LHRH Antagonist Research Articles

Efficacy and safety of neoadjuvant chemohormonal therapy for high-risk prostate cancer treated with robot-assisted laparoscopic radical prostatectomy: a propensity score-matched analysis (the MSUG94 group).

The optimal neoadjuvant regimen before radical prostatectomy (RP) in patients with high-risk (HR) prostate cancer (PCa) remains to be determined. This retrospective multicenter cohort study assessed the effectiveness and safety of neoadjuvant chemohormonal therapy (NCHT) in patients with HR-PCa undergoing robot-assisted laparoscopic radical prostatectomy (RALP). We reviewed the datasets of 1023 subjects who underwent RALP at nine Japanese facilities between September 2012 and October 2023. The enrolled patients were divided into two groups using propensity score matching: a RALP-alone group and those who underwent NCHT followed by RALP (NCHT group). The NCHT regimen consisted of a luteinizing hormone-releasing hormone antagonist and tegafur-uracil for at least 3months before RALP. The primary endpoint was biochemical recurrence (BCR) after RALP. The secondary endpoint was the surgical specimen pathology findings. Propensity score matching identified 139 individuals for each group. Median follow-up was 18.2months. During follow-up, BCR was observed in 41 patients (29.5%) in the RALP-alone group and 22 patients (15.8%) in the NCHT group (p = 0.010). Pathological results showed significantly more organ-confined PCa and significantly fewer positive surgical margins or lymphovascular invasion in the NCHT group than in the RALP-alone group. The 2-yr biochemical recurrence-free survival (BRFS) was 72.7% and 74.7% in the RALP-alone and NCHT groups, respectively (p = 0.086). Two patients (1.4%) experienced grade 3 liver disorder as an NCHT-related adverse event. The results suggest that NCHT can safely treat HR-PCa and may reduce the incidence of BCR when combined with RALP.

Impact of Castration on the Sexual Life in Young Women at the National Institute of Oncology of Rabat, Morocco

Introduction: Castration, also referred to as hormonal suppression, is generally understood as the halt of hormone production by the ovaries in premenopausal women. This can occur through medical means, such as the administration of LH-RH agonists or antagonists that act reversibly on the hypothalamic- pituitary axis, or through surgical or radical methods that permanently eliminate hormonal production. Castration is primarily recommended for premenopausal women with hormone receptor-positive breast cancer. Regardless of the approach used, it produces side effects akin to those experienced during menopause, including hot flashes, anxiety, depressive disorders, and trophic changes that may affect sexual function. Thus, our study seeks to investigate the effects of castration on sexual life in our patients undergoing treatment for hormone receptor-positive breast cancer. Materials and Methods: This study was carried out at a day hospital to assess the effects of mainly medical, but also surgical and radical castration on couple dynamics in 50 patients, averaging 40 years of age, who are being treated for hormone receptor-positive breast cancer, regardless of whether it is localized or metastatic. Results: The majority of patients report experiencing side effects associated with castration, especially hot flashes, which affect nearly all patients, as well as depressive and anxiety disorders. However, it remains challenging to determine whether these issues are directly linked to the disease or its treatment. Additionally, many patients face sexual disturbances, including decreased libido and vaginal dryness, which significantly impact couple dynamics in almost 50% of cases. Conclusion: Investigating the effects of castration on sexuality, particularly regarding couple dynamics, highlights a significant yet sensitive topic. This issue, often considered taboo, represents a major side effect of prolonged treatment in long-term survivors. Therefore, it is essential to engage in regular discussions and collaborate with specialists, especially sexologists, to enhance tolerance and achieve lasting improvements in quality of life.

Effectiveness of surgical castration by bilateral subcapsular orchiectomy as monotherapy for the treatment of advanced prostate cancer.

Prostate cancer is the most common malignancy in men and the second cause of death due to cancer [1]. Treatment of prostate cancer has been a field of many progresses, but the discovery of the role of androgen in the genesis of prostate cancer by Hugins and Hodges is really a milestone in the treatment of advanced prostate cancer [2]. In patients with advanced prostate cancer, options for androgen ablation include bilateral orchiectomy, therapy with luteinizing hormone-releasing hormone (LHRH) analogues and antagonists, and combined androgen blockade (typically a LHRH analogue plus a first-generation anti-androgen). Although orchiectomy remains the historical gold standard for androgen ablation, LHRH therapy is considered to be equivalent therapeutically. Medical castration has the advantage to induce less psychological effects comparatively to the surgery, reason why in developed countries patients are managed with medical therapy [3]. However, LHRH agonists cannot induce a complete castration levels of testosterone in some patients [4]. Instead, surgical castration can completely eliminate remaining testosterone produced by the Leydig cells in testes [5]. According to the latest recommendations of the European Association of Urology (EAU), androgen deprivation therapy (ADT) is the firstline indication in patients with advanced and metastatic PCa [6]. This first line is made of LHRH agonists, surgical castration representing the second line [7] And Several techniques of surgical castration have been described with comparable results in terms of patient survival and quality of life, but the sub-capsular technique of preserving testicular albuginea and epididymis is the most commonly used [8]. The relatively high cost of chemical castration is a constraint in the therapeutic choice in developing countries [9]. Therefore, surgical castration is an interesting alternative because of its simplicity and affordability in patients, most of whom have no health insurance. In Togo, most patients diagnosed with prostate cancer are at the metastasis stage, and surgical castration is often used as first-line treatment [10]. The aim of this study was to assess the biological and clinical effectiveness of surgical castration as the sole treatment in patients with advanced prostate cancer.

A practical guide for the use of apalutamide for non-metastatic castration-resistant prostate cancer in Australia.

Studies of patients with castrate-resistant prostate cancer at high risk of developing overt metastases but with no current evidence of evaluable disease on computed tomography or bone scan non-metastatic castrate-resistant prostrate cancer have demonstrated increased metastasis-free survival and overall survival following treatment with the next-generation oral anti-androgen apalutamide (in addition to therapies that aim to lower testosterone to castrate levels) or luteinizing hormone-releasing hormone antagonist or surgical castration. Patients receiving apalutamide can be managed by medical oncologists, radiation oncologists, or urologists, preferably as part of a multidisciplinary team. However, the importance of additional safety monitoring for significant adverse effects and drug interactions should not be underestimated. The toxicities of apalutamide are manageable with experience and should be managed proactively to minimize their impact on patients. Monitoring of patients for apalutamide-specific toxicities, including skin rash, hypothyroidism, and QT prolongation should be carried out regularly, particularly in the first few months following initiation. Monitoring should continue alongside monitoring for toxicities of androgen deprivation, including cardiovascular risk, hot flashes, weight gain, bone health, muscle wasting, and diabetic risk. This review is a practical guide to the use of apalutamide describing the management of patients including dosing and administration, toxicities, potential drug interactions, and safety monitoring requirements.

Exploring sexual health in premenopausal patients with hormone positive early breast cancer: Comparison between LHRH and oophorectomy.

e23172 Background: Ovarian function suppression (OFS) is recommended for premenopausal patients with hormone (HR) positive early breast cancer at higher risk of recurrence. This is achieved with the use of the luteinizing hormone–releasing hormone agonist (LHRH) or oophorectomy. Sexual health is an important aspect for women with breast cancer, although unfortunately this issue is often not addressed. The aim of this study was to explore sexual health issues in premenopausal HR-positive patients with LHRH vs. Oophorectomy. Methods: A prospective observational study was conducted during the period of June 2023 and December 2023, enrolling premenopausal patients with Early stage HR positive (HER2 positive or negative) breast cancer diagnosed between 2017 and 2023, who were treated with OFS and remained free of disease. Involved patients were divided in two groups: Group A – received LHRH and Groups B - underwent oophorectomy. All patients were surveyed with EORTC QLQ-BR-45 questionnaire during their follow-up or scheduled LHRH injection visits at clinic. The questionnaire included Functional (F) and Symptom (S) scales evaluating sexual functioning, sexual enjoyment, endocrine therapy symptoms, endocrine sexual symptoms. Results: It was planned to enroll 100 patients in the study, but only 34 patients (24 in Group A, 10 in Group B) consented to participate, the majority of patients did not want to share their sexual life issues, even anonymously. Of those enrolled, median age was similar (42 in group A, 43 in group B), all had stage I-II breast cancer, and all were in continued remission at the time of enrollment. A similar proportion had HER2 positive disease (25% and 20%, respectively). Far more people in Group A were treated with breast conserving surgery (67% vs 30%, respectively) with 20% of participants in in Group B undergoing bilateral mastectomy. More volunteers received chemotherapy in Group A (88% vs 60% in group B). Among those in Group B, 6 of 10 were previously treated with LHRH before oophorectomy and the procedure was done due to endometrial hyperplasia (n = 3), known BRCA mutation (n = 1), persistent estrogen levels despite LHRH (n = 1), and patient preference (n = 5). More patients had a partner at enrollment in group B (90% vs 67% in Group A); only one person identified as a lesbian (enrolled in group B). F score S > 60 was noted in more Group A vs Group B participants (50% vs 30%). More people in Group A had S score S < 40, indicating higher quality of life (79% vs 50%, respectively). Conclusions: The study suggests that sexuality after cancer is a difficult area to study in Georgia, likely due to cultural issues. While we could not account for the contribution of known variables that impact sexuality in this population (e.g. surgery type, chemotherapy) due to small numbers, our data suggest that LHRH antagonist use may have a lesser risk to sexual function compared to oophorectomy.

Relationship between circulating FSH levels and body composition and bone health in patients with prostate cancer who undergo androgen deprivation therapy: The BLADE study.

Among its extragonadal effects, follicle-stimulating hormone (FSH) has an impact on body composition and bone metabolism. Since androgen deprivation therapy (ADT) has a profound impact on circulating FSH concentrations, this hormone could potentially be implicated in the changes of fat body mass (FBM), lean body mass (LBM), and bone fragility induced by ADT. The objective of this study is to correlate FSH serum levels with body composition parameters, bone mineral density (BMD), and bone turnover markers at baseline conditions and after 12 months of ADT. Twenty-nine consecutive non-metastatic prostate cancer (PC) patients were enrolled from 2017 to 2019 in a phase IV study. All patients underwent administration of the luteinizing hormone-releasing hormone antagonist degarelix. FBM, LBM, and BMD were evaluated by dual-energy x-ray absorptiometry at baseline and after 12 months of ADT. FSH, alkaline phosphatase, and C-terminal telopeptide of type I collagen were assessed at baseline and after 6 and 12 months. For outcome measurements and statistical analysis, t-test or sign test and Pearson or Spearman tests for continuous variables were used when indicated. At baseline conditions, a weak, non-significant, direct relationship was found between FSH serum levels and FBM at arms (r = 0.36) and legs (r = 0.33). Conversely, a stronger correlation was observed between FSH and total FBM (r = 0.52, p = 0.006), fat mass at arms (r = 0.54, p = 0.004), and fat mass at trunk (r = 0.45, p = 0.018) assessed after 12 months. On the other hand, an inverse relationship between serum FSH and appendicular lean mass index/FBM ratio was observed (r = -0.64, p = 0.001). This is an ancillary study of a prospective trial and this is the main limitation. FSH serum levels after ADT could have an impact on body composition, in particular on FBM. Therefore, FSH could be a promising marker to monitor the risk of sarcopenic obesity and to guide the clinicians in the tailored evaluation of body composition in PC patients undergoing ADT. This research was partially funded by Ferring Pharmaceuticals. The funder had no role in design and conduct of the study, collection, management, analysis, and interpretation of the data and in preparation, review, or approval of the manuscript. clinicalTrials.gov NCT03202381, EudraCT Number 2016-004210-10.

Patient preference on once-daily oral versus injectable androgen deprivation therapy for Asian patients with advanced prostate cancer

PurposeThe study aimed at investigating prostate cancer patients’ choice of androgen deprivation treatment (ADT) and possible factors that would affect their preferences of ADT.MethodsThis was a single-centre cross-sectional study investigating the usage and preferences of ADT. Consecutives prostate cancer patients who were receiving injectable luteinizing hormone-releasing hormone (LHRH) agonist or antagonist were recruited from the prostate cancer clinic in a tertiary academic hospital. Patients who received bilateral orchidectomy or those who could not consent to the study were excluded. Disease characteristics, treatment information and patient background were documented. The survey collected information related to their change in ADT regimen, preferences on drug usage (routes and frequency of administration) and their reasons. A hypothetical set of three drug formularies was designed. Questions regarding patient preference and the contributing reasons raised in the format of questionnaire.Results100 patients completed the survey. Most patients started with more frequent injections (3-monthly, 54%; 1-monthly, 38%) and switched to 6-monthly injections (89%) at the time of the survey. Primary reasons for the change were healthcare opinion (72%) and less frequent treatment (51%).Three options of ADT (oral daily, 1-monthly and 6-monthly injection) with the same efficacies and side effect profile were offered: 61% preferred 6-monthly injection, 1% preferred 1-monthly injection and 38% preferred oral regimen. When patients were informed of lower cardiovascular side effects in 1-monthly injection or daily oral drug, patients’ preference was 56% (6-monthly), 6% (1-monthly), and 39% (oral). Patients with polypharmacy (more than 5 regular medications) were more inclined to choose injections (p = 0.025). Patient age, educational background, employment status, marriage status and disease status were not found to be statistically significant contributing factors to patient preference.Conclusion6-monthly ADT injection was the preferred ADT despite greater cardiovascular risks. Among 1-monthly or daily oral LHRH antagonist, more patients prefer oral option. Convenience factor was highly valued.

Efficacy of Degarelix in the Neoadjuvant Setting in Managing Locally Advanced Prostate Cancer.

Background Prostate cancer holds a substantial presence in the global cancer landscape, and a considerable proportion of diagnoses occur at late stages, particularly in India. Management of locally advanced prostate cancer necessitates a multimodal treatment strategy. A critical part of this strategy is neoadjuvant androgen deprivation therapy, typically administered via luteinizing hormone-releasing hormone (LHRH) analogs. This study explores the potential of an alternative approach: neoadjuvant therapy with degarelix, an LHRH antagonist, and its impact on perioperative and postoperative outcomes in patients undergoing radical prostatectomy for locally advanced or high-risk prostate cancer. Methodology We conducted a retrospective, non-randomized clinical study at Apollo Hospitals in Chennai, India. Patients diagnosed with locally advanced or high-risk prostate cancer who underwent radical prostatectomy were included. Participants were patients treated with neoadjuvant degarelix and subsequent radical prostatectomy between March 2020 and June 2022. We excluded patients receiving radical radiotherapy, those switching from LHRH agonists to antagonists, and those contraindicated for androgen deprivation therapy due to existing comorbidities. For comparison, we selected a group from the institutional database who received conventional treatment (i.e., without neoadjuvant therapy). Results The study compared two groups, each with 32 patients. The groups had no significant difference in total operative duration and console times. The postoperative pathological assessment showed significantly lower margin positivity rates and notable pathological downstaging in the group receiving neoadjuvant degarelix compared to the control group. The incidence of node positivity, prostate-specific antigen levels at three months postoperative, and number of pads used per day at one month did not differ significantly between the two groups. Conclusions Our study suggests that neoadjuvant degarelix could notably enhance patient outcomes in locally advanced prostate cancer management. The benefits include improved symptom control, significant reductions in margin positivity rates, and facilitated surgical procedures. Neoadjuvant degarelix therapy could potentially enhance the feasibility of the surgical intervention in locally advanced prostate cancer management, thus suggesting a promising pathway for improved patient care.

Efficacy and Safety of Neoadjuvant Luteinizing Hormone-Releasing Hormone Antagonist and Tegafur-Uracil Chemohormonal Therapy for High-Risk Prostate Cancer.

This retrospective single-center cohort study evaluated the efficacy and safety of a combination of neoadjuvant luteinizing hormone-releasing hormone (LHRH) antagonist and tegafur-uracil (UFT) therapy (NCHT) and investigated the medical records of patients with high-risk PCa who underwent robot-assisted radical prostatectomy (RARP). The therapy was followed by RARP for high-risk PCa. The enrolled patients were divided into two groups: low-intermediate-risk PCa patients who underwent RARP without neoadjuvant therapy (non-high-risk) and those who underwent NCHT followed by RARP (high-risk group). This study enrolled 227 patients (126: non-high-risk and 101: high-risk group). Patients in the high-risk-group had high-grade cancer compared to those in the non-high-risk-group. At the median follow-up period of 12.0 months, there were no PCa deaths; two patients (0.9%) died of other causes. Twenty patients developed biochemical recurrence (BCR); the median time until BCR was 9.9 months after surgery. The 2-year biochemical recurrence-free survival rates were 94.2% and 91.1% in the non-high-risk and high-risk-group, respectively (p = 0.465). Grade ≥3 NCHT-related adverse events developed in nine patients (8.9%). This study indicates that combining neoadjuvant LHRH antagonists and UFT followed by RARP may improve oncological outcomes in patients with high-risk PCa.

PD21-08 PERSISTENT TESTOSTERONE SUPPRESSION AFTER CESSATION OF ANDROGEN DEPRIVATION THERAPY FOR PROSTATE CANCER

You have accessJournal of UrologyCME1 Apr 2023PD21-08 PERSISTENT TESTOSTERONE SUPPRESSION AFTER CESSATION OF ANDROGEN DEPRIVATION THERAPY FOR PROSTATE CANCER Nicholas Deebel, Jessica Delgado, Jesse Ory, Justin Loloi, Ari Bernstein, Sirpi Nackeeran, and Ranjith Ramasamy Nicholas DeebelNicholas Deebel More articles by this author , Jessica DelgadoJessica Delgado More articles by this author , Jesse OryJesse Ory More articles by this author , Justin LoloiJustin Loloi More articles by this author , Ari BernsteinAri Bernstein More articles by this author , Sirpi NackeeranSirpi Nackeeran More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003287.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Androgen deprivation therapy (ADT) is frequently used in the treatment of localized PCa. Many men receiving temporary ADT for localized prostate cancer fail to achieve baseline testosterone (T) levels after cessation. However, current literature limits the ability to predict prolonged testosterone deficiency (TD) based on ADT regimen and duration. Testosterone recovery in men with localized prostate cancer receiving temporary ADT was assessed. METHODS: A globally federated health research network (TriNetX) was used to identify men diagnosed with prostate cancer undergoing temporary ADT. Inclusion criteria consisted of: a clinically localized prostate cancer and eugonadal mean baseline T level (>300 ng/dL). Prior to starting ADT two cohorts were identified: Men receiving LHRH antagonists or LHRH agonists and men receiving combined ADT (LHRH agonist and antiandrogens). Further stratification was based on treatment duration of 6 months (short-term) or 18 months (long-term) to compare T recovery profiles 5 years after ADT cessation. RESULTS: A total of 28,583 men received LHRH agonist or antagonist therapy alone and 20,188 men received combination ADT. A total of 46.7% of men who received short-term LHRH agonists or antagonists and 40.6% of men who received short-term combined ADT recovered to mean baseline T levels at 5 years (p = 0.06). Only men who received short-term LHRH agonist/antagonists recovered to a mean eugonadal level at 5 year follow-up. Meanwhile, 50% of men who received long-term LHRH agonist/antagonist therapy and 10.7% of men who received long-term combined ADT recovered to mean baseline T levels at 5 years (p < 0.0001). However, neither group recovered to a mean eugonadal T level. CONCLUSIONS: Most patients failed to recover to mean baseline and eugonadal T levels at 5-year follow-up. Given that TD is associated with a myriad of adverse effects such as metabolically adverse changes in body composition, increased insulin resistance, impaired bone health, and hypogonadal symptoms, serum T levels must be closely followed in men receiving ADT following treatment cessation. Source of Funding: NIH Grant R01 DK130991 and Clinician Scientist Development Grant from the ACS to RR © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e593 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nicholas Deebel More articles by this author Jessica Delgado More articles by this author Jesse Ory More articles by this author Justin Loloi More articles by this author Ari Bernstein More articles by this author Sirpi Nackeeran More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF downloadLoading ...

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 (&lt;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&lt;0.001); adjusted: HR=2.29, 95% CI [1.93, 2.71], p&lt;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.

The difference in serum testosterone recovery between Gn-RH Antagonist and LH-RH agonist among patients with prostate cancer treated with radiation therapy.

382 Background: Only limited data exist related to the serum testosterone (TST) recovery after discontinuation of Gn-RH antagonist (Degarelix acetate). In the present study, we investigated the difference in serum testosterone (TST) recovery between LH-RH agonist and Gn-RH antagonist among prostate cancer (Pca) patients received radiation therapy in combination with androgen deprivation therapy (ADT). Methods: We analyzed the association between TST levels after the end of endocrine therapy and clinical factors in 130 patients who underwent ADT for prostate cancer at Chiba University hospital between May 2003 and May 2020. The proportional hazards model and Kaplan-Meier methods were used for the statistical analysis. Results: The median patient age and PSA were 72 years, and 16.8ng/mL, respectively. The median initial TST and nadir TST were 457 ng/dL, and 20ng/dL, respectively. The median duration of ADT was 857 days. As factors affect the speed of recovery to the castration level (TST 50 ng/dL), univariate analysis showed that Gn-RH antagonist presented the significantly shorter TST recovery compared to those of LH-RH agonist (HR 1.9, p=0.0078), together with the duration of hormone therapy (857 days) and Nadir TST level (20 ng/dL), GS8 and PSA (16.8ng/mL). Multivariate analysis showed that Nadir TST level was an independent predictor (HR 2.0, p=0.0093). As factors affect the speed of recovery to the physiological level (TST 200 ng/dL), univariate analysis showed that Gn-RH antagonist presented the significantly shorter TST recovery compared to those of LH-RH agonist (HR 2.1, p=0.0064). Multivariate analysis showed that duration was the only independent predictor (HR0.34, p=0.0029). Kaplan-Meier curve demonstrated shorter time for the TST recovery in Gn-RH antagonist compared to the LH-RH agonist for the castration level (p=0.0064) and the physiological level (p=0.0052). Conclusions: TST recoveries were significantly shorter in Pca patients treated with Gn-RH antagonist than LH-RH agonist. Nadir TST value, duration, and a type of LH-RH drug may comprehensively suggest us the dynamics of TST recovery after ADT. [Table: see text]

Persistent Testosterone Suppression After Cessation of Androgen Deprivation Therapy for Prostate Cancer.

Introduction Many men receiving temporary androgen deprivation therapy (ADT) for localized prostate cancer fail to achieve baseline testosterone levels after cessation. Testosterone recovery in men with localized prostate cancer receiving temporary ADT was assessed. Methods A global federated health research network (TriNetX) was used to identify men diagnosed with prostate cancer undergoing temporary ADT. Two cohorts were identified: men receiving luteinizing hormone-releasing hormone (LHRH) antagonists or LHRH agonists, and men receiving combined ADT (LHRH agonist and antiandrogens). Further stratification was based on a treatment duration of six months (short-term) or 18 months (long-term) to compare testosterone (T) recovery profiles five years after ADT cessation. Results A total of 28,583 men received LHRH agonist or antagonist therapy alone, and 20,188 men received combination ADT. A total of 46.7% of men who received short-term LHRH agonists or antagonistsand 40.6% of men who received short-term combined ADT, recovered to mean baseline T levels at five years. Only men who received short-term LHRH agonists/antagonists recovered to eugonadal levels at the five-year follow-up. Around 50% of men who received long-term LHRH agonist/antagonist therapy and 10.7% of men who received combined ADT, recovered to mean baseline T levels at five years. However, neither group recovered to eugonadal T levels. Conclusions At the five-year follow-up after ADT cessation, most patients failed to recover to their mean baseline and eugonadal T levels. Given that testosterone deficiency is associated with metabolically adverse changes in body composition, increased insulin resistance, impaired bone health, and hypogonadal symptoms, serum T levels must be closely monitored in men receiving ADT following treatment cessation.

Advancements in the treatment of metastatic hormone-sensitive prostate cancer.

In the last decade, there have been substantial improvements in the outcome of the management of metastatic hormone-sensitive prostate cancer (mHSPC) following the development of several novel agents as well as by combining several therapeutic strategies. Although the overall survival (OS) of mHSPC is shown to improve with intense androgen deprivation therapy (ADT), combined with docetaxel, as well as other novel hormonal therapy agents, or alongside local intervention to the primary neoplasm. Notably, luteinizing hormone-releasing hormone (LHRH) antagonists are known to cause fewer cardiovascular side effects compared with LHRH agonists. Thus, in this mini review, we explore the different approaches in the management of mHSPC, with the aim that we may provide useful information for both basic scientists and clinicians when managing relevant clinical situations.

An observational multicenter study to evaluate the efficacy and safety of degarelix® for prostate cancer in routine clinical practice

Background. Prostate cancer (PCa) is an actual disease and a frequent oncological pathology in men. The main methods of radical treatment of patients with PCa are radical prostatectomy and radiation therapy. Radical prostatectomy s the most commonly used method of therapy in patients with localized PCa. Adjuvant hormone therapy after surgical treatment is the standard method of therapy in patients with the presence of lymph node metastases. At the same time, the standard approach of treatment of patients with metastatic PCa is combination therapy with medical (using of analogues or antagonists of luteinizing hormone-releasing hormone (LHRH) or surgical castration in combination with chemotherapy with docetaxel or new generation antiandrogens (enzalutamide or apalutamide)). Numerous studies have demonstrated the importance of achieving minimum testosterone levels at all stages of drug therapy in patients with PCa. It has also been shown that the use of LHRH analogues may be less effective to the use of LHRH antagonists (degarelix) in relation to the effectiveness of testosterone suppression. Thus, conducting a study aimed at studying the effectiveness of testosterone suppression using LHRH antagonists in various clinical situations and patient populations in real clinical practice is a very actual task.Aim. To evaluate the effectiveness and safety of castration therapy using degarelix in real clinical practice and in various clinical situations.Materials and methods. The object of an observational non-interventional study was 132 patients with PCa from 13 cancer centers of Russian Federation who were treated with LHRH antagonist degarelix. The study was non-interventional (observational), retrospectively-prospective, open multicenter and not randomized. In accordance with the design of the study, depending on the clinical situation, patients were divided into 3 groups: group A (n = 52; 39.4 %) – patients with primary metastatic hormone-sensitive PCa, who were shown to undergo combined drug treatment with castration therapy as one of the components; group B (n = 43; 32.6 %) – patients, who underwent combined hormonal and radiation treatment (ADT + radiation therapy); group C (n = 37; 28 %) – patients who underwent surgical treatment (radical prostatectomy with extended PLND) with the presence of metastases in the lymph nodes identified by the results of a morphological examination (pN1).Results and conclusion. As a result of a non-interventional observational study, high efficacy of androgen-deprivation therapy with the use of degarelix was demonstrated in relation to the suppression of testosterone and PSA in patients with primary metastatic and locally advanced PCa in various clinical situations, as well as low toxicity and satisfactory tolerability of this variant of hormonal treatment.

MP48-02 PERSISTENT TESTOSTERONE SUPPRESSION AFTER CESSATION OF ANDROGEN DEPRIVATION THERAPY FOR LOCALIZED PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022MP48-02 PERSISTENT TESTOSTERONE SUPPRESSION AFTER CESSATION OF ANDROGEN DEPRIVATION THERAPY FOR LOCALIZED PROSTATE CANCER Jessica Delgado, Jesse Ory, Joshua Bitran, Ruben Blachman Braun, Sirpi Nackeeran, and Ranjith Ramasamy Jessica DelgadoJessica Delgado More articles by this author , Jesse OryJesse Ory More articles by this author , Joshua BitranJoshua Bitran More articles by this author , Ruben Blachman BraunRuben Blachman Braun More articles by this author , Sirpi NackeeranSirpi Nackeeran More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002619.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Introduction: ADT plays a fundamental role in the treatment of localized prostate cancer. However, there is limited data regarding testosterone recovery in men who have received ADT for localized prostate cancer. Identification of T recovery profiles associated with ADT will facilitate personalization of ADT regimens and guide future treatment strategies to minimize the risk of T deficiency in patients following treatment for prostate cancer. Objective: Temporary use of Androgen Deprivation Therapy (ADT) is a cornerstone in the treatment of localized prostate cancer. However, the ability for testosterone to recover after ADT is not well understood. The aim of this study was to investigate testosterone recovery in men with localized prostate cancer following ADT. METHODS: A global federated health research network (TriNetX) was used to identify men with a diagnosis of prostate cancer who underwent temporary use of ADT. Three cohorts were identified: Men who received LHRH antagonists, LHRH agonists, and men who received combined ADT (LHRH agonist and antiandrogens). Further stratification was based on treatment duration of 6 or 18 months to compare T recovery profiles 5 years after ADT cessation. RESULTS: A total of 17,884 men received LHRH agonists alone, 12,767 men received combined ADT, and 628 men received LHRH antagonist therapy alone. Eugondal mean baseline T level (>300 ng/dL) prior to starting ADT was an inclusion criterion for all men. Five years after ADT cessation, 36% of patients who received LHRH agonists recovered eugondal T levels, 26% recovered after LHRH antagonist therapy, and 36.8% recovered after combined ADT. Overall, more than half of men who received ADT failed to recover eugondal T levels even 5 years after treatment cessation. CONCLUSIONS: Five years after ADT cessation for localized prostate cancer, incomplete testosterone recovery persists in >50% of the men. Since, testosterone deficiency will lead to metabolically adverse changes in body composition, increased insulin resistance, impaired bone health, and poor quality of life, serum T levels need to be closely followed in men receiving ADT. Source of Funding: Funding to access the TriNetX database was provided in part by an educational grant from Acerus Pharmaceuticals. Acerus Pharmaceuticals was not involved in the planning, design, writing or any other aspect of this project. © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e820 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jessica Delgado More articles by this author Jesse Ory More articles by this author Joshua Bitran More articles by this author Ruben Blachman Braun More articles by this author Sirpi Nackeeran More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF DownloadLoading ...

HF01-13 FROM TORTURE TO THERAPY: THE HISTORY OF HUMAN CASTRATION

You have accessJournal of UrologyCME1 May 2022HF01-13 FROM TORTURE TO THERAPY: THE HISTORY OF HUMAN CASTRATION Antonio Nacchia, Riccardo Lombardo, Cosimo De Nunzio, and Andrea Tubaro Antonio NacchiaAntonio Nacchia More articles by this author , Riccardo LombardoRiccardo Lombardo More articles by this author , Cosimo De NunzioCosimo De Nunzio More articles by this author , and Andrea TubaroAndrea Tubaro More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002541.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Castration is any action, surgical or chemical, by which an individual loses the use of the gonads, particularly testicles. Surgical castration consists in bilateral orchiectomy and chemical castration uses pharmaceutical drugs to deactivate the testes. Human castration is a practice known from Sumerian time as cruel torture. In history, it has been a religious practice or instrument to obtain eunuch slaves or white voices. Aim of our study was to explore the history of human castration. METHODS: A literature review on human castration was performed through Medline, PubMed and Google Scholar, searching words “castration”, “orchiectomy” and “androgen deprivation”. RESULTS: The earliest records for intentional human castration to produce eunuchs are from the Sumerian city of Lagash in the 21st century BC. Ancient Greeks and ancient Romans used it to produce eunuch slaves. During Byzantine Empire, it was considered such as a punishment. In Arabian countries castration started to be used to obtain faithful harem guardians since 750 AD and then, during the Ottoman Empire, the Imperial Harem was a powerful institution of the Sultan. From the late 16th century castration was carried out in Italy to preserve the unbroken male voice into adult life. In 1941 Huggins and Hodges demonstrated control of prostate cancer growth rate by androgens and showed that there is no better way to achieve temporary control of prostate cancer growth than androgen deprivation (AD). The earliest method of AD is represented by the bilateral orchiectomy, which means a definitive therapy for the patient. In 1944 treatment with Diethylstilbestrol was described as to the first method of reversible castration. In 1979 Schally et al showed that advanced prostate cancer patients treated with daily doses of LHRH agonists experienced a 75% decrease in serum testosterone levels and a marked reduction in cancer-associated bone pain. Medical castration by means of medrossiprogesterone acetate or cyproterone acetate is also used for convicted rapist or sex offenders in some countries. Although more expensive, medical castration is nowadays the standard considering its hypothetical reversible effect and the psychological trauma related to surgery. CONCLUSIONS: The possibility to change male habitus through surgical castration has been evident since the 11th century BC and used to punish or to create specific workers such as eunuchs or singers. Just only in the last century the role of surgical castration has been associated with prostate cancer treatment and LHRH agonist and antagonist have become the new standard to induce castration. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e216 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Antonio Nacchia More articles by this author Riccardo Lombardo More articles by this author Cosimo De Nunzio More articles by this author Andrea Tubaro More articles by this author Expand All Advertisement PDF DownloadLoading ...

Androgen Flare after LHRH Initiation Is the Side Effect That Makes Most of the Beneficial Effect When It Coincides with Radiation Therapy for Prostate Cancer.

Simple SummaryProstate cancer tumor growth is stimulated by androgens. Surgical castration or medical castration using long-acting luteinizing hormone-releasing hormone (LHRH) agonists or antagonists is the backbone of the treatments of metastatic disease. Treatment of locally advanced prostate cancer was accomplished with radiation therapy alone until multiple studies showed that combining radiation therapy with LHRH agonists results in significant survival benefit. While the goal of the use of LHRH agonists was to suppress testosterone levels during radiation, we show, through review of previous studies, that survival benefit was achieved only when LHRH was initiated during the course of radiation, and thus androgen flare during the first 1–3 weeks after the initiation of LHRH is most likely the reason for higher survival. Androgens drive tumor cells into mitosis, and mitotic death is the dominant mechanism of tumor cell kill by radiation.Treatment of metastatic prostate cancer was historically performed via bilateral orchiectomy to achieve castration. An alternative to surgical castration is the administration of subcutaneous recombinant luteinizing hormone-releasing hormone (LHRH). LHRH causes the pituitary gland to produce luteinizing hormone (LH), which results in synthesis and secretion of testosterone from the testicles. When LHRH levels are continuously high, the pituitary gland stops producing LH, which results in reduced testosterone production by the testicles. Long-acting formulations of LHRH were developed, and its use replaced surgical orchiectomy in the vast majority of patients. Combining LHRH and radiation therapy was shown to increase survival of prostate cancer patients with locally advanced disease. Here, we present a hypothesis, and preliminary evidence based on previous randomized controlled trials, that androgen surge during radiation, rather than its suppression, could be responsible for the enhanced prostate cancer cell kill during radiation. Starting LHRH agonist on the first day of radiation therapy, as in the EORTC 22863 study, should be the standard of care when treating locally advanced prostate cancer. We are developing formulations of short-acting LHRH agonists that induce androgen flare, without subsequent androgen deprivation, which could open the door for an era in which locally advanced prostate cancer could be cured while patients maintain potency.

Persistent Testosterone Suppression After Cessation of Androgen Deprivation Therapy for Localized Prostate Cancer

ABSTRACT Introduction ADT plays a fundamental role in the treatment of localized prostate cancer. However, there is limited data regarding testosterone recovery in men who have received ADT for prostate cancer. Identification of T recovery profiles associated with ADTs will facilitate personalization of ADT regimens and guide future treatment strategies to minimize the risk of T deficiency in patients with prostate cancer. Objective Temporary use of Androgen Deprivation Therapy (ADT) is a cornerstone in the treatment of localized prostate cancer. However, the ability for testosterone to recover after ADT is not well understood. The aim of this study was to investigate testosterone recovery in men with prostate cancer following varying ADT modalities and treatment durations. Methods A global federated health research network (TriNetX) was used to identify men with a diagnosis of prostate cancer who underwent temporary use of ADT. Three cohorts were identified: Men who received LHRH antagonists, LHRH agonists, and men who received combined ADT (LHRH agonist and antiandrogens). Further stratification was based on treatment duration of 6 or 18 months to compare T recovery profiles at follow up periods of 2 and 5 years. Results A total of 17,884 men received LHRH agonists alone, 12,767 men received combined ADT, and 628 men received LHRH antagonist therapy alone. Eugondal mean baseline T level (&amp;gt;300 ng/dL) prior to starting ADT was an inclusion criterion for all men. Five years after ADT cessation, 36% of patients who received LHRH agonists recovered eugondal T levels, 26% recovered after LHRH antagonist therapy, and 36.8% recovered after combined ADT. Overall, more than half of men who received ADT failed to recover eugondal T levels even 5 years after treatment cessation. Conclusions Five years after ADT cessation, incomplete testosterone recovery persists in more than 50% of men. Testosterone deficiency will lead to metabolically adverse changes in body composition, increased insulin resistance, impaired bone health, and poor quality of life and needs to be evaluated even after cessation of ADT. Disclosure No

A review of clinical evidence to assess differences in efficacy and safety of luteinizing hormone-releasing hormone (LHRH) agonist (goserelin) and LHRH antagonist (degarelix).

Luteinizing hormone-releasing hormone agonist (LHRH-A), goserelin, and antagonist, degarelix, are both indicated for the treatment of advanced prostate cancer (PCa); however, large comparative trials evaluating their efficacy and safety are lacking. In this review, we assessed the available evidence for both the drugs. Although degarelix achieves an early rapid decline in testosterone (T) and prostate-specific antigen (PSA) levels, median T and PSA levels, in addition to prostate volume and International Prostate Symptom Scores, become comparable with goserelin over the remaining treatment period. Degarelix causes no initial flare, therefore it is recommended in patients with spinal metastases or ureteric obstruction. Goserelin achieves lower PSA, improved time to progression, and better survival outcomes when administered adjunctively to radiotherapy compared with radiotherapy alone, with significant results even over long-term follow-up. The evidence supporting adjuvant degarelix use is limited. Goserelin has better injection site safety, single-step delivery, and an efficient administration schedule compared with degarelix, which has significantly higher injection site reactions and less efficient administration mechanism. There is conflicting evidence about the risk of cardiovascular disease (CVD), and caution is required when using LHRH-A in patients with preexisting CVD. There is considerable long-term evidence for goserelin in patients with advanced PCa, with degarelix being a more recent option. The available comparative evidence of goserelin versus degarelix has several inherent limitations related to study design, sample size, conduct, and statistical analyses, and hence warrants robust prospective trials and long-term follow-up.