Androgen Deprivation Therapy Monotherapy Research Articles

Do Indian men have similar oncological outcomes with abiraterone plus androgen deprivation therapy in the setting of metastatic hormone-sensitive prostate cancer? A prospective observational study

ABSTRACT Introduction: Combination of abiraterone with androgen deprivation therapy (ADT) has better survival outcomes than ADT alone in metastatic Hormone-sensitive prostate cancer (mHSPC) in the Western population. In this prospective (Clinical Trials Registry-India [CTRI] registered) observational study, we present the comparative oncological outcomes of ADT alone and ADT + abiraterone in Indian patients, which is not available currently. Methods: This study (CTRI-number-CTRI/2020/07/026545) included newly diagnosed mHSPC patients from January 2020 to June 2023 in a tertiary care hospital, urology department. Patients fulfilling inclusion criteria were advised ADT with abiraterone (A + ADT), and those not affording received ADT monotherapy (ADT). The primary endpoint was overall survival (OS). Secondary outcomes included prostate-specific antigen (PSA) decline >90%, radiographic progression-free survival (rPFS), and PSA progression-free survival (pPFS). Results: Out of 278 patients with mHSPC, 163 patients were excluded and 115 were analyzed (ADT = 40 vs. A + ADT = 75). After a median follow-up of 20.3 months, 11 of 40 (27.5%) in ADT-only arm and 15 of 75 (20%) in ADT + abiraterone arm had died (Hazard-ratio of death 0.72; 95% confidence interval 0.68–0.88; P < 0.001). A PSA decline of >90% was seen in 85% in the ADT alone group and 93.3% in the ADT + abiraterone group. Significantly better outcomes of the ADT + abiraterone were seen in the secondary endpoints of rPFS (P < 0.001) and pPFS (P < 0.001). The OS benefit was 28% reduction in risk of death in our study versus 37% and 38% in STAMPEDE and LATITUDE, respectively. pPFS and rPFS were also poorer in Indian subsets. Conclusions: Abiraterone with ADT improves OS, PSA response, rPFS, and pPFS in the Indian population akin to the Western data but with poorer OS, rPFS, and PSA progression-free survival on comparison.

Identifying Suitable Patients for Overcoming Androgen Deprivation Monotherapy in De Novo Metastatic Hormone-Sensitive Prostate Cancer.

Although metastatic hormone-sensitive prostate cancer (mHSPC) treatments have evolved, androgen deprivation therapy (ADT) remains a widely used regimen. Therefore, this study sought patients who did not progress to castration-resistant prostate cancer (CRPC) but received ADT monotherapy and factors affecting overall survival (OS) in de novo mHSPC. De novo mHSPC patients who received ADT treatment were included. ADT included luteinizing hormone-releasing hormone agonists with or without anti-androgen. The total cohort was divided into two groups relative to CRPC progression within two years. Logistic analysis was used to identify factors that did not progress CRPC within two years. Cox regression was used to assess the independent predictors for OS. The total cohort was divided into the no-CRPC within two years group (n = 135) and the CRPC within two years group (n = 126). Through multivariate logistic analysis, the life expectancy (odds ratio [OR] 0.95, 95% CI 0.91-0.99, p = 0.014) and Gleason scores (≥9 vs. ≤8; OR 0.43, 95% CI 0.24-0.75, p = 0.003) were associated with the group without castration-resistant prostate cancer progression within two years. The multivariate Cox model revealed that life expectancy (hazard ratio [HR] 0.951, 95% CI 0.904-0.999, p = 0.0491), BMI (HR 0.870, 95% CI 0.783-0.967, p = 0.0101), and CCI (≥2 vs. <2; HR 2.018, 95% CI 1.103-3.693, p = 0.0227) were significant predictive factors for OS. Patients with long life expectancy and a Gleason score of 9 or more were more likely to develop mCRPC while alive. Patients with short life expectancy, low BMI, and worsening comorbidity were more likely to die before progressing to CRPC. Although intensified treatment is essential for oncologic outcomes in mHSPC, shared decision making is integral for patients who may not benefit from this treatment.

Unpacking overuse of androgen deprivation therapy for prostate cancer to inform de-implementation strategies

BackgroundMany men with prostate cancer will be exposed to androgen deprivation therapy (ADT). While evidence-based ADT use is common, ADT is also used in cases with no or limited evidence resulting in more harm than benefit, i.e., overuse. Since there are risks of ADT (e.g., diabetes, osteoporosis), it is important to understand the behaviors facilitating overuse to inform de-implementation strategies. For these reasons, we conducted a theory-informed survey study, including a discrete choice experiment (DCE), to better understand ADT overuse and provider preferences for mitigating overuse.MethodsOur survey used the Action, Actor, Context, Target, Time (AACTT) framework, the Theoretical Domains Framework (TDF), the Capability, Opportunity, Motivation–Behavior (COM-B) Model, and a DCE to elicit provider de-implementation strategy preferences. We surveyed the Society of Government Service Urologists listserv in December 2020. We stratified respondents based on the likelihood of stopping overuse as ADT monotherapy for localized prostate cancer (“yes”/“probably yes,” “probably no”/“no”), and characterized corresponding Likert scale responses to seven COM-B statements. We used multivariable regression to identify associations between stopping ADT overuse and COM-B responses.ResultsOur survey was completed by 84 respondents (13% response rate), with 27% indicating “probably no”/“no” to stopping ADT overuse. We found differences across respondents who said they would and would not stop ADT overuse in demographics and COM-B statements. Our model identified 2 COM-B domains (Opportunity–Social, Motivation–Reflective) significantly associated with a lower likelihood of stopping ADT overuse. Our DCE demonstrated in-person communication, multidisciplinary review, and medical record documentation may be effective in reducing ADT overuse.ConclusionsOur study used a behavioral theory-informed survey, including a DCE, to identify behaviors and context underpinning ADT overuse. Specifying behaviors supporting and gathering provider preferences in addressing ADT overuse requires a stepwise, stakeholder-engaged approach to support evidence-based cancer care. From this work, we are pursuing targeted improvement strategies.Trial registrationClinicalTrials.gov, NCT03579680

Abstract 3812: Treatment guideline concordance for patients with metastatic hormone-sensitive prostate cancer (mHSPC) in the United States in IRONMAN, the International Registry for Men with Advanced Prostate Cancer

Abstract Background: Treatment intensification strategies with an androgen receptor pathway inhibitor (ARPI) and/or docetaxel chemotherapy in addition to androgen deprivation therapy (ADT) are guideline recommended treatment options for patients with metastatic hormone-sensitive prostate cancer (mHSPC). Prevalence of guideline concordant care for mHSPC patients in the US and its changes over time are not well characterized. Methods: The International Registry for Men with Advanced Prostate Cancer (IRONMAN) is a prospective cohort study of patients with newly diagnosed mHSPC and castration-resistant prostate cancer (CRPC). Therapies are captured by site personnel and by directly capturing data from treating physicians via physician questionnaires (PQ). We included all US patients with mHSPC enrolled from 2018 to January 1, 2023 with a completed PQ at enrollment. We examined patient characteristics, first-line treatments for mHSPC, and guideline concordance of first-line treatments. Guideline concordance was defined as a treatment regimen listed in the first National Comprehensive Cancer Network guidelines version for the year prior to treatment. Patients enrolled in clinical trials were excluded from analysis of treatment guideline concordance. Results: Among the 636 US participants with mHSPC, physicians completed PQs for 458 participants (72%). Participants had a median age of 68 years (interquartile range 62 - 75). Three hundred eight (78%) were White, 72 (18%) were Black, 13 (3%) were other races/ethnicities: 65 did not report race. First-line treatment for mHSPC based on the PQ was most commonly ADT + ARPI (59%) followed by ADT + docetaxel (17%), ADT monotherapy (14%), ADT + first-generation antiandrogen (3%), ADT + ARPI + docetaxel (3%), and other treatments (5%). Overall, 384 (86%) participants received first-line treatment that was guideline concordant at the time of treatment. Treatment guideline concordance was highest in 2018 (99%) when ADT monotherapy was considered as guideline concordant but then decreased to 80% in 2019 and remained largely stable from 2019 to 2022 (85%). Overall, rates of guideline concordance were similar when stratified by race (88% for White patients vs 85% for Black patients), age (90% for patients &amp;lt;65 years old vs 85% for patients ≥65 years old), and treatment at a Comprehensive Cancer Center (CCC) (87% at CCC vs 86% at non-CCC). Conclusion: Among patients with mHSPC treated in the US at 38 cancer centers, proportions of guideline concordant first-line treatment were high and remained stable over time, despite changes in approved therapies. Future efforts to understand reasons for treatment decisions will be important to better understand the relatively uncommon situations in which guidelines and actually received treatments differ for patients with mHSPC. Citation Format: Hannah Dzimitrowicz McManus, Lauren Howard, Kerri-Anne Crowell, Terry Hyslop, Jake Vinson, Dana E. Rathkopf, Philip Kantoff, Lorelei A. Mucci, Daniel George, Konrad Stopsack. Treatment guideline concordance for patients with metastatic hormone-sensitive prostate cancer (mHSPC) in the United States in IRONMAN, the International Registry for Men with Advanced Prostate Cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3812.

Characterizing the real-world economic burden of metastatic castration-sensitive prostate cancer in the United States

Aims To describe healthcare resource utilization (HRU) and costs of patients with metastatic castration-sensitive prostate cancer (mCSPC). Methods Linked data from Flatiron Metastatic PC Core Registry and Komodo’s Healthcare Map were evaluated (01/2016-12/2021). Patients with chart-confirmed diagnoses for metastatic PC without confirmed castration resistance in Flatiron who initiated androgen deprivation therapy (ADT) monotherapy or advanced therapy for mCSPC in 2017 or later (index date) with a corresponding pharmacy or medical claim in Komodo Health were included. Advanced therapies considered were androgen-receptor signaling inhibitors, chemotherapies, estrogens, immunotherapies, poly ADP-ribose polymerase inhibitors, and radiopharmaceuticals. Patients with <12 months of continuous insurance eligibility before index were excluded. Per-patient-per-month (PPPM) all-cause and PC-related HRU and costs (medical and pharmacy; from a payer’s perspective in 2022 $USD) were described in the 12-month baseline period and follow-up period (from the index date to castration resistance, end of continuous insurance eligibility, end of data availability, or death). Results Of 871 patients included (mean age: 70.6 years), 52% initiated ADT monotherapy as their index treatment without documented advanced therapy use. During baseline, 31% of patients had a PC-related inpatient admission and 94% had a PC-related outpatient visit; mean all-cause costs were $2551 PPPM and PC-related costs were $839 PPPM with $787 PPPM attributable to medical costs. Patients had a mean follow-up of 15 months, during which 38% had a PC-related inpatient admission and 98% had a PC-related outpatient visit; mean all-cause costs were $5950 PPPM with PC-related total costs of $4363 PPPM, including medical costs of $2012 PPPM. Limitations All analyses were descriptive; statistical testing was not performed. Treatment effectiveness and clinical outcomes were not assessed. Conclusion This real-world study demonstrated a significant economic burden in mCSPC patients, and a propensity to use ADT monotherapy in clinical practice despite the availability and guideline recommendations of advanced life-prolonging therapies.

Real-world treatment patterns in patients with BRCA 1/2-positive (BRCA+) metastatic castration-resistant prostate cancer (mCRPC) initiating first-line (1L) therapy.

52 Background: Patients with BRCA+ mCRPC have an aggressive disease course. Recently, they have been shown to be responsive to treatment with poly ADP-ribose polymerase inhibitors, such as niraparib, olaparib, and rucaparib, used in combination with abiraterone acetate and prednisone or prednisolone, or as monotherapy. This study aimed to describe real-world treatment patterns and outcomes among patients with BRCA+ mCRPC. Methods: De-identified electronic health records from the Flatiron Health – Foundation Medicine Inc. (FMI) Metastatic PC Clinico-Genomic Database (01/01/2011 – 06/30/2022) were used to select BRCA+ mCRPC patients initiating 1L therapy on or after 01/01/2019 or monotherapy with androgen deprivation therapy (ADT). Patients were classified as recipients of ADT monotherapy if they used ADT at mCRPC diagnosis and did not initiate any subsequent advanced PC therapy. Distribution, line of therapy (LOT) sequences, and reasons for censoring were described in 1L, and among patients who advanced to second-line (2L) therapy. Flatiron Health and FMI did not participate in data analyses. Results: A total of 98 treated patients with BRCA+ mCRPC were included (mean age 72 years, 58% White, 15% Black, 55% Medicare-insured), 19 of whom received ADT monotherapy (mean age 70 years, 53% White, 26% Black, 47% Medicare-insured). The top five treatment regimens for mCRPC were ADT monotherapy (19%), enzalutamide (ENZ; 14%), olaparib (OLA; 13%), abiraterone acetate (AA; 11%), and docetaxel (DOC; 10%), with 14% of patients receiving ≥1 medication. The main reasons for censoring in patients with ADT monotherapy were death (52.6%), loss to follow-up (26.3%), and end of data availability (21.1%). Among the 79 patients treated with other than ADT monotherapy in 1L, 43.0% (n=34) did not advance to 2L, of which 35.3% were lost to follow-up, 29.4% died (median time-to-death: 2.25 months), 29.4% were censored at the end of data availability, and 5.9% initiated a clinical trial drug. The most prescribed 2L therapies were DOC (22.2%), OLA (20.0%), AA (13.3%), and ENZ (11.1%). In those who advanced to 2L (n=45), the most common 1L → 2L treatment sequences were OLA → DOC (11.1%), ENZ → DOC (6.7%), AA → ENZ (6.7%), and AA → OLA (6.7%). In patients receiving 2L, 51.1% (n=23) did not advance to third-line therapy, of which 34.8% died, 34.8% were lost to follow-up, 26.1% were censored at the end of data availability, and 4.3% initiated a clinical trial drug. Conclusions: Among treated patients with BRCA+ mCRPC, ADT monotherapy, ENZ, OLA, AA, and DOC were most commonly used. The majority of ADT monotherapy patients died, while a substantial proportion of patients initiating 1L therapy died or initiated a clinical trial drug and did not advance to 2L, suggesting unmet need for more effective 1L treatment for patients with BRCA+ mCRPC.

Underutilization of androgen deprivation therapy (ADT) intensification for the treatment of men with metastatic hormone-sensitive prostate cancer (mHSPC): A systematic review of real-world database studies.

66 Background: In the last decade, intensification of ADT with chemotherapy or androgen receptor pathway inhibitors (ARPi) has shown clinical benefits for men with mHSPC compared to ADT alone and has been recommended for mHSPC in clinical guidelines. The transition of these guidelines into real-world practice was investigated by several studies; however, these data have not been systematically summarized across the globe. Thus, we conducted a systematic literature review of real-world database (RWD) studies to summarize treatment patterns in mHSPC. Methods: An electronic search was performed in PubMed and Embase (covering citations until July 2023) and for relevant conferences of the past 2 years to identify RWD studies examining treatment patterns in men with mHSPC. Treatment patterns were summarized by overall study population across major geographies and factors associated with ADT intensification were described. Results: Of 2,325 retrieved citations, 29 studies met the inclusion criteria, with a total of 344,473 men with mHSPC covering study periods from 2014 to 2021. Most were cohort studies (n=26), utilizing electronic medical records (EMR)/chart reviews (n=18), and with RWDs from the United States (US) (n=21), followed by Europe (n=8), and Asia (n=6). Most studies included men with a median age of ≥70 years (n=23) and &gt;80% of men had an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0/1 (n=5 of 8). In the US, most studies showed that ADT monotherapy was predominantly utilized (&gt;50%), followed by ADT/ARPi (20-40%), and ADT/chemotherapy (10-20%). Abiraterone was the most frequently used ARPi followed by enzalutamide. In Europe, most studies also reported ADT monotherapy (&gt;45%), followed by ADT/ARPi (11-25%), or ADT/chemotherapy (12-34%). In Asia, ADT monotherapy (&gt;62%) was the most common treatment in most studies, with low use of ADT/ARPIs (&lt;20%), and ADT/chemotherapy (&lt;15%). A few studies with recent EMR data (covering the 2020-21 data period) from cancer centers/registries showed high use of ADT/ARPi (&gt;40%) in both the US and Europe. Reported quantitative factors (n=13) associated with intensification beyond ADT were high disease burden (spread of metastases, high volume), young age, ECOG PS 0/1, low comorbidities, and treating physician specialty-oncologist; qualitative factors (n=2) were patient preference, unsatisfactory response to ADT treatment, ability to tolerate adverse events, and lack of cost barriers. Conclusions: This comprehensive review shows ADT monotherapy remained highly utilized across major geographies until 2021 despite new evidence and updated guideline recommendations. However, the utilization of intensified treatment with ARPi combinations is slowly increasing after the recent approvals in mHSPC.

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 .

Cost Effectiveness of Systemic Treatment Intensification for Metastatic Hormone-sensitive Prostate Cancer: Is Triplet Therapy Cost Effective?

Background and objectiveThere has been a shift toward systemic treatment intensification for men with metastatic hormone-sensitive prostate cancer (mHSPC). Recent trials have demonstrated the efficacy of triplet therapy with an androgen receptor signalling inhibitor (ARSI), docetaxel, and androgen deprivation therapy (ADT). However, ARSI treatment is expensive. The objective was to determine the cost effectiveness of current treatments strategies for men with mHSPC. MethodsWe developed a Markov state-transition model to simulate outcomes for men with newly diagnosed mHSPC. For the simulation, patients were entered in the model in the mHSPC disease state before progressing to castration-resistant disease and finally dying from prostate cancer. Costs were calculated from a USA health sector perspective in 2022 US dollars. Deterministic and probabilistic sensitivity analyses were conducted to account for uncertainty in the parameter estimates. We also performed scenario analyses for costs in the UK and Australian health sectors.Key findings and limitations: Treatment intensification with doublet and triplet therapy resulted in an improvement in quality-adjusted survival for all strategies in comparison to ADT monotherapy. However, only docetaxel doublet therapy was cost effective at standard thresholds, with an incremental cost-effectiveness ratio of $13647. The cost of ARSIs needed to be discounted by 47–70% before they were cost effective. Only medication costs impacted the model results. If the generic price for abiraterone acetate is used, then triplet therapy with abiraterone is the best-value option. Similar results were obtained for analyses for the UK and Australian health sectors. Conclusionsand clinical implications: Treatment intensification with ARSIs in men with mHSPC results in better quality-adjusted survival but is not cost effective according to standard thresholds. The costs of these medications would need to be heavily discounted before they are cost effective. The cost of generic ARSIs, once available, would render these strategies cost effective. Patient summaryThis report examines whether increasing the number of systemic drugs used to treat a patient’s metastatic hormone-sensitive prostate cancer is cost effective for the health care system. We found that the additional cost of triplet therapy does not justify the increase in patient benefit.

Oral chemotherapeutic agents in metastatic hormone-sensitive prostate cancer: A network meta-analysis of randomized controlled trials.

Multiple oral chemotherapeutic agents for metastatic hormone-sensitive prostate cancer (mHSPC) have been developed for conjugated use with conventional androgen deprivation therapy (ADT). Several randomized controlled trials (RCTs) report significant benefits in mHSPC patients. Therefore, we compared overall survival (OS) and progression-free survival (PFS) benefits among considerable mHSPC oral chemotherapeutic agents. We investigated mHSPC treatment efficacy through a systematic RCT-trial literature review (PubMed, Embase, Web of Science, the Cochrane Library, and Scopus). Two reviewers independently screened, extracted data, and assessed bias risk in duplicate. We identified 18 RCTs (n=13,509). Concerning OS, ADT+abiraterone, ADT+abiraterone+docetaxel, ADT+apalutamide, ADT+bicalutamide, ADT+darolutamide+docetaxel, ADT+enzalutamide, ADT+orteronel, and ADT+rezvilutamide were more effective than the standard of care (SOC). Comparing PFS, most treatments were more effective than SOC, excluding ADT+bicalutamide, nilutamide, flutamide, ADT+bicalutamide+palbociclib, and ADT+nilutamide. ADT+docetaxel with androgen receptor targeted agent (ARTA) triplet therapy was not among the top three treatments determined through ranking analysis. Novel oral chemotherapeutic agent combination therapies must replace current ADT monotherapy and ADT+docetaxel SOC. Even so, ADT+docetaxel with ARTA triplet therapy still is not the best mHSPC treatment and requires further study.

PD16-06 EXAMINING TESTOSTERONE RECOVERY IN ANDROGEN DEPRIVATION THERAPY FOR PROSTATE CANCER

You have accessJournal of UrologyCME1 Apr 2023PD16-06 EXAMINING TESTOSTERONE RECOVERY IN ANDROGEN DEPRIVATION THERAPY FOR PROSTATE CANCER Mark A. Preston, Jessica R. Marden, Noam Kirson, Esmond Nwokeji, Raj Gandhi, Allison Briggs, Katherine Gaburo, Sarah Hanson, and Alicia K. Morgans Mark A. PrestonMark A. Preston More articles by this author , Jessica R. MardenJessica R. Marden More articles by this author , Noam KirsonNoam Kirson More articles by this author , Esmond NwokejiEsmond Nwokeji More articles by this author , Raj GandhiRaj Gandhi More articles by this author , Allison BriggsAllison Briggs More articles by this author , Katherine GaburoKatherine Gaburo More articles by this author , Sarah HansonSarah Hanson More articles by this author , and Alicia K. MorgansAlicia K. Morgans More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003271.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Androgen deprivation therapy (ADT) used in prostate cancer (PC) can delay testosterone (T) recovery (TR) after treatment cessation. Data are lacking on the clinical impact of prolonged TR. This real-world study examined clinical events among PC patients with and without TR after discontinuing injectable ADT. METHODS: A retrospective longitudinal cohort study was conducted using electronic medical records (Optum’s de-identified Market Clarity Data, 2010–2021). Eligible patients had a PC diagnosis, initiated first-line ADT monotherapy, and had ≥1 serum T level within 1 year of ADT discontinuation. Patients were classified as having TR (serum T >280 ng/dL) or no TR within 1 year of ADT discontinuation. Clinical outcomes examined included myocardial infarction, cerebrovascular accident, diabetes, depression, hot flashes, sexual dysfunction, and bone complications. The proportion of patients with events at 12 months were reported. Multivariate Cox proportional hazards models estimated hazard ratios (HRs) for TR vs non-TR cohorts, adjusting for demographics and baseline clinical events. RESULTS: 1553 patients were identified in the TR (n=390) and non-TR (n=1163) cohorts. Median age at ADT initiation was 70.3 years with 94.8% receiving a luteinizing hormone-releasing hormone agonist. Baseline median serum T was 254.0 ng/dL among patients with available data. During the 1-year post-ADT discontinuation, median serum T levels were 330.5 ng/dL for TR and 32.7 for non-TR cohorts. At 12 months post-discontinuation, a higher proportion of TR vs non-TR patients had sexual dysfunction, while lower proportions had new onset diabetes and depression (Table 1). Adjusted Cox analyses showed TR patients had a lower risk of diabetes (HR=0.47 [95% CI 0.27–0.79], p=0.005) vs the non-TR cohort and trended toward lower risk of depression (HR=0.58 [0.33–1.02], p=0.059) but a higher risk of sexual dysfunction (HR=1.33 [0.99–1.78], p=0.060). CONCLUSIONS: Patients with recovered serum T within 1 year of ADT discontinuation were less likely to experience diabetes. Trends showed a lower rate of depression and sexual dysfunction as potentially correlated with time to TR. Sexual dysfunction may have been higher among TR patients due to greater levels of sexual interest post ADT. Source of Funding: Myovant Sciences, Inc. in collaboration with Pfizer, Inc © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e491 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mark A. Preston More articles by this author Jessica R. Marden More articles by this author Noam Kirson More articles by this author Esmond Nwokeji More articles by this author Raj Gandhi More articles by this author Allison Briggs More articles by this author Katherine Gaburo More articles by this author Sarah Hanson More articles by this author Alicia K. Morgans More articles by this author Expand All Advertisement PDF downloadLoading ...

Adherence to standard of care (SOC) therapy for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC): A single-institution analysis.

103 Background: Androgen deprivation therapy (ADT) has been the backbone of treatment for mHSPC for decades. In recent years, multiple randomized controlled trials demonstrating an overall survival (OS) benefit of combination treatment (e.g. ADT + novel hormonal agent and/or chemotherapy) has made this the current SOC. Large real-world reports have shown a significant number of patients are still being treated below the SOC with ADT alone, but these databases do not include patient level data to help understand the rationale for treatment decisions. We reviewed our institution’s treatment patterns for mHSPC to better understand why some patients are being treated with ADT alone. Methods: We conducted a retrospective analysis on patients who initiated treatment for mHSPC from 2017-2021 at Cleveland Clinic. Patient characteristics were recorded, including age and histology. Treatment characteristics, including location of treatment, treatment regimen, and treatment rationale (if not treated with SOC) were noted. Results: Four hundred forty-nine patients were included, with diagnosis of metastatic disease made at a median of 63 years, of which 446 started treatment with systemic therapy. The vast majority of patients were managed by a medical oncologist (95.5%). About half of the patients (49.8%) received treatment at the main campus, with the remaining patients being treated at an affiliated regional hospital (28.7%) or outpatient medical center (21.5%). Additional characteristics are shown. Out of the 446, 40 (9.0%) patients received ADT alone. Reasons for ADT monotherapy included patient preference (n = 13), cost (n = 2), and poor functional status/comorbidities (n = 4). Twenty (50%) of the patients who got ADT alone had no documented rationale for why this treatment plan was elected. One patient was lost to follow-up. For patients who received only ADT, 12 were treated at main campus, 20 were treated at a regional hospital, and 8 were treated at an outpatient medical center. Conclusions: At our institution, adherence to treatment up to SOC for mHSPC was better than previous real-world reports. There were documented reasons for not treating mHSPC up to SOC combination therapy for half of the patients who got ADT monotherapy. It remains unclear why the remaining half did not get combination therapy up to the SOC. [Table: see text]

Oncologists’ perspectives on metastatic hormone sensitive prostate cancer management.

84 Background: The treatment of metastatic hormone sensitive prostate cancer (mHSPC) has evolved over the past 7 years. Combination therapies with either [Androgen deprivation therapy (ADT) + Docetaxel] or [ADT + androgen receptor signaling inhibitors (ARSi) such as abiraterone acetate/enzalutamide/apalutamide] have demonstrated overall survival (OS) benefit compared to ADT + placebo in mHSPC. Recently two trials (ARASENS and PEACE-1) also demonstrate an OS benefit from the addition of docetaxel to ADT + ARSi (abiraterone acetate or darolutamide) compared to ADT + docetaxel. Given these recent advances there is not a clear consensus on how to best manage patients with mHSPC as there are no head-to-head trials. In this study, we assess oncologists’ treatment preferences as it pertains to this subset of patients. Methods: An 8-item online survey was sent on September 6th, 2022 to medical oncologists in the United States. We described five different case scenarios and three demographic questionnaires. Cases consisted of patients with mHSPC both de novo and primary progressive with low and high volumes. Treatment options included ADT monotherapy, ADT + ARSi (doublet), or ADT + ARSi + docetaxel (triplet therapy). Respondents reported their practice setting, location, and years of clinical experience. Data was collected and analyzed via REDCap. Results: Surveys were completed by (n=83) medical oncologists across the US. 14.5% of respondents were from Kentucky; 51.8% have been in practice &lt; 10 years, 20.5% 10-20 years, and 27.7%&gt; 20 years. For patients with de novo high volume disease, 85.5% (71) preferred treatment with triplet therapy. For the same patient population, 94.4% (51) of university-based providers preferred triplet therapy vs 68.9% (20) of those in a non-academic setting. Preferences differed regarding patients with primary progressive high-volume disease in which 59.8% (49) preferred a triplet regimen while 37.8% (31) preferred a doublet regimen. Of those choosing triplet therapy, 53.7% (29) were from an academic institution while 71.4% (20) practiced in a nonacademic setting. Of those choosing doublet therapy, 42.6% (23) were from an academic institution versus 28.6% (8) in a nonacademic setting. For patients with de novo or primary progressive low volume disease, 81.5% of respondents preferred doublet therapy without a notable difference between academic and non-academic responders. Conclusions: We find a consensus in management of patients with de novo high volume mHSPC (prefer triplet) and de novo or primary progressive low volume disease (prefer doublet) regardless of practice setting, location, or practice duration. However, for patients with primary progressive high-volume disease, a higher percentage of non-academic providers prefer triplet therapy compared to their university counterparts.

Role of multidisciplinary team meetings in implementation of chemohormonal therapy in metastatic prostate cancer in daily practice.

The recommended treatment for a subset of patients with metastatic prostate cancer (mPC) changed from androgen deprivation therapy (ADT) to combinations with chemotherapy such as docetaxel. Implementation of new evidence from trials is however complex and challenging. We investigated the effect of multidisciplinary team meetings (MDTs) on adopting the newest emerging combination therapy in patients with mPC and assessed the overall survival of chemohormonal therapy in a real-world setting. All mPC patients diagnosed between October 2015 and April 2016 in the Netherlands were identified from the population-based Netherlands Cancer Registry (n = 962). Logistic regression analyses were performed to examine the role of patient- and tumor characteristics, with special emphasis on MDTs, on receiving chemohormonal therapy versus ADT monotherapy. Kaplan-Meier survival curves were used to assess overall survival (OS). As many patients received ADT monotherapy as chemohormonal therapy (both n = 452). Being discussed in a MDT as patient, younger age, less comorbidities, a better performance status and high-volume disease were significantly associated with receiving chemohormonal therapy compared to ADT monotherapy. After adjustment for these factors, the presence of a MDT was independently associated with the administration of chemohormonal therapy (OR 2.77, 95% CI 1.68-4.59). The 2-year OS was 82.1% (95% CI: 78.5-85.6%) for patients receiving chemohormonal therapy and 59.9% (95% CI: 55.4-64.4%) for patients receiving ADT monotherapy. Being discussed in a MDT is independently associated with the administration of chemohormonal therapy in this group of patients with mPC. This supports the hypothesis that implementation of innovative treatment options is facilitated by an organizational structure with MDTs.

Effect of upfront intensive therapy on oncological outcomes in older patients with high tumor burden metastatic castration-sensitive prostate cancer: A multicenter retrospective study.

The effect of upfront intensive therapy on the prognosis of older patients with metastatic castration-sensitive prostate cancer (mCSPC) remains unclear. Thus, we assessed the impact of older age (≥75 years) on oncological outcomes in mCSPC patients with a high tumor burden. This multicenter retrospective study included 252 patients aged ≥75 years treated with either upfront or conventional therapy between 2014 and 2021. We compared castration-resistant prostate cancer (CRPC)-free survival (FS) and overall survival (OS) between patients with androgen deprivation therapy (ADT) plus upfront intensive therapy (docetaxel [DTX] or abiraterone acetate [ABI] plus prednisolone) and conventional therapy (ADT monotherapy or ADT combined with bicalutamide). We evaluated the effect of upfront intensive therapy on prognosis by multivariable Cox regression analysis. The 231 patients enrolled in our study were classified in the conventional group (n = 148) or the upfront group (n = 104; DTX = 27 and ABI = 77). The upfront group had significantly prolonged CRPC-FS and OS compared with the conventional group, and this was also the case in the background-adjusted multivariable Cox regression analysis. Patients aged ≥75 years who received upfront intensive therapy had significantly longer CRPC-FS and OS compared with similar age patients treated with conventional therapy in real-world practice. The oncological benefit may not diminish in this older population.

Bridging the gap between oncology clinical trials and real-world data: evidence on replicability of efficacy results using German claims data.

Aims: Using German claims, the authors replicated the CHAARTED trial in metastatic hormone-sensitive prostate cancer. Methods: The authors identified metastatic hormone-sensitive prostate cancer patients replicating the inclusion/exclusion criteria of CHAARTED. Patients treated with docetaxel in combination with androgen deprivation therapy (ADT) at first line (docetaxel group) were compared with patients treated with ADT monotherapy (ADTmonogroup). After propensity score matching, overall survival was compared between the matched cohorts. Results: The authors included 441 patients. After propensity score matching, two equally sized matched cohorts of 74 patients each were compared in terms of overall survival. The hazard ratio (HR) was 0.71 (95% CI: 0.42-1.19), comparable to the HR in CHAARTED (HR: 0.72; 95% CI: 0.59-0.89). Conclusions: Using early comparative evidence from real-world data for regulatory and health technology assessment decisions is useful.

SYSTEMIC TRIPLE THERAPY IN METASTATIC HORMONE SENSITIVE PROSTATE CANCER (MHSPC).

For many years, androgen deprivation therapy (ADT) as monotherapy has been the gold standard for metastatic hormone-sensitive prostate cancer (mHSPC) treatment. Several studies have been published within the last decade demonstrating a significant survival advantage resulting from combining the treatment with standard ADT plus docetaxel or androgen receptor targeted therapy (ARTA) compared to ADT monotherapy. Recently published data of the PEACE-1 and ARASENS trials suggest that in the future, triple therapy might be a treatment option for patients with mHSPC.

Systemic Triple Therapy in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Ready for Prime Time or Still to Be Explored?

Simple SummaryCurrently, a combination therapy of standard androgen deprivation therapy (ADT) plus docetaxel or androgen receptor-axis-targeted therapy is the gold standard for metastatic hormone-sensitive prostate cancer (mHSPC) treatment. Compared to ADT monotherapy, combination treatment prolongs overall survival by at least 18 months. The latest data has shown that triple treatment with standard ADT plus docetaxel plus abiraterone is superior to standard ADT plus docetaxel. Ongoing clinical trials are investigating triple therapy protocols by affecting diverse signaling pathways that are pivotal in prostate cancer. In this review, we will explore if triple therapy has the potential to be the new standard for mHSPC treatment in the near future.For decades, mono androgen deprivation therapy (ADT) has been the gold standard for metastatic hormone-sensitive prostate cancer (mHSPC) treatment. Several studies have been published within the last seven years demonstrating a significant survival advantage by combination treatment with standard ADT plus docetaxel or androgen receptor-axis-targeted therapy (ARAT) compared to ADT monotherapy. As a result, overall survival can be prolonged by at least 18 months. Recently published congress data of the PEACE-1 study suggests that in the future, triple therapy might be the new gold standard. In addition to this study, which has shown that triple treatment with standard ADT plus docetaxel plus abiraterone is superior to standard ADT plus docetaxel, several other phase III triple therapy studies are currently ongoing. The different modes of action that are investigated reach from AR-targeting over mitotic inhibition and immunotherapy to PARP and AKT inhibition. In this review we will explore if triple therapy has the potential to be the new standard for mHSPC treatment in the near future.

MP24-13 PERCENTAGE AND RATIONALE OF GUIDELINE-DISCORDANT ANDROGEN DEPRIVATION THERAPY IN PROSTATE CANCER PATIENTS

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) II (MP24)1 Sep 2021MP24-13 PERCENTAGE AND RATIONALE OF GUIDELINE-DISCORDANT ANDROGEN DEPRIVATION THERAPY IN PROSTATE CANCER PATIENTS Renée Hogenhout, Ivo de Vos, Sebastiaan Remmers, Martijn Busstra, Lionne Venderbos, Monique Roobol, and the ERSPC Rotterdam Study Group Renée HogenhoutRenée Hogenhout More articles by this author , Ivo de VosIvo de Vos More articles by this author , Sebastiaan RemmersSebastiaan Remmers More articles by this author , Martijn BusstraMartijn Busstra More articles by this author , Lionne VenderbosLionne Venderbos More articles by this author , Monique RoobolMonique Roobol More articles by this author , and the ERSPC Rotterdam Study Group More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002015.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recommendations on Androgen Deprivation Therapy (ADT) for prostate cancer (PCa) patients arise from a critical appraisal of scientific evidence which is a lot of work. Despite these efforts, the known side-effects of ADT and the lack of benefit in certain risk groups, guidelines may not always be adhered to. Here, we determined guideline adherence to ADT recommendations and analyzed the physicians’ motivation in case of disconcordance. METHODS: We included subjects from the Rotterdam section of the European Randomized Study of Screening for PCa who were diagnosed with PCa in all stages since the publication of the first EAU guidelines on PCa in 2001 up to and including 2019, and received any form of ADT within the first year after diagnosis. They were categorized into guideline-concordant or -discordant ADT according to the EAU guidelines recommendations within the study period. RESULTS: A total of 1037/3211 (32%) men diagnosed with PCa received ADT within the first year after diagnosis, of which 162/1037 (16%) men received guideline-discordant ADT. In 79% (823/1037) ADT was administered guideline-concordant and in 4% (45/1037) adherence was not assessable due to incomplete medical files. In seven patients (4%) who were unfit/unwilling for curative treatment, lower urinary tract symptoms (LUTS) contributed to the decision to prescribe ADT monotherapy. These cases were also considered as not assessable since LUTS is not clearly defined as “symptomatic” in the guideline. Most of the guideline discordance was noticed in patients receiving ADT monotherapy for intermediate- and high-risk PCa (73%). A common reason for discordant prescription of ADT as monotherapy in this group was suspicion of (lymph node) metastases due to high PSA level (28%). Other reasons were unwillingness (24%) and/or unfitness (51%) to undergo curative treatment without being symptomatic. Three patients (3%) were symptomatic but not unfit or unwilling for curative treatment. In 16% of the discordant cases, prescription of ADT monotherapy was not motivated. CONCLUSIONS: Guidelines and clinical practice do not necessarily correspond. Physicians did not adhere to EAU guidelines on ADT in a Dutch cohort in 16% of the cases. However, guideline-discordant prescription of ADT may not always indicate “inappropriate” treatment. Physicians are able to make a more nuanced clinical assessment taking into account comorbidities, patients’ wishes and social context. Although guidelines support clinical decision-making, better defined and more tailored guidelines are needed. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e416-e417 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Renée Hogenhout More articles by this author Ivo de Vos More articles by this author Sebastiaan Remmers More articles by this author Martijn Busstra More articles by this author Lionne Venderbos More articles by this author Monique Roobol More articles by this author the ERSPC Rotterdam Study Group More articles by this author Expand All Advertisement Loading ...

Benefits of early salvage therapy on oncological outcomes in high-risk prostate cancer with persistent PSA after radical prostatectomy.

Patients with prostate-specific antigen (PSA) persistence are at the increased risk of disease progression. The aim of our study was to evaluate the impact of early salvage therapy on oncological outcomes in patients with persistent PSA after radical prostatectomy (RP). Within a single tertiary centre database, we identified men with persistent (≥ 0.1ng/ml) versus undetectable (< 0.1ng/ml) PSA 4-8weeks after RP for high-risk prostate cancer (HRPCa). The cumulative incidence function was used to estimate cancer-specific survival (CSS) and clinical progression-free survival (CPFS). The Kaplan-Meier method was used to estimate overall survival (OS). The effects on oncological outcomes of salvage radiotherapy (SRT) ± androgen deprivation therapy (ADT) vs. ADT monotherapy were tested in the subgroup of patients with persistent PSA. Of 414 consecutive patients who underwent RP for HRPC, 125 (30.2%) had persistent PSA. Estimated 10-year CPFS, CSS and OS for men with persistent vs. undetectable PSA were 63.8% vs. 93.5%, 78.5% vs. 98.3% and 54% vs. 83.2% (all p < 0.0001), respectively. In men with persistent PSA, ADT alone was associated with higher risk (hazard ratio (HR) for worse CSS (HR 3.9, p = 0.005) and OS (HR 4.7, p < 0.0001) but not for CP (HR 1.6, p = 0.2) when compared with SRT ± ADT. In patients who underwent RP for HRPCa, persistent PSA was associated with poor oncological outcomes. Early SRT ± ADT resulted in significantly improved CSS and OS in men with persistent PSA comparing with early androgen deprivation monotherapy.