Intermittent Androgen Deprivation Therapy Research Articles

The Androgen Deprivation Therapy Landscape in 2024 – Co-navigating the Available Options with Prostate Cancer Patients

This symposium convened during the 2024 European Association of Urology (EAU) Congress in Paris, France, focusing on the multifaceted aspects of prostate cancer (PCa) treatment from the patient’s perspective. The session delved into the nuanced needs, expectations, and treatment experiences encountered by individuals diagnosed with this condition. A pivotal aspect of the discussion centred on the imperative of ensuring patient awareness and informed consent, particularly concerning androgen deprivation therapy (ADT), given its array of potential side effects. ADT, a cornerstone in advanced PCa management, encompasses a spectrum of side effects including both physical and psychological dimensions. These include, but are not limited to, body hair loss, weight fluctuations, mood alterations, decreased libido, cognitive impairments, muscle atrophy, and bone density loss. Effective management of these side effects requires comprehensive support to be provided to patients to mitigate complications and optimise quality of life. The options for ADT were discussed, with their comparative strengths and challenges. ADT strategies take effect over different time periods (from 12 hours up to 4 weeks), exert varying effects on testosterone levels, and carry different side effect profiles. Selecting the optimal course of treatment for localised or locally advanced PCa requires consideration of whether the patient is at intermediate-, high-, or very high-risk of biochemical recurrence, and whether the intermediate-risk disease is classified as favourable intermediate-risk (FIR) or unfavourable intermediate-risk (UIR). While continuous ADT is the standard of care, intermittent ADT has been associated with significantly better quality of life scores for hot flushes, desire for sexual activity, and urinary symptoms, with a trend toward improvement in the level of fatigue. Furthermore, the interplay between PCa, ADT, and cardiovascular disease (CVD) was discussed to underscore the imperative for clinicians to assess the cardiovascular risks associated with ADT, particularly in patients with heightened cardiovascular vulnerability. Mitigating the adverse skeletal effects of ADT mandates a multifaceted approach encompassing nutritional supplementation, exercise regimens, and lifestyle modifications including alcohol cessation and smoking cessation. Integrating a prehabilitation checklist into clinical practice emerges as a pragmatic strategy to facilitate informed discussions regarding the potential adverse effects of ADT, enabling proactive support provision to optimise patient outcomes.

A joint-threshold Filippov model describing the effect of intermittent androgen-deprivation therapy in controlling prostate cancer

Intermittent androgen-deprivation therapy (IADT) can be beneficial to delay the occurrence of treatment resistance and cancer relapse compared to the standard continuous therapy. To study the effect of IADT in controlling prostate cancer, we developed a Filippov prostate cancer model with a joint threshold function: therapy is implemented once the total population of androgen-dependent cells (AC-Ds) and androgen-independent cells (AC-Is) is greater than the threshold value ET, and it is suspended once the population is less than ET. As the parameters vary, our model undergoes a series of sliding bifurcations, including boundary node, focus, saddle, saddle-node and tangency bifurcations. We also obtained the coexistence of one, two or three real equilibria and the bistability of two equilibria. Our results demonstrate that the population of AC-Is can be contained at a predetermined level if the initial population of AC-Is is less than this level, and we choose a suitable threshold value.

Current Clinical Aspects of Androgen Deprivation Therapy for Locally Advanced and Metastatic Prostate Cancer: A Scoping Review for Urologists and Medical Providers.

Prostate cancer (PCa) currently stands as the most common malignancy and the second most common cause of death in men worldwide. Dr. C. Huggins revolutionized the field of PCa treatment through his work investigating the therapeutic effects of androgen deprivation. These early surgical castration methods were expanded upon by integrating reversible pharmacologic castration via biologic agonists. Following this, intermittent ADT (iADT) became a medical substitute for its continuous counterpart. This data synthesis aims to highlight and assess the pertinent adverse effects of ADT, to compare mortality for PCa treatment plans, and consequently provide direction for clinicians in choosing the suitable systemic ADT approach. We performed a thorough systematic search across the PubMed database to identify prospective randomized clinical trials (RCTs) comparing continuous and intermittent androgen deprivation therapy (cADT and iADT). Our qualitative analysis aimed to evaluate the potential of iADT as an alternative treatment approach, emphasizing recent clinical outcomes. The analysis of randomized control trials in the literature revealed no discernable statistical difference in PCa-specific mortality in comparison of iADT and cADT treatments. Further, in the analysis of mortality due to non-PCa causes, iADT patients fared more favorably compared to cADT. Due to iADT's characteristics of being more cost-efficient and less likely to cause undesirable side effects, urologic healthcare professionals should be made aware of these findings when counseling patients on the optimal form of ADT and consulting for future treatment guidelines.

Is There a Place for De-escalating Therapy in Patients with Metastatic Hormone-sensitive Prostate Cancer?

Although intermittent androgen deprivation therapy was often recommended for metastatic hormone-sensitive cancer therapy in the past, we do not know whether its use can be extrapolated to combination therapy. Trials evaluating intermittent therapy are necessary as this strategy could improve patient quality of life and reduce adverse events and costs.

Androgen Deprivation Therapy in Prostate Cancer: A Practical Approach to Complex Clinical Scenarios

Androgen deprivation therapy (ADT) has been a cornerstone in the treatment of advanced prostate cancer (PCa) for many years, and continues to form the basis of current therapeutic approaches. However, a recent dramatic upsurge in the number of treatment options available in this area creates a responsibility for healthcare professionals to carefully select optimal drugs and combinations of drugs, to ensure the best outcomes and greatest quality of life for all patients. This requires a thorough understanding of clinical trial data, and an ability to apply this knowledge to everyday clinical practice. This article summarises presentations delivered during a symposium held on 29ᵗʰ November 2023 at the Global Congress on Prostate Cancer (PROSCA) 2023 in Málaga, Spain, where three distinguished speakers described and explored practical approaches to the use of ADT in complex clinical scenarios. Nazareno Suardi, Associate Professor of Urology at the University of Brescia, Italy, described approaches to manage ADT prescription when a patient presents with cardiovascular (CV) risk factors. Matthias Saar, Director and Chairman of the Department of Urology and Uro-oncology at the University Hospital Aachen, Germany, explored whether intermittent ADT remains an alternative in the new era of hormonal therapy. Alison Birtle, Consultant Clinical Oncologist at the Rosemere Cancer Centre, Lancashire Teaching Hospitals NHS Trust, Preston, UK, investigated the importance of drug choice in triplet or doublet therapy in patients with metastatic hormone-sensitive PCa (mHSPC). The meeting was chaired by Antoni Vilaseca, Senior Specialist in the Urology Service at the Hospital Clinic, University of Barcelona, Spain, who introduced the symposium, and also co-ordinated a question and answer session to conclude the meeting.

Clinical efficacy of different androgen deprivation therapies for prostate cancer and evaluation based on dynamic-contrast enhanced magnetic resonance imaging.

To evaluate the clinical efficacy of different androgen deprivation therapies for prostate cancer (PCa) based on dynamic-contrast enhanced magnetic resonance imaging (DCE-MRI). 104 patients with PCa were studied, all of whom were treated with androgen deprivation therapy. The patients were divided into a continuous group (continuous androgen deprivation therapy) and an intermittent group (intermittent androgen deprivation therapy) by random number table method, 52 cases/group. The therapeutic effect and DCE-MRI indices were compared and the relationship between DCE-MRI indices and clinical efficacy and the evaluation value of therapeutic efficacy were analyzed. The objective response rate (ORR) of the intermittent group was higher than that of the continuous group (p < 0.05), and there was no significant difference in disease control rate (DCR) between the two groups (p > 0.05). After treatment, volume transfer coefficient (Ktrans), reverse transfer constant (Kep), volume fraction (Ve), blood volume (BV), and blood flow (BF) in both groups were lowered, and those in the intermittent group were lower than the continuous group (p < 0.05). Ktrans, Kep, Ve, BF, and BV in the ORR group were lower than those in the non-ORR group (p < 0.05). Ktrans, Kep, Ve, BF, and BV were correlated with the therapeutic effect of PCa (p < 0.05). The AUC value of the combined detection of DCE-MRI indices in evaluating the therapeutic effect of PCa was greater than that of each index alone (p < 0.05). Compared with continuous androgen deprivation therapy, intermittent androgen deprivation therapy has better clinical efficacy in the treatment of PCa, and DCE-MRI indices are related to the treatment efficacy of PCa and have an evaluation value.

EORTC 2238 "De-Escalate": a pragmatic trial to revisit intermittent androgen deprivation therapy in the era of new androgen receptor pathway inhibitors.

The landscape of treating metastatic prostate cancer has evolved with the addition of Androgen Receptor pathway inhibitor (ARPI) to Androgen Deprivation Therapy (ADT), significantly improving survival rates. However, prolonged use of these therapies introduces notable side effects, prompting a need to revisit intermittent treatment duration. The EORTC 2238 De-Escalate trial is a pragmatic trial seeking to reassess the role of intermittent therapy in patients undergoing maximal androgen blockade (MAB) for metastatic hormone naïve prostate cancer (mHNPC), i.e., the combination of ADT with an ARPI, with the aims of reducing side effects, enhancing Quality of Life (QoL) and optimizing resource usage, while maintaining oncological benefits.

Salvage Androgen Deprivation Therapy as Potential Treatment for Recurrence after Robot-Assisted Radical Prostatectomy.

The efficacy of intermittent androgen deprivation therapy (ADT) for biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP) is unknown, and its usefulness in Japanese practice needs to be investigated. We conducted a retrospective analysis of 85 patients who underwent RARP and were selected for intermittent ADT for postoperative recurrence at Kanazawa University Hospital between 2009 and 2019. Intermittent ADT was administered for 2 years. If prostate-specific antigen levels increased post-treatment, intermittent ADT was reinitiated. The median follow-up period was 47 months. The 73 patients had completed the initial course of ADT, and 12 were under initial ADT. The 5-year castration-resistant prostate-cancer-free survival rates, cancer-specific survival, and overall survival were 92.7%, 98.3%, and 94.7%, respectively. A subgroup analysis of 69 patients who completed intermittent ADT was conducted to evaluate the BCR rate following initial ADT. The 5-year BCR-free survival rate was 53.2%. Multivariate analysis identified testosterone ≤ 0.03 ng/mL during ADT as the sole predictor of BCR after ADT. Salvage intermittent ADT may be an effective treatment option for BCR after RARP. In addition, it would be useful to confirm strong testosterone suppression as a criterion for transition to intermittent therapy.

Testosterone suppression and recovery in patients with advanced prostate cancer treated with intermittent androgen deprivation therapy (iADT) with relugolix.

70 Background: Many patients with advanced prostate cancer do not want to pursue continuous androgen deprivation therapy (cADT) because of concerns about side effects, and pursue iADT. However, even intermittent treatment with GNRH agonist therapy may not lead to rapid recovery of testosterone during the off-treatment period. In the pivotal HERO trial of relugolix (GNRH antagonist) the testosterone recovery time was in weeks [PMID 32469183]. The objective of the study was to measure the time to testosterone suppression to castrate level and time to recovery of serum testosterone to non-castrate level in real-world patients with advanced prostate cancer undergoing intermittent relugolix therapy. Methods: In this IRB-approved retrospective study, the eligibility was: patients with advanced prostate cancer undergoing iADT with relugolix. iADT with relugolix was defined as initiating relugolix at PSA ≥ 10 ng/ml and holding relugolix when PSA ≤ 4 ng/ml. The primary endpoints were: 1) time to serum castrate level of testosterone after relugolix initiation and 2) time to recovery to non-castrate level after discontinuation of relugolix. Castrate level of serum testosterone was defined as serum testosterone level ≤ 50 ng/dL. Results: Overall 25 consecutive patients with advanced prostate cancer treated with iADT with relugolix were eligible and included. The median age was 75 [range 68-88]. Patients with a Gleason score of ≥ 8 comprised 44% of the cohort. The median PSA at the start of therapy was 18.2 ng/ml [5.1 – 99.1 ng/ml]. Median time to testosterone ≤ 50 ng/dl after relugolix initiation was 1.13 months [0.67 – 2.5 months], and median time to testosterone recovery after relugolix discontinuation was 1.4 months [0.83 – 6.57 months]. The median PSA nadir achieved with relugolix was 2.02 ng/ml [0.1 – 4.8], and median time to PSA nadir was 1.35 months from initiation of therapy (0.67 – 4.8 months). Median time to PSA relapse ≥ 10 ng/dl after holding relugolix was 3.4 months (0.9 – 8.23 months). Conclusions: This is the first real-world study to show that iADT with relugolix is associated with a rapid time to testosterone suppression and recovery. These results may guide patients’ counseling, monitoring of serum testosterone and PSA levels in patients wishing to pursue iADT for advanced prostate cancer. These hypothesis-generating data need external validation.

Systemic and tumor-directed therapy for oligorecurrent metastatic prostate cancer (SATURN): Primary endpoint results of a phase II clinical trial.

174 Background: Nearly all men with metastatic hormone-sensitive prostate cancer who receive intermittent androgen deprivation therapy (ADT) will experience a relapse within six months of testosterone recovery. We hypothesized that intensifying intermittent ADT with dual next-generation androgen receptor signaling inhibitors (ARSIs) and adding metastasis-directed stereotactic body radiotherapy (SBRT) would significantly increase the number of men who remain relapse-free six months after testosterone recovery. Methods: Men with 1-5 extrapelvic metastases on prostate-specific membrane antigen (PSMA) PET/CT after initial treatment with definitive-intent radical prostatectomy were enrolled on this phase II study (NCT03902951). Men with visceral metastases were excluded. Patients were treated with 6 months of androgen annihilation therapy (AAT) using leuprolide, abiraterone acetate plus prednisone, and apalutamide. After the first month of AAT, patients received SBRT to all metastases with or without radiotherapy directed to the prostate bed and pelvic lymph nodes. The primary endpoint was the percentage of patients who maintained PSA &lt;0.05 ng/mL six months after testosterone recovery to ≥150 ng/dL, with the study powered to detect an improvement from 1% to 12%. Secondary endpoints included progression-free survival (PFS) starting from AAT initiation and, for patients whose testosterone recovered, eugonadal PFS starting from the time of testosterone recovery. Progression was defined as PSA ≥0.05 ng/mL. Results: 28 men enrolled from March 2021-June 2022. Median follow-up was 20 months (range: 14–27 months). Twenty patients (71.4%) completed six months of ADT with dual ARSIs and SBRT, 5 patients (17.9%) completed ADT with a single ARSI and SBRT, 1 patient (3.6%) completed six months of ADT monotherapy with SBRT, and 2 patients (7.1%) withdrew prematurely. 13/26 patients (50%) maintained PSA &lt;0.05 ng/mL six months after testosterone recovery (95% confidence interval [CI]: 32–67%) compared to the study hypothesis of 12%. Median PFS was 19.3 months (95% CI: 12.8–25.7). 1-year PFS was 69.2%. 21/26 patients (81%) had testosterone recovery at a median of 9.4 months (95% CI: 8.5–10.4) from the start of AAT. Median eugonadal PFS was 11.4 months (95% CI: 4.9–18.0). AAT had 21.4% grade 2 and 21.4% 3 toxicity rates. SBRT had 7.7% grade 2 and no grade 3 toxicity. Conclusions: Half of men with PSMA PET-defined oligorecurrent M1a-b disease who received six months of AAT and metastasis-directed SBRT remained relapse-free six months after testosterone recovery. The regimen was well tolerated, with 90% of patients completing six months of ADT and at least one next-generation ARSI. Further prospective data will evaluate whether dual ARSIs are necessary and the extent to which SBRT with short-course AAT outperforms SBRT with ADT monotherapy in this patient population. Clinical trial information: NCT03902951 .

EORTC GUCG 2238 De-escalate: A pragmatic trial to revisit intermittent androgen-deprivation therapy in metastatic hormone-naïve prostate cancer in the era of new AR pathway inhibitors.

TPS232 Background: The development of androgen receptor pathway inhibitors (ARPI) - abiraterone acetate, apalutamide, darolutamide and enzalutamide - has profoundly reshaped the management of metastatic hormone naïve prostate cancer (mHNPC). Seven trials demonstrated that combining these drugs with androgen deprivation therapy (ADT) reduces the risk of death by 20-40%, delays further treatment, and improves health-related quality of life (HR-QoL). These trials, however, suffer from two critical limitations: treatment duration and patient selection. Treatment usually continues until biochemical, radiological, or clinical progression, sometimes many years after drug initiation, exposing patients to chronic side effects affecting their QoL. Furthermore, registration trials include those not representative of the general population. Several sub-analyses of the registration trials demonstrated that patients achieving a PSA ≤0.2 ng/ml have prolonged overall survival (OS). In this study, we hypothesized that patients reaching PSA ≤ 0.2 ng/ml may benefit from treatment interruption without compromising OS. Methods: The primary goal of this academic-led, open-label, multicenter, pragmatic, randomized phase III study is to investigate whether intermittent maximum androgen blockade (iMAB) can be safely administered to mHNPC patients who reached a PSA ≤ 0.2 ng/mL at 6-12 months of continuous treatment (cMAB), as compared to continuing cMAB. Recommendations for restart include increasing clinical or radiological progression or PSA to ≥ 50% of diagnostic PSA with a maximum of 5 ng/mL.This will be demonstrated through the following co-primary objectives: 1) The proportion of patients who do not need to restart their MAB within one year of interruption is not less than 70%. 2) OS using an iMAB regimen at three years is non-inferior to continuous treatment. Secondary objectives include toxicity comparisons, HR-QoL (physical functioning, role functioning and fatigue scales of EORTC QLQ-C30, sexual activity scale of EORTC QLQ PR25), and assessing the impact on treatment resources of using an intermittent schedule. The study will include 1600 patients treated by cMAB for mHNPC for 6-12 months presenting with a PSA ≤ 0.2 ng/mL. Patients may have received docetaxel and radiotherapy as part of standard treatment. The PRECIS-2 (Pragmatic-Explanatory Continuum Indicator Summary) will be used to evaluate the study as a pragmatic trial. Clinical trial information: NCT05974774 .

Deep reinforcement learning identifies personalized intermittent androgen deprivation therapy for prostate cancer.

The evolution of drug resistance leads to treatment failure and tumor progression. Intermittent androgen deprivation therapy (IADT) helps responsive cancer cells compete with resistant cancer cells in intratumoral competition. However, conventional IADT is population-based, ignoring the heterogeneity of patients and cancer. Additionally, existing IADT relies on pre-determined thresholds of prostate-specific antigen to pause and resume treatment, which is not optimized for individual patients. To address these challenges, we framed a data-driven method in two steps. First, we developed a time-varied, mixed-effect and generative Lotka-Volterra (tM-GLV) model to account for the heterogeneity of the evolution mechanism and the pharmacokinetics of two ADT drugs Cyproterone acetate and Leuprolide acetate for individual patients. Then, we proposed a reinforcement-learning-enabled individualized IADT framework, namely, I$^{2}$ADT, to learn the patient-specific tumor dynamics and derive the optimal drug administration policy. Experiments with clinical trial data demonstrated that the proposed I$^{2}$ADT can significantly prolong the time to progression of prostate cancer patients with reduced cumulative drug dosage. We further validated the efficacy of the proposed methods with a recent pilot clinical trial data. Moreover, the adaptability of I$^{2}$ADT makes it a promising tool for other cancers with the availability of clinical data, where treatment regimens might need to be individualized based on patient characteristics and disease dynamics. Our research elucidates the application of deep reinforcement learning to identify personalized adaptive cancer therapy.

Abstract C017: Comparing prostate specific antigen dynamics between Black patients and White patients

Abstract Black men have the highest prostate cancer (PCa) mortality across all US population groups. We hypothesize that this may be the result of low participation from black men in clinical trials and socioeconomic facotrs. We use a simple mathematical model to investigate differences in PSA dynamics between black and white men undergoing androgen deprivation therapy (ADT). The model was calibrated to longitudinal PSA data from 57 PCa patients (N = 47 white, N = 10 black) receiving continuous androgen deprivation therapy (ADT). To compensate for the lack of data for black patients, propensity score matching was used to select 15 white patients that were most alike to the 10 black patients based on their Eastern Cooperative Oncology Group (ECOG) score, age, and tumor burden. Using a previously developed model of stem cell, non-stem, and prostate-specific antigen (PSA) dynamics, parameter analysis and leave-one-out process were used to determine which parameters should be uniform among all patients and which should be patient-specific to determine if any parameters showed a significant difference. Each patient’s parameter values were used to see if intermittent ADT (IADT) or adaptive ADT could extend the time to progression and narrow disparity gaps. We then sampled from the parameter distributions to create 50 black and 50 white in-silico patients to simulate continuous and intermittent ADT to further validate our results. The leave-one-out analysis found that a uniform ADT cytotoxicity resulted in the best Akaike Information Criteria score for black and white patients. A nested optimization was subsequently used to determine race-specific uniform cytotoxicity rates, while the remaining patient-specific parameters were determined. Statistical analysis found that black patients had a significantly higher stem cell self-renewal rate than the white patients. We hypothesize that this is primarily responsible for earlier progression in black patients. Simulations of continuous and intermittent ADT for real and in-silico patients showed that IADT and adaptive ADT can extend the time to progression (TTP) for both black and white patients. The TTP was extended by 50% for the black patients, and 25% for the white patients, thus the black patients had a greater benefit. However, the median TTP for black patients on IADT was less than that for white patients on continuous ADT. This suggests that further investigation of different treatments needs to be done to close disparity gaps. Our results show that stem cell self-renewal is driving differences in PSA dynamics between white and black patients. Intermittent Androgen Deprivation Therapy could potentially be a step in addressing the higher stem-cell self-renewal rate in black patients and narrowing the health disparity gap between black and white Pca patients. This valuable information can be used in the future to design race-specific treatment modalities to maximally delay time to progression. Citation Format: Alexandria Johnson, Renee Brady. Comparing prostate specific antigen dynamics between Black patients and White patients [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C017.

Intermittent Versus Continuous Androgen Deprivation Therapy for Biochemical Progression After Primary Therapy in Hormone-Sensitive Nonmetastatic Prostate Cancer: Comparative Analysis in Terms of CRPC-M0 Progression

IntroductionTo analyze whether the use of an intermittent (IAD) versus continuous (CAD) androgen deprivation therapy for the treatment of biochemical progression after primary treatments in prostate cancer can influence the development of nonmetastatic castration resistant prostate cancer (CRPC-M0). Patients170 male patients with an histologically confirmed diagnosis of PC, presenting a biochemical progression after primary treatments (82 after radical prostatectomy and 88 after external radiation therapy), nonmetastatic at imaging were considered for continuous (85 cases) or intermittent (85 cases) administration of androgen deprivation therapy. Methodswe retrospectively collect all data regarding histological diagnosis, primary treatment, imaging for M0-M1 staging, PSA at progression, time to biochemical progression from primary therapy, ADT used, IAD cycles, so to compare in 2 groups (IAD vs. CAD) time for progression from the beginning of ADT treatment and type of progression in terms of CRPC-M0 versus CRPC-M1 cases. Resultsno significant (P= .4955) difference in the whole CRPC progression was found between IAD (25.8%) and CAD (30.5%) treatment at a mean of 32.7 ± 7.02 months and 35.6 ± 13.1 months respectively (P= .0738). Mean PSA at CRPC development was significantly higher in the IAD group (5.16 ± 0.68 ng/mL) than in the CAD group (3.1 ± 0.7 ng/mL) (P < .001). In all cases, imaging to detect M status at CRPC development was PET TC scan. At univariate analysis CAD administration significantly increases the RR for CRPC-M0 progression (RR 3.48; 95%CI 1.66-7.29; P = .01) when compared to the IAD administration, and this effect at multivariate analysis remained significant and independent to the other variables (RR 2.34, 95%CI 1.52-5.33; P = .03). Conclusionsin our population with biochemical progression after primary treatment for PC, the intermittent administration of ADT significantly reduces the risk to develop CRPC-M0 disease when compared to a continuous administration of ADT, whereas no difference between the 2 strategies in terms of CRPC-M1 progression exists.

Biochemical recurrence in patients with prostate cancer after primary definitive therapy: treatment based on risk stratification.

Nearly one-third of patients with prostate cancer (PCa) experience biochemical recurrence (BCR) after primary definitive treatment. BCR increases the risk of distant metastasis and mortality in patients with prognostically unfavorable features. These patients are best managed with a tailored treatment strategy incorporating risk stratification using clinicopathological factors, next-generation imaging, and genomic testing. This narrative review examines the utility of risk stratification for the management of patients with BCR in the context of clinical trial data, referencing the latest recommendations by European and US medical societies. PubMed was searched for relevant studies published through May 21 2023 on treatment of patients with BCR after radical prostatectomy (RP) or external beam radiotherapy (EBRT). European and US guidelines support the risk-stratified management of BCR. Post-RP, salvage EBRT (with or without androgen deprivation therapy [ADT]) is an accepted treatment option for patients with BCR. Post-EBRT, local salvage therapies (RP, cryotherapy, high-intensity focused ultrasound, stereotactic body radiotherapy, and low-dose-rate and high-dose-rate brachytherapy) have demonstrated comparable relapse-free survival rates but differing adverse event profiles, short and long term. Local salvage therapies should be used for local-only relapses while ADT should be considered for regional or distant relapses. In practice, patients often receive ADT, with varying guidance for intermittent ADT vs. continuous ADT, due to consideration of quality-of-life effects. Despite a lack of consensus for BCR treatment among guideline associations and medical societies, risk stratification of patients is essential for personalized treatment approaches, as it allows for an informed selection of therapeutic strategies and estimation of adverse events. In lower-risk disease, observation is recommended while in higher-risk disease, after failed repeat local therapy, ADT and/or clinical trial enrollment may be appropriate. Results from ongoing clinical studies of patients with BCR should provide consensus for management.

Comparison of Intermittent and Continuous Androgen Deprivation Therapy in Prostate Cancer Patients: An Up-to-Date Meta-analysis for Urologists and Medical Providers.

Androgen deprivation therapy first became the treatment of choice for advanced prostate cancer in the 1940s with Charles Huggins' discoveries. Eight decades later, androgen deprivation therapy has significantly evolved, and yet is still utilized in various ways to treat certain forms of prostate cancer. For local recurrence after failed primary treatment and for locally advanced and metastatic disease, continuous androgen deprivation therapy has been standard of treatment. However, intermittent androgen deprivation therapy has emerged as a therapeutic alternative to continuous androgen deprivation therapy. The purpose of this meta-analysis is to provide an update on mortality, specifically prostate cancer-specific and nonprostate cancer causes, in order to offer some guidance when selecting the appropriate form of systemic androgen deprivation therapy. The PubMed database was searched for prospective randomized clinical trials. Inclusion and exclusion criteria were defined. Using statistical software, we analyzed random-effects models with the assumption that the data were randomly sampled, estimated the pooled log risk ratio, assessed heterogeneity, and created funnel plots to evaluate publication bias. A total of 12 randomized clinical trials met all inclusion criteria for final analysis. There was no statistically significant difference in prostate cancer-specific mortality between intermittent androgen deprivation therapy and continuous androgen deprivation therapy (RR=1.10 [0.85-1.42]). The analysis of nonprostate cancer mortality favored intermittent androgen deprivation therapy over continuous androgen deprivation therapy, but the difference was statistically insignificant (RR=0.94 [0.76-1.17]). These 2 treatment modalities can be considered as equivalent in long-term treatment outcomes. As intermittent androgen deprivation therapy is more cost-efficient and less likely to yield adverse side effects, future treatment guidelines should consider these advantages over continuous androgen deprivation therapy.

PD21-05 CARDIOVASCULAR OUTCOMES IN A POPULATION-BASED COHORT OF PROSTATE CANCER PATIENTS

You have accessJournal of UrologyCME1 Apr 2023PD21-05 CARDIOVASCULAR OUTCOMES IN A POPULATION-BASED COHORT OF PROSTATE CANCER PATIENTS Siqi Hu, Chun-Pin Chang, John Snyder, Vikrant Deshmukh, Michael Newman, Ankita Date, Carlos Carlos, Benjamin Haaland, Christy Porucznik, Lisa Gren, Alejandro Sanchez, Alejandro Sanchez, Shane Lloyd, Brock O’Neil, and Mia Hashibe Siqi HuSiqi Hu More articles by this author , Chun-Pin ChangChun-Pin Chang More articles by this author , John SnyderJohn Snyder More articles by this author , Vikrant DeshmukhVikrant Deshmukh More articles by this author , Michael NewmanMichael Newman More articles by this author , Ankita DateAnkita Date More articles by this author , Carlos CarlosCarlos Carlos More articles by this author , Benjamin HaalandBenjamin Haaland More articles by this author , Christy PorucznikChristy Porucznik More articles by this author , Lisa GrenLisa Gren More articles by this author , Alejandro SanchezAlejandro Sanchez More articles by this author , Alejandro SanchezAlejandro Sanchez More articles by this author , Shane LloydShane Lloyd More articles by this author , Brock O’NeilBrock O’Neil More articles by this author , and Mia HashibeMia Hashibe More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003287.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prostate cancer is the most common malignancy among men in the United States. Few studies have evaluated cardiovascular disease (CVD) risk comprehensively among prostate cancer patients with treatment dose-response relations. The primary aim of our study is to assess the incidence of cardiovascular diseases among prostate cancer patients compared to a general population cohort. A secondary aim is to investigate socioeconomic status (SES) and clinical risk factors for cardiovascular disorders among prostate cancer patients. METHODS: Cohorts of 18,134 cancer patients with prostate adenocarcinomas diagnosed between 2004 and 2017 and 73,470 men without cancer matched on age, birth state and follow-up time were identified. CVD diagnoses were identified from electronic medical records and statewide healthcare facilities data. Cox proportional hazard models were used to estimate hazard ratios (HRs), adjusted for race/ethnicity, education, baseline Body Mass Index (BMI), baseline Charlson Comorbidity Index (CCI), risk group, age at diagnosis, hyperlipidemia, smoking status, therapy type, and diagnosis year based on a comprehensive evaluation of confounding variables. RESULTS: The risks of CVDs, including hypertension, arterial diseases, and venous diseases, among prostate cancer survivors compared to general population were increased for all follow-up periods after cancer diagnosis (1-5 years: HR=1.17, 95% CI=1.13-1.20; 5-10 years: HR=1.11, 95% CI=1.07-1.16; 10-16 years: HR=1.13, 95% CI=1.06-1.21). The risk of CVD was increased with obesity, baseline comorbidities, lower SES, and advanced-stage cancer, and differed by first-course cancer treatment, with CVDs higher for androgen deprivation therapy (ADT) and conservative treatment. Compared to intermittent ADT, continuous ADT was associated with increased risks of all-cause mortality among prostate cancer patients (HR=1.78, 95% CI=1.04-3.05). We also observed that an increasing duration of ADT was associated with an increased risk of arterial diseases (dose-response p=0.022) and an increased risk of all-cause mortality (dose-response p value=0.0439). CONCLUSIONS: We found an increased risk of CVDs that lasted through 10-16 years post-prostate cancer diagnosis. Lifestyle interventions to decrease the risk of CVDs in prostate cancer survivors may be potentially beneficial to increasing life expectancy. Source of Funding: This work was supported by grants from the NIH (R01 CA244326, R21 CA185811, R03 CA159357, M.Hashibe, PI), the Huntsman Cancer Institute, and the Cancer Control and Population Sciences Program (HCI Cancer Center Support Grant P30CA042014). This research was supported by the Utah Cancer Registry, which is funded by the National Cancer Institute's SEER Program, Contract No. HHSN261201800016I, the US Center for Disease Control and Prevention's National Program of Cancer Registries, Cooperative Agreement No. NU58DP0063200-01, with additional support from the University of Utah and Huntsman Cancer Foundation. Partial support for all datasets within the Utah Population Database is provided by the University of Utah, Huntsman Cancer Institute and the Huntsman Cancer Institute Cancer Center Support grant, P30 CA42014 from the National Cancer Institute © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e591 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Siqi Hu More articles by this author Chun-Pin Chang More articles by this author John Snyder More articles by this author Vikrant Deshmukh More articles by this author Michael Newman More articles by this author Ankita Date More articles by this author Carlos Carlos More articles by this author Benjamin Haaland More articles by this author Christy Porucznik More articles by this author Lisa Gren More articles by this author Alejandro Sanchez More articles by this author Alejandro Sanchez More articles by this author Shane Lloyd More articles by this author Brock O’Neil More articles by this author Mia Hashibe More articles by this author Expand All Advertisement PDF downloadLoading ...

Uncommon Manifestation of Oligometastatic Prostate Cancer: Sister Mary Joseph Nodule.

A 76-year-old man with a history of prostate cancer diagnosed in 2008 developed biochemical recurrence in 2010 and started intermittent androgen deprivation therapy. In 2021, due to rising prostate-specific antigen, an 18 F-piflufolastat PSMA PET/CT was performed. It showed a radiotracer-avid sclerotic lesion in the right iliac bone and an indeterminate radiotracer-avid nodule in the umbilical region, demonstrating progressive enlargement and increased uptake on subsequent imaging. Pathologic analysis of the umbilical nodule revealed metastatic prostate cancer-a finding eponymically referred to as a Sister Mary Joseph nodule.

Association of intermittent or continuous androgen deprivation therapy with cardiovascular disease and endocrine/metabolic disorders in patients with nonmetastatic prostate cancer.

83 Background: Evidence on risks of cardiovascular disease (CVD) and endocrine/metabolic disorders associated with long-term intermittent and continuous androgen deprivation therapy (iADT and cADT, respectively) in patients (pts) with nonmetastatic prostate cancer (nmPC) is mixed. This real-world study examined these risks in pts with nmPC receiving iADT or cADT in the US. Methods: This was a retrospective cohort study of SEER-Medicare pts with nmPC initiating ADT (2010–2017), with ≥36 months of continuous insurance coverage, unless death occurred, and who did not receive chemotherapy or a second-generation anti-androgen during follow-up. iADT and cADT cohorts were defined by treatment patterns and gaps in therapy. Comorbidities and clinical events were identified using ICD-9/10-CM codes. Outcomes examined were major adverse cardiovascular events (MACE [myocardial infarction (MI), stroke, cardiomyopathy/heart failure (HF), pulmonary embolism (PE), ischemic heart disease (IHD), or all-cause mortality]) and endocrine/metabolic events (diabetes, hypercholesterolemia, bone fractures, or osteoporosis). Inverse probability of treatment-weighted Cox regression models estimated the adjusted hazard ratio (aHR) of the outcomes. Subgroup analyses examined pts by CVD history. A sensitivity analysis restricted the definition of MACE to include CVD-related mortality as a component, i.e., MACESA (MI, stroke, cardiomyopathy/HF, PE, IHD, or CVD-related mortality). Results: 10,655 pts were included; 2095 (20%) received iADT and 8560 (80%) cADT; 63% of iADT pts and 66% of cADT pts had baseline CVD history. Median follow-up was 44 and 48 months and time on ADT (excluding gaps for iADT pts) was 23 and 17 months for the iADT and cADT cohorts, respectively. In adjusted analyses, pts receiving cADT had a lower risk of MACE vs iADT. No difference in risk of endocrine/metabolic events was observed. Results for MACE were similar in pts with prior CVD history; however, there was no difference in risk of MACE in those without CVD history. Sensitivity analysis results for MACESA were similar to the main results. Conclusions: Pts with nmPC receiving cADT had a lower risk of MACE, and no difference in risk of endocrine/metabolic events, compared with iADT. There was no difference in risk of MACE in pts without a prior history of CVD. [Table: see text]

Association of intermittent vs continuous androgen deprivation therapy with cardiovascular disease and endocrine/metabolic disorders in patients with metastatic prostate cancer.

82 Background: There is mixed evidence on the risks of cardiovascular disease (CVD) and endocrine/metabolic disorders associated with long-term intermittent and continuous androgen deprivation therapy (iADT and cADT, respectively) for metastatic prostate cancer (mPC). This study examined these risks in patients (pts) with mPC receiving iADT vs cADT in the US. Methods: This was a retrospective cohort study of SEER-Medicare pts with mPC initiating ADT (2010–2017), with ≥36 months of continuous insurance coverage, unless death occurred, who did not receive chemotherapy or a second-generation anti-androgen during follow-up. iADT and cADT cohorts were defined by treatment patterns and gaps in therapy. Comorbidities and clinical events were identified using ICD-9/10-CM codes. Outcomes examined were major adverse cardiovascular events (MACE [myocardial infarction (MI), stroke, cardiomyopathy/heart failure (HF), pulmonary embolism (PE), ischemic heart disease (IHD), or all-cause mortality]) and endocrine/metabolic events (diabetes, hypercholesterolemia, bone fractures, or osteoporosis). Inverse probability of treatment weighting (IPTW) was used to adjust for differences between cohorts; weighted Cox models were used to estimate the hazard ratio (HR) of the outcomes. Subgroup analyses examined pts by CVD history; a sensitivity analysis was performed restricting the definition of MACE to include CVD-related mortality as a component, i.e., MACESA (MI, stroke, cardiomyopathy/HF, PE, IHD, or CVD-related mortality). Results: 2234 pts with mPC were included; 478 (21%) received iADT and 1756 (79%) cADT. Median follow-up time was 27 and 13 months, and time on ADT (excluding gaps for iADT pts) was 24 and 19 months for the iADT and cADT cohorts, respectively. Deaths occurred in 39% of iADT pts vs 55% of cADT pts; PC was the most common cause of death in both cohorts. In adjusted analyses, pts receiving cADT had a higher risk of MACE vs iADT. No differences in risk of endocrine/metabolic events were observed. Subgroup analysis showed that baseline history of CVD did not alter the results for MACE. Sensitivity analysis results showed no difference in risk of MACESA between pts receiving cADT vs iADT. Conclusions: Pts with mPC receiving cADT had a higher risk of MACE (including all-cause mortality), and no difference in risk of endocrine/metabolic events, compared with those receiving iADT. When MACE was restricted to include CVD-related mortality, there was no difference in risk between cohorts. [Table: see text]