Prostate Cancer Undergoing Androgen Deprivation Research Articles

Abstract CT233: Serum thymidine kinase 1 levels as a predictive marker for castration resistance in metastatic prostate cancer

Abstract Introduction Thymidine kinase 1 (TK1) is an enzyme associated with the cell division cycle; its levels increase during the S-phase of the cell cycle and decrease during the M-phase. In cancer TK1 release is increased both by increased cell proliferation and cell death. Thus, serum concentration of TK1 reflects the tumor volume, proliferation rate, and extent of cell death. Serum Thymidine Kinase 1 (sTK1) enzyme has been used as a prognostic, predictive, and monitoring biomarker in leukemia, Hodgkin's and non-Hodgkin's lymphomas. Additionally, sTK1 enzyme levels have been elevated in breast cancer and prostate cancer. This study evaluated whether sTK1 predicts the risk of castration resistance in patients with metastatic prostate cancer undergoing androgen deprivation therapy (ADT). Materials and Methods sTK1 levels was measured in men diagnosed with metastatic prostate cancer at 3 time points; before the initiation of ADT, 6 months after the start of treatment, and within 6 months before the development of castration resistance. Samples at study visits of ESTO2 trial, which compares atorvastatin to placebo in combination with ADT. The trial intervention was blinded at analysis. Cox regression modeling was used to assess whether sTK1 values predict the risk of castration resistance. sTK1 was analyzed both as continuous and categorical variable, stratified by median value 0.12 ng/ml. The time from the initiation of ADT to the formation of castration resistance, death, or a general index date (May 31, 2023) was used as the time-metric. Results The study included serum samples from 70 patients, of which 23 had developed castration resistance by May 31,2023. The median follow-up time was 13 months. The sTK1 value measured before ADT initiation did not predict the risk of castration resistance (HR 0.91, 95% CI 0.62-1.35). However, sTK1 at 6 months after the initiation of ADT or up to a maximum of 6 months before formation of castration resistance did predict the risk (HR 1.5, 95% CI 1.07-2.1 and HR 1.79, 95% CI 1.16-2.76, respectively). sTK1 predicted the risk at both measurement points also when analyzed as categorical variable. sTK1 was predictive only among men with metastatic disease; sTK1 no longer predicted the risk of castration resistance who started ADT for biochemically recurrent, non-metastatic disease. Conclusions Our findings suggest that sTK1 value can be used to predict the risk of progression to castration resistance during ADT in metastatic prostate cancer. However, these findings need validation from larger datasets. Citation Format: Aino Siltari, Paavo Raittinen, Jarno Riikonen, Juha Koskimäki, Tomi Pakarainen, Mikael Anttinen, Otto Ettala, Teuvo Tammela, Stig Linder, Teemu J. Murtola. Serum thymidine kinase 1 levels as a predictive marker for castration resistance in metastatic prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT233.

Identification of distinct symptom profiles in prostate cancer patients with cancer-related cognitive impairment undergoing androgen deprivation therapy: A latent class analysis

ObjectiveTo identify latent classes of cognitive impairment and co-occurring symptoms (fatigue, pain, sleep disturbance, depression) as clusters in patients with prostate cancer undergoing androgen deprivation therapy and to explore the predictors among distinct latent classes. MethodsA total of 228 patients with prostate cancer were recruited in this cross-sectional study. The assessment instrument included the Perceived Cognitive Impairment Scale, the Fatigue Severity Scale, the Athens Insomnia Scale, the Brief Pain Inventory, the Patient Health Questionnaire-9, the UCLA Loneliness Scale, the International Physical Activity Questionnaire - Short Form, the Charlson comorbidity index, and General Information questionnaire. The identification of different patient subgroups was done by the latent class analysis. ResultsThe study identified three distinct latent classes: all low symptoms (class 1, 32%), high depression symptoms (class 2, 37.7%), and high physical symptoms (fatigue, sleep disturbance, and pain) with high cognitive impairment (class 3, 30.3%). Patients who had higher Charlson comorbidity index (P ​= ​0.003) scores were more likely to be classified in class 3. Patients with higher loneliness scores (P ​< ​0.001; P ​< ​0.001) were significantly more likely to fall into class two or three than in class 1. However, having a higher level of physical activity (P ​= ​0.014; P ​< ​0.001) increased the likelihood of being in class 1. ConclusionsThis study exhibited the inter-individual variability of symptom experience in prostate cancer patients with cognitive impairment undergoing androgen deprivation therapy. The result suggests that more emphasis should be placed on screening for fatigue, sleep disturbance, and pain, and future interventions should focus on loneliness and physical activity.

Changes in Quality of Life and Sexual Function After Luteinizing Hormone-Releasing Hormone (LHRH) Agonists and Orchiectomy in Men With Metastatic Prostate Cancer: Results From a Randomized Trial.

Purpose To examine changes in quality of life (QoL) in men diagnosed with metastatic prostate cancer undergoing androgen deprivation therapy (ADT). Methods This was a phase IV trial where patients were randomized to either triptorelin or subcapsular orchiectomy. We report changes in QoL, functional and symptom scales, and sexual function. These were assessed using the validated questionnaires, namely, the European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (EORTC-QLQ-C30), European Organization of Research and Treatment of CancerQuality of Life Questionnaire Prostate Cancer 25 (EORTC-QLQ-PR25), and Erectile Hardness Scale (EHS) before treatment and at 12, 24, and 48 weeks, respectively. Data were analyzed using linear mixed models for repeated measures. Results Fifty-seven men with a median age of 74 years were randomized. The pooled analyses showed that QoL (p=0.003), emotional function (p<0.001), urinary symptoms (p=0.011), and hormonal treatment-related symptoms (p<0.001) changed significantly between visits. Improvement from baseline in QoL (mean change: 6.8 points (95% confidence interval (CI 95% CI): 2.1; 11.5)), emotional function (6.9 points: 3.3, 10.6), and urinary symptoms (-7.7 points (-12.3; -3.0)) was most pronounced at 24 weeks. Hormonal treatment-related symptoms (8.9 points (95% CI: 5.9; 12.0)) worsened. No significant differences between treatment groups were observed. At baseline, 29 men (51%) reported interest in sex, 18 were sexually active, and 12 had erections hard enough for penetration. At 48 weeks seven reported interest in sex, five were sexually active, and one man had a hard enough erection for penetration. Conclusions Men with newly diagnosed metastatic prostate cancer experience improved QoL and emotional function after starting ADT. Urinary symptoms improved, while hormonal treatment-related symptoms worsened. Interest in sex and sexual activity was retained in a proportion of men despite ADT.

Systemic interrogation of immune-oncology-related proteins in patients with locally advanced prostate cancer undergoing androgen deprivation and intensity-modulated radiotherapy

PurposeThe primary objective was to establish whether blood-based leucine-rich alpha-2-glycoprotein (LRG1) can predict outcomes in patients with locally advanced prostate cancer undergoing androgen-deprivation therapy (ADT) and radiotherapy (RT) and to determine how it may relate to 92 immune-oncology (I-O)-related proteins in this setting.MethodsBaseline blood level of LRG1 from patients treated with ADT and RT enrolled in the CuPCa (n = 128) and IMRT (n = 81) studies was measured using ELISA. A longitudinal cohort with matched blood samples from start of ADT, start of RT, and end of RT protocol from 47 patients from the IMRT cohort was used to establish levels of I-O proteins by high-multiplexing Proximal Extension Assay by Olink Proteomics.Statistical analyses using Kaplan–Meier, Cox regression, and LIMMA analyses were applied to predict the prognostic value of LRG1 and its correlation to I-O proteins.ResultsHigh baseline levels of LRG1 predicted a low frequency of treatment failure in patients undergoing ADT + RT in both the CuPCa and the IMRT cohorts. LRG1 was moderately correlated with CD4, IL6, and CSF1. We identified I-O proteins predicting metastatic failure (MF) at different timepoints.ConclusionLRG1 biomarker is associated with I-O proteins and can be used to improve stratification and monitoring of prostate cancer patients undergoing ADT + RT. This work will require further in-depth analyses in independent cohorts with treatment outcome data.Graphical abstractStudy outline. A) Study cohorts. B) Sampling time points in a longitudinal cohort.

Lower pretreatment serum testosterone level predicts poor prognosis in the patients with metastatic hormone-sensitive prostate cancer undergoing androgen deprivation therapy.

This study aimed to reveal the association between pretreatment serum testosterone levels and prognosis in patients with metastatic hormone-sensitive prostate cancer treated with androgen deprivation therapy. A total of 91 patients were included in this retrospective study. Clinical data were obtained through chart review. Multivariate cox proportional hazards analyses addressed the impact of variables on castration-resistant prostate cancer-free and overall survivals. During a median follow-up of 41.7months, 61 (67%) and 49 (54%) patients developed castration-resistant prostate cancer and died, respectively. The median castration-resistant prostate cancer-free and overall survivals were 15.5 and 59.9months, respectively. The cutoff value for discriminating between low- and high-testosterone levels was determined as 450ng/dl by calculating the receiver operating characteristic curve. Patients in the low-testosterone group (n=37) had a significantly higher body mass index, worse comorbidities represented by the higher Charlson comorbidity index and higher serum lactate dehydrogenase levels, than those in the high-testosterone group (n=54). Castration-resistant prostate cancer free and overall survivals were significantly shorter in the low-testosterone group than in the high-testosterone group (P=0.021 and P<0.001, respectively). Multivariate analysis identified testosterone level of <450ng/dl as an independent factor predicting development of castration-resistant prostate cancer (hazard ratio 2.28, P=0.007), along with high-volume disease and Gleason score 9-10. Similarly, testosterone level of <450ng/dl was independently associated with shorter overall survival (hazard ratio 2.84, P=0.006), along with higher Charlson comorbidity index, visceral metastasis and higher alkaline phosphatase level. Lower baseline serum testosterone levels predict poor prognosis in patients with metastatic hormone-sensitive prostate cancer.

Epidemiological profile of COVID-19 in patients with prostate cancer undergoing androgen deprivation therapy at a Brazilian Cancer Center.

To describe the epidemiological aspects of COVID-19 in patients with prostate cancer who received androgen deprivation therapy and those who did not. We retrospectively analyzed the medical records of patients with prostate cancer undergoing androgen deprivation therapy and those who did not undergo androgen deprivation therapy. These patients were treated at the A.C.Camargo Cancer Center between March 2020 and March 2021. Of the 78 patients with prostate cancer and positive RT-PCR test results, 50% were undergoing androgen deprivation therapy, and 49% were experiencing a non-metastatic biochemical relapse. Of these, 80.6% were symptomatic on the day of examination compared to 97.2% in the Control Group. A total of 82.1% of the patients receiving androgen deprivation therapy required hospitalization, with 30.8% admitted to the intensive care unit compared to 21.6% in the Control Group. There was no statistically significant difference in the use of a high-flow oxygen cannula, the need for orotracheal intubation and mechanical ventilation, the need for dialysis, multiple organ failure, or death. A significant difference was found between the groups in terms of the average length of stay in the intensive care unit. Androgen deprivation therapy was not associated with protective factors or potential treatments in patients with prostate cancer and COVID-19. Although the number of patients analyzed was limited, and there may have been a selection bias, this is a unique study that cannot be expanded or replicated in similar (unvaccinated) populations.

Cancer Therapy-Related Cardiac Dysfunction in Patients With Prostate Cancer Undergoing Androgen Deprivation Therapy.

Background The risk of cardiac dysfunction for patients with prostate cancer undergoing androgen deprivation therapy (ADT) in the real-world setting remains unclear. Methods and Results A total of 1120 patients with prostate cancer and a baseline echocardiography scan were identified from Chang Gung Research Database between January 1, 2001 and December 31, 2019. Patients were treated with gonadotropin-releasing hormone agonist therapy, gonadotropin-releasing hormone antagonist therapy, or bilateral orchiectomy. Changes in left ventricular ejection fraction (LVEF) were further assessed in 421 patients using repeated measurements of LVEF before and during ADT treatment. The incidence of cancer therapy-related cardiac dysfunction (CT-RCD) was evaluated and defined as a ≥10% absolute decline in LVEF from baseline to a value of <53%. Among 421 patients undergoing ADT, LVEF declined from 66.3±11.3% to 62.5±13.6% (95% CI of mean difference: -5.0% to -2.7%) after a mean follow-up period of 1.6±0.8 years. CT-RCD occurred in 58 patients (13.7%) with a nadir LVEF of 40.3±9.1% after ADT. Lower baseline LVEF was significantly associated with CT-RCD (odds ratio, 1.07 [95% CI, 1.04-1.10]). The area under the curve of baseline LVEF for discriminating CT-RCD was 75.6%, with the corresponding optimal cutoff value of 64.5% (sensitivity, 79.3%; specificity, 67.2%). Conclusions ADT with gonadotropin-releasing hormone agonist therapy, gonadotropin-releasing hormone antagonist therapy, and bilateral orchiectomy were associated with an increased risk of CT-RCD in patients with prostate cancer. In addition, lower baseline LVEF was a significant predictor of CT-RCD in patients with prostate cancer undergoing treatment with ADT.

A multicentre randomised controlled trial of a guided self-help cognitive behavioural therapy to MANage the impact of hot flushes and night sweats in patients with prostate CANcer undergoing androgen deprivation therapy (MANCAN2)

BackgroundAndrogen deprivation therapy (ADT) is prescribed to almost half of all men diagnosed with prostate cancer. Although ADT is effective treatment, with virtually all men with advanced disease showing initial clinical response, it is associated with troublesome side effects including hot flushes and night sweats (HFNS). HFNS can be both frequent and severe and can have a significant impact on quality of life (QoL). They can occasionally be so debilitating that patients stop ADT altogether, despite the increased risk of disease relapse or death. Previous research has found that guided self-help cognitive behavioural therapy (CBT) can be effective in reducing HFNS due to ADT when delivered by a clinical psychologist. MANCAN2 aims test whether we can train the existing NHS Prostate Cancer Nurse Specialist (CNS) team to deliver guided self-help CBT and whether it is effective in reducing the impact of HFNS in men undergoing ADT.MethodsMANCAN2 is a phase III multicentre randomised controlled trial and process evaluation. Between 144 and 196 men with prostate cancer who are currently receiving ADT and are experiencing problematic HFNS will be individually randomised in a 1:1 ratio in groups of 6–8 participants to either treatment as usual (TAU) or participation in the guided self-help CBT intervention plus TAU. A process evaluation using the normalisation process theory (NPT) framework will be conducted, to understand the CNS team’s experiences of delivering the intervention and to establish the key influencers to its implementation as a routine practice service. Fidelity of implementation of the intervention will be conducted by expert assessment. The cost-effectiveness of the intervention and participant adherence to the trial intervention will also be assessed.DiscussionMANCAN2 will advance the program of work already conducted in development of management strategies for HFNS. This research will determine whether the severity of ADT-induced HFNS in men with prostate cancer can be reduced by a guided self-help CBT intervention, delivered by the existing NHS prostate cancer CNS team, within a multicentre study. The emphasis on this existing team, if successful, should facilitate translation through to implementation in routine practice.Trial registrationISRCTN reference 58720120. Registered 13 December 2022

(297) Evaluation of Endothelial Function and Metabolic Profile in Patients with Prostate Cancer Undergoing Androgen Deprivation Therapy

Abstract Introduction Androgen deprivation therapy (ADT) has been the cornerstone of prostate cancer treatment. ADT delays cancer progression, alleviates cancer-related symptoms, and is associated with survival gains. Despite these established benefits, the therapy comes with known side effects, such as increased cardiovascular adverse events and metabolic changes. Despite the well-established association between the level of circulating testosterone and endothelial integrity, the direct effects of ADT on endothelial function remain controversial. Objective The aim of the present study was to investigate the impact of ADT on endothelial function, through the analysis of vascular parameters of the brachial artery, and the measurement of serum inflammatory markers. It was also our goal to evaluate early impact of ADT on anthropometric and metabolic parameters Methods We prospectively evaluated men with moderate to high-risk prostate cancer treated with ADT from January to July 2022 at our institution. Patients with decompensated diabetes mellitus (HbA1c &amp;gt;9%), active smokers or smokers who have ceased for less than 5 years and those with confirmed diagnosis of peripheral artery disease, coronary artery disease, angina, congestive heart failure, myocardial infarction, coronary revascularization or stroke, were excluded. Brachial artery assessment included vascular diameter and flow-mediated (endothelium-dependent) vasodilation (FMD) using high-resolution B-mode ultrasound. Our metabolic and inflammatory profile included serum measurement of total cholesterol and fractions, triglycerides, fasting glucose, glycated hemoglobin, basal insulin, C-reactive protein, and bioimpedance assessment of body fat distribution. All measurements were performed at baseline and after 3 months of ADT initiation with goserelin acetate 10.80mg. Results A total of 14 men with mean age of 67.9 ± 6.9 years were included. The prevalence of diabetes in the present cohort was 21.4%. FMD demonstrated a slight increase following ADT, which did not reach statistical significance after 3 months (median 2.2% vs. 5.0%; p = 0.8224 – Figure 1). Baseline brachial artery diameter significantly decreased with ADT compared to baseline (median diameter 0.43cm vs 0.40cm; p = 0.006). With regard to the metabolic profile, ADT significantly increased insulin resistance: fasting insulin levels (mean 9.67 ± 6.09 vs 13.19 ± 7.47; p = 0.002), glycated hemoglobin (mean 5.79% ± 0.47 vs 6.22% ± 0.75; p = 0.009) and homeostatic model assessment insulin resistance increased significantly after 3 months (p = 0.006). Low-density lipoprotein cholesterol (mean 112.00 ± 27.35 vs 128.90 ± 29.00; p = 0.01) and triglycerides (mean 145.40 ± 78.52 vs 168.20 ± 105.80; p = 0.03) concentrations were higher after 3 months of ADT. No significant differences were found in body fat distribution. Conclusions Although the present study has not demonstrated a significant change in brachial artery FMD, we verified an important and surprisingly early worsening of the metabolic profile with ADT, especially increased insulin resistance and dyslipidemia, which represent well-established risk factors for cardiovascular events. Disclosure No

Exercise Associated with Cognitive Function in Older Men with Prostate Cancer Undergoing Androgen Deprivation Therapy.

To examine associations between exercise and cognitive function in older men undergoing hormone therapy for prostate cancer. Men ≥ 65years old with prostate cancer, currently undergoing androgen deprivation therapy for ≥ 6months (n = 50), completed the Godin-Shephard Leisure-Time Physical Activity Questionnaire, and standard neuropsychological tests. Pearson's correlations and linear regressions were used to examine associations between exercise and cognitive performance. Exercise was significantly positively correlated with performance on tests of memory, attention, and executive function. Linear regressions showed that when controlling for age and education, exercise remained a significant predictor of attention and executive function performance (p < 0.05), and showed moderate, but statistically non-significant effects on memory performance (p < 0.10). Greater exercise is associated with better functioning in multiple cognitive domains in men with prostate cancer undergoing hormone therapy, providing proof-of-concept evidence that exercise may be a feasible intervention to limit cognitive dysfunction in prostate cancer patients.

Tautomycin and enzalutamide combination yields synergistic effects on castration-resistant prostate cancer

The androgen receptor (AR) plays an essential role in prostate cancer progression and is a key target for prostate cancer treatment. However, patients with prostate cancer undergoing androgen deprivation therapy eventually experience biochemical relapse, with hormone-sensitive prostate cancer progressing into castration-resistant prostate cancer (CRPC). The widespread application of secondary antiandrogens, such as enzalutamide, indicates that targeting AR remains the most efficient method for CRPC treatment. Unfortunately, neither can block AR signaling thoroughly, leading to AR reactivation within several months. Here, we report an approach for suppressing reactivated AR signaling in the CRPC stage. A combination of the protein phosphatase 1 subunit α (PP1α)-specific inhibitor tautomycin and enzalutamide synergistically inhibited cell proliferation and AR signaling in LNCaP and C4-2 cells, as well as in AR variant-positive 22RV1 cells. Our results revealed that enzalutamide competed with residual androgens in CRPC, enhancing tautomycin-mediated AR degradation. In addition, the remaining competitive inhibitory role of enzalutamide on AR facilitated tautomycin-induced AR degradation in 22RV1 cells, further decreasing ARv7 levels via a full-length AR/ARv7 interaction. Taken together, our findings suggest that the combination of tautomycin and enzalutamide could achieve a more comprehensive inhibition of AR signaling in CRPC. AR degraders combined with AR antagonists may represent a new therapeutic strategy for CRPC.

Clinical significance of prostate volume and testosterone reduction on lower urinary tract symptoms in patients with prostate cancer undergoing androgen deprivation therapy

To investigate the effect of both prostate volume and serum testosterone changes on lower urinary tract symptoms in patients with prostate cancer undergoing androgen deprivation therapy. A total of 167 patients who received androgen deprivation therapy for prostate cancer treatment from January 2010 to August 2020 were enrolled in this retrospective study. Changes in the International Prostate Symptom Score (IPSS) in the patient groups stratified by prostate volume and the amount of testosterone reduction were assessed every 4 weeks until 12 weeks after androgen deprivation therapy initiation. Longitudinal mixed models were used to assess the adjusted effects of prostate volume and testosterone reduction on IPSS change. All mean values of IPSS-total score (IPSS-total), voiding subscore (IPSS-vs), and storage subscore (IPSS-ss) significantly decreased from baseline to week 12 in both patients with small (< 33 mL) and large (≥ 33 mL) prostates. The mean values of IPSS-total, IPSS-vs, and IPSS-ss similarly decreased in patients with large prostate with a baseline IPSS-total of ≥ 13. However, in those with small prostate, IPSS-ss specifically remained unchanged, while IPSS-total and IPSS-vs significantly decreased. In addition, only in patients with small prostate (< 33 mL), patients with lesser testosterone reduction (< Δ400 ng/dL) showed greater improvement in IPSS-ss by 7.5% compared with those with greater testosterone reduction (≥ Δ400 ng/dL). In conclusion, although androgen deprivation therapy generally improves lower urinary tract symptoms, it may worsen specifically storage symptoms in patients with relatively small prostate and greater testosterone reduction. Our finding suggests that testosterone may influence lower urinary tract symptoms in these patients.

171P Clinical significance of prostate volume and testosterone reduction on lower urinary tract symptoms in patients with prostate cancer undergoing androgen deprivation therapy

171P Clinical significance of prostate volume and testosterone reduction on lower urinary tract symptoms in patients with prostate cancer undergoing androgen deprivation therapy

1416P Associations between metformin and mortality risks in Asian diabetic patients with prostate cancer undergoing androgen deprivation therapy: A retrospective cohort study

Metformin is associated with lower risks of developing prostate cancer (PCa), but its association with mortality in PCa is unclear. This study examined the associations between metformin use concurrent with androgen deprivation therapy (ADT) and mortality risks in Asian, diabetic patients with PCa. Diabetic adults with PCa receiving any ADT attending public hospitals in Hong Kong between December 1999 and March 2021 were retrospectively identified. Patients with <6 months of medical castration without subsequent bilateral orchidectomy, <6 months of concurrent metformin use and ADT, or missing baseline HbA1c were excluded. Metformin users had ≥6 months of concurrent metformin use and ADT, while non-users had no concurrent metformin use and ADT or never used metformin. Included patients were followed up until September 2021. The primary outcome was PCa-related mortality. The secondary outcome was all-cause mortality. Inverse probability treatment weighting was used to balance covariates. 1971 patients (1284 metformin users and 687 non-users; mean age 76.2±7.8 years) were studied. Over a mean follow-up of 4.1±3.2 years, metformin users had significantly lower risks of PCa-related mortality (weighted hazard ratio (wHR) 0.49 [95% confidence interval 0.39-0.61], p<0.001) and all-cause mortality (wHR 0.53 [0.46-0.61], p<0.001), independent of diabetic control or status of chronic kidney disease. Such associations appeared stronger in patients without androgen receptor antagonist or chemotherapy use (Table).Table: 1416PWeighted comparisons of outcomes by metformin usage with subgroups for androgen receptor antagonist or chemotherapy usage. Weighted hazard ratios (wHR) [95% confidence interval (CI)] were referenced against metformin non-usersAll patientsNever received androgen receptor antagonist or chemotherapy (N=1096)Received androgen receptor antagonist or chemotherapy (N=875)p value for interactionwHR [95% CI]p valuewHR [95% CI]p valuewHR [95% CI]p valueProstate cancer-related mortality0.49 [0.39, 0.61]<0.0010.38 [0.27, 0.52]<0.0010.59 [0.43, 0.81]0.0010.017All-cause mortality0.53 [0.46, 0.61]<0.0010.48 [0.40, 0.57]<0.0010.60 [0.48, 0.75]<0.0010.048 Open table in a new tab Metformin use concurrent with ADT was associated with lower risks of mortality in Asian, diabetic patients with PCa. Its role as adjuvant therapy for PCa warrants further study.

Exercise Adherence in Men with Prostate Cancer Undergoing Androgen Deprivation Therapy: A Systematic Review and Meta-Analysis.

Simple SummaryProstate cancer treatments, including androgen deprivation therapy, can lead to a range of undesirable physical and psychological alterations for men. Participating in regular exercise has been shown to reduce the severity of these changes, providing an opportunity to improve the lives of these patients. There are a range of exercise interventions described in the literature; however, it is unknown what the optimal type of exercise to encourage adherence is. This systematic review and meta-analysis investigates exercise intervention adherence of patients receiving androgen deprivation therapy while identifying some of the effects of exercise on some physiological outcomes. It also includes a qualitative perspective to describe the issues relating to exercise for this population in both real-life and intervention settings. This research is vital, as future research may benefit from the understanding of the factors that will encourage exercise participation in this population.Androgen deprivation therapy (ADT) for prostate cancer treatment is associated with adverse physiological changes; however, exercise can improve outcomes. This systematic review and meta-analysis aimed to determine exercise intervention adherence and its effects on physiological outcomes in men diagnosed with prostate cancer undergoing ADT. Uniquely, this review incorporated a meta-aggregation of qualitative data, providing perspectives from the men’s experiences. A systematic review and meta-analysis were completed following PRISMA guidelines. Databases (CINAHL, Cochrane, PubMed) were searched for studies using “prostate cancer”, “exercise intervention”, and “androgen deprivation therapy”. Quantitative randomised controlled trials describing adherence to exercise interventions were selected, with qualitative articles selected based on descriptions of experiences around participation. Subgroup meta-analyses of adherence, exercise mode, and intervention duration were completed for quality of life, aerobic fitness, fatigue, and strength. In total, 644 articles were identified, with 29 (n = 23 quantitative; n = 6 qualitative) articles from 25 studies included. Exercise had no effects (p < 0.05) on quality of life and fatigue. Significant effects (all p < 0.05) were observed for aerobic fitness, and upper- and lower-body strength. Adherence to exercise-based interventions was 80.38%, with improvements observed in aerobic fitness and strength. Subgroup analysis revealed exercise adherence impacted fatigue and strength, with greater improvements observed in programs >12-weeks.

Symptom burden profiles in men with advanced prostate cancer undergoing androgen deprivation therapy.

To identify symptom burden profiles among men with advanced prostate cancer undergoing androgen-deprivation therapy and examine their association with baseline sociodemographic and medical characteristics and psychosocial outcomes over time. Latent profile analysis was employed to identify distinct groups based on the Expanded Prostate Index Composite and the McGill Pain Questionnaire at baseline. Psychosocial outcomes were assessed at baseline, 6- and 12-month follow-ups. Three profiles emerged: "high symptom burden," "high sexual bother," and "low symptom burden." Men with "high symptom burden" were younger and exhibited higher baseline levels of depression, stress, cancer-specific distress, and anxiety than men in the other two groups. However, men with "high symptom burden" also demonstrated improvement in these psychosocial outcomes over time. Men with advanced prostate cancer who experience multiple co-occurring symptoms demonstrate worse psychosocial adjustment. Patients with substantial symptom burden, and specifically young men, may benefit from prompt referral to supportive care services.

Impact of Androgen Deprivation on Oxidative Stress and Antioxidant Status in Nigerian Patients With Prostate Cancer Undergoing Androgen Deprivation Therapy.

PURPOSEProstate cancer (CaP) incidence and mortality rate are increasing in Africa. Some have linked oxidative stress with the pathogenesis of cancer. This study assessed the levels of malondialdehyde (MDA), nitric oxide (NO), total plasma peroxide (TPP), and total antioxidant capacity (TAC) in Nigerian patients with CaP.PATIENTS AND METHODSOne hundred twenty patients with CaP and 100 apparently healthy controls were consecutively recruited into this case-control study. The patients with CaP were divided into treatment-naïve and androgen deprivation therapy (ADT)–treated groups. Anthropometric indices were measured, and MDA, NO, TAC, and TPP were assayed by colorimetric methods. The t test and analysis of variance were used in analysis of data; statistical significance was set at P < .05, and 95% CIs were reported.RESULTSThe patients with CaP had significantly higher waist-hip ratios and NO (P = .0001), TPP (P = .001), oxidative stress index (OSI; P = .003), and MDA values (P = .002) than controls. The treatment-naive patients with CaP had significantly higher waist-hip ratios (P = .011) and TPP (P = .013), MDA (P = .011), and NO values (P = .0001) and lower TAC values (P = .013) compared with the controls. The ADT-treated patients had higher waist-hip ratios (P = .0001) and TPP (P = .005), OSI (P = .005), MDA (P = .011), and NO values (P = .0001) than the controls. However, the treatment-naive patients had significantly higher NO values (P = .05) only compared with the ADT-treated patients. There was a significantly positive correlation between MDA and duration of treatment (r = 0.280, P = .018) in ADT-treated patients with CaP.CONCLUSIONThis study demonstrated that patients with CaP have higher levels of TPP, MDA, and NO and lower levels of TAC compared with men without CaP. In addition, even in patients with CaP undergoing treatment, TPP and MDA levels remained high.

Improving Physical and Mental Health in Patients with Prostate Cancer Undergoing Androgen Deprivation Therapy: Strategies to Promote and Improve Physical Activity Quality and Quantity.

Prostate cancer continues to be one of the highest-incident cancers among men. Reducing serum testosterone with androgen deprivation therapy (ADT) is a common effective treatment. While well-demonstrated for cancer suppression, there are numerous adverse effects caused by ADT that can contribute to short- and long-term prognosis. Increased levels of physical activity (PA) during treatment may reduce these side effects. However, uptake of PA is low. The purpose of this review is to identify and evaluate the current literature on strategies to promote and increase the levels of PA in patients with prostate cancer undergoing ADT. Electronic databases including CINAHL, MEDLINE, PsychINFO, Scopus, and grey literature were searched using Google Scholar up until April 2020. At present the most appropriate modes and dosages of PA for specific ADT toxicities is not known. It is established that some PA in the form of exercise, whether aerobic or resistance, is better than being sedentary for improvements in physical health, but beyond this prescription specifics have not been established. Further research is required to understand the impact of PA on the mental and physical health of men with prostate cancer undergoing ADT. Being physically active and avoiding sedentary behaviour is important for men with prostate cancer undergoing ADT, especially the implementation of strength training. PA in the form of exercise can assist in reducing the adverse physical side effects in the short- and long-term, with limited understanding of the effects on mental health. PA improves mental health outcomes across populations, which may also translate to men with prostate cancer, although further research is required. An important strategy to improve PA within the prostate cancer population is to provide an early referral to an exercise professional, such as an accredited exercise physiologist/clinical exercise physiologist or physical therapist/physiotherapist, and is supported by research as best practice for people affected by cancer undergoing active treatment.

Rise in serum folate after androgen deprivation associated with worse prostate cancer-specific survival

IntroductionHigh folate has an association with advanced prostate cancer and levels of testosterone. Herein, we perform a translational study to investigate the inverse response of serum folate in prostate cancer patients initiating androgen deprivation therapy (ADT) and a mirrored animal model. MethodsA retrospective study was performed using the South Texas Veterans Healthcare System to identify patients with prostate cancer on ADT. We documented testosterone and folate levels before and after ADT initiation (defined by a reduction in testosterone by 50 ng/ml) as compared to those already on ADT (maintenance). Our primary outcome was overall mortality with secondary outcome of prostate cancer-specific mortality. In parallel, we tested castration of C57BL/6J mice on folate-defined diet to determine if folate levels change with response to androgen deprivation. Students’ t test on continuous variables and Chi-squared test on dichotomous variables was performed along with Kaplan-Meier for time to event analysis. ResultsWe identified 56 men with prostate cancer undergoing androgen deprivation in which folate levels had been determined. 15 out of 16 (94%) men initiating ADT had increases in their folate, which is substantially more than 67% in maintenance group (P = 0.04). We identified more rapid time to death from prostate cancer if folate levels increased to levels >200 ng/ml above their baseline (P = 0.03). Mice models demonstrated a significant rise in serum red blood cell folate after mice were castrated (P = 0.03) by an average of 1.5x over pre-castrated baseline level. By contrast, sham-castrated mice showed no increase in serum folate levels over baseline. ConclusionOur study suggests that men with substantial rises in folate after initiating ADT may be associated with worse prostate cancer-specific and overall survival. Our translational experiments in mice confirmed correlation between rising in folate levels post-castration. Given this study, further investigation is warranted on the role of dietary folate consumption during initiation of ADT and progression to castrate-resistant prostate cancer.

Examining the effects of creatine supplementation in augmenting adaptations to resistance training in patients with prostate cancer undergoing androgen deprivation therapy: a randomised, double-blind, placebo-controlled trial

IntroductionCreatine supplementation has consistently been demonstrated to augment adaptations in body composition, muscle strength and physical function in a variety of apparently healthy older adults and clinical populations. The effects...