Androgen Deprivation Therapy In Patients Research Articles

Androgen deprivation therapy, neoadjuvant androgen deprivation therapy, and adjuvant androgen deprivation therapy in patients with locally advanced prostate cancer: a multi-center real-world retrospective study.

Determining the potential benefit of neoadjuvant androgen deprivation therapy (ADT) and adjuvant ADT in patients with locally advanced prostate cancer (LAPC) undergoing complete resection. 139 patients diagnosed with cT3-4, or cN+ LAPC in Xiangya Hospital and The First Affiliated Hospital of University of South China from 2010 to 2021 were collected. Cancer-specific survival (CSS) and overall survival (OS) of patients were assessed using Kaplan-Meier and Cox proportional risk analysis. We also analyzed the functional outcomes of two subgroups of patients who underwent radical prostatectomy (RP). Of the 182 patients with cT3-4, or cN+ LAPC, 139 patients (76.4%) were enrolled in the study with a 5-year survival rate of 82.3%. 45 patients (32.4%) received ADT alone, 46 patients (33.1%) received neoadjuvant ADT before surgery, and the remaining 48 patients (34.5%) received surgery with adjuvant ADT. Neoadjuvant ADT before surgery and surgery with adjuvant ADT were associated with significantly improved survival compared with ADT alone. Multivariate Cox models showed that neoadjuvant ADT before surgery (hazard ratio [HR], 0.29; 95% CI 0.13-0.92) or surgery with adjuvant ADT (HR, 0.26; 95% CI 0.16-0.78) was associated with improved CSS compared with ADT alone. Regional lymph node metastasis, positive lymphovascular invasion, and Gleason score 9 + were independent predictors of LAPC CSS and OS. More patients in the neoadjuvant ADT before surgery group achieved final continence status within 12 months after surgery (93.48% v 77.08%). CSS and OS were significantly prolonged in cT3-4, or cN+ LAPC patients who received neoadjuvant ADT before surgery and surgery with adjuvant ADT compared to ADT alone.

Immediate Versus Delayed Exercise on Health-related Quality of Life in Patients Initiating Androgen Deprivation Therapy: Results from a Year-long Randomised Trial

Background and objectiveAn array of treatment-related toxicities result from androgen deprivation therapy (ADT) in patients with prostate cancer (PCa), compromising function and health-related quality of life (HRQoL). Exercise has been demonstrated to counter a number of these adverse effects including decreased HRQoL; however, when exercise should be initiated is less clear. This study aims to examine whether commencing exercise when ADT is initiated rather than later during treatment is more effective in countering adverse effects on HRQoL. MethodsMen with PCa (48–84 yr) initiating ADT were randomised to immediate exercise (IMEX; n = 54) or delayed exercise (DEL; n = 48) for 12 mo. IMEX consisted of 6 mo of supervised resistance/aerobic/impact exercise commenced at the initiation of ADT with 6 mo of follow-up. DEL consisted of 6 mo of usual care followed by 6 mo of the same exercise programme. HRQoL was assessed using the Short Form-36 at baseline and 6 and 12 mo. Intention to treat was utilised for the analyses that included group × time repeated-measures analysis of variance using log transformed data. Key findings and limitationsThere were a significant group × time interaction for the physical functioning domain (p = 0.045) and physical component summary score (p = 0.005), and a significant time effect for bodily pain (p < 0.001) and vitality domains (p < 0.001), with HRQoL maintained in IMEX and declining in DEL at 6 mo. Exercise in DEL reversed declines in vitality and in the physical component summary score, with no differences at 12 mo compared with baseline. Limitations include treatment alterations during the intervention. Conclusions and clinical implicationsConcurrently initiating exercise and ADT in patients with PCa preserves HRQoL, whereas exercise initiated while on established ADT regimens reverses declines in some HRQoL domains. Patient summaryTo avoid initial treatment-related adverse effects on health-related quality of life, exercise medicine should be initiated at the start of treatment.

Immediate Versus Delayed Exercise In Patients Initiating Androgen Deprivation Therapy: Effects On Quality Of Life

Immediate Versus Delayed Exercise In Patients Initiating Androgen Deprivation Therapy: Effects On Quality Of Life

Darolutamide in Combination With Androgen-Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer From the Phase III ARANOTE Trial.

For patients with metastatic hormone-sensitive prostate cancer (mHSPC), delaying progression to castration-resistant disease is important not only for overall survival (OS) but also for patients' quality of life . Darolutamide plus androgen-deprivation therapy (ADT) with docetaxel improved OS versus ADT and docetaxel in patients with mHSPC. The ARANOTE trial evaluated darolutamide and ADT without chemotherapy in patients with mHSPC. In this global phase 3 trial, patients were randomized 2:1 to receive darolutamide 600 mg twice daily or placebo, with concomitant ADT. The primary endpoint was radiological progression-free survival (rPFS). From March 2021 to August 2022, 669 patients were randomized (darolutamide n=446; placebo n=223). At the primary cutoff date (June 7, 2024), darolutamide plus ADT significantly improved rPFS by 46% versus placebo plus ADT (hazard ratio [HR] 0.54; 95% confidence interval [CI], 0.41-0.71; P<0.0001), with consistent benefits across subgroups, including high- and low-volume disease. OS results were suggestive of benefit with darolutamide versus placebo (HR 0.81; 95% CI, 0.59-1.12) and clinical benefits were seen across all other secondary endpoints, including delayed time to castration-resistant prostate cancer (HR 0.40; 95% CI, 0.32-0.51) and time to pain progression (HR 0.72; 95% CI, 0.54-0.96). Adverse events were similar in the two groups. Notably, the incidence of fatigue was lower in patients receiving darolutamide (5.6%) versus those receiving placebo (8.1%), and fewer patients receiving darolutamide (6.1%) versus placebo (9.0%) discontinued treatment due to adverse events. These results confirm the efficacy and tolerability of darolutamide plus ADT in patients with mHSPC, demonstrating clinically and statistically significant improvement in rPFS and a favorable safety profile consistent with prior phase 3 darolutamide trials.

Inhibitors of the transactivation domain of androgen receptor as a therapy for prostate cancer

The androgen receptor (AR) is a modular transcription factor which functions as a master regulator of gene expression. AR protein is composed of three functional domains; the ligand-binding domain (LBD); DNA-binding domain (DBD); and the intrinsically disordered N-terminal transactivation domain (TAD). AR is transactivated upon binding to the male sex hormone testosterone and other androgens. While the AR may tolerate loss of its LBD, the TAD contains activation function-1 (AF-1) that is essential for all AR transcriptional activity. AR is frequently over-expressed in most prostate cancer. Currently, androgen deprivation therapy (ADT) in the form of surgical or chemical castration remains the standard of care for patients with high risk localized disease, advanced and metastatic disease, and those patients that experience biochemical relapse following definitive primary treatment. Patients with recurrent disease that receive ADT will ultimately progress to lethal metastatic castration-resistant prostate cancer. In addition to ADT not providing a cure, it is associated with numerous adverse effects including cardiovascular disease, osteoporosis and sexual dysfunction. Recently there has been a renewed interest in investigating the possibility of using antiandrogens which competitively bind the AR-LBD without ADT for patients with hormone sensitive, non-metastatic prostate cancer. Here we describe a class of compounds termed AR transactivation domain inhibitors (ARTADI) and their mechanism of action. These compounds bind to the AR-TAD to inhibit AR transcriptional activity in the absence and presence of androgens. Thus these inhibitors may have utility in preventing prostate cancer growth in the non-castrate setting.

Analysis of risk factors for disease progression after salvage radiation therapy with androgen deprivation therapy in prostate cancer patients who have prostate-specific antigen persistence after radical prostatectomy.

To assess risk factors of disease progression after salvage radiation therapy (SRT) with androgen deprivation therapy (ADT) in case of prostate-specific antigen (PSA) persistence after radical prostatectomy (RP). We analyzed 57 patients who received SRT with ADT between 2013 and 2019 due to PSA persistence after RP. The endpoint was disease progression defined by biochemical recurrence or clinical recurrence. Age, Pre-RP PSA level, Gleason score, pathologic stage, presence of pelvic lymph node dissection, surgical margins, and PSA at 6-8 weeks after RP were analyzed as predictive factors for disease progression. Kaplan-Meier method and Cox regression models were used for data analysis. At a median follow-up of 38 months (interquartile range, 26-61), 17 patients had disease progression. Pathologic T stage (pT3b vs. pT3a or lower; hazard ratio [HR] = 9.20; p = 0.035) and PSA level at 6-8 weeks after RP (≥2.04 vs. <2.04 ng/mL; HR = 5.85; p = 0.002) were predictors of disease progression. The 5-year disease progression-free survival rate was 46.7% in pT3b group as compared to 92.9 % in pT3a or lower group, and 18.4% for PSA ≥2.04 ng/mL after RP as compared to 79.2% for PSA <2.04 ng/mL. Pathological T stage (pT3b) and post RP PSA ≥2.04 ng/mL are independent risk factors of disease progression after SRT with ADT in patients with PSA persistence after RP.

Quality of life and testosterone recovery after androgen deprivation therapy in patients with high-risk prostate cancer: Long-term data from a phase III trial.

11098 Background: No prospectively collected data exist assessing the impact a hypogonadal status has on quality of life (QoL). Using data from a randomized Phase III trial in high-risk prostate cancer (HRPC) and based on Patient Reported Outcomes (PRO), we compared QoL between patients (pts) with or without testosterone (T) recovery after ADT. Methods: From 10/2000 to 01/2008, 630 pts with HRPC were randomised to 36 (310 pts) vs. 18 months (320 pts) of ADT. We assessed QoL by the validated EORTC 30 items regrouped into 9 scales and the PR 25 items into 5 scales. All items and scales scores were linearly transformed to a 0 to100 points scale. T measured at baseline and during follow-ups. T recovery was defined as a return to normal level. PRO measured up to 5 years. We estimated means and standard deviation of items and scales for each group at each time point. We analyzed all items and scales scores with general linear model with repeated measures to evaluate changes between patients who did versus those who did not recover T to a normal level, over time, in both ADT groups. P-value &lt;0.01 was considered statistically significant to account for multiple comparisons and a difference in mean scores of ≥10 points was considered clinically relevant. Results: 494/630 patients were retained for the analysis. 515 had proper T data available (baseline and follow-up) from whom 21 were excluded (no QoL data). With a median follow-up of 13.1 years, the two groups were well-balanced. Over a period of 21 years, 5 982 T measurements were available: 3590 in 314 pts in the and 2392 in the 18- and 36-month cohort, respectively. A total of 256 (51.8%) recovered T to, at least, a pre-castrate level. A significantly higher percentage of pts recovered a normal T level in the 18-month cohort as compared to the 36-month (56.4% vs. 43.9%, p=0.008). Among pts regaining T to a normal level, the median time to recovery was significantly faster for the 18 compared to the 36-month cohort, 3.0 (95% CI: 2.55 to 3.65) vs. 5.00 (4.50 to 5.96) years, p&lt;0.001. Considering the unified 55 items, overall adherence to QoL questionnaires (QoLQ) was 83.1% (4554/5480), 88.2% vs. 93.3% at baseline and 61.5% vs 58.3% at 5 years, for 18 vs. 36-month, respectively. Patients recovering T had a significantly better QoL. In 32 out of 55 items and in 10 out of 21 scales (p&lt;0.01) in the 18-month and 30 out of 55 items and 10 out of 21 scales the 36-month cohort. Also 9 items and one scale reached clinical relevance in the 18-month cohort and 10 items and one scale in the 36-month cohort. Conclusions: In HRPC treated with RT and long-term ADT, T recovery to normal level is associated with major improvements in QoL in several domains. Since a higher proportion of pts recover a normal T level in a much shorter time without apparent detriment in long term outcomes, our results suggest that 18-month may be the most appropriate ADT duration for these pts.

Darolutamide plus androgen-deprivation therapy in patients with high-risk biochemical recurrence of prostate cancer: A phase 3, randomized, double-blind, placebo-controlled study (ARASTEP).

Darolutamide plus androgen-deprivation therapy in patients with high-risk biochemical recurrence of prostate cancer: A phase 3, randomized, double-blind, placebo-controlled study (ARASTEP).

Within-trial hospitalization resource utilization and budget impact analysis for darolutamide in metastatic hormone-sensitive prostate cancer using ARASENS.

ARASENS was a randomized, double-blind, phase 3 trial comparing darolutamide + docetaxel + androgen deprivation therapy (ADT) with placebo + docetaxel + ADT in patients with metastatic hormone-sensitive prostate cancer (mHSPC). To use clinical trial data from ARASENS to understand whether the addition of darolutamide to docetaxel + ADT leads to increased hospitalizations and to estimate the budget impact on the US health care system. We used mixed-effects negative binomial regression to estimate hospitalization and intensive care unit (ICU) admission rates and length of hospital stay (LoHS) counts. Hospitalization rates were estimated per treatment arm for the period during and after administration of docetaxel. Based on these estimates, a budget impact analysis evaluated the hospitalization costs (including ICU admissions) and standalone ICU hospitalization costs for the totality of the US population over a 5-year time horizon. The analysis compared a scenario without darolutamide vs one with darolutamide included in the US payer formulary. Hospitalization estimates were varied in a one-way sensitivity analysis. The first 4 months of treatment (when patients were receiving docetaxel) were associated with increased hospitalizations across both arms. The addition of darolutamide was associated with a numerical reduction in the rate of hospitalization (per year) due to any reason both during docetaxel treatment (1.01 visits per year [95% CI = 0.82-1.20] vs 1.18 visits per year [95% CI = 0.96-1.41]) and after docetaxel treatment (0.28 visits per year [95% CI = 0.23-0.34] vs 0.33 visits per year [95% CI = 0.27-0.40]). Darolutamide was associated with a marginally longer LoHS per hospitalization compared with placebo (+1.90 days per year) both during and after docetaxel treatment. ICU admissions were low in the ARASENS data; admission rates were assumed to be the same during and after docetaxel treatment. ICU admission rate estimates were equivalent across arms (0.02 visits per year [95% CI = 0.01-0.03]). The budget impact per treated member per month represents a cost-neutral option after Year 5 with a cumulative budget impact of -$9.71. The addition of darolutamide to docetaxel + ADT was associated with a numerically lower rate of hospitalization but marginally longer LoHS compared with docetaxel + ADT alone. Darolutamide represents a cost-neutral alternative per treated member per month compared with docetaxel + ADT with regard to hospitalizations at the end of a 5-year time horizon.

A practical guide for assessing and managing cardiovascular risk during androgen-deprivation therapy in patients with prostate cancer.

Prostate cancer is the most common malignancy among men worldwide, and androgen-deprivation therapy (ADT) is a mainstay of treatment. There are observational data demonstrating an increased risk of cardiovascular events in patients who receive ADT, particularly those who have an elevated baseline cardiovascular risk. Because, for most patients with prostate cancer, death is predominantly from noncancer-related causes, cardiovascular disease and its risk factors should be optimized during cancer treatment. This review provides an overview of the landscape of ADT treatment and serves as a guide for appropriate cardiovascular screening and risk-mitigation strategies. The authors emphasize the importance of shared communication between the multidisciplinary cancer team and primary care to improve baseline cardiovascular screening and treatment of modifiable risk factors within this higher risk population.

The effect of dose-escalation radiotherapy with simultaneous-integrated-boost on the use of short-term androgen deprivation therapy in patients with intermediate risk prostate cancer.

To compare the biochemical failure (FFBF) and prostate cancer specific survival (PCSS) rates of patients with intermediate-risk prostate cancer (IR-PC) who were treated with 6 months of androgen deprivation therapy (ADT) with 78 Gy to the prostate, those treated with ADT and focal boost (FB) of 86 Gy to intraprostatic lesion (IPL) using the simultaneous-integrated boost (SIB) technique, and those treated with SIB alone. A retrospective analysis of 320 IR-PC patients treated between January 2012 and April 2021 was performed. Patients were divided into three groups based on their treatment arm: 78 + ADT (109 patients, 34.1%), 78/86 (102 patients, 31.8%), and 78/86 + ADT. Univariable and multivariable analyses were used to determine prognostic factors for FFBF and PCSS. Median follow-up was 8.8 years. The 8-year FFBF and PCSS rates were 88.6% and 99.0%. Patients who received ADT had significantly higher pretreatment PSA levels and clinical tumor stage. Disease progression occurred in 45 patients (7.3%) at a median of 41.9 months after definitive radiotherapy (RT). Younger age, positive core biopsy (PCB) ≥ 50%, and the absence of ADT were all independent predictors of poor FFBF in multivariate analysis, whereas patients with PCB < 50% who were also given ADT had better PCSS. Patients treated with 78/86 Gy alone had worse FFBF than those treated with 78 Gy and ADT (Hazard ratio [HR] = 3.39 [95% CI = 1.46-7.88]; p = 0.005), as well as than those treated with 78/86 Gy and ADT (HR = 3.21 [95% CI = 1.23-6.46]; p = 0.009). However, FB to IPL has no effect on PCSS in multivariable analysis. There was no significant difference between treatment groups in terms of acute and late Grade ≥2 genitourinary or gastrointestinal toxicity. Our findings demonstrated that patients who received 78/86 alone did worse than patients who received ADT with either 78 or 78/86 Gy. However, because IR-PC patients are so diverse, additional prospective trials are needed to validate our findings.

Bone-Modifying Agents in Patients With High-Risk Metastatic Castration-Sensitive Prostate Cancer Treated With Abiraterone Acetate

The association between the use of bone-modifying agents (BMAs) and the outcomes among patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with abiraterone acetate plus prednisone (AAP) remains unclear. To investigate the association between BMA use and the outcomes of patients with mCSPC receiving AAP. In this cohort study, a post hoc analysis of individual participant data from the LATITUDE trial was performed. The LATITUDE trial, a phase 3 randomized clinical trial, aimed to assess the efficacy of AAP and androgen deprivation therapy (ADT) vs dual-placebo and ADT in patients with high-risk mCSPC (data cutoff, August 15, 2018). Eligible patients had newly diagnosed prostate cancer with metastases and at least 2 of 3 high-risk factors (Gleason score ≥8, presence of ≥3 lesions on bone scan, or presence of measurable visceral metastasis). The trial was conducted at 235 sites in 34 countries. Data for the present study were evaluated from July 18 to September 23, 2023. Use of BMAs was defined as the administration of bisphosphonates and denosumab within 90 days before and after randomization. The primary outcomes were time to skeletal-related events (SREs) and overall survival (OS). An SRE was defined as a clinical or pathological fracture, spinal cord compression, palliative radiation to bone, or surgery involving bone. Differences in these outcomes were examined using the restricted mean survival time from inverse probability of treatment weighting-adjusted Kaplan-Meier curves, estimated until the last event was observed (longest time observed, 63.9 months). Treatment × covariate interactions were analyzed using weighted Cox proportional hazards regression models for the total cohort. In the total cohort of 1199 patients (956 [79.7%] younger than 75 years), 597 (49.8%) received AAP and ADT, including 474 (79.4%) younger than 75 years and 384 (64.3%) with more than 10 bone metastases (AAP cohort); 602 (50.2%) were treated with dual placebo and ADT, including 482 (80.1%) younger than 75 years and 377 (62.6%) with more than 10 bone metastases (ADT cohort). In the AAP cohort, 132 patients (22.1%) received BMAs, while in the ADT cohort, 131 (21.8%) did. Zoledronic acid was the most frequently administered BMA in both the AAP (93 [70.5%]) and the ADT (88 [67.2%]) cohorts. During the median follow-up of 51.8 (IQR, 47.2-57.0) months in the AAP cohort, BMA use was associated with a longer time to SRE (difference, 7.8 [95% CI, 4.2-11.3] months) but not with OS (difference, 1.6 [95% CI, -2.5 to 5.8] months). In the ADT cohort, BMA use was associated with both time to SRE (difference, 9.3 [95% CI, 5.2-13.3] months) and OS (difference, 5.5 [95% CI, 3.2-9.8] months). No evidence was found that the outcomes of BMA varied by AAP or ADT (hazard ratio for time to SRE, 0.99 [95% CI, 0.48-2.08]; P = .99 for interaction; hazard ratio for OS, 1.31 [95% CI, 0.88-1.96]; P = .18 for interaction). The findings of this cohort study suggest that use of BMAs was associated with a longer time to SRE in patients with high-risk mCSPC treated with ADT, with or without AAP, suggesting that BMA use might provide benefits to this population.

Weight variation during androgen deprivation therapy in patients with localized prostate cancer: Data from two prospective randomized trials.

296 Background: In prostate cancer (PCa) treated with androgen deprivation therapy (ADT) and radiotherapy (RT), limited prospective data exist regarding weight variation during ADT. Using our prospective data from two phase III trials we compare the magnitude of weight variation during different duration of ADT. Methods: 400 patients (pts) with intermediate risk PCa received 6 months of ADT (Bicalutamide 1 month (m) and Goserelin 10,8 mg x 2), and 630 pts with high-risk PCa were treated with 18 or 36m of ADT (Bicalutamide 1m and Goserelin 10,8 mg x 6 or 12). Pts’ weights were measured at baseline then at each Goserelin dose. 463/1030 pts were excluded from the analysis: 90 no or incomplete ADT, 127 no initial weight and 246 no weight at the end of ADT. Regular patient weighing was available in 567/1030 pts (55%) from whom 250, 191 and 124 received, respectively, 6, 18 or 36m of ADT. Pt’s characteristics and weights were compared with Kruskal-Wallis and Chi squared test between groups of ADT. Multivariable logistic regression was performed to assess predictors of weight gain over 2 kg. Variables included were duration of ADT, age ≥65 vs. &lt; 65 and baseline comorbidities (cardiovascular disease, diabetes, chronic obstructive pulmonary disease, hypertension). Results: Comparing weights between the beginning and the end of ADT, 375/567 (66.1%) pts gained and 192/567 (33.9%) lost weight. The mean ± SD weight gain at the end of ADT was significantly higher in pts receiving 18m of ADT (1.98 ± 4.05) or 36m (2.38 ± 5.15) compared to pts receiving only 6m (0.98 ± 3.10, p=0.003). As ADT duration increased (6, 18 or 36m), weight gain over 2 kg (34.1% vs. 48.2% vs. 53.2%, p&lt;0.001) and over 4 kg (12.7% vs. 26.2% vs. 36.3%, p&lt;0.001) significantly increased. In multivariable logistic regression, predictors of weight gain over 2 kg were 18m ADT [OR=1.85 (1.25-2.74), p=0.002] and 36m ADT [OR=2.23 (1.43-3.48), p&lt;0.001] compared to 6m ADT and non-diabetic pts (OR=2.13 (1.28-3.54), p=0.003). Age was not a factor. In the 375 pts who gained weight, the rate of patients that gained 0.1 to 2 kg, 2.1 to 4 kg and more than 4 kg were respectively (47.2%, 33.1% and 19.6%) in the 163 receiving 6m ADT, (30.3%, 32.6% and 37.1%) in 132 pts receiving 18m ADT, and (17.6%, 26.3% and 56.4%) in the 80 pts receiving 36m ADT. In the 192 pts who lost weight, the rate of patients that lost 0.1 to 2 kg, 2.1 to 4 kg and more than 4 kg were respectively (62.9%, 21.3% and 15.6%) in 89 receiving 6m ADT, (50.8%, 27.1% and 22.1%) in 59 pts receiving 18m ADT and (59.1%, 15.9% and 25%) in 44 pts receiving 36m ADT. Conclusions: ADT is not associated with weight gain in all pts. Based on our prospective data, one third of pts lose weight at the end of ADT. However, weight gain above 2 kg or 4 kg increases with ADT duration and non-diabetics pts, regardless of age. Weight monitoring in pts receiving ADT should be done regularly and pts counseled accordingly.

Racial and ethnic differences in the receipt of metabolic syndrome risk factor screening and treatment among individuals with prostate cancer treated with androgen deprivation therapy.

29 Background: Racial and ethnic health disparities in prostate cancer screening, and treatment constitute the largest of all cancer disparities. Androgen deprivation therapy (ADT) is widely used in the treatment of localized or metastatic prostate cancer. However, ADT is associated with toxic cardiovascular and metabolic adverse events that may occur as early as 6 months of therapy initiation. This study aimed to assess racial/ethnic differences and longitudinal changes in metabolic syndrome risk factor (MSRF) screening/treatment among patients with prostate cancer treated with ADT at a university-affiliated comprehensive cancer center in the southwestern U.S. between 2010-2021. We also aimed to identify patient and healthcare provider factors that influence MSRF screening among study sample. Methods: A retrospective observational cohort study of 803 patients treated with ADT for at least six months at the cancer center was conducted. Patients were followed three months pre- to 12 months post-ADT initiation to evaluate MSRF screening/treatment. Determination of MSRF screening was based on primary care provider referral for MSRF screening/treatment or receipt of blood glucose, lipid profile, and blood pressure screening within six months post-treatment with ADT. Patients were considered treated for MSRF if they were started or continued therapy (within six months of ADT initiation) with science advisory guideline recommended treatments. Results: Guideline-concordant MSRF screening rate approached 23.5%; MSRF treatment rate was 76.9%. A higher treatment rate in MSRF treatment was found for NHW compared to Hispanic men ( p=0.02). We found a significant difference in the proportion of patients receiving MSRF screening across all racial/ethnic groups ( p=0.03). MSRF screening rates from 13.9% to 35.6% were observed over the 10-year data collection period. Patients with dyslipidemia at baseline had higher odds of having MSRF screening than patients without dyslipidemia ( p&lt;0.0001). Oncologists with &gt;20 years of experience had higher odds of providing MSRF screening compared with &lt;10 years of experience ( p=0.006). Conclusions: Minority populations had significantly lower odds of having MSRF screening than NHW patients after adjusting for clinical and socio-economic variables. Closer clinical attention and education, as well as the development and implementation of innovative practice tools and interventions to optimize MSRF screening and treatment are warranted to mitigate the harmful adverse effects of ADT in patients with prostate cancer.

Rate of hospitalization and length of hospital stay during and post docetaxel for darolutamide in metastatic hormone-sensitive prostate cancer using ARASENS.

228 Background: ARASENS was a randomized, double-blind, Phase III trial of darolutamide (daro) + docetaxel + androgen deprivation therapy (ADT) vs. placebo (pbo) + docetaxel + ADT in patients with metastatic hormone sensitive prostate cancer (mHSPC). We sought to compare rates of hospitalizations and length of hospital stay (LoS) per patient due to any reason, and due to adverse events (AE) during or post docetaxel using data from ARASENS. Methods: We used mixed effects negative binomial regression to estimate time-varying rate of hospitalization and LoS by patient. Patients with records that began on the same start date were considered duplicates and were condensed into one visit, using the latest end date. Patients with multiple records with overlapping time periods were combined into one visit. A constant hospitalization rate assumption was considered inappropriate since docetaxel is administered for 6-cycles (~4.14 months). Hospitalizations that began within and after first 4 months of treatment were grouped together. Conversely, LoS was assumed to be time invariant. Results: The first 4 months of treatment (when patients were receiving docetaxel) were associated with increased hospitalization both due to any reason and to AE (Table 1). Daro was associated with a numerical reduction in rate of hospitalization (per year) due to any reason during docetaxel (0.75 days [95% CI: 0.61, 0.88]) vs. pbo (0.91 days [95% CI: 0.75, 1.07]) and after docetaxel (0.31 days [95% CI: 0.26, 0.37]) vs. pbo (0.38 days [95% CI: 0.31, 0.45]). A similar trend was observed for hospitalizations due to AE. Daro was associated with a marginally longer LoS per hospitalization compared with pbo (+1.90 days). Similar results were seen for LoS due to AE (+1.67 days). Conclusions: Daro was associated with a numerically lower rate of hospitalization, but marginally longer LoS compared to pbo. A lower rate of hospitalization was observed post docetaxel as opposed to during docetaxel. Clinical trial information: NCT102799602 . [Table: see text]

Cost-effectiveness of rezvilutamide versus bicalutamide and androgen-deprivation therapy in patients with highvolume, metastatic, hormone-sensitive prostate cancer.

Background: Rezvilutamide, a novel androgen-receptor inhibitor with limited blood-brain barrier penetration, exhibits significant antitumour activity against highvolume, metastatic, hormone-sensitive prostate cancer (mHSPC). In this study, we aimed to compare the cost-effectiveness of rezvilutamide and bicalutamide as first-line treatments for untreated prostate cancer among Chinese patients, in order to evaluate the efficacy of rezvilutamide. Methods: In this study, we utilized partition survival model to assess the cost-effectiveness of rezvilutamide and bicalutamide treatments for highvolume mHSPC. The model was developed using TreeAge Pro 2022 software and relied on clinical data obtained from the CHART trial. Transition probabilities were estimated from the reported survival probabilities in trials using parametric survival modeling. From the perspective of the Chinese healthcare system, we calculated quality-adjusted life years (QALYs), incremental cost-effectiveness ratio (ICER), and lifetime cost. A lifetime horizon and an annual discount rate of 5% were employed. To address modeling uncertainties, we conducted one-way sensitivity analysis and probabilistic sensitivity analysis. Results: The cost of rezvilutamide versus bicalutamide were $62700 and $13200. Rezvilutamide had an ICER of $41900 per additional QALYs gained compared with bicalutamide. Research indicated that rezvilutamide achieved at least an 28.20% probability of cost-effectiveness at the threshold of $38223.34/QALY. One-way sensitivity analysis revealed that the results were sensitive to utility of PD. Scenario analysis showed that rezvilutamide was cost-effectiveness if its price was reduced by more than 10%. Conclusion: Based on the analysis at the current price, rezvilutamide was found to be less cost-effective for patients with highvolume mHSPC compared to bicalutamide in China.

Apalutamide versus bicalutamide in combination with androgen deprivation therapy for metastatic hormone sensitive prostate cancer

The objective of this study is to compare the efficacy of apalutamide and bicalutamide in combination with androgen deprivation therapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC). We retrospectively collected the data of about 330 patients with metastatic hormone-sensitive prostate cancer at our hospital and affiliated hospitals between December 2013 and August 2023. Sixty-one patients were administered apalutamide (240 mg/day) with androgen deprivation therapy (group A), and 269 patients were administered bicalutamide (80 mg/day) with androgen deprivation therapy (group B). Propensity score matching was used to adjust for clinical background factors between the two groups. PSA progression-free survival and overall survival were significantly longer in group A than in group B among the matched patients. Apalutamide therapy was a significant independent factor for OS in matched patients. The second progression-free survival of group A was significantly longer than that of group B in matched patients. Patients treated with apalutamide achieved ≥ 90% PSA decline from baseline faster and in larger numbers than those with bicalutamide. Apalutamide combined with ADT may be superior to bicalutamide alone in terms of OS and PSA-PFS in patients with mHSPC.

Comparative effectiveness of multiple androgen receptor signaling inhibitor medicines with androgen deprivation therapy for metastatic hormone-sensitive prostate cancer: a study in the real world.

The current treatment strategy for metastatic Hormone-Sensitive Prostate Cancer (mHSPC) is the combination of Androgen Receptor Signaling Inhibitors (ARSIs) medicines with androgen deprivation therapy (ADT). However, there is a lack of real-world data comparing the efficacy of different ARSI pharmaceuticals. Therefore, the objective of this study was to compare the effectiveness and safety of bicalutamide, abiraterone, enzalutamide, and apalutamide in combination with ADT for patients with mHSPC. We retrospectively analyzed 82 patients diagnosed with mHSPC, including 18 patients treated with abiraterone acetate with prednisone, 21 patients with enzalutamide, 20 patients with apalutamide, and 23 patients with bicalutamide. We evaluated PSA progression-free survival (PSA-PFS), imaging progression-free survival (r PFS), castration resistance progression-free survival (CRPC-PFS), and overall survival (OS) using Kaplan-Meier survival analyses. Additionally, we explored relevant factors affecting prognosis through univariate and multivariate Cox risk-proportionality models. PSA response rates at 3, 6, and 12 months, nadir PSA levels (nPSA), and time to nadir (TTN) in different medication subgroups after treatment were documented, and we used one-way ANOVA to determine the effect of these measures on patient prognosis. In comparison with bicalutamide, both enzalutamide and apalutamide have shown significant advantages in delaying disease progression among mHSPC patients. Specifically, enzalutamide has been found to significantly prolong PSA-PFS (HR 2.244; 95% CI 1.366-3.685, p=0.001), rPFS (HR 2.539; 95% CI 1.181-5.461; p= 0.007), CRPC-PFS (HR 2.131; 95% CI 1.295-3.506; p= 0.003), and OS (HR 2.06; 95% CI 1.183-3.585; P=0.005). Similarly, apalutamide has significantly extended PSA-PFS (HR 5.071; 95% CI 1.711-15.032; P= 0.003) and CRPC-PFS (HR 6.724; 95% CI 1.976-22.878; P=0.002) among patients. On the other hand, the use of abiraterone in combination with ADT did not demonstrate a significant advantage in delaying diseases progression when compared with the other three agents in mHSPC patients. There were no significant differences in overall adverse event rates among the four pharmaceuticals in terms of safety. Additionally, the observation of PSA kinetics revealed that enzalutamide, apalutamide, and abiraterone acetate had a significant advantage in achieving deep PSA response (PSA ≤ 0.2 ng/ml) compared with bicalutamide (p=0.007 at 12 months). Enzalutamide and apalutamide exhibited preeminence efficacy, with no substantial difference observed between the two medications. Abiraterone, enzalutamide, and apalutamide were found to significantly reduce and stabilize PSA levels in mHSPC patients more quickly and thoroughly than bicalutamide. Furthermore, enzalutamide and apalutamide were found to significantly prolong survival and delay disease progression in mHSPC patients compared with bicalutamide. It should be noted that abiraterone did not demonstrate a significant advantage in delaying disease compared with enzalutamide and apalutamide. After conducting drug toxicity analyses, it was determined that there were no significant differences among the four drugs.

Simple and Epididymal-Sparing Orchiectomy for Surgical Castration in Stage IV Prostate Cancer.

Background: Androgen deprivation therapy, the mainstay of treatment for patients with advanced prostate cancer, can be either medical or surgical. Surgery has cost benefits compared to medical treatment. In this study, we evaluated the use of simple and epididymal-sparing orchiectomy in 2 different practice settings for the treatment of metastatic prostate cancer. Methods: We reviewed patients who underwent surgical castration for metastatic prostate cancer between 2011 and 2022. The primary outcome was achieving castration-level total testosterone of <50 ng/dL. We also compared the characteristics of patients who were seen at a public academic teaching hospital vs those who were seen at a private community hospital (oncology group practice), and we evaluated the impact of orchiectomy approach (simple vs epididymal-sparing orchiectomy) on patient outcomes. Results: We analyzed 101 patients who underwent orchiectomy: 40 (39.6%) at a public academic teaching hospital and 61 (60.4%) at a private community hospital (oncology group practice). Of these patients, 81 (80.2%) underwent simple orchiectomy and 20 (19.8%) underwent epididymal-sparing orchiectomy. Forty-nine patients (48.5%) had previously received medical androgen deprivation therapy, 9 (18.4%) of whom had medication adherence issues. Patient age, race, and marital status differed significantly between hospital facilities. The overall surgical complication rate was 3.0%. Postoperative total testosterone levels were available for 81 patients, drawn a median of 57 days after surgery [IQR 30, 123]. All patients had castrate-level total testosterone (median 10 ng/dL [IQR 9, 19]) postoperatively, with no differences seen between surgery location (P= 0.84) or surgical technique (P= 0.90). Conclusion: Simple or epididymal-sparing orchiectomy is safe and effective for surgical castration and is an alternative to medical androgen deprivation therapy for patients diagnosed with metastatic prostate cancer regardless of the practice demographics.

Impact of androgen deprivation therapy in patients with unfavorable intermediate-risk prostate cancer receiving brachytherapy-based dose-escalated radiation therapy

Impact of androgen deprivation therapy in patients with unfavorable intermediate-risk prostate cancer receiving brachytherapy-based dose-escalated radiation therapy