Cessation Of Androgen Deprivation Therapy Research Articles

Hypofractionated radiation therapy combined with androgen deprivation therapy for clinically node-positive prostate cancer.

This study aimed to analyze the treatment outcomes of combined definitive radiation therapy (RT) and androgen deprivation therapy (ADT) for clinically node-positive prostate cancer. Medical records of 60 patients with clinically suspected metastatic lymph nodes on radiological examination were retrospectively analyzed. Eight patients (13.3%) were suspected to have metastatic common iliac or para-aortic lymph nodes. All patients underwent definitive RT with a dose fractionation of 70 Gy in 28 fractions. ADT was initiated 2-3 months before RT and continued for at least 2 years. Biochemical failure rate (BFR), clinical failure rate (CFR), overall survival (OS), and prostate cancer-specific survival (PCSS) were calculated, and genitourinary and gastrointestinal adverse events were recorded. The median follow-up period was 5.47 years. The 5-year BFR, CFR, OS, and PCSS rates were 19.1%, 11.3%, 89.0%, and 98.2%, respectively. The median duration of ADT was 2.30 years. BFR and CFR increased after 3 years, and 11 out of 14 biochemical failures occurred after the cessation of ADT. Grade 2 and beyond late genitourinary and gastrointestinal toxicity rates were 5.0% and 13.3%, respectively. However, only two grade 3 adverse events were reported, and no grade 4-5 adverse events were reported. Patients with non-regional lymph node metastases did not have worse BFR, CFR, or adverse event rates. This study reported the efficacy and tolerable toxicity of hypofractionated definitive RT combined with ADT for clinically node-positive prostate cancer. Additionally, selected patients with adjacent non-regional lymph node metastases might be able to undergo definitive RT combined with ADT.

Two Elderly Men with Myasthenia Gravis during Androgen Deprivation Therapy for Prostate Cancer.

Myasthenia gravis (MG) development is female-dominant in younger patients and male-dominant in older patients. The reason for the sex-ratio inversion in elderly MG patients remains unclear. One possible explanation is the decrease in androgen secretion that occurs with aging, as androgen has an immunosuppressive function. We experienced two elderly men who developed MG after initiating androgen deprivation therapy (ADT) for treatment of prostate cancer and whose symptoms were ameliorated after ADT cessation. Our cases indicate that MG in older male patients can be caused by an androgen effect.

Clinical outcomes in patients with metastatic castrate-resistant prostate cancer treated with abiraterone with or without ongoing androgen deprivation therapy: A retrospective case-control study.

Abiraterone and concurrent androgen deprivation therapy (ADT) are used in the treatment of patients with metastatic castration-resistant prostate cancer. Recently, it has been suggested that the use of abiraterone alone (without ADT) may have comparable efficacy to abiraterone with ongoing ADT. Here, we sought to assess the impact of ADT cessation in patients beginning abiraterone for castration-resistant prostate cancer. We identified 39 patients at our institution who received abiraterone alone (with discontinuation of ADT) between 2011 and 2022. We then procured a comparable group of 39 patients (matched by age, Gleason score, and prostate-specific antigen [PSA] level) who received abiraterone with ongoing ADT during the same period. We assessed and compared clinical outcomes in the two groups (abiraterone-alone vs. abiraterone-ADT) with respect to PSA response rates, PSA progression-free survival, and overall survival. Results were adjusted using Cox proportional-hazards multivariable models. The median PSA before treatment initiation was 12.7 (range: 0.2-199) ng/mL in the abiraterone-alone group and 15.5 (range: 0.6-212) ng/mL in the abiraterone-ADT group. Use of abiraterone alone adequately suppressed testosterone levels in 35/37 (94.6%) patients. Patients receiving abiraterone alone had a median PSA reduction of 80.2% versus 79.5% in patients receiving abiraterone plus ADT. The median PSA progression-free survival in patients receiving abiraterone alone was 27.4versus 25.8 months in patients receiving abiraterone plus ADT (hazard ratio [HR] 1.10; 95% confidence interval [CI] 0.65-1.71; p = 0.82). In addition, abiraterone alone was associated with an overall survival of 3.6versus 3.1 years in patients receiving abiraterone plus ADT (HR 0.90; 95% CI 0.50-1.62; p = 0.72). There were no differences in PFS or OS between groups after performing Cox multivariable regression analyses. Use of abiraterone alone was associated with comparable clinical outcomes to patients who received abiraterone together with ADT. Further prospective studies are warranted to evaluate the impact of abiraterone alone on treatment outcomes and cost savings.

Testosterone recovery following androgen suppression and prostate radiotherapy (TRANSPORT): Updated individual patient data meta-analyses from the MARCAP consortium.

5096 Background: Time to testosterone recovery (TR) following androgen deprivation therapy (ADT) and radiotherapy for prostate cancer varies following cessation of ADT. We aimed to quantify the association between time to TR and duration of ADT and patient age. Methods: We identified prospective randomized trials of prostate radiotherapy and ADT in the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) consortium for which prospectively collected serial testosterone values were available. The time to non-castrate TR (NCTR) (>1.7ng/mL), non-hypogonadal TR (NHTR) (>8.0ng/mL) and full TR (FTR) (>10.5ng/mL) were estimated from the end date of prescribed ADT using the Kaplan Meier method. Cox regression was used to evaluate the differences in time to TR for men aged <65 years and ≥65 years for each duration of ADT. Interaction effects between ADT duration and patient age on TR were evaluated. Results: 2628 men from 5 trials (TROG 9601, TROG 0304, PCSIII, PCSIV, and Ottawa-01) met the inclusion criteria for analysis. Of these, 236, 1485, 731, and 176 men had 3-, 6-, 18-, and 36-months of ADT respectively. 1502 (57%) men had baseline (pre-ADT) testosterone data available, of which 99% (1494/1502) had non-castrate testosterone (>1.7ng/mL), and 78% (1178/1502) had normal testosterone (>10.5ng/mL) at baseline. At last follow-up, there were 96% (2522/2628), 77% (2035/2628) and 65% (1700/2628) of men who had NCTR, NHTR and FTR respectively. The median time (range) to NCTR was 1.9 (0.2-60), 6.2 (0.0-92), 6.3 (0.0-92), and 15.7 (0.1-75) months for men who had 3-, 6-, 18- and 36-months of ADT, respectively. The median time (range) to NHTR was 2.5 (0.4-73), 11.2 (0.1-93), 17.7 (0.2-92), and 53.4 (5.3-76) months for men who had 3-, 6-, 18- and 36-months of ADT, respectively. The median time (range) to FTR was 5.8 (0.4-72), 16.7 (0.3-95), and 26.0 (0.2-90) for men who had 3-, 6-, and 18-months of ADT, respectively, while the median time to FTR was not reached in men who had 36-months of ADT. In men who had 6-months of ADT, men aged ≥65 years were 35% (95%CI=26-43%) less likely to have FTR compared to men aged <65 years, while for those who had 18-months of ADT, men aged ≥ 65 years were 52% (95%CI=41-60%) less likely to have FTR compared to men aged < 65 years. There was no statistically significant interaction between the effect of ADT duration and age on the time to FTR (interaction P=0.07 for the entire cohort). Conclusions: In this updated individual patient-data meta-analysis of prospectively collected serial testosterone data from 5 randomized trials, substantial delay in FTR in men who had longer duration of ADT was observed, consistent with prior analyses. Approximately 1-in-3 men did not have FTR, which may have life-long impacts on their quality of life.

(060) Chronology of Endogenous Testosterone Recovery Following Androgen Deprivation Therapy Cessation – Results From a Prospective Analysis

Abstract Introduction Testosterone (T) recovery after androgen deprivation therapy (ADT) is reported in the literature from 7 to 96%, with data mainly from retrospective studies using variable definitions for this event. Age, Diabetes and ADT duration may affect the timing and completeness of recovery Objective Prospectively evaluate the chronology of T recovery following ADT cessation Methods This is a secondary analysis of a prospective oncological study designed to evaluate the impact of neoadjuvant use of ADT in combination with abiraterone acetate and prednisone with or without apalutamide in patients with high-risk prostate cancer. Both regimens were administered for 3 months before radical prostatectomy (RP). Early morning Total T (TT) levels were collected (immunoassay) at baseline and periodically (3, 6 and 12 months) after ADT cessation. 3 outcomes for T recovery were evaluated: return to non-castrate level (TT >50 ng/dL), to normal T (TT ≥ 300 ng/dL) and back to baseline level (BTB –TT≥ baseline level). We performed a time-to-event analysis and reported the cumulative incidence of each outcome. Multivariable analysis was conducted to investigate predictors of recovery Results In this preliminary report, from 64 initially enrolled patients, 1 year follow-up T data from 50 pts were available. Mean age was 64.6 ± 5.89 years, 28% had type 2 diabetes (DM) and 61% hypertension (HTN). Mean TT levels were 450 ± 170ng/dl at baseline, 112. 7± 96.9 at 3m, 208.5 ±197 at 6m, 337.7 ± 170 at 9m and 378.2 ± 166 at 12 m. Figure 1 shows the cumulative incidence of each outcome according to time. Median time to achieve T>50 was 5 m, to achieve T>300 was 9.1m and BTB 13.13 m. At 1 year, 98% had returned back from castrate-level, 76% had TT normalized and 42% had return BTB. In a multivariable analysis including DM, HTN, age and baseline T, only baseline T was associated with a greater chance of recovery, with 88.5% of those with baseline T > 450 ng/dl achieving normal T at 1y vs 46.9% for patients with baseline T < 450 ng/dl (HR: 3.56, p< 0.001) Conclusions In this prospective analysis of a population exposed to neoadjuvant short-term ADT, T recovery rates after 1 year showed that the vast majority (98%) had returned back from castrate level (median time 5m), about 2/3 recovered back to normal levels (median time 9,1m) and less than half returned to BTB level. Baseline TT was the only predictor of T recovery Disclosure Yes, this is sponsored by industry/sponsor: Source of Funding: Janssen-Cilag Farmacêutica Ltda Clarification Industry funding only - investigator initiated and executed study

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 ...

Testosterone Recovery Following Androgen Suppression and Prostate Radiotherapy (TRANSPORT): Individual patient data meta-analysis from the MARCAP Consortium.

366 Background: The kinetics of testosterone recovery (TR) vary following cessation of androgen deprivation therapy (ADT) of various durations when given in combination with radiotherapy for prostate cancer. Time to TR will impact on quality of life. We aim to identify factors affecting the time to TR following ADT use. Methods: We included trials of prostate radiotherapy and ADT in the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) consortium for which prospectively collected serial testosterone data is available. Time to non-hypogonadal TR (NHTR) (&gt;8.0nmol/L) and time to full TR (FTR) (&gt;10.5nmol/L) were estimated from the date of first available testosterone at trial enrolment to the date of TR using the Kaplan-Meier method. The effect of interactions between duration of ADT and patients’ age on TR was evaluated. Results: There were 1439 men with non-castrate testosterone at baseline (&gt;1.7nmol/L) who met the inclusion criteria for analysis, of which 220, 765 and 454 men had 3-, 6-, and 18-months of ADT. There were 959 (67%) men who had FTR at last follow-up. For men who had 3-, 6-, and 18-months of ADT, the median time (range) to NHTR were 5.5 (1.6-76.3), 12.2 (0.8-53.6), and 30.1 (2.8-90.4) months respectively, while the median time (range) to FTR were 6.2 (1.8-75.7), 15.2 (0.8-86.0), and 36.0 (18.1-85.5) months respectively. In the subset of 1160 men who had normal testosterone at baseline (&gt;10.5nmol/L), 851 (69%) men had FTR, with a median time (range) to FTR of 5.5 (1.8-75.7), 12.7 (1.8-86.0), and 30.8 (18.1-84.1) months for men who had 3-, 6- and 18-months ADT, respectively. For any given duration of ADT, men aged above 65 years were less likely to have FTR compared to those aged under 65 years – HR=0.67 (95%CI=0.46-0.99), HR=0.80 (95%CI=0.67-0.96), HR=0.64 (95%CI=0.51-0.81) for men who had 3-, 6-, and 18-months ADT respectively. There was no evidence of interaction between the effect of ADT duration on time to FTR and age (interaction P=0.3 for entire cohort). Conclusions: This is the largest pooled analysis of prospectively collected serial testosterone data from randomized trials, indicating substantial delay in FTR in men receiving longer durations of ADT. Approximately one-third of the men did not achieve FTR, which may have life-long impact on quality of life.

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.

Evaluation of Patients with Localized Prostate Cancer in whom Long-Term Successful Androgen Deprivation Therapy was Ceased

We evaluated the clinical course of patients with localized prostate cancer in whom long-term successful androgen deprivation therapy (ADT) was ceased. Study subjects were 24 patients with stage B prostate cancer who were initially treated with ADT for a median duration of 93 months. The median age at the cessation of ADT was 84 years. The median nadir serum prostate specific antigen (PSA) level was 0.022 ng/ml. The median duration of follow-up from the cessation of ADT was 31 months. During follow-up, five patients showed PSA elevation of ≥2 ng/ml from the nadir. Serum testosterone level was tested in 20 patients, and five showed testosterone recovery ≥0.5 ng/ml. Seven patients died from diseases other than prostate cancer, but there were no deaths caused by prostate cancer. This study demonstrated that long-term successful ADT for localized prostate cancer could be ceased with adequate follow-up evaluation.

Extraction of Treatment Information From Electronic Health Records and Evaluation of Testosterone Recovery in Patients With Prostate Cancer.

Data quality and standardization remain a challenge when analyzing real-world clinical data. We built a clinical research database, using machine learning and natural learning processing, and investigated factors influencing testosterone recovery (T-recovery) in patients with localized prostate cancer (LPC) after initial androgen deprivation therapy (ADT). Medication and treatment-associated dates missing in structured tables were extracted from patient notes using ConceptMapper, an automated data extraction tool, standardized and curated in Sema4 clinical research database. ADT usage duration was evaluated, and T-recovery in patients with LPC was analyzed by the Kaplan-Meier method and multivariable Cox proportional hazards models. We assessed the prognostic value of post-ADT T-recovery with prostate-specific antigen progression-free survival and failure-free survival. In total, 4,125 of 30,832 (13.4%) patients with prostate cancer had medication exclusively from notes with high precision and recall, F1 score ≥ 0.95. Association of dates with medication usage had a F1 score of 0.76. ADT duration estimation had higher accuracy combining information from notes to tables from electronic medical record (70% v 45%). Baseline testosterone was the strongest predictor of T-recovery in these patients. Patients with a baseline testosterone ≥ 300 ng/dL recovered in 9.79 versus 38 months for patients with baseline testosterone < 300 ng/dL (P < .0001). Shorter prostate-specific antigen progression-free interval was observed for patients with T-recovery (≥ 300 ng/dL) at 6 months after ADT cessation compared with patients without T-recovery (< 300 ng/dL; 13.7 v 25.1 months; P = .055). We augmented structured electronic medical record data with data extracted from notes and improved the accuracy of medication information for patients. ADT exposure and T-recovery in patients with LPC produced results consistent with the literature and clinical experience and illustrates the power of applying machine learning methods to enhance the quality of real-world evidence in answering clinically relevant questions.

Testosterone (T) recovery profiles after short-term androgen deprivation therapy (ADT)

ABSTRACT Introduction ADT plays a major role in several scenarios for men with prostate cancer. T recovery after ADT cessation may be incomplete with 10% of men estimated to suffer persistent castrate levels after long-term ADT. Objective The objective of this study was to evaluate T recovery after short courses of ADT. Methods Study population included men treated with ≤6 months of ADT in association with radiation therapy (RT). Early morning T levels were collected at baseline and periodically after ADT cessation. T recovery after ADT cessation was analyzed in 2 ways: improvement to non-castrate level (T ≥50 ng/dL), and recovery to normal (T ≥ 300 ng/dL). Recovery rates and median survival time were estimated using Kaplan-Meier statistics and predictors analyzed using Cox proportional hazard ratios. Results 88 men with a mean age of 68 ± 8 years at time of ADT were analyzed. Median duration of ADT was 3.1 months; 56% had an ADT duration between 1-3 months and 44% between 4-6 months. Mean pre-ADT T level was 390 ± 158 ng/dL. After cessation of ADT, median time to non- castrate levels was 9.3 (IQR = 6.3 – 18.5) months and 15.8 (IQR = 8.3 - 33.8) ‘months for recovery to T ≥300 ng/dL. Higher baseline T levels (T &amp;gt; 400 ng/dL) was associated with a faster recovery to normal T level (HR = 1.80, 95% CI = 1.09 – 2.95), but not to non-castrate level. Neither age &amp;gt; 65 years, prevalent diabetes, nor ADT duration of 4-6 months vs ≤ 3 months were significantly associated with a slower T recovery. Conclusions Most of our patients remained with low T levels one year after the cessation of ADT. Higher baseline T was associated with faster T recovery to normal (T ≥ 300 ng/dL). Disclosure Work supported by industry: no.

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 ...

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

Testosterone Recovery after Androgen Deprivation Therapy in Prostate Cancer: Building a Predictive Model.

To analyze the variability, associated actors, and the design of nomograms for individualized testosterone recovery after cessation of androgen deprivation therapy (ADT). A longitudinal study was carried out with 208 patients in the period 2003 to 2019. Castrated and normogonadic testosterone levels were defined as 0.5 and 3.5 ng/mL, respectively. The cumulative incidence curve described the recovery of testosterone. Univariate and multivariate analyzes were performed to predict testosterone recovery with candidate prognostic factors prostate-specific antigen at diagnosis, clinical stage, Gleason score from biopsy, age at cessation of ADT, duration of ADT, primary therapy and use of LHRH (luteinizing hormone-releasing hormone) agonists. The median follow-up duration in the study was 80 months (interquartile range, 49-99 mo). Twenty-five percent and 81% of patients did not recover the castrate and normogonadic levels, respectively. Duration of ADT and age at ADT cessation were significant predictors of testosterone recovery. We built two nomograms for testosterone recovery at 12, 24, 36, and 60 months. The castration recovery model had good calibration. The C-index was 0.677, with area under the receiver operating characteristic curve (AUC-ROC) of 0.736, 0.783, 0.782, and 0.780 at 12, 24, 36, and 60 months, respectively. The normogonadic recovery model overestimated the higher values of probability of recovery. The Cindex was 0.683, with AUC values of 0.812, 0.711, 0.708 and 0.693 at 12, 24, 36, and 60 months, respectively. Depending on the age of the patient and the length of treatment, clinicians may stop ADT and the castrated testosterone level will be maintained or, if the course of treatment has been short, we can estimate if it will return to normogonadic levels.

MP36-02 TESTOSTERONE (T) RECOVERY PROFILES AFTER SHORT-TERM ANDROGEN DEPRIVATION THERAPY (ADT)

You have accessJournal of UrologySexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II (MP36)1 Sep 2021MP36-02 TESTOSTERONE (T) RECOVERY PROFILES AFTER SHORT-TERM ANDROGEN DEPRIVATION THERAPY (ADT) Jose M Flores, Bruno Nascimento, Nicole Benfante, Elizabeth Schofield, and John P Mulhall Jose M FloresJose M Flores More articles by this author , Bruno NascimentoBruno Nascimento More articles by this author , Nicole BenfanteNicole Benfante More articles by this author , Elizabeth SchofieldElizabeth Schofield More articles by this author , and John P MulhallJohn P Mulhall More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002045.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: ADT plays a major role in several scenarios for men with prostate cancer. T recovery after ADT cessation may be incomplete with 10% of men estimated to suffer persistent castrate levels after long-term ADT. The objective of this study was to evaluate T recovery after short courses of ADT. METHODS: Study population included men treated with ≤6 months of ADT in association with radiation therapy (RT). Early morning T levels were collected at baseline and periodically after ADT cessation. T recovery after ADT cessation was analyzed in 2 ways: improvement to non-castrate level (T≥50 ng/dL), and recovery to normal (T≥300 ng/dL). Recovery rates and median survival time were estimated using Kaplan-Meier statistics and predictors analyzed using Cox proportional hazard ratios. RESULTS: 88 men with a mean age of 68±8 years at time of ADT were analyzed. Median duration of ADT was 3.1 months; 56% had an ADT duration between 1-3 months and 44% between 4-6 months. Mean pre-ADT T level was 390±158 ng/dL. After cessation of ADT, median time to non- castrate levels was 9.3 (IQR=6.3–18.5) months and 15.8 (IQR=8.3-33.8) `months for recovery to T≥300 ng/dL. Higher baseline T levels (T>400 ng/dL) was associated with a faster recovery to normal T level (HR=1.80, 95% CI=1.09–2.95), but not to non-castrate level. Neither age >65 years, prevalent diabetes, nor ADT duration of 4-6 months vs ≤3 months were significantly associated with a slower T recovery. CONCLUSIONS: Most of our patients remained with low T levels one year after the cessation of ADT. Higher baseline T was associated with faster T recovery to normal (T≥300 ng/dL). Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e636-e636 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jose M Flores More articles by this author Bruno Nascimento More articles by this author Nicole Benfante More articles by this author Elizabeth Schofield More articles by this author John P Mulhall More articles by this author Expand All Advertisement Loading ...

MP36-14 A PROSPECTIVE ANALYSIS OF TESTOSTERONE (T) RECOVERY PROFILES AFTER NEOADJUVANT MAXIMAL ANDROGEN BLOCKADE IN HIGH-RISK LOCALIZED PROSTATE CANCER

You have accessJournal of UrologySexual Function/Dysfunction: Medical, Hormonal & Non-surgical Therapy II (MP36)1 Sep 2021MP36-14 A PROSPECTIVE ANALYSIS OF TESTOSTERONE (T) RECOVERY PROFILES AFTER NEOADJUVANT MAXIMAL ANDROGEN BLOCKADE IN HIGH-RISK LOCALIZED PROSTATE CANCER Rubens Pedrenho Neto, Bruno C. G. Nascimento, Diogo Assed Bastos, Jose de Bessa Junior, Eder Nisi Ilario, Claudio Bovolenta Murta, Mauricio Dener Cordeiro, Rafael Ferreira Coelho, John P. Mulhall, Miguel Srougi, and William Carlos Nahas Rubens Pedrenho NetoRubens Pedrenho Neto More articles by this author , Bruno C. G. NascimentoBruno C. G. Nascimento More articles by this author , Diogo Assed BastosDiogo Assed Bastos More articles by this author , Jose de Bessa JuniorJose de Bessa Junior More articles by this author , Eder Nisi IlarioEder Nisi Ilario More articles by this author , Claudio Bovolenta MurtaClaudio Bovolenta Murta More articles by this author , Mauricio Dener CordeiroMauricio Dener Cordeiro More articles by this author , Rafael Ferreira CoelhoRafael Ferreira Coelho More articles by this author , John P. MulhallJohn P. Mulhall More articles by this author , Miguel SrougiMiguel Srougi More articles by this author , and William Carlos NahasWilliam Carlos Nahas More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002045.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Intensification of androgen deprivation therapy (ADT) is currently being investigated as a neoadjuvant strategy for high-risk prostate cancer (PC). Variable T recovery profiles are reported after ADT use, mainly from retrospective studies. This study was undertaken prospectively to evaluate T recovery after ADT cessation. METHODS: In this prospective randomized phase 2 study evaluating the neoadjuvant use of ADT in combination with abiraterone acetate plus prednisone with or without apalutamide in high-risk localized PC, T recovery data was obtained. Both study regimens were administered for 3 months before radical prostatectomy (RP). Serum early morning total T (TT) levels were collected at baseline and periodically (3, 6 and 12 months) after the end of ADT. Based on previous literature patient age, diabetes and baseline T level were selected as potential predictors of T recovery. We analyzed: T return to non-castrate level (TT>50 ng/dL), return to normal (TT>300 ng/dL), and return back to baseline level (BTB). Patient numbers, to date, do not allow us to compare the impact of the two different ADT regimens on the different rates of T recovery. RESULTS: The study has enrolled 62 patients (pts) so far (planned accrual of 64 pts) and data from 17 men with 12 months follow-up were available for this preliminary analysis. Mean age was 67±11 years old. Mean TT values were 434±109 ng/dL at baseline and 348±109 ng/dL 12 m after ADT cessation. At 12 m, 6% of men remained at castrate level, 30% had TT<300 ng/dL and 53% had returned BTB. Mean baseline TT was significantly different between those with normal and abnormal T at 1 year (491 ± 100 vs 342±48; p=0.031) and all patients with baseline TT>400 ng/dL returned to eugonadal status. For patients with DM compared to without, recovery BTB at 1 year was lower (16% vs 83%; OR 7.5; 0.9-57, p=0.11). CONCLUSIONS: T recovery is dependent on baseline T and presence of diabetes. To date, one third of patients failed to normalize T levels 1 year after discontinuation of ADT and 1/20 remaining castrate. Source of Funding: Janssen-Cilag Farmacêutica Ltda © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e641-e641 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rubens Pedrenho Neto More articles by this author Bruno C. G. Nascimento More articles by this author Diogo Assed Bastos More articles by this author Jose de Bessa Junior More articles by this author Eder Nisi Ilario More articles by this author Claudio Bovolenta Murta More articles by this author Mauricio Dener Cordeiro More articles by this author Rafael Ferreira Coelho More articles by this author John P. Mulhall More articles by this author Miguel Srougi More articles by this author William Carlos Nahas More articles by this author Expand All Advertisement Loading ...

PD05-12 PERSISTENT TESTOSTERONE SUPPRESSION AFTER CESSATION OF ANDROGEN DEPRIVATION THERAPY FOR LOCALIZED PROSTATE CANCER: AN ELECTRONIC HEALTH RECORDS NETWORK STUDY OF 66 MILLION PEOPLE

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) I (PD05)1 Sep 2021PD05-12 PERSISTENT TESTOSTERONE SUPPRESSION AFTER CESSATION OF ANDROGEN DEPRIVATION THERAPY FOR LOCALIZED PROSTATE CANCER: AN ELECTRONIC HEALTH RECORDS NETWORK STUDY OF 66 MILLION PEOPLE Joshua Bitran, Daniel Gonzalez, Jesse Ory, Maxwell Towe, and Ranjith Ramasamy Joshua BitranJoshua Bitran More articles by this author , Daniel GonzalezDaniel Gonzalez More articles by this author , Jesse OryJesse Ory More articles by this author , Maxwell ToweMaxwell Towe More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001969.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Temporary use of Androgen Deprivation Therapy (ADT) is a cornerstone in the treatment of localized prostate cancer. While ADT is typically used for a defined period of time in these patients, the ability for testosterone to recover afterwards is not well understood. The aim of this study was to investigate the kinetics of testosterone recovery following varying types and lengths of temporary ADT. METHODS: We used a global federated health research network (TriNetX) to identify men with a diagnosis of prostate cancer who underwent temporary use of ADT. Three cohorts were identified: LHRH agonist only, combined ADT (LHRH agonist and antiandrogens), and LHRH antagonist only. In each cohort, testosterone levels were gathered for patients that underwent ADT therapy for at least 2 years. Men were excluded if they received ADT after this time period. Testosterone levels for men in the same age group at time of diagnosis of prostate cancer who never received ADT were used as a control. RESULTS: A total of 34,079 men received LHRH agonists, 16,054 men received combined ADT with LHRH agonist and antiandrogen, and 2307 men received LHRH antagonist. Mean age was similar in all three cohorts (71+/-10 years). 70% of patients were white, 14% African American, 2% Asian, and 14% unknown race. None of the men who received either LHRH agonist or combined ADT for 2 years or longer recovered to eugonadal levels (T>300ng/dL) even after 5 years of cessation (mean T levels = 159 ng/dL or 169 ng/dL, respectively). However, 50% of men who received LHRH antagonist for 2 years recovered T levels to eugonadal range after 5 years of cessation (mean T = 382 ng/dL). The control group consisted of 5727 men with prostate cancer who never received ADT or testosterone therapy (mean age at diagnosis, 71 years). Mean testosterone levels ranged from 340 at diagnosis to 402 5 years after diagnosis. CONCLUSIONS: Five years after ADT cessation, incomplete testosterone recovery persists in majority of the 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 closely followed-up in men receiving ADT and should continue after cessation of treatment. Source of Funding: Clinician Scientist Development Award from American Cancer Society © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e61-e61 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joshua Bitran More articles by this author Daniel Gonzalez More articles by this author Jesse Ory More articles by this author Maxwell Towe More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement Loading ...

Recovery of serum testosterone following neoadjuvant androgen deprivation therapy in Japanese prostate cancer patients treated with low-dose rate brachytherapy

Objective To investigate the time course of total testosterone (TT) recovery after cessation of androgen deprivation therapy (ADT) in Japanese patients treated with brachytherapy. Methods In total, 125 patients with prostate cancer received 6 months of neoadjuvant ADT (nADT) followed by low-dose rate (LDR) brachytherapy. TT was measured every 3 months after cessation of nADT, and some predictive factors affecting TT recovery were analyzed. Results The cumulative incidence rates of TT recovery to normal levels (TT ≥ 3.0 ng/mL) after 12 and 24 months cessation were 49.6% and 81.6%, respectively. The median interval to recover to normal TT was 15 months. In multivariate analysis, the use of a gonadotropin-releasing hormone (GnRH) antagonist as nADT significantly earlier improved to recovery to normal TT level (p = 0.046). Conversely, higher body mass index (BMI) and hypertension significantly prolonged TT recovery to normal (p = 0.026 and p = 0.026, respectively). Conclusions Approximately one-fifth of patients still had low TT levels 2 years after the cessation of 6 months nADT before LDR brachytherapy. Use of a GnRH agonist, higher BMI, and hypertension were the predictive factors for slower TT recovery to normal TT levels after the cessation of nADT.

Testosterone Recovery Profiles After Cessation of Androgen Deprivation Therapy for Prostate Cancer

IntroductionAndrogen deprivation therapy (ADT) is frequently used in the treatment of prostate cancer worldwide. Variable testosterone (T) recovery profiles after ADT cessation have been cited. AimTo evaluate T recovery after cessation of ADT. MethodsWe reviewed our institutional prospectively maintained database of patients with prostate cancer who received ADT. Serum early morning total T (TT) levels, collected at baseline and periodically after ADT cessation, were analyzed. Patient age, baseline T level, duration of ADT, and presence of diabetes and sleep apnea were selected as potential predictors of T recovery. 3 metrics of T recovery after 24 months of ADT cessation were analyzed: return to non-castrate level (TT > 50 ng/dL), return to normal (T > 300 ng/dL), and return back to baseline level (BTB). Multivariable time-to-event analysis (Cox proportional hazards), χ2 test, logistic regression model, and Kaplan-Meier curve were performed to define impact of the above predictors on time and chance of T recovery. Main Outcome MeasuresTime and chance of T recovery to non-castrate level (TT > 50 ng/dL), return to normal (T > 300 ng/dL), and return BTB. Results307 men with a mean age of 65 ± 8 years were included. Mean duration of ADT was 17 ± 25 months, and median follow-up was 31 ± 35 months. Mean TT values were 379 ng/dL at baseline and 321 ng/dL at >24 months. At 24 months after cessation of ADT, 8% of men remained at castrate level, 76% returned to TT >300 ng/dL, and 51% had returned BTB. Lower baseline T levels (TT < 400 ng/dL) and ADT duration >6 months were associated with a lower likelihood of recovery to normal TT at 24 months. Age >65 years and receiving ADT for >6 months were significantly associated with a slower T recovery. Clinical ImplicationsT recovery after ADT is not certain and may take longer than expected. Considering the range of side effects of low T, we believe that these findings must be discussed with patients before initiating such therapies. Strengths & LimitationsOur strengths consisted of a relatively large database, long follow-up, and clinically meaningful endpoints. Limitations included the retrospective design of the study. ConclusionT recovery rates after ADT cessation vary according to patient age, ADT duration, and baseline T levels. Approximately one-quarter of patients failed to normalize their TT level, and one-tenth of men remained at castrate levels 24 months after ADT cessation.Nascimento B, Miranda EP, Jenkins LC, et al. Testosterone Recovery Profiles After Cessation of Androgen Deprivation Therapy for Prostate Cancer. J Sex Med 2019;16:872–879.

Persisting adverse body composition changes 2 years after cessation of androgen deprivation therapy for localised prostate cancer.

Hypogonadism from androgen deprivation therapy (ADT) for prostate cancer causes adverse body composition changes associated with insulin resistance and decreased quality of life (QoL). Our objective was to assess whether adverse body composition changes improve after cessation of ADT. Prospective case-control study in a tertiary referral hospital. Thirty-four men newly commencing ADT (cases, median age: 67.6 years (interquartile range: 64.6-72.0)) and 29 age-matched (70.6 years (65.3-72.9)) prostate cancer controls not on ADT were assessed 2 years after cessation of ADT (median: 4.4 years). Serum testosterone, body composition, handgrip strength, frailty and QoL were measured. Using a mixed model, the mean adjusted differences (MADs (95% CI)) between groups from baseline to study end are reported. Twenty-seven cases and 19 controls completed the study. Median duration of ADT was 2.3 years (interquartile range: 1.8-3.1). Two years after cessation of ADT, total testosterone remained lower (MAD: -3.4 nmol/L (-6.3 to -0.5), P < 0.022), fat mass (2214 g (490-3933), P = 0.025) and insulin resistance (homeostasis model assessment of insulin resistance: 0.69 (0.31-1.07), P < 0.001) remained higher in cases, whereas lean mass (-1450 g (-2259 to -640), P < 0.001) and physical component of QoL remained lower than controls (-11.9 (-16.4 to -7.4), P < 0.001). Two years after ADT cessation, metabolically adverse changes in body composition, increased insulin resistance and reduced QoL persisted. This may be related to incomplete testosterone recovery. Persisting adverse effects need to be considered in the risk to benefit assessment of ADT and proactive mitigation should continue after cessation of treatment.