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Frontiers in Endocrinology 2024Testosterone replacement therapy (TRT) is a generally accepted method treating for aging-related late-onset hypogonadism (LOH). However, the efficacy and safety of TRT... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Testosterone replacement therapy (TRT) is a generally accepted method treating for aging-related late-onset hypogonadism (LOH). However, the efficacy and safety of TRT remain controversial. An updated systematic review and meta-analysis aimed to determine the effectiveness and security of TRT treating for LOH.
METHODS
Randomized controlled trials (RCTs) of TRT for LOH were searched in the databases of Pubmed, Embase, Clinicaltrials.gov and Cochrane from 1990 to 2023 and an updated meta-analysis was conducted.
RESULTS
The results of 28 RCTs involving 3461 patients were included and scrutinized in this analysis. Among these, 11 RCTs were of long-term duration (≥12 months), while 18 RCTs were short-term studies (<12 months) comparing TRT with a placebo. TRT modalities comprised injection, oral administration, and transdermal administration. International Index of Erectile Function (IIEF) (Weighted Mean difference (WMD) 3.26; 95%; 95% confidence interval (CI) 1.654.88; P<0.0001) was obviously improved in the TRT group. International Prostate Symptom Score (IPSS) (WMD 0.00; 95% CI -0.450.45; P=1.0), Prostate Volume (PV) (WMD 0.38; 95% CI -0.641.41; P=0.46), Maximum Flow Rate (Qmax) (WMD 1.86; 95% CI -0.984.69; P=0.20), Postvoid Residual Urine Volume (PVR) (WMD 3.20; 95% CI -5.8712.28; P=0.49) and Prostate-Specific Antigen (PSA) (WMD 0.08; 95% CI -0.000.17; P=0.06) were not significantly statistical between two groups.
CONCLUSION
This meta-analysis reveals that TRT could improve the IIEF score of hypogonadal men without detriment to the IPSS score, PV, Qmax, PVR and PSA regardless of the administration method or duration of treatment.The meta-analysis was registered at PROSPERO (CRD42023413434).
Topics: Humans; Male; Erectile Dysfunction; Hypogonadism; Prostate; Prostate-Specific Antigen; Testosterone; Aging
PubMed: 38344665
DOI: 10.3389/fendo.2024.1335146 -
Cancer Treatment Reviews Nov 2023PARP inhibitors (PARPi) are a standard-of-care (SoC) treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). Several clinical trials... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
PARP inhibitors (PARPi) are a standard-of-care (SoC) treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). Several clinical trials have shown the potential of combining PARPi with other anticancer agents. Therefore, we conducted a systematic review and meta-analysis to comprehensively evaluate the efficacy and safety of PARPi in patients with metastatic prostate cancer.
METHODS
MEDLINE, Cochrane CENTRAL, EMBASE, CINAHL, and Web of Science were searched on March 22nd, 2023, for phase 2 or 3 clinical trials. Efficacy (progression-free survival [PFS], overall survival [OS], PSA decline >50% [PSA50], and objective response rate [ORR]) and safety outcomes were assessed in the included studies.
RESULTS
Seventeen clinical trials (PARPi monotherapy [n = 7], PARPi + androgen-receptor signaling inhibitors [ARSI] [n = 6], and PARPi + immune checkpoint inhibitors [ICI] [n = 4]) were included in the quantitative analyses. PARPi monotherapy improved radiographic PFS and OS over SoC in mCRPC patients with alterations in BRCA1 or BRCA2 genes but not in those with alterations in the ATM gene. Higher rates of PSA50 and ORR were reported in participants treated with PARPi + ARSI than in single-agent PARPi or PARPi + ICI. Although the rate of high-grade adverse events was similar across all groups, treatment discontinuation was higher in patients treated with PARPi-based combinations than PARPi monotherapy.
CONCLUSION
The efficacy of PARPi is not uniform across mCRPC patients with alterations in DNA damage repair genes, and optimal patient selection remains a clinical challenge. No unexpected safety signals for this class of agents emerged from this analysis.
Topics: Male; Humans; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms, Castration-Resistant; Immune Checkpoint Inhibitors; Patient Selection; Progression-Free Survival
PubMed: 37716332
DOI: 10.1016/j.ctrv.2023.102623 -
European Urology Open Science Aug 2023Identifying malignant tissue and leaving adjacent structures undisturbed constitute an ongoing challenge in prostate cancer (PCa) surgery. Image and radioguided surgical... (Review)
Review
CONTEXT
Identifying malignant tissue and leaving adjacent structures undisturbed constitute an ongoing challenge in prostate cancer (PCa) surgery. Image and radioguided surgical technologies targeting the prostate-specific membrane antigen (PSMA) receptor may facilitate identification and removal of diseased tissue.
OBJECTIVE
To perform a systematic review of the clinical studies on PSMA-targeted surgery.
EVIDENCE ACQUISITION
The MEDLINE (OvidSP), Embase.com, and Cochrane Library databases were searched. Identified reports were critically appraised according to the Idea, Development, Exploration, Assessment, Long-term framework criteria. The risk of bias (RoB) was assessed as per the Risk Of Bias In Non-randomized Studies-of Interventions tool. The strengths and limitations of the techniques and corresponding oncological outcomes were extracted as areas of interest. Data were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.
EVIDENCE SYNTHESIS
In total, 29 reports were selected, including eight prospective studies, 12 retrospective analyses, and nine case reports, all with a high or an unclear RoB. In 72.4% of studies, PSMA targeting was achieved via radioguided surgery (RGS), predominantly using Tc-PSMA-I&S (66.7%). Hybrid approaches that complement RGS with optical guidance are emerging. The majority of studies retrieved were pilot studies with a short follow-up. In 13 reports, salvage lymph node surgery was discussed (44.8%). In 12 more recent reports (41.4%), PSMA targeting was studied in primary PCa surgery (50.0% lymph nodes and 50.0% surgical margins), and four studied both primary and salvage surgery (13.8%). Overall, specificity was higher than sensitivity (median 98.9% and 84.8%, respectively). Oncological outcomes were discussed only in reports on the use of Tc-PSMA-I&S in salvage surgery (median follow-up of 17.2 mo). A decline in prostate-specific antigen level of >90% ranged from 22.0% to 100.0%, and biochemical recurrence ranged from 50.0% to 61.8% of patients.
CONCLUSIONS
In PSMA-targeted surgery, most studies address salvage PSMA-RGS using Tc-PSMA-I&S. Available evidence suggests that the specificity of intraoperative PSMA targeting is higher than the sensitivity. The studies that included follow-up did not yet objectify a clear oncological benefit. Lacking solid outcome data, PSMA-targeted surgery remains investigational.
PATIENT SUMMARY
In this paper, we review recent advances in prostate-specific membrane antigen (PSMA)-targeted surgery, which is used to help identify and remove prostate cancer. We found good evidence to suggest that PSMA targeting helps identify prostate cancer during surgery. The oncological benefits have yet to be investigated further.
PubMed: 37361200
DOI: 10.1016/j.euros.2023.05.014 -
Insights Into Imaging Aug 2023In recent decades, diverse nomograms have been proposed to predict extraprostatic extension (EPE) in prostate cancer (PCa). We aimed to systematically evaluate the... (Review)
Review
PURPOSE
In recent decades, diverse nomograms have been proposed to predict extraprostatic extension (EPE) in prostate cancer (PCa). We aimed to systematically evaluate the accuracy of MRI-inclusive nomograms and traditional clinical nomograms in predicting EPE in PCa. The purpose of this meta-analysis is to provide baseline summative and comparative estimates for future study designs.
MATERIALS AND METHODS
The PubMed, Embase, and Cochrane databases were searched up to May 17, 2023, to identify studies on prediction nomograms for EPE of PCa. The risk of bias in studies was assessed by using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). Summary estimates of sensitivity and specificity were obtained with bivariate random-effects model. Heterogeneity was investigated through meta-regression and subgroup analysis.
RESULTS
Forty-eight studies with a total of 57 contingency tables and 20,395 patients were included. No significant publication bias was observed for either the MRI-inclusive nomograms or clinical nomograms. For MRI-inclusive nomograms predicting EPE, the pooled AUC of validation cohorts was 0.80 (95% CI: 0.76, 0.83). For traditional clinical nomograms predicting EPE, the pooled AUCs of the Partin table and Memorial Sloan Kettering Cancer Center (MSKCC) nomogram were 0.72 (95% CI: 0.68, 0.76) and 0.79 (95% CI: 0.75, 0.82), respectively.
CONCLUSION
Preoperative risk stratification is essential for PCa patients; both MRI-inclusive nomograms and traditional clinical nomograms had moderate diagnostic performance for predicting EPE in PCa. This study provides baseline comparative values for EPE prediction for future studies which is useful for evaluating preoperative risk stratification in PCa patients.
CRITICAL RELEVANCE STATEMENT
This meta-analysis firstly evaluated the diagnostic performance of preoperative MRI-inclusive nomograms and clinical nomograms for predicting extraprostatic extension (EPE) in prostate cancer (PCa) (moderate AUCs: 0.72-0.80). We provide baseline estimates for EPE prediction, these findings will be useful in assessing preoperative risk stratification of PCa patients.
KEY POINTS
• MRI-inclusive nomograms and traditional clinical nomograms had moderate AUCs (0.72-0.80) for predicting EPE. • MRI combined clinical nomogram may improve diagnostic accuracy of MRI alone for EPE prediction. • MSKCC nomogram had a higher specificity than Partin table for predicting EPE. • This meta-analysis provided baseline and comparative estimates of nomograms for EPE prediction for future studies.
PubMed: 37606802
DOI: 10.1186/s13244-023-01486-7 -
The British Journal of Nutrition Mar 2024Phytosterols/phytostanols are bioactive compounds found in vegetable oils, nuts and seeds and added to a range of commercial food products. Consumption of... (Review)
Review
Phytosterols/phytostanols are bioactive compounds found in vegetable oils, nuts and seeds and added to a range of commercial food products. Consumption of phytosterols/phytostanols reduces levels of circulating LDL-cholesterol, a causative biomarker of CVD, and is linked to a reduced risk of some cancers. Individuals who consume phytosterols/phytostanols in their diet may do so for many years as part of a non-pharmacological route to lower cholesterol or as part of a healthy diet. However, the impact of long term or high intakes of dietary phytosterols/phytostanols has not been on whole-body epigenetic changes before. The aim of this systematic review was to identify all publications that have evaluated changes to epigenetic mechanisms (post-translation modification of histones, DNA methylation and miRNA expression) in response to phytosterols/phytostanols. A systematic search was performed that returned 226 records, of which eleven were eligible for full-text analysis. Multiple phytosterols were found to inhibit expression of histone deacetylase (HDAC) enzymes and were also predicted to directly bind and impair HDAC activity. Phytosterols were found to inhibit the expression and activity of DNA methyl transferase enzyme 1 and reverse cancer-associated gene silencing. Finally, phytosterols have been shown to regulate over 200 miRNA, although only five of these were reported in multiple publications. Five tissue types (breast, prostate, macrophage, aortic epithelia and lung) were represented across the studies, and although phytosterols/phytostanols alter the molecular mechanisms of epigenetic inheritance in these mammalian cells, studies exploring meiotic or transgenerational inheritance were not found.
Topics: Male; Animals; Humans; Phytosterols; Noncommunicable Diseases; Cholesterol; Epigenesis, Genetic; Neoplasms; MicroRNAs; Mammals
PubMed: 37955052
DOI: 10.1017/S0007114523002532 -
Diagnostics (Basel, Switzerland) Aug 2023Deep learning (DL), often called artificial intelligence (AI), has been increasingly used in Pathology thanks to the use of scanners to digitize slides which allow us to... (Review)
Review
Deep learning (DL), often called artificial intelligence (AI), has been increasingly used in Pathology thanks to the use of scanners to digitize slides which allow us to visualize them on monitors and process them with AI algorithms. Many articles have focused on DL applied to prostate cancer (PCa). This systematic review explains the DL applications and their performances for PCa in digital pathology. Article research was performed using PubMed and Embase to collect relevant articles. A Risk of Bias (RoB) was assessed with an adaptation of the QUADAS-2 tool. Out of the 77 included studies, eight focused on pre-processing tasks such as quality assessment or staining normalization. Most articles ( = 53) focused on diagnosis tasks like cancer detection or Gleason grading. Fifteen articles focused on prediction tasks, such as recurrence prediction or genomic correlations. Best performances were reached for cancer detection with an Area Under the Curve (AUC) up to 0.99 with algorithms already available for routine diagnosis. A few biases outlined by the RoB analysis are often found in these articles, such as the lack of external validation. This review was registered on PROSPERO under CRD42023418661.
PubMed: 37627935
DOI: 10.3390/diagnostics13162676 -
International Journal of Radiation... Jul 2023Current risk-stratification systems for prostate cancer (PCa) do not sufficiently reflect the disease heterogeneity. Genomic classifiers (GC) enable improved risk... (Review)
Review
Current risk-stratification systems for prostate cancer (PCa) do not sufficiently reflect the disease heterogeneity. Genomic classifiers (GC) enable improved risk stratification after surgery, but less data exist for patients treated with definitive radiation therapy (RT) or RT in oligo-/metastatic disease stages. To guide future perspectives of GCs for RT, we conducted (1) a systematic review on the evidence of GCs for patients treated with RT and (2) a survey of experts using the Delphi method, addressing the role of GCs in personalized treatments to identify relevant fields of future clinical and translational research. We performed a systematic review and screened ongoing clinical trials on ClinicalTrials.gov. Based on these results, a multidisciplinary international team of experts received an adapted Delphi method survey. Thirty-one and 30 experts answered round 1 and round 2, respectively. Questions with ≥75% agreement were considered relevant and included in the qualitative synthesis. Evidence for GCs as predictive biomarkers is mainly available to the postoperative RT setting. Validation of GCs as prognostic markers in the definitive RT setting is emerging. Experts used GCs in patients with PCa with extensive metastases (30%), in postoperative settings (27%), and in newly diagnosed PCa (23%). Forty-seven percent of experts do not currently use GCs in clinical practice. Expert consensus demonstrates that GCs are promising tools to improve risk-stratification in primary and oligo-/metastatic patients in addition to existing classifications. Experts were convinced that GCs might guide treatment decisions in terms of RT-field definition and intensification/deintensification in various disease stages. This work confirms the value of GCs and the promising evidence of GC utility in the setting of RT. Additional studies of GCs as prognostic biomarkers are anticipated and form the basis for future studies addressing predictive capabilities of GCs to optimize RT and systemic therapy. The expert consensus points out future directions for GC research in the management of PCa.
Topics: Male; Humans; Consensus; Prostatic Neoplasms; Genomics
PubMed: 36596346
DOI: 10.1016/j.ijrobp.2022.12.038 -
European Urology Oncology Nov 2023Many liquid biomarkers have entered clinical practice with the praise to improve the detection of clinically significant prostate cancer (csPCa), helping avoid... (Review)
Review
CONTEXT
Many liquid biomarkers have entered clinical practice with the praise to improve the detection of clinically significant prostate cancer (csPCa), helping avoid unnecessary prostate biopsies.
OBJECTIVE
We aimed to assess the diagnostic accuracy of multianalyte biomarkers for csPCa detection using multiple thresholds.
EVIDENCE ACQUISITION
A comprehensive literature search was done through PubMed, Web of Science, and Scopus in March 2023 for prospective and retrospective studies reporting the diagnostic performance of liquid biomarkers for detecting csPCa. The outcomes of interest were the diagnostic performance of liquid biomarkers for csPCa detection and identification of optimal thresholds for each biomarker.
EVIDENCE SYNTHESIS
Overall, 49 studies were eligible for this meta-analysis. Using each representative threshold based on the Youden Index, the pooled sensitivity and specificity for detecting csPCa were 0.85 and 0.37 for prostate cancer gene 3 (PCA3), 0.85 and 0.52 for prostate health index (PHI), 0.87 and 0.58 for four kallikrein (4K), 0.82 and 0.56 for SelectMDx, 0.85 and 0.54 for ExoDx, and 0.82 and 0.59 for mi prostate score (MPS), respectively. The diagnostic odds ratio was highest for 4K (8.84), followed by MPS (7.0) and PHI (6.28). According to the meta-analysis incorporating multiple thresholds, the corresponding sensitivity was 0.77 for 4K, 0.69 for PHI, and 0.63 for PCA3; specificity was 0.72 for PHI, 0.70 for 4K, and 0.69 for PCA3.
CONCLUSIONS
Regarding the detection of csPCa, 4K had the highest diagnostic performance among the commercial liquid biomarkers. Based on the optimal thresholds calculated by the present meta-analysis, 4K had the highest sensitivity and PHI had the highest specificity for detecting csPCa. Nevertheless, clinical decision-making requires combination strategies between liquid and imaging biomarkers.
PATIENT SUMMARY
Novel biomarkers for prostate cancer detection were useful for more accurate diagnosis of clinically significant prostate cancer to avoid unnecessary biopsies.
PubMed: 37981495
DOI: 10.1016/j.euo.2023.10.029 -
Psycho-oncology Nov 2023To evaluate the evidence base for patient, oncological, and treatment prognostic factors associated with multiple mental wellbeing outcomes in prostate cancer patients. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To evaluate the evidence base for patient, oncological, and treatment prognostic factors associated with multiple mental wellbeing outcomes in prostate cancer patients.
METHODS
We performed a literature search of MEDLINE, EMBASE, and CINAHL databases including studies evaluating patient, oncological, or treatment factors against one of five mental wellbeing outcomes; depression, anxiety, fear of cancer recurrence, masculinity, and body image perception. Data synthesis included a random effects meta-analysis for the prognostic effect of individual factors if sufficient homogenous data was available, with a structured narrative synthesis where this was not possible.
RESULTS
A final 62 articles were included. Older age was associated with a reducing odds of depression (OR 0.97, p = 0.04), with little evidence of effect for other outcomes. Additionally, baseline mental health status was related to depression and increasing time since diagnosis was associated with reducing fear of recurrence, albeith with low certainty of evidence. However, few other patient or oncological factors demonstrated any coherent relationship with any wellbeing outcome. Androgen deprivation therapy was associated with increased depression (HR 1.65, 95% CI 1.41-1.92, p < 0.01) and anxiety, however, little difference was seen between other treatment options. Overall, whilst numerous factors were identified, most were evaluated by single studies with few evaluating masculinity and body image outcomes.
CONCLUSION
We highlight the existing evidence for prognostic factors in mental wellbeing outcomes in prostate cancer, allowing us to consider high-risk groups of patients for preventative and treatment measures. However, the current evidence is heterogenous with further work required exploring less conclusive factors and outcomes.
Topics: Male; Humans; Prostatic Neoplasms; Depression; Prognosis; Androgen Antagonists; Neoplasm Recurrence, Local; Quality of Life
PubMed: 37789603
DOI: 10.1002/pon.6225 -
Cureus Sep 2023Our systematic review aimed to assess the effectiveness and suitability of holmium laser enucleation of the prostate (HoLEP) as a treatment for benign prostatic... (Review)
Review
Our systematic review aimed to assess the effectiveness and suitability of holmium laser enucleation of the prostate (HoLEP) as a treatment for benign prostatic hyperplasia (BPH) in comparison to transurethral resection of the prostate (TURP). We analyzed 12 studies involving male participants aged 45-85 years, all of whom had BPH. In our analysis, we compared HoLEP and TURP, with a focus on several primary outcomes, including postoperative International Prostate Symptom Score (IPSS), postvoid residual (PVR) volume, maximum flow rate (Qmax), and changes in sexual function post-treatment. HoLEP demonstrated advantages in certain aspects when compared to TURP. HoLEP generally resulted in an improved postoperative IPSS in some studies, but not all studies showed a significant difference when compared to TURP. HoLEP was associated with improved Qmax in most studies, but one study found no significant difference between HoLEP and TURP. Patients who underwent HoLEP showed improvement in the PVR volume in some studies, while others found no significant change in the PVR volume with either HoLEP or TURP. Some studies reported a reduction in orgasm and ejaculatory scores following TURP, while no significant changes were observed in erectile function, intercourse satisfaction, and overall satisfaction scores. It is worth noting that previous reviews and meta-analyses had limited data on the effects of HoLEP and TURP on sexual dysfunction. TURP is associated with a higher risk of morbidity and mortality, which has led to its replacement with HoLEP as the gold standard for treating BPH, particularly due to its size-independent applicability. HoLEP also demonstrated greater efficacy in the postoperative period.
PubMed: 37905244
DOI: 10.7759/cureus.46173