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BMJ Open May 2024Androgen deprivation therapy (ADT), a common treatment for prostate cancer, has debilitating impacts on physical and psychological quality of life. While some...
Effectiveness of educational and psychological survivorship interventions to improve health-related quality of life outcomes for men with prostate cancer on androgen deprivation therapy: a systematic review.
OBJECTIVES
Androgen deprivation therapy (ADT), a common treatment for prostate cancer, has debilitating impacts on physical and psychological quality of life. While some interventions focus on managing the physical side effects of ADT, there is a paucity of interventions that also address psychosocial and educational needs. The objective of this systematic review was to identify psychological and educational survivorship interventions targeting health-related quality of life (HRQoL) outcomes in men on ADT.
DESIGN
A systematic review of randomised controlled trials.
DATA SOURCES
Web of Science, Cochrane, EBSCO Host, PubMed, SCOPUS from inception (1984) to 28 January 2023.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Psychological and/or educational survivorship interventions targeting HRQoL outcomes for men on ADT; minimum 80% of participants on ADT; used a validated HRQoL outcome measure; published in English in a peer-reviewed journal.
DATA EXTRACTION AND SYNTHESIS
Data extraction using pre-specified study criteria was conducted. Heterogeneity of eligible studies precluded a meta-analysis.
RESULTS
A total of 3381 publications were identified with eight meeting the criteria. Interventions were either psychological with a cognitive behavioural approach (n=4), or educational with (n=2) or without (n=2) psychoeducational components.Two studies reported a statistically significant improvement using a specific HRQoL measure. Most studies were not adequately powered and/or included small sample sizes limiting the conclusions that can be drawn on effectiveness. The most effective interventions were (i) individually based, (ii) educational with a psychoeducational component, (iii) supplemented with information packages and/or homework and (iv) included personalised needs assessments.
CONCLUSION
There is a paucity of literature reporting psychological and educational survivorship interventions targeting HRQoL outcomes for men on ADT. What is urgently needed are person-centred survivorship interventions that are flexible enough to identify and address individual needs, taking into account the impact ADT has on both physical and psychological quality of life.
PROSPERO REGISTRATION NUMBER
CRD4202230809.
Topics: Humans; Male; Quality of Life; Prostatic Neoplasms; Androgen Antagonists; Patient Education as Topic; Cancer Survivors; Survivorship; Randomized Controlled Trials as Topic
PubMed: 38777593
DOI: 10.1136/bmjopen-2023-080310 -
JACC. CardioOncology Oct 2023Androgen deprivation therapy is the cornerstone of treatment for patients with advanced prostate cancer. Meta-analysis of small, oncology-focused trials suggest...
BACKGROUND
Androgen deprivation therapy is the cornerstone of treatment for patients with advanced prostate cancer. Meta-analysis of small, oncology-focused trials suggest gonadotropin-releasing hormone (GnRH) antagonists may be associated with fewer adverse cardiovascular outcomes compared with GnRH agonists.
OBJECTIVES
This study sought to determine whether GnRH antagonists were associated with fewer major adverse cardiovascular events compared with GnRH agonists.
METHODS
Electronic databases were searched for all prospective, randomized trials comparing GnRH antagonists with agonists. The primary outcome was a major adverse cardiovascular event as defined by the following standardized Medical Dictionary for Regulatory Activities terms: "myocardial infarction," "central nervous system hemorrhages and cerebrovascular conditions," and all-cause mortality. Bayesian meta-analysis models with random effects were fitted.
RESULTS
A total of 11 eligible studies of a maximum duration of 3 to 36 months (median = 12 months) enrolling 4,248 participants were included. Only 1 trial used a blinded, adjudicated event process, whereas potential bias persisted in all trials given their open-label design. A total of 152 patients with primary outcome events were observed, 76 of 2,655 (2.9%) in GnRH antagonist-treated participants and 76 of 1,593 (4.8%) in agonist-treated individuals. Compared with GnRH agonists, the pooled OR of GnRH antagonists for the primary endpoint was 0.57 (95% credible interval: 0.37-0.86) and 0.58 (95% credible interval: 0.32-1.08) for all-cause death.
CONCLUSIONS
Despite the addition of the largest, dedicated cardiovascular outcome trial, the volume and quality of available data to definitively answer this question remain suboptimal. Notwithstanding these limitations, the available data suggest that GnRH antagonists are associated with fewer cardiovascular events, and possibly mortality, compared with GnRH agonists.
PubMed: 37969642
DOI: 10.1016/j.jaccao.2023.05.011 -
European Urology Oncology Feb 2024Since 2015 there have been major advances in the management of primary metastatic hormone-sensitive prostate cancer (mHSPC) following the publication of key clinical... (Review)
Review
Does Research from Clinical Trials in Metastatic Hormone-sensitive Prostate Cancer Treatment Translate into Access to Treatments for Patients in the "Real World"? A Systematic Review.
CONTEXT
Since 2015 there have been major advances in the management of primary metastatic hormone-sensitive prostate cancer (mHSPC) following the publication of key clinical trials that demonstrated significant clinical benefits with docetaxel chemotherapy or novel hormone therapy (NHT) in addition to androgen deprivation therapy (ADT). Despite these advances, there is evidence to show that these treatments are not being utilised for mHSPC in clinical practice.
OBJECTIVE
To determine the utilisation of docetaxel and NHT in mHSPC in routine practice and the determinants of variation in their use.
EVIDENCE ACQUISITION
MEDLINE and Embase were searched systematically for studies on utilisation of treatments for primary mHSPC that were based on regional or national data sets and published after January 2005. Study results were summarised using a narrative synthesis.
EVIDENCE SYNTHESIS
Thirteen papers were included in the analysis, six full-text articles and seven abstracts, on studies that included a total of 166 876 patients. The utilisation rate of treatment intensification with either docetaxel or NHT (enzalutamide, apalutamide, or abiraterone) in addition to ADT ranged from 9.3% to 38.1% across the studies. Younger, White patients with fewer comorbidities and living in more urban settings were more likely to be prescribed treatment intensification. Patients treated in private academic institutions by oncologists were more likely to receive docetaxel or NHT. Socioeconomic status did not impact receipt of systemic therapy. NHT utilisation rates appear to have increased over time.
CONCLUSIONS
These results highlight the need to change the approach to the treatment of primary mHSPC in the real world by harnessing the practice-changing results from recent trials in this setting to optimise upfront systemic therapy for this patient population.
PATIENT SUMMARY
We reviewed the use of treatments for primary metastatic hormone-sensitive prostate cancer that showed a benefit in key clinical trials. We found that these treatments are underused, particularly among certain patient groups.
Topics: Male; Humans; Prostatic Neoplasms; Docetaxel; Androgen Antagonists; Treatment Outcome; Hormones; Health Services Accessibility
PubMed: 37380578
DOI: 10.1016/j.euo.2023.05.002 -
Clinical Genitourinary Cancer Apr 2024Castration resistant prostate cancer (CRPC) is a challenging subset of prostate cancer associated with an extensive metastatic profile and high mortality. Ketoconazole... (Meta-Analysis)
Meta-Analysis Review
Castration resistant prostate cancer (CRPC) is a challenging subset of prostate cancer associated with an extensive metastatic profile and high mortality. Ketoconazole is a nonselective steroid 17α-hydroxylase/17,20 lyase (CYP17A1) inhibitor and is employed as a second line treatment option for CRPC with an established efficacy profile in patients. The aim of this study is to assess the efficacy of ketoconazole containing regimens for CRPC in terms of prostate specific antigen (PSA) decline rate using a systematic review and meta-analysis. In this review, an electronic search was carried out on PubMed, Cochrane CENTRAL, Scopus, and Google Scholar to find relevant literature. Random effects model was used to assess pooled PSA decline rate and 95% CIs. Publication bias was assessed using the funnel plot symmetry and one-tailed Egger's and Begg's test. In all cases, P-value <.05 was indicative of significant results. The review is registered with PROSPERO: CRD42023466536. A total of 483 articles were retrieved after database searching, out of which 23 studies (having a total of 1315 patients) were included in the review based on prespecified criteria. The PSA decline rate was reported in the 14 observational studies (having 964 patients) and 9 experimental studies (having 351 patients). Pooled results revealed that 48.6% (95% CI 43.1-54.2; P-value <.001; I = 73.24%) of participants achieved more than 50% decline in PSA (602/1315 participants). Sensitivity analysis using the leave-one-out method revealed no substantial change in pooled effect estimates; (Risk Ratio) RR 47.2% to RR 49.8% demonstrating the robustness of our results. There was no evidence of publication bias as assessed from the funnel plot symmetry. Ketoconazole containing regimens have shown moderate efficacy in high risk CRPC patients as demonstrated by the pooled results. Hence, a ketoconazole based chemotherapy can be added to patients' regimen if there is a persistent rise in PSA levels after androgen deprivation therapy.
Topics: Male; Humans; Prostatic Neoplasms; Prostate-Specific Antigen; Ketoconazole; Prostatic Neoplasms, Castration-Resistant; Androgen Antagonists
PubMed: 38296679
DOI: 10.1016/j.clgc.2024.01.003 -
Clinical Genitourinary Cancer Jun 2024Second-generation androgen receptor axis-targeting (ARAT) agents have become a standard treatment for patients with advanced prostate cancer (PC), however much remains... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Second-generation androgen receptor axis-targeting (ARAT) agents have become a standard treatment for patients with advanced prostate cancer (PC), however much remains unknown about the potential cardiovascular toxicities.
PATIENTS AND METHODS
We performed a systematic search of PubMed, Embase, Web of Science, and Cochrane library for randomized controlled trials of patients receiving ARAT agents for PC from inception to March 2023. The odds ratios (ORs) of all-grade and high-grade cardiovascular adverse events (CVAEs) for patients treated with and without ARAT agents were pooled for meta-analysis. Subgroup analyses based on PC type and treatment regimen were conducted.
RESULTS
A total of 15 double-blind placebo-controlled phase 3 trials comprising 15,842 patients were included. In addition to hot flush and hypertension of any degree of severity, inclusion of ARAT agents was associated with a significantly higher risk of acute myocardial infarction (OR: 1.96, 95% CI: 1.05-3.68, P = .04), myocardial infarction (OR: 2.44, 95% CI: 1.27-4.66, P = .007) and angina pectoris (OR: 2.00, 95% CI: 1.00-4.02, P = .05). With regard to individual ARAT agents, enzalutamide was associated with a significantly higher risk of acute myocardial infarction (OR: 3.11, 95% CI: 1.17-8.28, P = .02), coronary artery disease (OR: 8.33, 95% CI: 1.54-44.95, P = .01), and high-grade hypertension (OR: 4.94, 95% CI: 1.11-22.06, P = .04), while abiraterone and apalutamide were associated with a significantly higher risk of angina pectoris (OR: 5.48, 95% CI: 1.23-24.33, P = .03) and myocardial infarction (OR: 7.00, 95% CI: 1.60-30.62, P = .01), respectively.
CONCLUSION
The inclusion of ARAT agents was associated with a significantly higher risk of several CVAEs. Clinicians should remain vigilant, both in pre-treatment screening and monitoring for clinical symptoms and signs, when considering ARAT agent particularly for patients with pre-existing risk factors.
Topics: Humans; Male; Randomized Controlled Trials as Topic; Prostatic Neoplasms; Cardiovascular Diseases; Androgen Receptor Antagonists; Receptors, Androgen; Phenylthiohydantoin; Benzamides; Clinical Trials, Phase III as Topic; Nitriles; Thiohydantoins; Androstenes
PubMed: 38584004
DOI: 10.1016/j.clgc.2024.102066 -
The Prostate May 2024Androgen deprivation therapy (ADT) is an effective treatment for advanced prostate cancer (PCa). Multiple studies have highlighted serious consequences this therapy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Androgen deprivation therapy (ADT) is an effective treatment for advanced prostate cancer (PCa). Multiple studies have highlighted serious consequences this therapy poses to mental health, particularly depression. We aimed to review the incidence and association between ADT in men with PCa and the risk of depression.
METHODS
We systematically searched multiple databases, including MEDLINE, Scopus till August 2023 for studies that compared ADT versus control for treating PCa reporting depression as outcome. Meta-analysis was performed using random-effects models and results presented as odds ratios (ORs) with 95% confidence interval (CI). Quality assessment of the included studies was conducted using Joanna Briggs Institute critical appraisal checklists.
RESULTS
A total of 38 studies (17 retrospective studies, 16 prospective studies, two cross-sectional studies and two randomized trials) with 360,650 subjects met the inclusion criteria and were included in this meta-analysis. The estimated pooled incidence of depression among ADT patients is 209.5 (95% CI = 122.3; 312.2) per 1000 patients. There is statistically significant relationship between ADT treatment and depression (OR = 1.46, 95% CI = 1.28, 1.67; p = 0, I= 86.4%). The results remained consistent across various subgroups. No risk of publication bias was detected by funnel plot and Eggers's test (p > 0.05).
CONCLUSION
There is a higher risk of depression for men receiving ADT. Further studies evaluating optimal treatments for depression in men on ADT are warranted.
Topics: Male; Humans; Androgen Antagonists; Prostatic Neoplasms; Androgens; Depression; Retrospective Studies; Prospective Studies; Cross-Sectional Studies; Antineoplastic Agents, Hormonal
PubMed: 38372065
DOI: 10.1002/pros.24676 -
Environmental Research Jul 2024Human fertility is impacted by changes in lifestyle and environmental deterioration. To increase human fertility, assisted reproductive technology (ART) has been... (Review)
Review
Human fertility is impacted by changes in lifestyle and environmental deterioration. To increase human fertility, assisted reproductive technology (ART) has been extensively used around the globe. As early as 2009, the Endocrine Society released its first scientific statement on the potential adverse effects of environmental endocrine-disrupting chemicals (EDCs) on human health and disease development. Chemicals known as phthalates, frequently employed as plasticizers and additives, are common EDCs. Numerous studies have shown that phthalate metabolites in vivo exert estrogen-like or anti-androgenic effects in both humans and animals. They are associated with the progression of a range of diseases, most notably interference with the reproductive process, damage to the placenta, and the initiation of chronic diseases in adulthood. Phthalates are ingested by infertile couples in a variety of ways, including household products, diet, medical treatment, etc. Exposure to phthalates may exacerbate their infertility or poor ART outcomes, however, the available data on phthalate exposure and ART pregnancy outcomes are sparse and contradictory. Therefore, this review conducted a systematic evaluation of 16 papers related to phthalate exposure and ART pregnancy outcomes, to provide more aggregated results, and deepen our understanding of reproductive outcomes in infertile populations with phthalate exposure.
Topics: Phthalic Acids; Humans; Female; Pregnancy; Fertilization in Vitro; Infertility; Endocrine Disruptors; Environmental Pollutants; Environmental Exposure; Pregnancy Outcome; Male
PubMed: 38609072
DOI: 10.1016/j.envres.2024.118825 -
Nutrients Feb 2024The changes in body composition during androgen deprivation therapy (ADT) in patients suffering from prostate cancer (PCa) are recognized by professionals more often as... (Meta-Analysis)
Meta-Analysis Review
The changes in body composition during androgen deprivation therapy (ADT) in patients suffering from prostate cancer (PCa) are recognized by professionals more often as biomarker for effective treatment. The aim of this study was to investigate the impact of ADT on the sarcopenia development in PCa. The following databases were used: PubMed, Embase, Web of Science and Scopus databases. Out of 2183 studies, 7 were included in this review. The fixed-effect model was used in the meta-analysis. A significant increase in SATI (Subcutaneous Adipose Tissue Index) of 0.32 (95% CI: 0.13-0.51) = 0.001, decrease in SMI (Skeletal Muscle Index) of -0.38 (95% CI: -0.57 to -0.19) < 0.0001, and SMD (Skeletal Muscle Density) of -0.46 (95% CI: -0.69 to -0.24) < 0.0001 were observed. No statistical association was visible between ADT and changes in BMI (Body Mass Index), 0.05 (95% CI: -0.18-0.28), = 0.686, and VATI (Visceral Adipose Tissue Index): 0.17 (95% CI: -0.02 to 0.37), = 0.074. In conclusion, the ADT significantly contributes to the body composition changes and sarcopenia development.
Topics: Male; Humans; Sarcopenia; Prostatic Neoplasms; Androgen Antagonists; Androgens; Muscle, Skeletal
PubMed: 38474784
DOI: 10.3390/nu16050656 -
Minerva Urology and Nephrology Apr 2024Patients with high-risk prostate cancer (HRPCa) are prone to have worse pathological features, resulting in early biochemical recurrence after radical prostatectomy...
INTRODUCTION
Patients with high-risk prostate cancer (HRPCa) are prone to have worse pathological features, resulting in early biochemical recurrence after radical prostatectomy (RP). There is an urgent need to develop novel treatment strategies for this group of patients to optimize their outcomes. The purpose of this study is to perform a systematic review of the role of neoadjuvant hormonal therapy (NHT) followed by RP in HRPCa patients.
EVIDENCE ACQUISITION
We performed a systematic review of the following databases, MEDLINE (PubMed), EMBASE, Cochrane Library, and clinical Trial.gov; between January 2007 and August 2023, following the PRISMA guidelines.
EVIDENCE SYNTHESIS
After screening and deduplication, we included ten studies from an initial pool of 1275. The risk of bias was low in observational studies but ranged from moderate to low in controlled trials. Five studies utilized traditional androgen deprivation treatments (ADT), revealing favorable pathological outcomes but inconsistency in evaluating oncological results. Additionally, four studies focused on RP combined with androgen receptor pathway inhibitors (ARPIs) in the NHT setting, all showing primarily positive pathological outcome, with no clear evidence of an oncological benefit. Limited long-term follow-up data and a shortage of randomized controlled trials were evident among all the studies included in this review, regardless of the type of hormonal treatment used.
CONCLUSIONS
Different hormonal treatments, including traditional ADT and ARPIs, yield positive pathology outcomes. Oncological evidence remains limited, echoing older findings predating ARPIs. Definitive conclusions require longer follow-ups and precise patient selection. Currently, insufficient evidence support ARPIs' superiority over conventional therapy before RP.
Topics: Humans; Prostatectomy; Prostatic Neoplasms; Male; Androgen Antagonists; Neoadjuvant Therapy; Risk Assessment
PubMed: 38742549
DOI: 10.23736/S2724-6051.24.05630-1 -
European Urology Mar 2024
Meta-Analysis
Re: Which Patients with Metastatic Hormone-sensitive Prostate Cancer Benefit from Docetaxel: A Systematic Review and Meta-analysis of Individual Participant Data from Randomised Trials.
Topics: Male; Humans; Docetaxel; Prostatic Neoplasms; Androgen Antagonists; Hormones; Antineoplastic Combined Chemotherapy Protocols; Randomized Controlled Trials as Topic
PubMed: 38087732
DOI: 10.1016/j.eururo.2023.11.007