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Journal of Translational Medicine Jan 2021The ability of tumor cells to spread from their origin place and form secondary tumor foci is determined by the epithelial-mesenchymal transition process. In epithelial... (Meta-Analysis)
Meta-Analysis Review
The ability of tumor cells to spread from their origin place and form secondary tumor foci is determined by the epithelial-mesenchymal transition process. In epithelial tumors such as prostate cancer (PCa), the loss of intercellular interactions can be observed as a change in expression of polarity proteins. Epithelial cells acquire ability to migrate, what leads to the formation of distal metastases. In recent years, the interest in miRNA molecules as potential future treatment options has increased. In tumor microenvironment, miRNAs have the ability to regulate signal transduction pathways, where they can act as suppressors or oncogenes. MiRNAs are secreted by cancer cells, and the changes in their expression levels are closely related to a cancer progression, including epithelial-mesenchymal transition. These molecules offer new diagnostic and therapeutic possibilities. Therapeutics which make use of synthesized RNA fragments and mimic or block miRNAs affected in PCa, may lead to inhibition of tumor progression and even disease re-emission. Based on appropriate qualification criteria, we conducted a selection process to identify scientific articles describing miRNAs and their relation to epithelial-mesenchymal transition in PCa patients. The studies were published in English on Pubmed, Scopus and the Web of Science before August 08, 2019. Hazard ratios (HRs) and 95% confidence intervals (CI) as well as total Gleason score were used to assess the concordance between miRNAs and presence of metastases. A total of 13 studies were included in our meta-analysis, representing 1608 PCa patients and 15 miRNA molecules. Our study clarifies a relationship between the clinicopathological features of PCa and the aberrant expression of several miRNA as well as the complex mechanism of miRNA molecules involvement in the induction and promotion of the metastatic mechanism in PCa.
Topics: Cell Line, Tumor; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Male; MicroRNAs; Neoplasm Grading; Prognosis; Prostatic Neoplasms; Tumor Microenvironment
PubMed: 33413466
DOI: 10.1186/s12967-020-02644-x -
European Urology Jul 2023The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for...
Impact of Epithelial Histological Types, Subtypes, and Growth Patterns on Oncological Outcomes for Patients with Nonmetastatic Prostate Cancer Treated with Curative Intent: A Systematic Review.
CONTEXT
The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for conventional PCa and so different approaches may be needed.
OBJECTIVE
To compare oncological outcomes for conventional and UH PCa in men with localized disease treated with curative intent.
EVIDENCE ACQUISITION
A systematic review adhering to the Referred Reporting Items for Systematic Reviews and Meta-Analyses was prospectively registered on PROSPERO (CRD42022296013) was performed in July 2021.
EVIDENCE SYNTHESIS
We screened 3651 manuscripts and identified 46 eligible studies (reporting on 1 871 814 men with conventional PCa and 6929 men with 10 different PCa UHs). Extraprostatic extension and lymph node metastases, but not positive margin rates, were more common with UH PCa than with conventional tumors. PCa cases with cribriform pattern, intraductal carcinoma, or ductal adenocarcinoma had higher rates of biochemical recurrence and metastases after radical prostatectomy than for conventional PCa cases. Lower cancer-specific survival rates were observed for mixed cribriform/intraductal and cribriform PCa. By contrast, pathological findings and oncological outcomes for mucinous and prostatic intraepithelial neoplasia (PIN)-like PCa were similar to those for conventional PCa. Limitations of this review include low-quality studies, a risk of reporting bias, and a scarcity of studies that included radiotherapy.
CONCLUSIONS
Intraductal, cribriform, and ductal UHs may have worse oncological outcomes than for conventional and mucinous or PIN-like PCa. Alternative treatment approaches need to be evaluated in men with these cancers.
PATIENT SUMMARY
We reviewed the literature to explore whether prostate cancers with unconventional growth patterns behave differently to conventional prostate cancers. We found that some unconventional growth patterns have worse outcomes, so we need to investigate if they need different treatments. Urologists should be aware of these growth patterns and their clinical impact.
Topics: Humans; Male; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms
PubMed: 37117107
DOI: 10.1016/j.eururo.2023.03.014 -
Medical Principles and Practice :... 2023Actinium-225 (Ac-225) labelled PSMA RLT has been tested recently in metastatic castration-resistant prostate cancer (mCRPC), with encouraging results. Ac-225, being an... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Actinium-225 (Ac-225) labelled PSMA RLT has been tested recently in metastatic castration-resistant prostate cancer (mCRPC), with encouraging results. Ac-225, being an alpha emitter, is expected to have higher efficacy and fewer side effects compared to the beta-emitters such as Lutetium-177. We have performed a meta-analysis to assess the therapeutic responses, survival effects, and significant side effects of Ac-225 PSMA RLT in patients with mCRPC.
METHODOLOGY
Systematic literature search was carried out from five electronic databases PubMed/MEDLINE, SCOPUS, EMBASE, Web of Science, and Cochrane Library until March 2021. Eight studies were found to be eligible for this metanalysis.
RESULTS
Eight studies with 226 patients were analyzed in this metanalysis. 81% (95% CI 73-89) patients had a decline in PSA levels. 60% of the patients showed more than 50% PSA decline. Two studies assessed survival effects of radioligand naïve patients compared to patients who had received Lu-PSMA therapy previously and the pooled HR for radioligand naïve patients is 0.22. The most common toxicity reported was xerostomia in 167 patients out of 226 patients (73.9%, 95% CI 67.6-79.5%); however, most of them were confined to grade I and II levels. Other reported side effects include hematologic toxicity and nephrotoxicity.
CONCLUSION
Ac-PSMA RLT is a safe and potentially effective treatment option for patients with mCRPC.
Topics: Male; Humans; Actinium; Prostatic Neoplasms, Castration-Resistant; Prostate-Specific Antigen; Prostate; Dipeptides; Treatment Outcome; Retrospective Studies
PubMed: 37247612
DOI: 10.1159/000531246 -
Frontiers in Endocrinology 2023econd-generation androgen receptor inhibitors (SGARIs), namely enzalutamide, apalutamide, and darolutamide, are good for improving survival outcomes in prostate cancer... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
econd-generation androgen receptor inhibitors (SGARIs), namely enzalutamide, apalutamide, and darolutamide, are good for improving survival outcomes in prostate cancer patients, but some researchers have shown that using SGARIs increases side effects, which complicates clinicians' choice of. Therefore, we performed this network meta-analysis to assess the efficacy and toxicity of several SGARIs in the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC), non-metastatic castration-resistant prostate cancer (nmCRPC), and metastatic castration-resistant prostate cancer (mCRPC).
METHODS
We searched PubMed, EMBASE and Cochrane Library databases from January 2000 to December 2022 to identify randomized controlled studies associated with SGARIs. We use Stata 16.0 and R 4.4.2 for data analysis, hazard ratio (HR) with 95% confidence intervals (CI) were used to assess the results.
RESULTS
This meta-analysis included 7 studies with a total of 9488 patients. In mHSPC, enzalutamide and darolutamide had a positive effect on overall survival (OS) (HR, 0.70; 95% CI, 0.59-0.82), but we did not find a difference in their efficacy to improve OS (HR, 1.19; 95% CI, 0.75-1.89). Also in nmCRPC, enzalutamide, apalutamide and darolutamide were beneficial for metastasis-free survival (MFS) (HR, 0.32; 95% CI, 0.25-0.41). Compared to darolutamide, enzalutamide (HR, 0.71; 95% CI, 0.54-0.93) and apalutamide (HR, 0.68; 95% CI, 0.51-0.91) prolonged MFS, but there was no difference in efficacy between enzalutamide and apalutamide (HR, 0.97; 95% CI, 0.73-1.28). Finally in mCRPC, there was no significant difference in indirect effects on OS between pre- and post-chemotherapy enzalutamide (HR, 0.89; 95% CI, 0.70-1.13). However, using enzalutamide before chemotherapy to improve radiographic progression-free survival (rPFS) was a better option (HR, 2.11; 95% CI, 1.62-2.73).
CONCLUSION
The SGARIs used in each trial were beneficial for the primary endpoint in the study. Firstly there was no significant difference in the effect of enzalutamide and darolutamide in improving OS in patients with mHSPC. Secondly improving MFS in patients with nmCRPC was best achieved with enzalutamide and apalutamide. In addition both pre- and post-chemotherapy use of enzalutamide was beneficial for OS in mCRPC patients, but for improving rPFS pre-chemotherapy use of enzalutamide should be preferred.The INPLASY registration number of this systematic review is INPLASY202310084.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Receptors, Androgen; Network Meta-Analysis; Phenylthiohydantoin; Androgen Receptor Antagonists
PubMed: 36967752
DOI: 10.3389/fendo.2023.1134719 -
Frontiers in Immunology 2022To review the role of inflammation in the occurrence and development of benign prostatic hyperplasia (BPH), we searched PubMed for the latest published articles up to... (Review)
Review
To review the role of inflammation in the occurrence and development of benign prostatic hyperplasia (BPH), we searched PubMed for the latest published articles up to February 2021 using the following key words: "benign prostatic hyperplasia", "inflammation", "pathogenesis" and "disease development". Articles were obtained and reviewed to provide a systematic review of the current progress of the role of inflammation in the pathogenesis and progression of BPH. Inflammation contributes to the initiation and maintenance of unregulated cell proliferation and is closely related to the occurrence and development of BPH. Its action pathways include tissue damage and subsequent chronic healing, autoimmunity, and coaction with androgens. During the progression of inflammation, macrophages, interleukin-8 (IL-8), interleukin-1 (IL-1) and other inflammatory-related substances aggregate locally and cause BPH through various biochemical pathways. At the same time, BPH can also counteract inflammation to expand its scope and aggravate the situation. Inflammation can independently affect the development of BPH in a variety of ways, and it can also interact with androgens. In the course of treatment, early intervention in the occurrence and development of inflammation in prostate tissue can slow down the progression of BPH. The combination of standard therapies and anti-inflammatory measures may provide valuable new ideas for the treatment of BPH.
Topics: Aging; Androgens; Anti-Inflammatory Agents; Humans; Inflammation; Male; Prostatic Hyperplasia
PubMed: 35386711
DOI: 10.3389/fimmu.2022.842008 -
BMJ Open Jan 2021To conduct a systematic review with meta-analysis of cohort studies to evaluate the association of coffee consumption with the risk of prostate cancer. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To conduct a systematic review with meta-analysis of cohort studies to evaluate the association of coffee consumption with the risk of prostate cancer.
DATA SOURCES
PubMed, Web of Science and Embase were searched for eligible studies up to September 2020.
STUDY SELECTION
Cohort studies were included.
DATA EXTRACTION AND SYNTHESIS
Two researchers independently reviewed the studies and extracted the data. Data synthesis was performed via systematic review and meta-analysis of eligible cohort studies. Meta-analysis was performed with the "" and "" commands in Stata 14.0.
MAIN OUTCOMES AND MEASURES
Prostate cancer was the main outcome. It was classified as localised prostate cancer which included localised or non-aggressive cancers; advanced prostate cancer which included advanced or aggressive cancers; or fatal prostate cancer which included fatal/lethal cancers or prostate cancer-specific deaths.
RESULTS
Sixteen prospective cohort studies were finally included, with 57 732 cases of prostate cancer and 1 081 586 total cohort members. Higher coffee consumption was significantly associated with a lower risk of prostate cancer. Compared with the lowest category of coffee consumption, the pooled relative risk (RR) was 0.91 (95% CI 0.84 to 0.98), I= 53.2%) for the highest category of coffee consumption. There was a significant linear trend for the association (p=0.006 for linear trend), with a pooled RR of 0.988 (95% CI 0.981 to 0.995) for each increment of one cup of coffee per day. For localised, advanced and fatal prostate cancer, the pooled RRs were 0.93 (95% CI 0.87 to 0.99), 0.88 (95% CI 0.71 to 1.09) and 0.84 (95% CI 0.66 to 1.08), respectively. No evidence of publication bias was indicated in this meta-analysis.
CONCLUSIONS
This study suggests that a higher intake of coffee may be associated with a lower risk of prostate cancer.
Topics: Coffee; Cohort Studies; Humans; Male; Prospective Studies; Prostatic Neoplasms; Risk; Risk Factors
PubMed: 33431520
DOI: 10.1136/bmjopen-2020-038902 -
Pain Research & Management 2023Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex male dysfunction, mostly seen in young and middle-aged men with a history of more than... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex male dysfunction, mostly seen in young and middle-aged men with a history of more than 3 months. As a traditional therapy of Traditional Chinese Medicine, acupuncture has been proven an effective method to treat CP/CPPS in recent years. Though some meta-analyses on acupuncture for chronic prostatitis were published in 2018 and 2019, most of the included studies were low in quality according to the JADAD score (JADAD < 4). The conclusions of acupuncture for CP/CPPS remain indefinite.
PURPOSE
This review aims to evaluate the efficacy of acupuncture for CP/CPPS by including high-quality literature only (JADAD ≥ 4) to provide a reliable basis for clinical applications and research.
METHOD
Nine electronic databases were searched from inception to March 1, 2022, and only randomized controlled trials (RCT) with high-quality (JADAD ≥ 4) were included. Data were analyzed using Review Manager 5.3. and was verified through trial sequential analysis (TSA). We carried out a sensitivity analysis for the heterogeneity ( ≥ 50%). Publication bias was explored using a funnel plot.
RESULT
Ten RCTs (11 trials) of high-quality methodology involving 798 patients were included. Meta-analysis showed that compared to sham acupuncture (SAT) and western medicine (WM), acupuncture (AT) played superior roles for CP/CPPS patients in pain score, NIH-CPSI score, quality of life score, urinary symptom, and efficacy rate. As for the adverse effects, 4 RCTs described mild hematoma and pain in AT and SAT groups, while specific symptoms including nausea, abdominal pain, dizziness, and low blood pressure were reported in WM groups.
CONCLUSION
This meta-analysis indicated that acupuncture has measurable benefits on CP/CPPS, and security has also been ensured. However, this meta-analysis only included 10 RCTs; thus, RCTs with a larger sample size and longer-term observation are required to verify the effectiveness of acupuncture further in the future.
Topics: Male; Middle Aged; Humans; Chronic Pain; Prostatitis; Chronic Disease; Acupuncture Therapy; Pelvic Pain
PubMed: 36960418
DOI: 10.1155/2023/7754876 -
International Braz J Urol : Official... 2022To report the prevalence of the definitions used to identify post-prostatectomy incontinence (PPI) after laparoscopic radical prostatectomy (LRP), and to compare the... (Review)
Review
PURPOSE
To report the prevalence of the definitions used to identify post-prostatectomy incontinence (PPI) after laparoscopic radical prostatectomy (LRP), and to compare the rates of PPI over time under different criteria.
MATERIALS AND METHODS
In the period from January 1, 2000, until December 31, 2017, we used a recently described methodology to perform evidence acquisition called reverse systematic review (RSR). The continence definition and rates were evaluated and compared at 1, 3, 6, 12, and >18 months post-operative. Moreover, the RSR showed the "natural history" of PPI after LRP.
RESULTS
We identified 353 review articles in the systematized search, 137 studies about PPI were selected for data collection, and finally were included 203 reports (nr) with 51.436 patients. The most used criterion of continence was No pad (nr=121; 59.6%), the second one was Safety pad (nr=57; 28.1%). A statistically significant difference between continence criteria was identified only at >18 months (p=0.044). From 2013 until the end of our analysis, the Safety pad and Others became the most reported.
CONCLUSION
RSR revealed the "natural history" of PPI after the LRP technique, and showed that through time the Safety pad concept was mainly used. However, paradoxically, we demonstrated that the two most utilized criteria, Safety pad and No pad, had similar PPI outcomes. Further effort should be made to standardize the PPI denomination to evaluate, compare and discuss the urinary post-operatory function.
Topics: Humans; Laparoscopy; Male; Prostate; Prostatectomy; Urinary Incontinence
PubMed: 35168312
DOI: 10.1590/S1677-5538.IBJU.2021.0632 -
World Journal of Urology Mar 2023The diagnosis of prostate cancer (PCa) still relies on the performance of both targeted (TB) and systematic biopsies (SB). Micro-ultrasound (mUS)-guided biopsies... (Meta-Analysis)
Meta-Analysis
PURPOSE
The diagnosis of prostate cancer (PCa) still relies on the performance of both targeted (TB) and systematic biopsies (SB). Micro-ultrasound (mUS)-guided biopsies demonstrated a high sensitivity in detecting clinically significant prostate cancer (csPCa), which could be comparable to that of magnetic resonance imaging (MRI)-TB, but their added value has not been compared to SB yet.
METHODS
We conducted a systematic review and meta-analysis, based on Medline, EMBASE, Scopus, and Web of Science, in accordance with PRISMA guidelines, to compare mUS-guided biopsies to SB.
RESULTS
Based on the literature search of 2957 articles, 15 met the inclusion criteria (2967 patients). Most patients underwent mUS-guided biopsies, followed by MRI-TB and SB. Respectively 5 (n = 670) and 4 (n = 467) studies, providing raw data on SB, were included in a random-effect meta-analysis of the detection rate of csPCa, i.e. Gleason Grade Group (GGG) ≥ 2 or non-csPCa (GGG = 1). Overall, PCa was detected in 56-71% of men, with 31.3-49% having csPCa and 17-25.4% having non-csPCa. Regarding csPCa, mUS-guided biopsies identified 196 and SB 169 cases (Detection Ratio (DR): 1.18, 95% CI 0.83-1.68, I = 69%), favoring mUS-guided biopsies; regarding non-csPCa, mUS-guided biopsies identified 62 and SB 115 cases (DR: 0.55, 95% CI 0.41-0.73, I = 0%), also favoring mUS-guided biopsies by decreasing unnecessary diagnosis.
CONCLUSION
Micro-ultrasound-guided biopsies compared favorably with SB for the detection of csPCa and detected fewer non-csPCa than SB. Prospective trials are awaited to confirm the interest of adding mUS-guided biopsies to MRI-TB to optimize csPCa detection without increasing overdiagnosis of non-csPCa.
Topics: Male; Animals; Mice; Humans; Prospective Studies; Prostatic Neoplasms; Image-Guided Biopsy; Ultrasonography; Ultrasonography, Interventional
PubMed: 35835886
DOI: 10.1007/s00345-022-04087-z -
European Urology Jan 2024In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand...
BACKGROUND
In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications.
OBJECTIVE
We aimed to critically review developments in molecular hybrid imaging and systemic radioligand therapy, to reach a multidisciplinary consensus on the current state of the art in PCa.
DESIGN, SETTING, AND PARTICIPANTS
The results of a systematic literature search informed a two-round Delphi process with a panel of 28 PCa experts in medical or radiation oncology, urology, radiology, medical physics, and nuclear medicine. The results were discussed and ratified in a consensus meeting.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Forty-eight statements were scored on a Likert agreement scale and six as ranking options. Agreement statements were analysed using the RAND appropriateness method. Ranking statements were analysed using weighted summed scores.
RESULTS AND LIMITATIONS
After two Delphi rounds, there was consensus on 42/48 (87.5%) of the statements. The expert panel recommends PSMA PET to be used for staging the majority of patients with unfavourable intermediate and high risk, and for restaging of suspected recurrent PCa. There was consensus that oligometastatic disease should be defined as up to five metastases, even using advanced imaging modalities. The group agreed that [Lu]Lu-PSMA should not be administered only after progression to cabazitaxel and that [Ra]RaCl remains a valid therapeutic option in bone-only metastatic castration-resistant PCa. Uncertainty remains on various topics, including the need for concordant findings on both []FDG and PSMA PET prior to [Lu]Lu-PSMA therapy.
CONCLUSIONS
There was a high proportion of agreement among a panel of experts on the use of molecular imaging and theranostics in PCa. Although consensus statements cannot replace high-certainty evidence, these can aid in the interpretation and dissemination of best practice from centres of excellence to the wider clinical community.
PATIENT SUMMARY
There are situations when dealing with prostate cancer (PCa) where both the doctors who diagnose and track the disease development and response to treatment, and those who give treatments are unsure about what the best course of action is. Examples include what methods they should use to obtain images of the cancer and what to do when the cancer has returned or spread. We reviewed published research studies and provided a summary to a panel of experts in imaging and treating PCa. We also used the research summary to develop a questionnaire whereby we asked the experts to state whether or not they agreed with a list of statements. We used these results to provide guidance to other health care professionals on how best to image men with PCa and what treatments to give, when, and in what order, based on the information the images provide.
Topics: Humans; Male; Molecular Imaging; Nuclear Medicine; Positron-Emission Tomography; Precision Medicine; Prostatic Neoplasms
PubMed: 37743194
DOI: 10.1016/j.eururo.2023.09.003