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Current Oncology (Toronto, Ont.) May 2022Health economic evaluations are needed to assess the impact on the healthcare system of emerging treatment patterns for advanced prostate cancer. The objective of this... (Review)
Review
The Health Economics of Metastatic Hormone-Sensitive and Non-Metastatic Castration-Resistant Prostate Cancer-A Systematic Literature Review with Application to the Canadian Context.
Health economic evaluations are needed to assess the impact on the healthcare system of emerging treatment patterns for advanced prostate cancer. The objective of this study is to review the scientific literature identifying cost-effectiveness and cost analyses that are assessing treatments for metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC). : On 29 June 2021, we searched the scientific (MEDLINE, Embase, and EBSCO) and grey literature for health economic studies targeting mHSPC and nmCRPC. We used the CHEC-extended checklist and the Welte checklist for risk-of-bias assessment and transferability analysis, respectively. : We retained 20 cost-effectiveness and 4 cost analyses in the mHSPC setting, and 14 cost-effectiveness and 6 cost analyses in the nmCRPC setting. Docetaxel in combination with androgen deprivation therapy (ADT) was the most cost-effective treatment in the mHSPC setting. Apalutamide, darolutamide, and enzalutamide presented similar results vs. ADT alone and were identified as cost-effective treatments for nmCRPC. An increase in costs as patients transitioned from nmCRPC to mCRPC was noted. : We concluded that there is an important unmet need for health economic evaluations in the mHSPC and nmCRPC setting incorporating real-world data to support healthcare decision making.
Topics: Androgen Antagonists; Canada; Docetaxel; Hormones; Humans; Male; Prostatic Neoplasms, Castration-Resistant
PubMed: 35621665
DOI: 10.3390/curroncol29050275 -
Minerva Urology and Nephrology Jun 2022
Meta-Analysis
Comment on: "Androgen receptor axis-targeted agents for non-metastatic castration-resistant prostate cancer impact on overall survival and safety profile: an updated systematic review and meta-analysis".
Topics: Androgen Antagonists; Androgen Receptor Antagonists; Antineoplastic Agents; Humans; Male; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen
PubMed: 35607782
DOI: 10.23736/S2724-6051.22.04948-5 -
European Urology Jul 2022Several recent randomised trials have evaluated the role of combination systemic treatment using androgen deprivation therapy (ADT) plus chemotherapy or an androgen... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Several recent randomised trials have evaluated the role of combination systemic treatment using androgen deprivation therapy (ADT) plus chemotherapy or an androgen receptor signaling inhibitor (ARSI) in patients with high-risk and/or unfavourable nonmetastatic prostate cancer (nmPC).
OBJECTIVE
To assess the outcomes associated with adding combination systemic treatment to primary definitive local therapy in patients with high-risk and/or unfavourable nmPC.
EVIDENCE ACQUISITION
We queried the PubMed, Web of Science, and Scopus databases and conference abstracts to identify prospective randomised trials examining the value of adding chemotherapy or an ARSI to ADT and primary local therapy with curative intent for nmPC. The primary endpoints were overall survival (OS), cancer-specific survival (CSS), metastasis-free survival (MFS), and failure-free survival (FFS). Secondary endpoints included adverse events (AEs) and pathologic outcomes.
EVIDENCE SYNTHESIS
We identified 15 randomised studies, of which nine evaluated chemohormonal and six investigated ARSI-based treatment strategies. In both radical prostatectomy (RP) and radiation therapy (RT) settings, addition of docetaxel to ADT was associated with significantly better CSS (pooled hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.49-0.95; p = 0.025), MFS (pooled HR 0.82, 95% CI 0.71-0.95; p = 0.008), and FFS (pooled HR 0.70, 95% CI 0.62-0.79; p < 0.001); the difference did not meet the conventional level of statistical significance for OS (pooled HR 0.86, 95% CI 0.73-1.01; p = 0.072). For patients treated with RT alone, docetaxel-based combination treatment did not meet the significance threshold set for OS (p = 0.3), CSS (p = 0.072), or MFS (p = 0.079), but the difference for FFS was statistically significant (pooled HR 0.72, 95% CI 0.63-0.84; p < 0.001). On network meta-analyses including RT studies, ARSI + ADT outperformed docetaxel + ADT for survival endpoints and had a more favourable AE profile.
CONCLUSIONS
Intensification of systemic therapy with docetaxel or an ARSI in addition to ADT improves oncologic endpoints in high-risk and/or unfavourable nmPC treated with local definitive therapy. The highest efficacy was achieved with ARSI + ADT, specifically in patients treated with RT.
PATIENT SUMMARY
Our findings highlight that selected patients with high-risk nonmetastatic prostate cancer benefit from intensification of systemic therapy beyond hormonal treatment.
Topics: Androgen Antagonists; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Humans; Male; Prospective Studies; Prostatic Neoplasms
PubMed: 35465985
DOI: 10.1016/j.eururo.2022.03.031 -
Healthcare (Basel, Switzerland) Mar 2022Since the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, various potential targeted therapies for SARS-CoV-2 infection have been... (Review)
Review
Since the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, various potential targeted therapies for SARS-CoV-2 infection have been proposed. The protective effects of mineralocorticoid receptor antagonists (MRA) against tissue fibrosis, pulmonary and systemic vasoconstriction, and inflammation have been implicated in potentially attenuating the severity of SARS-CoV-2 infection by inhibiting the deleterious effects of aldosterone. Furthermore, spironolactone, a type of MRA, has been suggested to have a beneficial effect on SARS-CoV-2 outcomes through its dual action as an MRA and antiandrogen, resulting in reduced transmembrane protease receptor serine type 2 (TMPRSS2)-related viral entry to host cells. In this study, we sought to investigate the association between MRA antagonist therapy and mortality in SARS-CoV-2 patients via systematic review and meta-analysis. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE and EMBASE databases were searched for studies that reported the incidence of mortality in patients on MRA with SARS-CoV-2 infection. Pooled odds ratio (OR) and 95% confidence interval (CI) of the outcome were obtained using the random-effects model. Five studies with a total of 1,388,178 subjects (80,903 subjects receiving MRA therapy) met the inclusion criteria. We included studies with all types of MRA therapy including spironolactone and canrenone and found no association between MRA therapy and mortality in SARS-CoV-2 infection (OR = 0.387, 95% CI: 0.134-1.117, = 0.079).
PubMed: 35455823
DOI: 10.3390/healthcare10040645 -
Einstein (Sao Paulo, Brazil) 2022To evaluate whether the addition of statins to the new antiandrogens (enzalutamide or abiraterone) affects overall survival in patients with metastatic... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate whether the addition of statins to the new antiandrogens (enzalutamide or abiraterone) affects overall survival in patients with metastatic castration-resistant prostate cancer.
METHODS
We searched studies in English language including the keywords statins, overall survival, and metastatic castration-resistant prostate cancer, at PubMed® (MEDLINE®), Embase and Cochrane databases.
RESULTS
A total of 195 articles were initially identified, but only four met the inclusion criteria and were selected for the meta-analysis. A total of 955 patients, 632 on the new antiandrogens only group, and 323 on the new antiandrogens + statins group, were analyzed. In all four studies the combination therapy (new antiandrogens + statin) was well tolerated, regardless of which new antiandrogens were used. Neither the type of statin nor the doses and duration of use were well specified in the studies. The combination therapy in metastatic castration-resistant prostate cancer was associated with an overall survival improvement, and a 46% reduction in death (hazard ratio of 0.54; 95%CI 0.34-0.87; p<0.01) in multivariate analysis.
CONCLUSION
There seems to be a clinical benefit with the association of statins to the new antiandrogens in patients with metastatic castration-resistant prostate cancer, suggesting longer overall survival with no important collateral effect. However, due to fragility of the studies available in the literature, we are not yet capable of recommending this combination of drugs in the clinical practice. Further randomized prospective studies are warranted to confirm these beneficial outcomes.
Topics: Androgen Antagonists; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome
PubMed: 35384986
DOI: 10.31744/einstein_journal/2022RW6339 -
PloS One 2022Androgen deprivation therapy is a common treatment for prostate cancer. However, this therapy is associated with various adverse effects, such as increased body fat and... (Meta-Analysis)
Meta-Analysis
Androgen deprivation therapy is a common treatment for prostate cancer. However, this therapy is associated with various adverse effects, such as increased body fat and decreased bone mineral density. Exercise may be useful for ameliorating these adverse effects, although it is not completely effective. This review aimed to clarify how exercise interventions influenced body composition and bone mineral density and to explore the most effective exercise program among prostate cancer patients who received androgen deprivation therapy. We searched the PubMed, EMBASE, Web of Science, EBSCO, and Cochrane Library databases for reports of randomised controlled trials that were published until October 2021. All studies involved prostate cancer patients who received androgen deprivation therapy and completed aerobic exercise, resistance exercise, and/or impact exercise training. Outcomes were defined as lean body mass, body fat mass, body fat rate, regional and whole-body bone mineral density. Thirteen reports regarding 12 randomised clinical trials (715 participants) were included. Relative to the control group, exercise intervention provided a higher lean body mass (mean difference: 0.88, 95% confidence interval: 0.40 to 1.36, P<0.01), a lower body fat mass (mean difference: -0.60, 95% confidence interval: -1.10 to -0.10, P<0.05), and a lower body fat rate (mean difference: -0.93, 95% confidence interval: -1.39 to -0.47, P<0.01). Subgroup analyses revealed greater efficacy for exercise duration of ≥6 months (vs. <6 months) and exercise immediately after the therapy (vs. delayed exercise). No significant differences were observed in the bone mineral density outcomes. Exercise can help ameliorate the adverse effects of androgen deprivation therapy in body composition, with combination exercises including resistance exercise, 8-12 repetition maximum of resistance exercise intensity, prolonged exercise duration, and performing exercise immediately after therapy providing better amelioration. And the combination of resistance and impact exercise appears to be the best mode for improving the bone mineral density.
Topics: Adipose Tissue; Androgen Antagonists; Body Composition; Bone Density; Exercise Therapy; Humans; Male; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 35167609
DOI: 10.1371/journal.pone.0263918 -
Physical Therapy Mar 2022Men with prostate cancer (PCa) receiving androgen deprivation therapy (ADT) experience the loss of bone mineral density (BMD) and lean body mass, which can increase...
OBJECTIVE
Men with prostate cancer (PCa) receiving androgen deprivation therapy (ADT) experience the loss of bone mineral density (BMD) and lean body mass, which can increase their risk of falls and fractures. Physical exercise programs with appropriate components and dosage are suggested to preserve BMD and muscle strength, thereby potentially reducing accidental falls and fractures and associated morbidity and mortality. These benefits can be obtained if exercise programs are feasible and safe and if patient adherence is adequate. This systematic review investigates the feasibility and safety of exercise programs aimed at preventing the risk of accidental falls and fractures and BMD loss in men with PCa undergoing ADT.
METHODS
MEDLINE, Embase, CINAHL, and the Cochrane Library were searched from database inception to June 7, 2021. Randomized controlled trials were included when they analyzed the feasibility and safety of experimental exercise programs targeting bone health in men with PCa receiving ADT. Two reviewers independently selected the studies, assessed their methodological quality, and extracted the data. Exercise feasibility was measured through recruitment, retention, and adherence rates. Exercise safety was measured through the number, type, and severity of adverse events. Furthermore, the components, setting, intensity, frequency, and duration of exercise programs were extracted.
RESULTS
Ten studies were included, with a total of 633 participants. Exercise consisted of a combination of aerobic, resistance, and impact-loading exercise or football training. Exercise is feasible in men with PCa undergoing ADT, although football training should be prescribed with caution for safety reasons.
CONCLUSION
Multicomponent exercise programs targeting bone health seem feasible and safe in this population; however, adverse events should be systematically documented according to current guidelines.
IMPACT
The study shows that men with PCa receiving ADT can safely perform exercise programs to preserve bone health and supports that those programs should become part of lifestyle habits.
LAY SUMMARY
Men with PCa who are receiving ADT can safely perform exercise programs to preserve bone health and should make exercise an important part of their lifestyle.
Topics: Androgen Antagonists; Androgens; Bone Density; Exercise; Exercise Therapy; Feasibility Studies; Humans; Male; Prostatic Neoplasms
PubMed: 34972863
DOI: 10.1093/ptj/pzab288 -
Archivio Italiano Di Urologia,... Dec 2021Serenoa repens (SR) is a plant used to treat benign prostatic hyperplasia and prostatitis. We know that SR act as a 5α-reductase inhibitor, moreover, several studies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Serenoa repens (SR) is a plant used to treat benign prostatic hyperplasia and prostatitis. We know that SR act as a 5α-reductase inhibitor, moreover, several studies have proved that SR has anti-inflammatory and antioxidant properties. There is some belief among patients that SR may negatively impact male sexual function. Such belief is circulating in non-medical social networks and is perhaps maintained by patients as a result of incorrect web surfing. However, it is also possible that SR may exert a "nocebo" effect thus negatively impacting on the general well-being of patients.
OBJECTIVE
The aim of this study is to investigate whether SR is causing negative effects on male sexual function.
METHODS
To ascertain the effect of SR on male sexual function, we conducted a systematic review and meta-analysis, by performing an electronic database search in accordance with the PRISMA guidelines.
RESULTS
Out of 20 included papers, 8 papers reported comparisons of SR with placebo, and 7 studies reported comparisons of SR with tamsulosin. The standardized mean difference of changes from baseline scores of sexual function was not significantly different between SR and placebo (SMD: 0.43, 95% CI: 0.18 to 1.05; I^2 = 95%). Similarly, no significant mean differences in the Male Sexual Function-4 (MSF-4) test scores were found between SR and tamsulosin (SMD: -0.31, 95% CI: -0.82 to 0.19; I^2 = 90%).
CONCLUSIONS
We found no statistically significant differences between negative effects on sexual function in patients treated with SR compared to patients who received placebo. The results of our meta-analysis are similar to those of other systematic reviews. Studies are warranted to ascertain whether any such effects might occur as a result of a nocebo effect.
Topics: 5-alpha Reductase Inhibitors; Androgen Antagonists; Humans; Male; Plant Extracts; Prostatic Hyperplasia; Randomized Controlled Trials as Topic; Serenoa; Tamsulosin
PubMed: 34933534
DOI: 10.4081/aiua.2021.4.475 -
Clinical Genitourinary Cancer Apr 2022There was a high medical need for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) when several next-generation anti-androgens (apalutamide,... (Meta-Analysis)
Meta-Analysis Review
There was a high medical need for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) when several next-generation anti-androgens (apalutamide, enzalutamide, and darolutamide) demonstrated clinically relevant delays in metastasis onset. However, to date, few publications have assessed the pooled effect of these treatments on overall survival (OS). We performed a systematic review and meta-analysis of all randomized, placebo-controlled studies investigating a systemic treatment in nmCRPC. Publications were identified by searching several databases on April 7, 2021. The primary objective of this analysis was to determine the OS benefit. Secondary outcomes included the relative risk (RR) of adverse events (AEs) and grade 3-4 AEs. A sensitivity analysis with simulated data was also conducted to examine the influence of the study designs on the results. Three randomized controlled studies (SPARTAN, PROSPER, ARAMIS) met our inclusion criteria. Pooled meta-analyses showed a significant benefit in OS with the active agents versus placebo (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.65-0.83), as well as increased risk of any grade (RR 1.09, 95% CI 1.01-1.17) and grade 3-4 AEs (RR 1.50, 95% CI 1.23-1.83). The sensitivity analysis with SPARTAN-like simulated populations demonstrated that when using ARAMIS statistical design, OS would be statistically significant in 98.1% of the cases, at a shorter follow-up and with lower number of events. First-line treatment of nmCRPC patients with anti-androgens increased OS with an acceptable safety profile. In light of the different study designs and follow-up, results should be interpreted separately.
Topics: Androgen Antagonists; Androgen Receptor Antagonists; Humans; Immunotherapy; Male; Proportional Hazards Models; Prostatic Neoplasms, Castration-Resistant
PubMed: 34920959
DOI: 10.1016/j.clgc.2021.11.008 -
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