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Frontiers in Oncology 2023Olaparib has been proven for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This meta-analysis aims to comprehensively evaluate the efficacy...
Efficacy and safety of olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Olaparib has been proven for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This meta-analysis aims to comprehensively evaluate the efficacy and safety of the combination of olaparib and abiraterone in patients with mCRPC.
METHODS
The literature in PubMed, Embase, and Cochrane Library up until April 27, 2023, was systematically searched. In the studies included in this meta-analysis, olaparib combined with abiraterone was compared with abiraterone combined with placebo.
RESULTS
Two randomized controlled trials involving a total of 938 patients were included. Analysis indicated that olaparib combined with abiraterone significantly prolonged radiographic progression-free survival (rPFS: relative risk [RR] 0.66, 95% confidence interval [CI] 0.55-0.79), time to secondary progression or death (PFS2: hazard ratio [HR] 0.72, 95% CI 0.56-0.93), time to first subsequent therapy or death (TFST: HR 0.75, 95% CI 0.63-0.89), time to second subsequent therapy or death (TSST: HR 0.73, 95% CI 0.58-0.93), and confirmed prostate-specific antigen (PSA) response (RR 1.14, 95% CI 1.05-1.24). However, no statistically significant differences were found in the overall survival (OS: HR 0.87 95% CI 0.70-1.09), objective response rate (ORR: RR 0.97, 95% CI 0.70-1.33), and incidence of total adverse events (RR 1.07, 95% CI 0.94-1.22). A notable detail that the combination of olaparib and abiraterone was associated with an increased incidence of high-grade anemia (RR 7.47, 95% CI 1.36-40.88).
CONCLUSION
Olaparib combined with abiraterone is effective for patients with mCRPC. However, combination therapy has treatment-related adverse events compared with monotherapy, and this could be improved in future treatment management.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023432287.
PubMed: 37869079
DOI: 10.3389/fonc.2023.1265276 -
Supportive Care in Cancer : Official... Jul 2022The impact of prostate cancer on the mental wellbeing of patients is increasingly being appreciated. Two important aspects of this include fear of cancer recurrence... (Review)
Review
PURPOSE
The impact of prostate cancer on the mental wellbeing of patients is increasingly being appreciated. Two important aspects of this include fear of cancer recurrence (FCR) and prostate-specific antigen (PSA) anxiety. However, their prevalence, severity and associating factors remain poorly understood. Therefore, this review aims to evaluate the current evidence for the prevalence, severity and associating features of PSA anxiety and FCR.
METHODS
A systematic search of MEDLINE, EMBASE and PsycINFO databases was conducted by two independent reviewers. Observational studies measuring FCR and PSA anxiety in prostate cancer using validated measures were included. Outcome measures were prevalence of significant levels, mean scores and significant correlations of FCR and PSA anxiety scores with patient, disease, treatment or other mental health and quality of life outcomes.
RESULTS
One thousand one hundred forty-eight individual records underwent screening with 32 studies included. Median prevalence of significant FCR and PSA anxiety was 16% and 22% respectively across all studies. Longitudinal studies demonstrated severity of both symptoms peaks at diagnosis, with little variability, even several years following this. Evaluating associating factors revealed younger age, generalised quality of life and mental health symptoms to be important factors for both outcomes. Few studies evaluated associations and differences between other patient, disease and treatment characteristics.
CONCLUSION
FCR and PSA anxiety are prominent symptoms for prostate cancer patients and importantly when present, are associated with poorer quality of life and mental health symptoms. Screening for these constructs and referral to appropriate services should form part of routine follow-up care.
Topics: Anxiety; Fear; Humans; Male; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life
PubMed: 35106656
DOI: 10.1007/s00520-022-06876-z -
Frontiers in Endocrinology 2023Second-generation androgen receptor inhibitors (ARIs) have been developed and approved for treating castration-resistant prostate cancer (CRPC). There is a lack of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Second-generation androgen receptor inhibitors (ARIs) have been developed and approved for treating castration-resistant prostate cancer (CRPC). There is a lack of direct comparison of the therapeutic effects and adverse events between the conventional ARI (bicalutamide) and three second-generation ARIs (enzalutamide, apalutamide and darolutamide).
METHODS
Our network meta-analysis evaluated therapeutic effects and adverse events of the conventional ARI (bicalutamide) and the second-generation ARIs in treating CRPC. We systematically searched the Pubmed, Cochrane library and Embase databases for studies published until October 2022 and only randomized clinical trials (RCTs) were included. The progression-free survival, prostate-specific antigen (PSA) progression-free survival, overall survival (PFS/PSA-PFS/OS), PSA response rate and relative adverse events (AEs) of CRPC patients were collected and synthesized. We then performed subgroup analysis. The non-metastatic and metastatic CRPC (nm/mCRPC) observations were analyzed separately. Data analyses were performed using R software (4.2.1) based on Bayesian framework.
RESULTS
6,993 subjects from seven eligible RCTs were analyzed. Enzalutamide, apalutamide and darolutamide were more effective than bicalutamide in treating CRPC, and the performance of darolutamide was slightly worse than the other two second-generation ARIs. Similar adverse events rate were observed among the second-generation ARIs and bicalutamide. Apalutamide showed a slightly higher rate of Grade 3+ AEs, percentages of AE-related drug withdrawals and AE-related mortality. Patients receiving enzalutamide had significantly higher rate of hypertension and fatigue. In subgroup analysis, enzalutamide showed better therapeutic effects compared with bicalutamide in both nmCRPC and mCRPC groups. In nmCRPC group, enzalutamide and apalutamide had more benefits on PFS and PSA-PFS compared with darolutamide. We displayed the probability ranking map of PFS, PSA-PFS, OS, time to cytotoxic chemotherapy, PSA response rate and relative AE outcomes.
CONCLUSION
The current network meta-analysis indicated that the second-generation ARIs were superior to the conventional ARI, bicalutamide. The three second-generation ARIs showed incomplete equivalence on CRPC treatment. The darolutamide was slightly less effective compared with enzalutamide and apalutamide. The adverse events of apalutamide were worse than the others, but no statistical significance was observed among these vital AEs. All ARIs were generally well-tolerated. These results may provide reference to clinical decision and further direct comparison trials.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022370842.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen; Prostate-Specific Antigen; Network Meta-Analysis; Treatment Outcome; Androgen Receptor Antagonists
PubMed: 36843606
DOI: 10.3389/fendo.2023.1131033 -
Clinical Nutrition ESPEN Dec 2023Exercise is known to reduce adverse side effects of androgen-deprivation therapy (ADT) on quality of life, bone health and fatigue for prostate cancer (PCa) patients. We... (Meta-Analysis)
Meta-Analysis
Efficacy of multidisciplinary interventions in preventing metabolic syndrome and improving body composition in prostate cancer patients treated with androgen deprivation therapy: A systematic review and meta-analysis.
BACKGROUND
Exercise is known to reduce adverse side effects of androgen-deprivation therapy (ADT) on quality of life, bone health and fatigue for prostate cancer (PCa) patients. We conducted a systematic review with meta-analysis to evaluate the effect of multidisciplinary interventions on body composition and metabolic syndrome (MetS) in ADT-treated PCa patients.
METHODS
A systematic review and meta-analysis were conducted based on searches of EMBASE, MEDLINE, CENTRAL and Scopus databases from inception to March 2023. Participants included ADT-treated PCa patients who received multidisciplinary interventions including exercise, diet, nutrition, pharmacotherapy, bariatric surgery, or psychological/behavioural therapy. Primary outcomes were changes in body composition and MetS, with prostate-specific antigen (PSA) as a secondary outcome. After meta-analysis, results were reported in mean difference, 95% confidence interval and p-value, with forest plots. Additionally, we conducted subgroup analyses to compare the effect of different interventions.
RESULTS
Thirty-three articles met the eligibility criteria out of 1443 articles and 28 studies were included in meta-analysis. Of 33 studies, 17 included exercise-only interventions and 10 included exercise + diet/nutrition interventions, but no studies included diet/nutrition-only interventions. All studies employed multidisciplinary approaches in developing or delivering the interventions. Most studies (85%) had low-moderate risk of bias, thus providing good evidence to this review. Overall, interventions had a positive effect on body composition measures; lean mass (LM):0.82 kg (95% CI:0.47,1.17;p < 0.00001), body fat mass (BFM):-0.68 kg (95% CI:-1.12,-0.24;p = 0.002), fat-free mass:0.75 kg (95% CI:0.14,1.37;p = 0.02) and body fat percentage (BFP):-0.99% (95% CI:-1.29,-0.68;p < 0.00001), as well as on MetS; waist circumference:-1.95 cm (95% CI:-3.10,-0.79;p = 0.0009), systolic blood pressure:-3.43 mmHg (95% CI:-6.36,-0.50;p = 0.02) and diastolic blood pressure:-2.48 mmHg (95% CI:-4.19,-0.76;p = 0.005). Subgroup-analyses showed that a combined approach including exercise + diet/nutrition was most effective in improving BFP, WC, SBP and DBP whereas exercise was more effective in improving LM and BFM.
CONCLUSIONS
In ADT-treated PCa patients, multidisciplinary interventions, especially those combining exercise and diet/nutrition, can improve body composition and metabolic health.
Topics: Male; Humans; Prostatic Neoplasms; Androgen Antagonists; Androgens; Metabolic Syndrome; Quality of Life; Body Composition
PubMed: 38057016
DOI: 10.1016/j.clnesp.2023.09.001 -
Therapeutic Advances in Medical Oncology 2022Several therapies are available for the treatment of advanced/metastatic prostate cancer (PC). However, the systematic assessment of evidence pertaining to the use of... (Review)
Review
OBJECTIVES
Several therapies are available for the treatment of advanced/metastatic prostate cancer (PC). However, the systematic assessment of evidence pertaining to the use of these therapies in Asian patients is lacking.
METHODS
A systematic literature review (SLR) was conducted using PubMed/Medline search in May 2021 to identify the randomized/nonrandomized controlled trials (RCTs/non-RCTs) and real-world observational studies (prospective/retrospective). Only studies published as full manuscripts in English were included if reporting the efficacy, effectiveness, and/or safety of treatments in Asian patients with advanced/metastatic PC.
RESULTS
Of the 1,898 retrieved publications, 24 studies were included. These studies had patients with nonmetastatic castration-resistant PC (n = 2), metastatic castration-sensitive PC ( = 4), and metastatic castration-resistant PC ( = 18). Study designs included RCTs ( = 7), non-RCTs ( = 2), and real-world studies ( = 15). Treatments used in included studies were abiraterone acetate plus prednisone (AAP; = 6), enzalutamide, lutetium-177 prostate-specific membrane antigen (Lu-PSMA; = 4 each), docetaxel ( = 3), apalutamide, radium-223 ( = 2 each), darolutamide, cabazitaxel, and pembrolizumab ( = 1 each). The evidence from RCTs (i.e., ARAMIS, SPARTAN, ARCHES, TITAN, LATITUDE, PREVAIL) demonstrated the clinical benefits of apalutamide, darolutamide, enzalutamide, and AAP in terms of overall, disease-free, and metastasis-free survival in Asian patients. These treatments were reported to be well tolerated, with no new safety signals identified in Asian population. The efficacy and safety profiles in Asian patients were consistent with the overall trial population. Data from real-world studies supported the effectiveness and tolerability of AAP, enzalutamide, radium-223, docetaxel, cabazitaxel, Lu-PSMA, and pembrolizumab in patients with advanced/metastatic PC.
CONCLUSIONS
This SLR of the Asian data on therapies for advanced PC from the pivotal and real-world studies confirms similar efficacy and safety outcomes, consistent with the results from the pivotal clinical trials. These findings will help clinicians make better treatment decisions in clinical practice for patients with advanced/metastatic PC.
PubMed: 36407784
DOI: 10.1177/17588359221131525 -
European Urology Oncology Jun 2024Testing for mutations in Breast Cancer Gene 1/2 (BRCA) has emerged as a novel decision-making tool for clinicians. Patients with metastatic castration-resistant prostate... (Meta-Analysis)
Meta-Analysis Comparative Study Review
Poly (ADP-ribose) Polymerase Inhibitors Have Comparable Efficacy with Platinum Chemotherapy in Patients with BRCA-positive Metastatic Castration-resistant Prostate Cancer. A Systematic Review and Meta-analysis.
CONTEXT
Testing for mutations in Breast Cancer Gene 1/2 (BRCA) has emerged as a novel decision-making tool for clinicians. Patients with metastatic castration-resistant prostate cancer (mCRPC) harboring pathogenic BRCA mutations can benefit from poly (ADP-ribose) polymerase inhibitor (PARPi) and platinum treatments, whereas the impact of the mutation on sensitivity to cabazitaxel and prostate-specific membrane antigen (PSMA)-ligand therapy is currently unknown.
OBJECTIVE
To assess the efficacy of PARPi, platinum, cabazitaxel, and PSMA-ligand therapies in BRCA-positive mCRPC.
EVIDENCE ACQUISITION
Databases were queried in February 2022. We performed data synthesis by using both proportional and individual patient data. For prostate-specific antigen (PSA) response rate (≥50% decrease from baseline [PSA50]) evaluation, we pooled event rates with 95% confidence intervals (CIs). Progression-free (PFS) and overall (OS) survival analyses with individual patient data were performed with the mixed-effect Cox proportional hazard model and single-arm random-effect analysis, providing pooled medians.
EVIDENCE SYNTHESIS
We included 23 eligible studies with 901 BRCA-positive mCRPC patients. PSA50 response rates for PARPi and platinum were 69% (CI: 53-82%), and 74% (CI: 49-90%), respectively. Analyses of OS data showed no difference between PARPi and platinum treatments (hazard ratio: 0.86; CI: 0.49-1.52; p = 0.6). The single-arm OS and PFS analyses revealed similarities among different PARPis; pooled PFS and OS medians were 9.7 mo (CI: 8.1-12.5) and 17.4 mo (CI: 12.7-20.1), respectively.
CONCLUSIONS
Our data revealed that different PARPis were similarly effective in terms of PFS and OS. Moreover, we found that PARPi and platinum therapy were comparable in terms of PSA50 response rate and OS, highlighting that platinum is a valid treatment option for BRCA-positive mCRPC patients. However, prospective interventional studies comparing these agents are essential to provide a higher level of evidence.
PATIENT SUMMARY
In this report, we found that different poly (ADP-ribose) polymerase inhibitors had similar efficacy, and platinum was a valid treatment option in BRCA-positive metastatic castration-resistant prostate cancer patients.
Topics: Humans; Prostatic Neoplasms, Castration-Resistant; Poly(ADP-ribose) Polymerase Inhibitors; Male; Treatment Outcome; BRCA2 Protein; Antineoplastic Agents; Neoplasm Metastasis; BRCA1 Protein
PubMed: 37722977
DOI: 10.1016/j.euo.2023.09.001 -
European Urology Open Science Dec 2022Prostate cancer (PCa) is the second most common type of cancer in men. Individualized risk stratification is crucial to adjust decision-making. A variety of molecular... (Review)
Review
CONTEXT
Prostate cancer (PCa) is the second most common type of cancer in men. Individualized risk stratification is crucial to adjust decision-making. A variety of molecular biomarkers have been developed in order to identify patients at risk of clinically significant PCa (csPCa) defined by the most common PCa risk stratification systems.
OBJECTIVE
The present study aims to examine the effectiveness (diagnostic accuracy) of blood or urine-based PCa biomarkers to identify patients at high risk of csPCa.
EVIDENCE ACQUISITION
A systematic review of the literature was conducted. Medline and EMBASE were searched from inception to March 2021. Randomized or nonrandomized clinical trials, and cohort and case-control studies were eligible for inclusion. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Pooled estimates of sensitivity, specificity, and area under the curve were obtained.
EVIDENCE SYNTHESIS
Sixty-five studies ( = 34 287) were included. Not all studies included prostate-specific antigen-selected patients. The pooled data showed that the Prostate Health Index (PHI), with any cutoff point between 15 and 30, had sensitivity of 0.95-1.00 and specificity of 0.14-0.33 for csPCa detection. The pooled estimates for SelectMDx test sensitivity and specificity were 0.84 and 0.49, respectively.
CONCLUSIONS
The PHI test has a high diagnostic accuracy rate for csPCa detection, and its incorporation in the diagnostic process could reduce unnecessary biopsies. However, there is a lack of evidence on patient-important outcomes and thus more research is needed.
PATIENT SUMMARY
It has been possible to verify that the application of biomarkers could help detect prostate cancer (PCa) patients with a higher risk of poorer evolution. The Prostate Health Index shows an ability to identify 95-100 for every 100 patients suffering from clinically significant PCa who take the test, preventing unnecessary biopsies in 14-33% of men without PCa or insignificant PCa.
PubMed: 36388432
DOI: 10.1016/j.euros.2022.10.017 -
Avicenna Journal of Medicine 2020Globally, prostate cancer (PCa) is the second most preponderant cancer in men. It contributes to the high mortality-to-incidence ratio reported in West Africa and Asia... (Review)
Review
Globally, prostate cancer (PCa) is the second most preponderant cancer in men. It contributes to the high mortality-to-incidence ratio reported in West Africa and Asia largely due to low screening. The mortality risk is determined or predicted based on the prevalence of high-risk or aggressive PCa using a scoring or grading system such as Gleason score (GS), Gleason grade (GG), and prostate-specific antigen (PSA) level. In this review, peer-reviewed articles found on databases such as Google Scholar, Scopus, Web of Science, PubMed Central and, EMBASE were selected based on adherence to clinical guidelines for the classification of PCa. In West Africa and Asia, the result revealed that the frequency of high-risk PCa was 42% and 51.2% based on GS, 48.8% and 25.3% based on GG pattern, and 87.5% and 44.3% based on PSA level >10 ng/mL, respectively. Data revealed a high prevalence of high-risk PCa both in West Africa and Asia when compared with developed countries. However, the prevalence of high-risk PCa is higher in West Africa than in Asia. Studies have shown that high-risk PCas are associated with germline mutations and such mutations are prevalent in blacks and Asians than in whites. Thus, testing for germline mutations in patients with GS of ≥ 7, GG ≥ 3, high prostate density, low prostate volume, and PSA levels of >4.0 ng/mL may identify those at risk of developing lethal PCa and could reduce the mortality rates in Asia and West Africa.
PubMed: 32832424
DOI: 10.4103/ajm.ajm_19_20 -
Journal of Clinical Medicine Oct 2021Prostate-specific membrane antigen (PSMA) is not sufficiently overexpressed in a small proportion of prostate cancer (PCa) patients, who require other strategies for... (Review)
Review
BACKGROUND
Prostate-specific membrane antigen (PSMA) is not sufficiently overexpressed in a small proportion of prostate cancer (PCa) patients, who require other strategies for imaging and/or treatment. We reviewed potential targets other than PSMA for PCa theranostics in nuclear medicine that have already been tested in humans.
METHODS
We performed a systematic web search in the PubMed and Cochrane databases, with no time restrictions by pooling terms ("prostate cancer", "prostatic neoplasms") and ("radioligand", "radiotracer"). Included articles were clinical studies. The results were synthetized by the target type.
RESULTS
We included 38 studies on six different targets: gastrin-releasing peptide receptors (GRPRs) ( = 23), androgen receptor ( = 11), somatostatin receptors ( = 6), urokinase plasminogen activator surface receptor ( = 4), fibroblast activation protein ( = 2 studies) and integrin receptors ( = 1). GRPRs, the most studied target, has a lower expression in high-grade PCa, CRPC and bone metastases. Its use might be of higher interest in treating earlier stages of PCa or low-grade PCa. Radiolabeled fibroblast activation protein inhibitors were the most recent and promising molecules, but specific studies reporting their interest in PCa are needed.
CONCLUSION
Theranostics in nuclear medicine will continue to develop in the future, especially for PCa patients. Targets other than PSMA exist and deserve to be promoted.
PubMed: 34768432
DOI: 10.3390/jcm10214909 -
European Urology Open Science Oct 2022The advantages of minimally invasive surgery for radical prostatectomy (RP) have been demonstrated in a number of systematic reviews (SRs). However, the rigorous study... (Review)
Review
CONTEXT
The advantages of minimally invasive surgery for radical prostatectomy (RP) have been demonstrated in a number of systematic reviews (SRs). However, the rigorous study selection process for SR means that a lot of information can be excluded, leading to a very specific clinical scenario that is often unrepresentative of real life. Our new reverse SR methodology generates a heterogeneous population database that covers a wide range of clinical scenarios.
OBJECTIVE
To compare perioperative surgical results and complications for open retropubic RP (RRP), laparoscopic RP (LRP), and robot-assisted RP (RARP) in a reverse SR.
EVIDENCE ACQUISITION
Eight databases were searched for SRs on RRP, LRP, or RARP between 2000 and 2020 (80 SRs). All references used in these SRs were captured for analysis (1724 articles). Perioperative outcomes and complications were compared among the RRP, LRP, and RARP approaches.
EVIDENCE SYNTHESIS
We identified 559 (32.4%) reports on RRP, 413 (23.9%) on LRP, and 752 (43.7%) on RARP, involving 1 353 485 patients overall. RARP showed a significantly higher annual volume of surgery per surgeon (AVSS) in comparison to RRP and LRP (mean 64.29, 43.26, and 41.47, respectively), a higher percentage of low-risk patients (prostate-specific antigen <10 ng/ml, Gleason <7, stage
CONCLUSIONS
Our reverse SR involved a wide real-life representative sample and reference values established in the literature and revealed that minimally invasive surgery had the best perioperative and complication results, especially RARP, which was associated with less complex cases, higher annual surgeon volume, and greater performance.
PATIENT SUMMARY
We used a wide sample representative of real-life surgical practice and reference values established in the literature for three techniques for removal of the prostate to guide patients and physicians in deciding the best surgical treatment for prostate cancer according to availability.
PubMed: 36110904
DOI: 10.1016/j.euros.2022.08.015