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Current Oncology (Toronto, Ont.) Dec 2022In recent years, significant changes have occurred in metastatic hormone-sensitive prostate cancer (mHSPC) management, where docetaxel and new androgen receptor pathway... (Meta-Analysis)
Meta-Analysis
Addition of New Androgen Receptor Pathway Inhibitors to Docetaxel and Androgen Deprivation Therapy in Metastatic Hormone-Sensitive Prostate Cancer: A Systematic Review and Metanalysis.
In recent years, significant changes have occurred in metastatic hormone-sensitive prostate cancer (mHSPC) management, where docetaxel and new androgen receptor pathway inhibitors (ARPI) have been shown to improve overall survival (OS) compared to androgen deprivation therapy (ADT). Recent data could once again radically change mHSPC treatment. PEACE-1 and ARASENS trials demonstrated a survival benefit of the addition of ARPI to docetaxel and ADT combination (triplet therapy), compared to docetaxel and ADT. With multiple options to choose from, it is crucial to identify the patients who would benefit most from triplet therapy. In this meta-analysis, we evaluated the activity of the triplet therapy versus docetaxel plus ADT in mHSPC. A systematic review of PubMed/Medline, Embase, and the proceedings of major international meetings was performed. Five RCTs fulfilled the inclusion criteria. PEACE-1 and ARASENS studies reported disease-free survival (DFS) and OS. Post hoc analysis of three other trials evaluated the combination of ARPI, docetaxel and ADT. Globally, 2538 patients were included (1270 triplet therapy; 1268 docetaxel + ADT). Triplet therapy was associated with improved OS (hazard ratio (HR) 0.74; 95% confidence interval (CI), 0.66-0.83, < 0.00001). A statistically significant benefit was shown in high-volume mHSPC patients (HR 0.76; 95% CI 0.59-0.97, = 0.03) and in patients with de novo metastatic disease (HR 0.73; 95% CI, 0.64-0.82, < 0.00001). The addition of ARPI to standard therapy was associated with DFS improvement (HR 0.41; 95% CI, 0.35-0.49, < 0.00001). This metanalysis shows a significant OS benefit from concomitant administration of ARPI, docetaxel and ADT in high volume and de novo mHSPC.
Topics: Humans; Male; Androgens; Docetaxel; Prostatic Neoplasms; Androgen Receptor Antagonists; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36547161
DOI: 10.3390/curroncol29120747 -
International Journal of Molecular... Dec 2022Hidradenitis suppurativa (HS) is a chronic inflammatory disease manifesting in inverse body regions. In a systematic review, the role of hormones in HS will be presented... (Review)
Review
Hidradenitis suppurativa (HS) is a chronic inflammatory disease manifesting in inverse body regions. In a systematic review, the role of hormones in HS will be presented to better understand the pathomechanisms of HS. The review is based on the PRISMA criteria. Systematic research was carried out using keywords. Subsequently, the data were analyzed based on the clinical response and other relevant information. The main focus of our systematic review was on HS manifestation, exacerbation, sex hormones, antiandrogen therapy, thyroid function, polycystic ovary syndrome, insulin resistance, and adipokines. In HS, there appears to be a dysregulated adipokine release that is shifted towards pro-inflammatory adipokines. Insulin resistance is significantly more common in HS than in healthy patients regardless of BMI, age, and gender. Insulin resistance in HS patients leads to further cardiovascular disease. The mechanism of insulin resistance and role of adipokines should be investigated in future studies to better provide the pathomechanisms of HS. The role of androgens seems to be important in a certain subgroup of female patients. Anti-androgenic therapy can be useful and helpful in some patients. However, further studies are needed to better understand the hormonal relationship in HS.
Topics: Humans; Female; Insulin Resistance; Hidradenitis Suppurativa; Androgens; Gonadal Steroid Hormones; Androgen Antagonists
PubMed: 36499573
DOI: 10.3390/ijms232315250 -
JAMA Network Open Nov 2022Epidemiological evidence supports a role for statins in improving survival in advanced prostate cancer, particularly among men receiving androgen-ablative therapies. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Epidemiological evidence supports a role for statins in improving survival in advanced prostate cancer, particularly among men receiving androgen-ablative therapies.
OBJECTIVE
To study the association between statin use and survival among men with prostate cancer receiving androgen deprivation therapy (ADT) or androgen receptor axis-targeted therapies (ARATs).
DATA SOURCES
This systemic review and meta-analysis used sources from MEDLINE, EMBASE, Epub Ahead of Print, Cochrane Clinical Trials, Cochrane Systematic Reviews, and Web of Science from inception to September 6, 2022.
STUDY SELECTION
Observational studies reporting associations of concurrent statin use and survival outcomes (in hazard ratios [HRs]).
DATA EXTRACTION AND SYNTHESIS
Two authors independently abstracted all data. Summary estimates pooled multivariable HRs with 95% CIs using the generic inverse variance method with random-effects modeling. A priori specified subgroup and sensitivity analyses were undertaken, and heterogeneity, study quality, and publication bias were evaluated. Confidence in the evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.
MAIN OUTCOMES AND MEASURES
Overall mortality and prostate cancer-specific mortality (PCSM).
RESULTS
Twenty-five cohorts of 119 878 men (65 488 statin users [55%]) with more than 74 416 deaths were included. Concurrent statin use was associated with a 27% reduction in the risk of overall mortality (HR, 0.73 [95% CI, 0.66-0.82]; I2 = 83%) and a 35% reduction in the risk of PCSM (HR, 0.65 [95% CI, 0.58-0.73]; I2 = 74%), with substantial heterogeneity in both estimates. Subgroup analyses identified a PCSM advantage associated with statins for men receiving ARATs compared with ADT alone (HR, 0.40 [95% CI, 0.30-0.55] vs 0.68 [95% CI, 0.60-0.76]; P = .002 for difference). Confidence in the evidence was rated low for both outcomes.
CONCLUSIONS AND RELEVANCE
The findings of this meta-analysis show that concurrent statin use was associated with reduced overall mortality and PCSM among men receiving androgen-ablative therapies for advanced prostate cancer. These findings are limited by the observational nature of the data and residual unexplained interstudy heterogeneity. Randomized clinical trials are warranted to validate these results.
Topics: Male; Humans; Prostatic Neoplasms; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Androgens; Androgen Antagonists; Hormone Replacement Therapy
PubMed: 36449294
DOI: 10.1001/jamanetworkopen.2022.42676 -
Progres En Urologie : Journal de... Dec 2022Male gender has been shown to be a risk factor for COVID-19 infection, and men are more likely to develop severe disease. The aim of this study was to evaluate the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Male gender has been shown to be a risk factor for COVID-19 infection, and men are more likely to develop severe disease. The aim of this study was to evaluate the effect of androgen deprivation therapy (ADT) on the incidence of infection and severity of SARS-CoV-2 in prostate cancer patients.
METHODS
A systematic review and meta-analysis were performed after searching PubMed, Scopus, and ClinicalTrial.org databases, between January 2020 and March 2022. Analyses were interpreted through forest plots for the following parameters: risk of infection, hospitalization, intensive care admission, and SARS-CoV-2-related death, with random or fixed-effects models.
RESULTS
Fifteen articles were included in the systematic review and ten in the meta-analysis. Seven studies evaluated risk of infection in patients on ADT: OR=1.11 (95 % IC : [0.48-2.58] ; P=0.81). Six studies evaluated the risk of hospitalization in patients on ADT: TDA : OR=1.58 (95 % IC : [0.94-2.64] ; P=0.08). Seven studies evaluated risk of ICU admission in patients on ADT: OR=0.90 (95 % IC : [0.71-1.13] ; P=0.37). Nine studies evaluated mortality risk in patients on ADT: OR=1.07 (95 % IC : [0.61-1.87] ; P=0.82).
CONCLUSION
ADT does not protect against SARS-CoV-2 in prostate cancer patients, nor does it protect against hospitalization, ICU admission, or mortality. These results remain questionable given the retrospective nature of the majority of studies included in our meta-analysis.
Topics: Humans; Male; Androgen Antagonists; Prostatic Neoplasms; Androgens; COVID-19; Retrospective Studies; SARS-CoV-2; Risk Factors
PubMed: 36163317
DOI: 10.1016/j.purol.2022.09.005 -
ESMO Open Oct 2022Androgen-deprivation therapy (ADT) historically represented the milestone for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). Recently, combining... (Meta-Analysis)
Meta-Analysis Review
Addition of androgen receptor-targeted agents to androgen-deprivation therapy and docetaxel in metastatic hormone-sensitive prostate cancer: a systematic review and meta-analysis.
BACKGROUND
Androgen-deprivation therapy (ADT) historically represented the milestone for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). Recently, combining androgen receptor-targeted agents (ARTA) or docetaxel with ADT significantly improved clinical outcomes in this setting. The efficacy of the combined use of an ARTA with docetaxel and ADT (triplet), however, was unknown, and often conflicting data derived from subgroup analysis of randomized phase III trials. In order to better define the benefits and risks of the triplet in mHSPC, we carried out a systematic review and meta-analysis of available clinical trials.
METHODS
A literature search with no data restriction using Medline/PubMed, the Cochrane Library, and American Society of Clinical Oncology/European Society for Medical Oncology (ASCO/ESMO) Meeting abstracts was carried out up to April 2022. The meta-analysis was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statements. Overall survival (OS) was the primary endpoint; progression-free survival (PFS) and safety were secondary endpoints. For OS and PFS, summary hazard ratios (HRs) were calculated; for safety, risk ratio (RR) was assessed. Random- or fixed-effects models were used, depending on studies heterogeneity.
RESULTS
Five randomized clinical trials fulfilled the prespecified inclusion criteria. The triplet significantly improved OS (fixed-effect, HR = 0.74; P < 0.00001) and PFS (fixed-effect; HR = 0.50 for clinical PFS, HR = 0.49 for radiological PFS; P < 0.0001) compared with docetaxel plus ADT. We did not show heterogeneity between treatment efficacy and the disease burden, metachronous versus synchronous presentation, concomitant versus sequential strategy. Compared with docetaxel + ADT, the triplet did not increase the risk of adverse events (AEs) (RR = 1.00, P = 0.27 for any-grade AEs; RR = 1.13, P = 0.14 for severe AEs), except for severe hypertension (RR = 1.73, P = 0.001).
CONCLUSIONS
Emerging evidence supports the combination of an ARTA plus docetaxel and ADT in mHSPC patients. Given the availability of several strategies in this setting, clinical characteristics and drug safety profile may help clinicians select the appropriate treatment for mHSPC patients who are more likely to benefit from treatment intensification.
Topics: Male; Humans; Docetaxel; Androgen Antagonists; Prostatic Neoplasms; Androgens; Receptors, Androgen; Antineoplastic Combined Chemotherapy Protocols; Antineoplastic Agents
PubMed: 36152486
DOI: 10.1016/j.esmoop.2022.100575 -
European Urology Dec 2022Recent randomized controlled trials (RCTs) examined the role of adding androgen receptor signaling inhibitors (ARSIs), including abiraterone acetate (ABI), apalutamide,... (Meta-Analysis)
Meta-Analysis Review
Androgen Receptor Signaling Inhibitors in Addition to Docetaxel with Androgen Deprivation Therapy for Metastatic Hormone-sensitive Prostate Cancer: A Systematic Review and Meta-analysis.
CONTEXT
Recent randomized controlled trials (RCTs) examined the role of adding androgen receptor signaling inhibitors (ARSIs), including abiraterone acetate (ABI), apalutamide, darolutamide (DAR), and enzalutamide (ENZ), to docetaxel (DOC) and androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC).
OBJECTIVE
To analyze the oncologic benefit of triplet combination therapies using ARSI + DOC + ADT, and comparing them with available treatment regimens in patients with mHSPC.
EVIDENCE ACQUISITION
Three databases and meetings abstracts were queried in April 2022 for RCTs analyzing patients treated with first-line combination systemic therapy for mHSPC. The primary interests of measure were overall survival (OS) and progression-free survival (PFS). Subgroup analyses were conducted to assess the differential outcomes in patients with low- and high-volume disease as well as de novo and metachronous metastasis.
EVIDENCE SYNTHESIS
Overall, 11 RCTs were included for meta-analyses and network meta-analyses (NMAs). We found that the triplet combinations outperformed DOC + ADT in terms of OS (pooled hazard ratio [HR]: 0.74, 95% confidence interval [CI]: 0.65-0.84) and PFS (pooled HR: 0.49, 95% CI: 0.42-0.58). There was no statistically significant difference between patients with low- and high-volume disease in terms of an OS benefit from adding an ARSI to DOC +ADT (both HR: 0.79; p = 1). Based on NMAs, triplet therapy also outperformed ARSI + ADT in terms of OS (DAR + DOC + ADT: pooled HR: 0.74, 95% CI: 0.55-0.99) and PFS (ABI + DOC + ADT: HR: 0.68, 95% CI: 0.51-0.91, and ENZ + DOC + ADT: HR: 0.70, 95% CI: 0.53-0.93). An analysis of treatment ranking among de novo mHSPC patients showed that triplet therapy had the highest likelihood of improved OS in patients with high-volume disease; however, doublet therapy using ARSI + ADT had the highest likelihood of improved OS in patients with low-volume disease.
CONCLUSIONS
We found that the triplet combination therapy improves survival endpoints in mHSPC patients compared with currently available doublet treatment regimens. Our findings need to be confirmed in further head-to-head trials with longer follow-up and among various patient populations.
PATIENT SUMMARY
Our study suggests that triplet therapy with androgen receptor signaling inhibitor, docetaxel, androgen deprivation therapy prolongs survival in patients with metastatic hormone-sensitive prostate cancer compared with the current standard doublet therapy.
Topics: Humans; Male; Docetaxel; Androgen Antagonists; Androgens; Receptors, Androgen; Antineoplastic Combined Chemotherapy Protocols; Prostatic Neoplasms
PubMed: 35995644
DOI: 10.1016/j.eururo.2022.08.002 -
Clinical & Experimental Metastasis Dec 2022Androgen deprivation therapy (ADT) is the standard treatment of metastatic prostate cancer (PCa). However, metastases-directed therapies can delay the initiation or...
Androgen deprivation therapy (ADT) is the standard treatment of metastatic prostate cancer (PCa). However, metastases-directed therapies can delay the initiation or switch of systemic treatments and allow local control (LC) and prolonged progression-free survival (PFS), particularly in patients with lymph nodes (LN) oligometastases. We performed a systematic review on stereotactic body radiotherapy (SBRT) in this setting. Papers reporting LC and/or PFS were selected. Data on ADT-free survival, overall survival, and toxicity were also collected from the selected studies. Fifteen studies were eligible (414 patients), 14 of them were retrospective analyses. A high heterogeneity was observed in terms of patient selection and treatment. In one study SBRT was delivered as a single 20 Gy fraction, while in the others the median total dose ranged between 24 and 40 Gy delivered in 3-6 fractions. LC and PFS were reported in 15 and 12 papers, respectively. LC was reported as a crude percentage in 13 studies, with 100% rate in seven and 63.2-98.0% in six reports. Five studies reported actuarial LC (2-year LC: 70.0-100%). PFS was reported as a crude rate in 11 studies (range 27.3-68.8%). Actuarial 2-year PFS was reported in four studies (range 30.0-50.0%). SBRT tolerability was excellent, with only two patients with grade 3 acute toxicity and two patients with grade 3 late toxicity. SBRT for LN oligorecurrences from PCa in safe and provides optimal LC. However, the long-term effect on PFS and OS is still unclear as well as which patients are the best candidate for this approach.
Topics: Humans; Male; Androgen Antagonists; Prostatic Neoplasms; Radiosurgery; Retrospective Studies; Treatment Outcome
PubMed: 35980556
DOI: 10.1007/s10585-022-10183-6 -
Journal of Korean Medical Science Aug 2022Several cohort studies have explored the relationship between androgen deprivation therapy (ADT) and the severity of coronavirus disease 2019 (COVID-19). This study... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several cohort studies have explored the relationship between androgen deprivation therapy (ADT) and the severity of coronavirus disease 2019 (COVID-19). This study aimed to characterize the relationship between ADT and the severity of COVID-19 in patients with prostate cancer.
METHODS
A systematic search was conducted using PubMed, Embase, and Cochrane Library databases from the inception of each database until February 31, 2020. Patients with prostate cancer who were treated with ADT were assigned to treatment group while those patients who were not treated with ADT were assigned to the control group. Outcomes were severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) positivity, hospitalization, intensive care unit (ICU) admission, and death. The risk of bias was evaluated using ROBINS-I (Risk Of Bias In Non-randomized Studies of Interventions) tool.
RESULTS
Three studies with qualitative synthesis were included. Finally, two studies with quantitative synthesis having a total of 44,213 patients were included for the present systematic review. There was no significant difference in SARS-CoV-2 positive rate (odds ratio [OR], 0.52; 95% confidence intervals [Cis], 0.13-2.09; = 0.362), hospitalization (OR, 0.52; 95% CIs, 0.07-3.69; = 0.514), ICU admission (OR, 0.93; 95% CIs, 0.39-2.23, = 0.881), or death (OR, 0.88; 95% CIs, 0.06-12.06; = 0.934) between ADT and non-ADT groups.
CONCLUSION
Qualitative and quantitative analyses of previous studies revealed no significant effect of ADT on COVID-19. However, more studies with higher quality that explore biochemical and immunological factors involved are needed to confirm this finding in the future.
Topics: Androgen Antagonists; Androgens; COVID-19; Humans; Male; Prostatic Neoplasms; SARS-CoV-2
PubMed: 35942555
DOI: 10.3346/jkms.2022.37.e237 -
Cureus Jun 2022The purpose of this study was to investigate the relationship between androgen deprivation therapy (ADT) and cardiovascular events in men with prostate cancer.... (Review)
Review
The purpose of this study was to investigate the relationship between androgen deprivation therapy (ADT) and cardiovascular events in men with prostate cancer. Cardiovascular disease (CVD) is a primary cause of noncancer mortality in men with prostate cancer. Surveillance, Epidemiology, and End Results (SEER) Medicare-linked data revealed that CVD was responsible for about a quarter of deaths among men with prostate cancer, with a focus on the role of ADT as a contributing cause. We performed a literature search in November 2021 utilizing search engines such as PubMed, Scopus, Science Direct, and Google Scholar. Original publications with data published between 2006 and 2020 were used in the investigation of men with prostate cancer undergoing ADT treatment with a CVD outcome. Two reviewers independently examined the content of the studies and extracted data from the final papers after they had been validated for quality using quality assessment tools. A total of 14 observational studies and two randomized controlled trials are included in this systematic review. Sample sizes in the examined publications varied from 79 to 201,797 individuals. ADT was the intervention in all of the investigations. Seven of the included studies did not identify the type of ADT utilized; instead, they compared the outcomes of individuals who got ADT against those who did not. The specific type of ADT used is mentioned in the remaining nine studies included in the systematic review. Patients who got ADT, such as gonadotropin-releasing hormone (GnRH) agonists, combination androgen blockade, surgical castration, and oral anti-androgen, are compared to those who did not receive ADT to discover who had a better prognosis. In conclusion, even though ADT has several negative metabolic side effects that increase the risk of cardiovascular toxicity, published research utilizing a variety of designs has demonstrated inconsistency in the impact of ADT on cardiovascular outcomes. While the risk of CVD should be considered when prescribing ADT, the findings suggest that it should not be considered a contraindication if the expected benefit is substantial.
PubMed: 35891816
DOI: 10.7759/cureus.26209 -
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