, Kep and ve on DCE-MRI. Baseline variables were compared between patients with and without ADT using Student t-test. Area-under-the-curve (s) (AUCs) for the variables over the baseline, 3 and 9 mo were compared between the +/-ADT groups using Mann-Whitney test. Two patients received only diagnostic mpMRI and were excluded from the study. From the reminding 23 patients, 14 had 3 longitudinal mpMRI studies and 9 had 4. The data was acquired on 3T Discovery MR750 (n = 45) (GE, Waukesha, WI), 3T MR Magnetom Trio (n = 7), Skyra (23) and 1.5T Symphony (n = 3) (Siemens, Erlagen, Germany). Twelve patients received STADT. There were no significant differences in the means of baseline radiomics variables, including the volumes of prostate, PZ and TZ between the (+/-ADT) groups. Similarly, there was no statistical difference between the AUC of the GTV on ADC and perfusion parameters. ADC values increased significantly on average 30%, 44% and 47% after treatment. ve also increased significantly on average 108%, 91% and 124% from baseline. Because of the different scanners, T2-weighted intensities were not compared. The study indicates that ADT does not affect the overall delta radiomics variables before and after radiotherapy. Prostate cancer has long natural history with relatively low number of failures. We demonstrate and +/-ADT patients can be analyzed together, allowing for increased number of events. The ultimate goal of the project is to identify delta radiomics signature that relates very early response to patient outcome such that therapeutic adjustments may be made to improve long term outcome. While 17% increase in ADC before and after ADT have been previously reported, the large magnitude of changes (∼40 %) here indicate that the radiation effects drive the observed variations.

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.

Changes in Beck Depression Inventory scores in prostate cancer patients undergoing androgen deprivation therapy or prostatectomy.

ObjectivesAndrogen deprivation therapy (ADT) has seen increasing use as a prostate cancer treatment in recent years and has proven medically effective in numerous contexts. The treatment, however, is associated with a host of side effects including depression. Managing the psychological wellbeing of prostate cancer patients is important for maximizing their survival outcomes. Thus, this study aimed to evaluate depressive symptomatology in patients with androgen deprivation therapy (ADT) compared with that in patients who underwent prostatectomy and to explore the factors that affect depressive symptoms, which might occur during ADT.MethodsOne hundred and seven patients undergoing ADT (ADT group) and prostatectomy (Operation group) were enrolled. Adjustments were made for differences in characteristics between groups using a propensity score model with stabilized weights before treatment. Depressive symptoms between groups were compared using the Beck Depression Inventory (BDI) before treatment and six months after treatment initiation. To identify factors affecting depressive symptoms during ADT, multivariate regression analysis was performed on the mean change in BDI score, age, body mass index, testosterone level, prostate-specific antigen level, the international index of erectile function (IIEF), and the Gleason score.ResultsThe BDI score significantly increased in the ADT group compared to the operation group six months after treatment initiation (p < 0.001). Multivariate regression analysis revealed that before ADT, the BDI score was higher by 0.446 according to the IIEF. During ADT, the BDI score increased by 1.579 according to changes in BMI (p = 0.021) and decreased by 0.01 according to changes in testosterone levels (p = 0.034).ConclusionDepressive symptoms can be exacerbated in prostate cancer patients undergoing ADT. Efforts are needed to diagnose and treat depression appropriately, especially if depressive symptoms change in ADT patients with a high IIEF score before ADT, or reduced testosterone levels or increased BMI during ADT.

Androgen Deprivation Therapy for Prostatic Cancer in Patients With Torsades de Pointes.

BackgroundMen normally have shorter heart rate-corrected QT interval (QTc) than women, at least in part due to accelerating effects of testosterone on ventricular repolarization. Accumulating data suggest that androgen-deprivation therapy (ADT) used for the treatment of prostatic cancer, may increase Torsades de Pointes (TdP) risk by prolonging QTc. However, the evidence for such an association is currently limited to few case reports, in most cases deriving from the analysis of uncontrolled sources such as pharmacovigilance databases.ObjectiveTo better determine the clinical impact of ADT on TdP development, we examined the prevalence of this therapy in a consecutive cohort of 66 TdP patients, prospectively collected over a ~10 years period.Methods and ResultsWe found and described four patients who were under ADT for prostatic cancer when TdP occurred, and in two cases degenerated to cardiac arrest. Notably, in this unselected population, ADTs unexpectedly represented the second most frequently administered QT-prolonging medication in males (4/24, 17%), after amiodarone. Moreover, in the ADT patients, a blood withdrawal was performed within 24 h from TdP/marked QTc prolongation occurrence and circulating concentration of androgens and gonadothropins were measured. As expected, all cases showed markedly reduced testosterone levels (total, free, and available).ConclusionWe provide evidence that a significant proportion of patients developing TdP were under treatment with ADT for prostatic cancer, thus confirming the clinical relevance of previous pharmacovigilance signals. An accurate assessment of the arrhythmic risk profile should be included in the standard of care of prostatic cancer patients before starting ADT.