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Journal of Cancer Research and Clinical... Aug 2023The newly published ARASENS trial has demonstrated the clinical efficacy of darolutamide for metastatic hormone-sensitive prostate cancer (mHSPC). However, the use of... (Meta-Analysis)
Meta-Analysis
Based on ARASENS trial: efficacy and safety of darolutamide as an emerging option of endocrinotherapy for metastatic hormone-sensitive prostate cancer-an updated systematic review and network meta-analysis.
PURPOSE
The newly published ARASENS trial has demonstrated the clinical efficacy of darolutamide for metastatic hormone-sensitive prostate cancer (mHSPC). However, the use of darolutamide as the latest first-line androgen receptor pathway inhibitor for mHSPC has not been compared with other androgen receptor targeted agents (ARTAs). Given the lack of head-to-head randomized trials, we performed this updated meta-analysis to conduct indirect comparison for the efficacy and safety of darolutamide with other new-generation ARTAs.
METHODS
By searching the databases of PubMed, Scopus, Cochrane Library, and Embase, 9 large randomized controlled trials evaluating ARTAs for mHSPC patients were eventually screened according to PRISMA. We extracted data from overall survival, castration-resistant progression, and adverse events for network meta-analysis using the Bayesian and standard frequentist models.
RESULTS
Darolutamide combination emerged with superiority (HR = 0.68, 95%CrI = 0.57-0.81) among four androgen receptor inhibitors for patients with high Gleason score (HR = 0.71, 95%CrI = 0.59-0.86). Darolutamide was best tolerated in several androgen suppression-related adverse events (AEs).
CONCLUSION
Darolutamide appears to be an optional androgen receptor inhibitor for mHSPC patients, especially for patients with Gleason score ≥ 8. Its well-tolerated characteristic may provide a preferred drug option for patients with poor cardiovascular function and bone health.
Topics: Male; Humans; Receptors, Androgen; Prostatic Neoplasms, Castration-Resistant; Network Meta-Analysis; Bayes Theorem; Androgen Receptor Antagonists; Hormones; Androgen Antagonists; Randomized Controlled Trials as Topic
PubMed: 36856851
DOI: 10.1007/s00432-023-04658-6 -
Clinical Endocrinology May 2021Antiandrogens are frequently used with estradiol in transgender women seeking feminization. Antiandrogens act by various mechanisms to decrease the production or effects... (Review)
Review
Antiandrogens are frequently used with estradiol in transgender women seeking feminization. Antiandrogens act by various mechanisms to decrease the production or effects of testosterone, but it is unclear which antiandrogen is most effective at feminization. A systematic review was performed using PRISMA guidelines. We searched online databases (Medline, Embase and PsycINFO) and references of relevant articles for studies of antiandrogens in transgender women aged 16+ years to achieve feminization (namely changes in breast size, body composition, facial or body hair) or changes in serum total testosterone concentration when compared to placebo, estradiol alone or an alternative antiandrogen. Four studies fulfilled eligibility criteria and were included in a narrative review. The addition of cyproterone acetate, leuprolide and medroxyprogesterone acetate may be more effective than spironolactone or estradiol alone at suppressing the serum total testosterone concentration. Body composition changes appear similar in transgender women treated with estradiol and additional cyproterone acetate or leuprolide. No eligible studies adequately evaluated the effects of antiandrogens on breast development or facial and body hair reduction. It remains unclear which antiandrogen is most effective at achieving feminization. Cyproterone acetate, medroxyprogesterone acetate and leuprolide may be more effective than spironolactone at suppressing the serum total testosterone concentration. However, due to spironolactone's antagonism of the androgen receptor, it is unclear whether this results in clinically meaningful differences in feminization. Further research with clinically meaningful endpoints is needed to optimize the use of antiandrogens in transgender women.
Topics: Androgen Antagonists; Cyproterone Acetate; Female; Feminization; Humans; Male; Transgender Persons; Transsexualism
PubMed: 32926454
DOI: 10.1111/cen.14329 -
Urologic Oncology Sep 2024The influence of androgen suppression therapy (AST) on bladder cancer (BCa) remains controversial, as recent studies have not reached a consensus regarding the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The influence of androgen suppression therapy (AST) on bladder cancer (BCa) remains controversial, as recent studies have not reached a consensus regarding the relationship between AST and the incidence or prognosis of BCa.
MATERIALS AND METHODS
We perform an updated systematic review and meta-analysis utilizing the most recent evidence to investigate the potential influence of AST on the incidence and prognosis of BCa. A comprehensive literature search was performed on the PubMed, Medline, Embase, Web of Science, and the Cochrane Library databases to include potentially eligible studies. Hazard ratios (HR) and odds ratios (OR) were used to calculate the incidence and prognosis of BCa.
RESULTS
This meta-analysis included 22 studies with 700,755 participants which investigated the impact of AST on the risk and prognosis of BCa. The pooled results revealed no significant relation between AST and a decreased incidence of BCa (OR: 0.92, 95%CI: 0.77-1.09, P = 0.342). Subgroup analysis reported that patients receiving 5-alpha reductase inhibitors (5-ARIs) exhibited a significantly lower risk of BCa (OR: 0.83, 95%CI: 0.75-0.91, P < 0.001), while androgen deprivation therapy did not show a significant reduction (OR: 1.00, 95%CI: 0.46-2.16, P = 0.995). AST may also significantly improve the recurrence-free survival of patients with BCa (HR: 0.69, 95%CI: 0.50-0.95, P = 0.023). We also detected a significant improvement in OS among BCa patients who received 5-ARIs compared to those without 5-ARIs (HR: 0.82, 95%CI: 0.68-0.99, P = 0.037).
CONCLUSION
No significant correlation was found between AST and a decreased BCa incidence, while 5-ARIs have demonstrated efficacy in reducing BCa occurrence. Moreover, patients who received AST demonstrated improved prognosis.
Topics: Humans; Urinary Bladder Neoplasms; Androgen Antagonists; Incidence; Prognosis; Male
PubMed: 38729866
DOI: 10.1016/j.urolonc.2024.04.014 -
European Urology Focus Sep 2021Bladder cancer demonstrates striking gender-based differences in incidence, with a role for androgens possibly implicated in the development and progression of the... (Review)
Review
CONTEXT
Bladder cancer demonstrates striking gender-based differences in incidence, with a role for androgens possibly implicated in the development and progression of the disease. Emerging preclinical and clinical evidence suggests that there may be a role for antiandrogen therapy in bladder cancer.
OBJECTIVE
This systematic review assessed the current clinical evidence evaluating androgen suppressive therapy (AST) for the treatment or prevention of bladder cancer.
EVIDENCE ACQUISITION
Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, MEDLINE was searched for full-text articles detailing clinical outcomes or incidence of bladder cancer among patients who received AST, defined as gonadotropin-releasing hormone agonists or equivalent, androgen receptor antagonists, or 5-alpha reductase inhibitors.
EVIDENCE SYNTHESIS
A total of 12 studies were included. Five studies focused on prostate cancer patients, with one study in men with lower urinary tract symptoms. Among these studies, a lower incidence of bladder cancer was observed in five, with adjusted risk reduction estimates ranging from 7% to 47%. Six studies evaluating 11 820 bladder cancer patients investigated clinical outcomes among men who received a form of AST. Three out of four studies evaluating recurrence-free survival found a benefit for AST, with adjusted hazard ratios for recurrence of non-muscle-invasive cancer ranging from 0.29 to 0.53. Limitations included large variability in data sources and methodologies, as well as no data on tolerability.
CONCLUSIONS
Current evidence indicates that antiandrogen therapies exert a favorable influence on bladder tumors. Further prospective studies are needed to assess their therapeutic potential.
PATIENT SUMMARY
Androgen suppressive therapy is commonly prescribed for the treatment of prostate-related problems. Prior research indicates that there may be a role for these treatments in patients with bladder cancer. In this review, we evaluate the current evidence that strongly suggests that these agents may be effective against bladder cancer.
Topics: 5-alpha Reductase Inhibitors; Androgen Antagonists; Androgens; Carcinoma in Situ; Humans; Male; Prostatic Neoplasms; Urinary Bladder Neoplasms
PubMed: 33132108
DOI: 10.1016/j.euf.2020.10.002 -
Frontiers in Oncology 2021The purpose of this study was to summarize the existing evidence and develop a comprehensive systematic review of the impact of androgen suppression therapy (AST) on the...
PURPOSE
The purpose of this study was to summarize the existing evidence and develop a comprehensive systematic review of the impact of androgen suppression therapy (AST) on the incidence or clinical outcomes of bladder cancer.
METHODS
We systematically searched the PubMed and Embase databases from inception to June 20, 2021 to identify all observational studies examining the incidence or clinical outcomes of bladder cancer in patients who received AST. AST is defined as the use of 5-alpha reductase inhibitors (5-ARIs) or androgen deprivation therapy (ADT).
RESULTS
A total of 18 observational studies were included. Our results showed that AST was not significantly associated with a reduced risk of BCa incidence (OR: 0.92, 95% CI: 0.68-1.24) compared with the lack of AST. The subgroup analysis revealed that finasteride use was significantly associated with a reduction in the risk of BCa incidence (OR: 0.75, 95% CI: 0.64-0.88). Recurrence-free survival (RFS) was improved among AST users compared with nonusers (HR: 0.68, 95% CI: 0.48-0.95), while no significant difference between AST users versus nonusers was identified for cancer-specific survival (CSS), overall survival (OS) or progression-free survival (PFS).
CONCLUSION
Current evidence indicates that therapy with finasteride may represent a potential strategy aimed at reducing BCa incidence. Moreover, AST has a beneficial effect on the recurrence of bladder cancer. Further well-designed randomized trials or cohort studies with better characterized study populations are needed to validate our preliminary findings.
SYSTEMATIC REVIEW REGISTRATION
International Prospective Register of Systematic Reviews database [https://www.crd.york.ac.uk/PROSPERO/], identifier CRD42021261685.
PubMed: 34970495
DOI: 10.3389/fonc.2021.784627 -
Scandinavian Journal of Urology Jun 2016Objective Primary androgen deprivation therapy (ADT) remains the gold standard in the management of patients with advanced prostate cancer (PCa). ADT relieves symptoms... (Review)
Review
Objective Primary androgen deprivation therapy (ADT) remains the gold standard in the management of patients with advanced prostate cancer (PCa). ADT relieves symptoms and reduces tumor burden, but it has never been demonstrated to increase either PCa-specific or overall survival per se. Several trials have challenged this dogma. The aim of this study was to evaluate how endocrine therapy (ET) affects survival in different clinical settings of PCa. Materials and methods A review of published phase II, III and IV studies evaluating the effect of ET on survival was performed. Results In localized and locally advanced non-metastatic PCa, neoadjuvant ET before radical prostatectomy has no effect on survival. Neoadjuvant and adjuvant ET in combination with curatively intended radiotherapy results in PCa-specific and overall survival benefit, although the duration of ET remains under debate. In N + disease, the timing of ET is under debate, although data suggest that early ET is associated with decreased PCa-specific and overall mortality. In M + disease, no proper randomized trials have been performed in patients with newly diagnosed M1 disease. In metastatic castration-resistant PCa, two novel endocrine agents have been proven to increase overall survival significantly compared to placebo. Conclusions ET has never been proven to increase survival in newly diagnosed metastatic PCa in a randomized clinical trial. Nonetheless, a number of trials supports that ET with proper timing, sequencing and in combination with other therapeutic modalities increases survival in several stages of PCa.
Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Clinical Trials as Topic; Humans; Male; Orchiectomy; Prostatic Neoplasms; Survival Rate
PubMed: 26907159
DOI: 10.3109/21681805.2016.1142472 -
BMJ Open Nov 2015To evaluate efficacy and safety of gonadotropin-releasing hormone (GnRH) antagonists compared to standard androgen suppression therapy for advanced prostate cancer. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To evaluate efficacy and safety of gonadotropin-releasing hormone (GnRH) antagonists compared to standard androgen suppression therapy for advanced prostate cancer.
SETTING
The international review team included methodologists of the German Cochrane Centre and clinical experts.
PARTICIPANTS
We searched CENTRAL, MEDLINE, Web of Science, EMBASE, trial registries and conference books for randomised controlled trials (RCT) for effectiveness data analysis, and randomised or non-randomised controlled studies (non-RCT) for safety data analysis (March 2015). Two authors independently screened identified articles, extracted data, evaluated risk of bias and rated quality of evidence according to GRADE.
RESULTS
13 studies (10 RCTs, 3 non-RCTs) were included. No study reported cancer-specific survival or clinical progression. There were no differences in overall mortality (RR 1.35, 95% CI 0.63 to 2.93), treatment failure (RR 0.91, 95% CI 0.70 to 1.17) or prostate-specific antigen progression (RR 0.83, 95% CI 0.64 to 1.06). While there was no difference in quality of life related to urinary symptoms, improved quality of life regarding prostate symptoms, measured with the International Prostate Symptom Score (IPSS), with the use of GnRH antagonists compared with the use of standard androgen suppression therapy (mean score difference -0.40, 95% CI -0.94 to 0.14, and -1.84, 95% CI -3.00 to -0.69, respectively) was found. Quality of evidence for all assessed outcomes was rated low according to GRADE. The risk for injection-site events was increased, but cardiovascular events may occur less often by using GnRH antagonist. Available evidence is hampered by risk of bias, selective reporting and limited follow-up.
CONCLUSIONS
There is currently insufficient evidence to make firm conclusive statements on the efficacy of GnRH antagonist compared to standard androgen suppression therapy for advanced prostate cancer. There is need for further high-quality research on GnRH antagonists with long-term follow-up.
TRIAL REGISTRATION NUMBER
CRD42012002751.
Topics: Androgen Antagonists; Gonadotropin-Releasing Hormone; Humans; Male; Outcome Assessment, Health Care; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Treatment Failure
PubMed: 26567252
DOI: 10.1136/bmjopen-2015-008217 -
The Aging Male : the Official Journal... Dec 2022The aim of the meta-analysis was to explore effects of resistance exercise (RE) on body composition and physical function in patients with prostate cancer (PCa). (Meta-Analysis)
Meta-Analysis
The effects of resistance exercise on body composition and physical function in prostate cancer patients undergoing androgen deprivation therapy: an update systematic review and meta-analysis.
OBJECTIVE
The aim of the meta-analysis was to explore effects of resistance exercise (RE) on body composition and physical function in patients with prostate cancer (PCa).
DATA SOURCES
We searched the electronic databases of Pubmed, Embase, Cochrane, and web of science. Published studies have been collected from these databases. Search terms include RE PCa, with a deadline of 31 March 2022.
MAIN RESULTS
These studies showed significant improvements of body composition(Lean body mass MD: 1.12 95% CI [0.48, 1.76], < 0.01; Body fat rate MD: -1.12 95% CI [-1.99,-0.24], < 0.05; Appendicular skeletal mass MD: 0.74 95% CI [0.45, 1.03], < 0.01) and physical function (leg press MD: 77.95 95% CI [38.90, 117.00], < 0.01; stair climb MD:-0.30 95% CI [-0.49, -0.12], < 0.01). In addition, the improvement of Body fat mass (MD: -0.21 95% CI [-0.79, 0.37], > 0.05), 400 m walk (MD: -21.74 95% CI [-45.53, 2.05], > 0.05) and times up and go (MD: -0.50 95% CI [-1.03, 0.03], > 0.05) were not obvious. Subgroup analyses showed that RE for ≥ 6 months (compared with RE intervention for < 6 months) and starting exercise immediately after androgen deprivation therapy (ADT) (compared with delayed exercise after ADT) resulted in more significant improvements in body composition. Furthermore, the results showed that the exercise intensity of 8-12 RM significantly improved body composition.
CONCLUSIONS
RE seems to be a promising approach in order to improve body composition and physical function in PCa patients to offset their treatment-related side effects. RE should be used as a means of rehabilitation and care for PCa. Starting exercise immediately after ADT and extending exercise time while choosing the right intensity can better improve the patients' body composition and function.
REGISTRATION NUMBER
INPLASY202280019.
Topics: Male; Humans; Androgen Antagonists; Resistance Training; Prostatic Neoplasms; Androgens; Body Composition; Exercise Therapy
PubMed: 36382930
DOI: 10.1080/13685538.2022.2146670 -
Endokrynologia Polska 2015Chronic psychological distress can cause suppression of the hypothalamic-pituitary-testicular axis and thus lead to male hypogonadism, which is associated with... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Chronic psychological distress can cause suppression of the hypothalamic-pituitary-testicular axis and thus lead to male hypogonadism, which is associated with psycho-social dysfunction, chronic diseases, and as a result, considerable economic costs. Conversely, noise is a prototypal environmental stressor of growing importance, already linked to birth outcomes and diabetes. However, its effects on male testosterone levels have been paid little attention.
MATERIAL AND METHODS
This paper reports a systematic review and meta-analysis of experimental studies in rodents, which have examined the effect of chronic noise stress on serum testosterone levels. A systematic search in MEDLINE, EMBASE and the Internet yielded seven studies. A quality effects meta-analytical model was applied to compute pooled Hedges's g. Quality effects meta-regression was carried out as well.
RESULTS
We found pooled Hedges's g of -2.41 (95% CI: -3.28, -1.54), indicating a very large effect of noise exposure on testosterone. Metaregression confirmed that the overall duration of exposure explained a significant proportion of the variance across individual effect sizes (Q (1) = 3.95, p = 0.047). However, there was considerable inter-study heterogeneity (I2 = 82%) and publication bias (p = 0.016). After inputting two studies previously thought to be missing, the pooled effect dropped to g = -1.53 (95% CI: -3.01, -0.05).
CONCLUSIONS
Chronic noise exposure of ≈ 100 dB leads to a significant reduction of serum testosterone in male rodents. Research on humans is highly warranted, especially given the steady trend in Western societies for increasing the burden of both male hypogonadism and noise pollution.
Topics: Animals; Biomarkers; Noise; Rodent Diseases; Rodentia; Stress, Physiological; Testosterone
PubMed: 25754280
DOI: 10.5603/EP.2015.0007 -
Minerva Urologica E Nefrologica = the... Aug 2018Androgen-deprivation therapy (ADT) administered in neoadjuvant setting before radical prostatectomy (RP) represents an ideal in vivo human model to test the efficacy of... (Review)
Review
INTRODUCTION
Androgen-deprivation therapy (ADT) administered in neoadjuvant setting before radical prostatectomy (RP) represents an ideal in vivo human model to test the efficacy of hormonal treatments in prostate cancer (PCa). This review summarizes the findings from published studies specifically focused on the biological effects of ADT assessed on specimens from RP. The aim is to provide a base of knowledge that might be used to design future studies on neoadjuvant therapy for PCa.
EVIDENCE ACQUISITION
A systematic review of the literature was performed according to the PRISMA statements. Search protocol identified published studies including a detailed analysis on specimen from RP to assess the biological effects of neoadjuvant ADT. In November 2017, Medline, Embase, and Scopus databases were searched using the terms "neoadjuvant" AND ("hormone therapy" OR "androgen deprivation therapy") AND "prostate cancer" in the "Title/Abstract" fields. Effects of ADT were classified according to four pathways - suppression of cellular proliferation, induction of apoptosis, alteration of immune response and onset of hormonal refractoriness - and relative markers of response were identified.
EVIDENCE SYNTHESIS
From 1856 papers initially retrieved, 19 studies were finally selected and included into the present review. ADT was constituted by luteinizing hormone-releasing hormone (LH-RH) agonist alone in two, peripheral anti-androgen alone in one, both in 10, abiraterone acetate in one, unspecified in five. According to the above-mentioned four pathways, the following markers of response were identified: transcription of the oncogene TMPRSS2:ERG, translation of Aurora-A, coding of β1C integrin gene, translation of Ki-67, expression of nerve growth factors TrkA and p75NGFR, anti-angiogenic activity and micro-vessel density were involved into suppression of proliferation; mRNA transcription of bcl-2, expression of cleaved caspase-3 and translation of insulin growth factor binding protein 3, into induction of apoptosis; expression of IL-7 gene, programmed death-ligand 1, and increase of intra-prostatic T-cell population were related to alteration of immune response; finally, expression of heat shock protein 27 and de-differentiation of PCa to neuroendocrine cells, influenced the onset of hormonal refractoriness.
CONCLUSIONS
Despite a potential high interest, unexpectedly, only 19 heterogeneous studies investigated the effects of ADT through the analysis of specimens from RP. The present review summarizes the available evidences on this topic showing that ADT interferes on PCa at different levels that can be investigated by specific biological markers.
Topics: Androgen Antagonists; Humans; Male; Neoadjuvant Therapy; Orchiectomy; Prostate; Prostatectomy; Prostatic Neoplasms; Treatment Outcome
PubMed: 29392925
DOI: 10.23736/S0393-2249.18.03022-9