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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 -
Frontiers in Oncology 2021Enzalutamide, apalutamide, and darolutamide have all been approved by Food and Drug Administration to treat high-risk non-metastatic castration-resistant prostate cancer...
INTRODUCTION
Enzalutamide, apalutamide, and darolutamide have all been approved by Food and Drug Administration to treat high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) since 2018 based on interim results of several phase III clinical trials. Final analyses of long-term overall survival (OS) and adverse events (AEs) results of these trials have been successively published recently. To help clinical practice to precisely select optimal treatment for high-risk nmCRPC patients, we performed a network meta-analysis to indirectly compare the final long-term results among these medications.
METHODS
PubMed, EMBASE, and Cochrane Libraries were searched for phase III clinical trial that reports OS and AEs results in nmCRPC patients published before January 30, 2021. Primary outcome was OS; secondary outcomes were Time to first chemotherapy, Subsequent antineoplastic therapy rate, and AEs. Firstly, class-level effect was assessed as the second-generation androgen receptor antagonists (SGARAs) were regarded as one whole class compared with placebo through traditional meta-analysis by using Revman 5.4, then a Bayesian network meta-analysis was conducted to give indirect comparison among SGARAs by using R 3.5.3 software. Subgroup analysis of OS was only conducted in the certain subgroups which were available in all included studies.
RESULTS
Three eligible studies including 4,104 participants were finally selected. OS was significantly improved by the SGARAs as a class compared with placebo (HR, 0.74; 95% CI, 0.66-0.84). Darolutamide had the highest likelihood of providing best OS (p-score=0.802). SGARAs also significantly delayed the first time to chemotherapy (HR, 0.58; 95% CI, 0.50-0.66). Patients who received darolutamide experienced similar toxicity compared with placebo regarding AEs of grade 3 or higher (OR, 1.3; 95% CI, 1.0-1.7) and serious AEs (OR, 1.3; 95% CI, 0.99-1.6). When compared with darolutamide, enzalutamide caused significantly higher toxicity in terms of any AEs (OR, 2.3; 95% CI,1.5-3.7) and AEs of grade 3 or higher (OR, 1.6; 95% CI, 1.1-2.2), apalutamide caused significantly more AEs of grade 3 or higher (OR, 1.9; 95% CI, 1.4-2.7) and serious AEs (OR, 1.9; 95% CI, 1.3-2.8). Subgroup analysis showed that SGARAs as a group significantly improved OS in ECOG=1 population, although insignificant results were found in these patients from included studies.
CONCLUSIONS
SGARAs combined with ADT significantly improved OS when compared with ADT alone in high-risk nmCRPC patients. Darolutamide may not only provide best OS but also have the most favorable safety profile among the included SGARAs in high-risk nmCRPC patients.
PubMed: 34722276
DOI: 10.3389/fonc.2021.733202 -
Brachytherapy 2021The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of...
PURPOSE
The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of prostate cancer.
METHODS AND MATERIALS
The American Brachytherapy Society convened a task force for addressing key questions concerning ultrasound-based LDR prostate brachytherapy for the primary treatment of prostate cancer. A comprehensive literature search was conducted to identify prospective and multi-institutional retrospective studies involving LDR brachytherapy as monotherapy or boost in combination with external beam radiation therapy with or without adjuvant androgen deprivation therapy. Outcomes included disease control, toxicity, and quality of life.
RESULTS
LDR prostate brachytherapy monotherapy is an appropriate treatment option for low risk and favorable intermediate risk disease. LDR brachytherapy boost in combination with external beam radiation therapy is appropriate for unfavorable intermediate risk and high-risk disease. Androgen deprivation therapy is recommended in unfavorable intermediate risk and high-risk disease. Acceptable radionuclides for LDR brachytherapy include iodine-125, palladium-103, and cesium-131. Although brachytherapy monotherapy is associated with increased urinary obstructive and irritative symptoms that peak within the first 3 months after treatment, the median time toward symptom resolution is approximately 1 year for iodine-125 and 6 months for palladium-103. Such symptoms can be mitigated with short-term use of alpha blockers. Combination therapy is associated with worse urinary, bowel, and sexual symptoms than monotherapy. A prostate specific antigen <= 0.2 ng/mL at 4 years after LDR brachytherapy may be considered a biochemical definition of cure.
CONCLUSIONS
LDR brachytherapy is a convenient, effective, and well-tolerated treatment for prostate cancer.
Topics: Androgen Antagonists; Brachytherapy; Consensus; Humans; Male; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Retrospective Studies
PubMed: 34509378
DOI: 10.1016/j.brachy.2021.07.006 -
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 -
Frontiers in Endocrinology 2023Androgen deprivation therapy is the mainstay of medical treatment for prostate cancer (Pca); however, it is associated with an increased risk of adverse cardiovascular... (Meta-Analysis)
Meta-Analysis
Adverse cardiovascular effect following gonadotropin-releasing hormone antagonist versus GnRH agonist for prostate cancer treatment: A systematic review and meta-analysis.
BACKGROUND
Androgen deprivation therapy is the mainstay of medical treatment for prostate cancer (Pca); however, it is associated with an increased risk of adverse cardiovascular (CV) events and death. To date, CV death has been the leading noncancer cause of death in Pca patients. Both GnRH antagonists (an emerging class of drugs) and GnRH agonists (most frequently prescribed) are efficacious against Pca. However, the adverse effects, especially the adverse CV effect between them remain unclear.
METHODS
Through a literature search using MEDLINE, EMBASE and the Cochrane Library, all available studies comparing the safety of CV risk between GnRH antagonists and GnRH agonists in Pca patients were extracted. Comparisons of outcomes of interest between these two classes of drugs were calculated using the risk ratio (RR). Subgroup analyses were performed depending on the study design and preexisting CV disease at baseline.
RESULTS
Nine randomized controlled clinical trials (RCTs) and five real-world observational studies comprising 62160 Pca patients were included in our meta-analysis. Patients receiving GnRH antagonists experienced fewer CV events (RR: 0.66, 95% CI:0.53-0.82, P<0.001), CV death (RR:0.4, 95% CI: 0.24-0.67, P<0.001) and myocardial infarctions (RR: 0.71, 95% CI: 0.52-0.96, P=0.03). No difference was found in the incidence of stroke and heart failure. Moreover, GnRH antagonists were associated with fewer CV events in patients with preexisting CV disease but not in those without preexisting CV disease in the RCT series.
CONCLUSION
GnRH antagonists appear to offer favorable safety in terms of adverse CV events and CV death compared with GnRH agonists among men diagnosed with Pca, especially those who had established CV disease at baseline.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/inplasy-2023-2-0009/, identifier INPLASY202320009.
Topics: Humans; Male; Cardiovascular Diseases; Gonadotropin-Releasing Hormone; Hormone Antagonists; Observational Studies as Topic; Prostatic Neoplasms; Randomized Controlled Trials as Topic
PubMed: 37065739
DOI: 10.3389/fendo.2023.1157857 -
Journal of Clinical Oncology : Official... Sep 2020In men with localized prostate cancer, the addition of androgen-deprivation therapy (ADT) or a brachytherapy boost (BT) to external beam radiotherapy (EBRT) have been... (Meta-Analysis)
Meta-Analysis
PURPOSE
In men with localized prostate cancer, the addition of androgen-deprivation therapy (ADT) or a brachytherapy boost (BT) to external beam radiotherapy (EBRT) have been shown to improve various oncologic end points. Practice patterns indicate that those who receive BT are significantly less likely to receive ADT, and thus we sought to perform a network meta-analysis to compare the predicted outcomes of a randomized trial of EBRT plus ADT versus EBRT plus BT.
MATERIALS AND METHODS
A systematic review identified published randomized trials comparing EBRT with or without ADT, or EBRT (with or without ADT) with or without BT, that reported on overall survival (OS). Standard fixed-effects meta-analyses were performed for each comparison, and a meta-regression was conducted to adjust for use and duration of ADT. Network meta-analyses were performed to compare EBRT plus ADT versus EBRT plus BT. Bayesian analyses were also performed, and a rank was assigned to each treatment after Markov Chain Monte Carlo analyses to create a surface under the cumulative ranking curve.
RESULTS
Six trials compared EBRT with or without ADT (n = 4,663), and 3 compared EBRT with or without BT (n = 718). The addition of ADT to EBRT improved OS (hazard ratio [HR], 0.71 [95% CI, 0.62 to 0.81]), whereas the addition of BT did not significantly improve OS (HR, 1.03 [95% CI, 0.78 to 1.36]). In a network meta-analysis, EBRT plus ADT had improved OS compared with EBRT plus BT (HR, 0.68 [95% CI, 0.52 to 0.89]). Bayesian modeling demonstrated an 88% probability that EBRT plus ADT resulted in superior OS compared with EBRT plus BT.
CONCLUSION
Our findings suggest that current practice patterns of omitting ADT with EBRT plus BT may result in inferior OS compared with EBRT plus ADT in men with intermediate- and high-risk prostate cancer. ADT for these men should remain a critical component of treatment regardless of radiotherapy delivery method until randomized evidence demonstrates otherwise.
Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Brachytherapy; Chemoradiotherapy; Humans; Male; Network Meta-Analysis; Prostatic Neoplasms; Radiation Dosage; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome
PubMed: 32396488
DOI: 10.1200/JCO.19.03217 -
European Urology Sep 2020
Meta-Analysis
Topics: Adverse Drug Reaction Reporting Systems; Androgen Antagonists; Fatigue; Humans; Male; Prostatic Neoplasms
PubMed: 32636097
DOI: 10.1016/j.eururo.2020.06.052 -
International Journal of Molecular... Nov 2021The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and...
What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment.
The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in tumor cells. TME influences the survival/progression of prostate cancer (PC), enabling tumor cell immune-evasion also through the activation of the PD-1/PD-L1 axis. We have performed a systematic literature review according to the PRISMA guidelines, to investigate how the PD-1/PD-L1 pathway is influenced by TME and ISPs. Tumor immune-escape mechanisms include suppression/exhaustion of tumor infiltrating cytotoxic T lymphocytes, inhibition of tumor suppressive NK cells, increase in immune-suppressive immune cells (regulatory T, M2 macrophagic, myeloid-derived suppressor, dendritic, stromal, and adipocytic cells). IFN-γ (the most investigated factor), TGF-β, TNF-α, IL-6, IL-17, IL-15, IL-27, complement factor C5a, and other soluble molecules secreted by TME components (and sometimes increased in patients' serum), as well as and hypoxia, influenced the regulation of PD-L1. Experimental studies using human and mouse PC cell lines (derived from either androgen-sensitive or androgen-resistant tumors) revealed that the intracellular ERK/MEK, Akt-mTOR, NF-kB, WNT and JAK/STAT pathways were involved in PD-L1 upregulation in PC. Blocking the PD-1/PD-L1 signaling by using immunotherapy drugs can prevent tumor immune-escape, increasing the anti-tumor activity of immune cells.
Topics: Animals; B7-H1 Antigen; Cell Line, Tumor; Cytokines; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Killer Cells, Natural; Male; Mice; Programmed Cell Death 1 Receptor; Prostatic Neoplasms; T-Lymphocytes, Cytotoxic; Tumor Escape; Tumor Microenvironment; Wnt Signaling Pathway
PubMed: 34830209
DOI: 10.3390/ijms222212330 -
Acta Bio-medica : Atenei Parmensis Sep 2021External Beam Radiation Therapy (EBRT) is one of the option available for the treatment of clinically localized prostate cancer. In patients with radiorecurrent...
INTRODUCTION
External Beam Radiation Therapy (EBRT) is one of the option available for the treatment of clinically localized prostate cancer. In patients with radiorecurrent localized prostate cancer, Androgen Deprivation Therapy (ADT) is one of the most common therapeutic strategies. However, in the last decades, other salvage treatment options have been investigated, such as brachytherapy, cryoablation and High Intensity Focused Ultrasound (Hifu).
MATERIAL AND METHODS
The oncologic outcome of Hifu in a salvage setting after EBRT failure was investigated. We reviewed the literature from 2005 to 2020 in order to report the oncologic outcome of the technique.
RESULTS
A total of 1241 patients were analyzed, with a mean age of 68.6 years and a PSA value of 5.87 ng/mL before treatment. Mean follow-up was 24.3 months after treatment, ranging from 3 to 168 months.
CONCLUSION
Our review of the literature revealed that salvage Hifu is effective in the treatment of radiorecurrent clinically localized prostate cancer, with an overall survival of 85.2% at 5 years.
Topics: Aged; Androgen Antagonists; Humans; Male; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatic Neoplasms; Salvage Therapy; Treatment Outcome; Ultrasound, High-Intensity Focused, Transrectal
PubMed: 34487074
DOI: 10.23750/abm.v92i3.11475 -
Wiener Klinische Wochenschrift Aug 2020The aim of this systematic review is to provide an update on the effects of resistance exercise (RE) in patients with prostate cancer (PCa), with special attention to...
PURPOSE
The aim of this systematic review is to provide an update on the effects of resistance exercise (RE) in patients with prostate cancer (PCa), with special attention to the effects on sexual health.
METHODS
A systematic search of the literature was conducted in March 2020 using the databases PubMed, MEDLINE, EMBASE, SCOPUS and the Cochrane Library. Only randomized, controlled trials published after 31 December 2016 were included in this update. Additionally, articles from current and previous reviews were utilized to provide a brief summary of the effects on sexual health.
RESULTS
A total of 10 articles met the inclusion criteria, of which 5 were identified as independent studies. The remaining five articles presented additional data for studies, which have already been included. The identified studies further strengthened the evidence for positive effects on muscle strength, body composition and physical function. Positive effects on bone mineral density were apparent only when RE was combined with impact training. One article reported an improvement in fatigue and health-related quality of life. Only one study examined the effects of RE in isolation and three articles indicated positive effects of exercise on sexual health.
CONCLUSION
Recent evidence supports the use of RE in PCa patient rehabilitation as a countermeasure for treatment side effects. Further research is necessary to ascertain the optimal delivery methods and illuminate the effects on health-related quality of life (HRQOL), fatigue and sexual health.
Topics: Androgen Antagonists; Exercise; Exercise Therapy; Hand Strength; Humans; Male; Postural Balance; Prostatic Neoplasms; Quality of Life; Resistance Training; Time and Motion Studies
PubMed: 32681360
DOI: 10.1007/s00508-020-01713-x