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Cancers Sep 2019Trans-1-amino-3-F-fluorocyclobutanecarboxylic-acid (anti-[F]-FACBC) has been approved for the detection of prostate cancer (PCa) in patients with elevated... (Review)
Review
Trans-1-amino-3-F-fluorocyclobutanecarboxylic-acid (anti-[F]-FACBC) has been approved for the detection of prostate cancer (PCa) in patients with elevated prostate-specific-antigen following prior treatment. This review and meta-analysis aimed to investigate the diagnostic performance of F-FACBC positron emission tomography/computed-tomography (PET/CT) in the detection of primary/recurrent PCa. A bibliographic search was performed including several databases, using the following terms: "FACBC"/"fluciclovine" AND "prostate cancer"/"prostate" AND "PET"/"Positron Emission Tomography". Fifteen and 9 studies were included in the systematic reviews and meta-analysis, respectively. At patient-based analysis, the pooled sensitivity and specificity of F-FACBC-PET/CT for the assessment of PCa were 86.3% and 75.9%, respectively. The pooled diagnostic odds-ratio value was 16.453, with heterogeneity of 30%. At the regional-based-analysis, the pooled sensitivity of F-FACBC-PET/CT for the evaluation of primary/recurrent disease in the prostatic bed was higher than in the extra-prostatic regions (90.4% vs. 76.5%, respectively); conversely, the pooled specificity was higher for the evaluation of extra-prostatic region than the prostatic bed (89% vs. 45%, respectively). F-FACBC-PET/CT seems to be promising in recurrent PCa, particularly for the evaluation of the prostatic bed. Additional studies to evaluate its utility in clinical routine are mandatory.
PubMed: 31514479
DOI: 10.3390/cancers11091348 -
Cancer Causes & Control : CCC Aug 2022Observational studies and randomized controlled trials (RCTs) have shown an association between vitamin D levels and prostate cancer progression. However, evidence of... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Observational studies and randomized controlled trials (RCTs) have shown an association between vitamin D levels and prostate cancer progression. However, evidence of direct causality is sparse and studies have not examined biological mechanisms, which can provide information on plausibility and strengthen the evidence for causality.
METHODS
We used the World Cancer Research Fund International/University of Bristol two-stage framework for mechanistic systematic reviews. In stage one, both text mining of published literature and expert opinion identified testosterone as a plausible biological mechanism. In stage two, we performed a systematic review and meta-analysis to assess the evidence from both human and animal studies examining the effect of vitamin D on testosterone, and testosterone on advanced prostate cancer (diagnostic Gleason score of ≥ 8, development of metastasis) or prostate cancer-specific mortality.
RESULTS
A meta-analysis of ten human RCTs showed evidence of an effect of vitamin D on total testosterone (standardised mean difference (SMD) = 0.133, 95% CI = - 0.003-0.269, I = 0.0%, p = 0.056). Five human RCTs showed evidence of an effect of vitamin D on free testosterone (SMD = 0.173, 95% CI = - 0.104-0.450, I = 52.4%, p = 0.220). Three human cohort studies of testosterone on advanced prostate cancer or prostate cancer-specific mortality provided inconsistent results. In one study, higher levels of calculated free testosterone were positively associated with advanced prostate cancer or prostate cancer-specific mortality. In contrast, higher levels of dihydrotestosterone were associated with lowering prostate cancer-specific mortality in another study. No animal studies met the study eligibility criteria.
CONCLUSION
There is some evidence that vitamin D increases levels of total and free testosterone, although the effect of testosterone levels within the normal range on prostate cancer progression is unclear. The role of testosterone as a mechanism between vitamin D and prostate cancer progression remains inconclusive.
Topics: Humans; Male; Prostate; Prostatic Neoplasms; Testosterone; Vitamin D; Vitamins
PubMed: 35752985
DOI: 10.1007/s10552-022-01591-w -
Prostate Cancer and Prostatic Diseases Mar 2016Epidemiological data suggest that lower urinary tract symptoms (LUTSs) may be associated with metabolic syndrome (MetS). Inflammation has been proposed as a candidate... (Review)
Review
BACKGROUND
Epidemiological data suggest that lower urinary tract symptoms (LUTSs) may be associated with metabolic syndrome (MetS). Inflammation has been proposed as a candidate mechanism at the crossroad between these two clinical entities. The aim of this review article is to evaluate the role of MetS-induced inflammation in the pathogenesis and progression of LUTS.
METHODS
A systematic review was conducted using the keywords 'metabolic syndrome and lower urinary tract symptoms' within the title search engines including PubMed, Web of Science and the Cochrane Library for relevant research work published between 2000 and January 2015. The obtained literature was reviewed by the primary author (QH) and was assessed for eligibility and standard level of evidence.
RESULTS
Total of 52 articles met the eligibility criteria. On the basis of database search during the past 15 years and our systematic review of prospective and retrospective cohorts, case-control trials, observational studies and animal data identified a possible link between MetS-induced inflammation and LUTS including BPH, bladder outlet obstruction, overactive bladder, urinary incontinence and other possible urinary tract abnormalities.
CONCLUSIONS
There is convincing evidence to suggest that MetS and inflammation could be important contributors to LUTS in men, particularly in the development of BPH. However, the role of MetS-induced inflammation remains unclear in overactive bladder, urinary incontinence and etiology of LUTS progression.
Topics: Humans; Inflammation; Lower Urinary Tract Symptoms; Male; Metabolic Syndrome; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Urinary Bladder
PubMed: 26391088
DOI: 10.1038/pcan.2015.43 -
Journal of Cancer 2020: No consensus has been reached on the definite associations among prostatitis, benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Hence, this meta-analysis...
: No consensus has been reached on the definite associations among prostatitis, benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Hence, this meta-analysis was conducted to explore their triadic relation by summarizing epidemiological evidence. : Systematical and comprehensive retrieval of online databases PubMed, PMC, EMBASE and Web of Science was performed to acquire eligible studies, up to April 1st, 2019. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to clarify their correlations. : A total of 42 studies were enrolled in the quality assessment and 35 were finally included in the meta-analyses. Among them, 27 studies were included to describe the association between prostatitis and PCa (OR=1.72, 95% CI=1.44-2.06, =90.1%, <0.001). 21 studies presented significant evidence about the relation between BPH and PCa (OR=2.16, 95% CI=1.75-2.88, =97.1%, <0.001). Due to the huge heterogeneity among studies, those with obvious outliers were excluded based on the Galbraith plots. Ultimately, 17 studies were screened out to assess the association between prostatitis and PCa (OR=1.59, 95% CI=1.48-1.70, =29.4%, =0.123). Meanwhile, 8 studies were retained to evaluate the association between BPH and PCa (OR=3.10, 95% CI=2.87-3.35, =8.4%, =0.365). As for the relation between prostatitis and BPH, a case-control study and a cohort study both supported that prostatitis could enhance the risk of BPH. : Significant correlations were revealed among prostatitis, BPH and PCa. Prostatitis or BPH could lead to escalating risks of PCa. Meanwhile, people with a history of prostatitis might be more vulnerable to BPH.
PubMed: 31892984
DOI: 10.7150/jca.37235 -
European Urology Dec 2014An association between tobacco smoking and prostate cancer (PCa) incidence and mortality was suggested in an earlier meta-analysis of 24 prospective studies in which... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
An association between tobacco smoking and prostate cancer (PCa) incidence and mortality was suggested in an earlier meta-analysis of 24 prospective studies in which dose-response associations and risks per unit of tobacco use were not examined.
OBJECTIVE
We investigated the association between several measures of tobacco use and PCa mortality (primary outcome) and incidence (secondary outcome) including dose-response association.
EVIDENCE ACQUISITION
Relevant articles from prospective studies were identified by searching the PubMed and Web of Science databases (through January 21, 2014) and reference lists of relevant articles. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random effects methods. We also calculated population attributable risk (PAR) for smoking and PCa mortality.
EVIDENCE SYNTHESIS
We included 51 articles in this meta-analysis (11823 PCa deaths, 50349 incident cases, and 4,082,606 cohort participants). Current cigarette smoking was associated with an increased risk of PCa death (RR: 1.24; 95% CI, 1.18-1.31), with little evidence for heterogeneity and publication bias. The number of cigarettes smoked per day had a dose-response association with PCa mortality (p=0.02; RR for 20 cigarettes per day: 1.20). The PAR for cigarette smoking and PCa deaths in the United States and Europe were 6.7% and 9.5%, respectively, corresponding to >10000 deaths/year in these two regions. Current cigarette smoking was inversely associated with incident PCa (RR: 0.90; 95% CI, 0.85-0.96), with high heterogeneity in the results. However, in studies completed in 1995 or earlier (considered as completed before the prostate-specific antigen screening era), ever smoking showed a positive association with incident PCa (RR: 1.06; 95% CI, 1.00-1.12) with little heterogeneity.
CONCLUSIONS
Combined evidence from observational studies shows a modest but statistically significant association between cigarette smoking and fatal PCa. Smoking appears to be a modifiable risk factor for PCa death.
PATIENT SUMMARY
Smoking increases the chance of prostate cancer death. Not smoking prevents this harm and many other tobacco-related diseases.
Topics: Humans; Incidence; Male; Observational Studies as Topic; Prospective Studies; Prostatic Neoplasms; Risk Factors; Smoking; Tobacco Products
PubMed: 25242554
DOI: 10.1016/j.eururo.2014.08.059 -
Current Oncology (Toronto, Ont.) Oct 2023Prostate cancer ranks as the second most common malignancy in males. Prostate cancer progressing on androgen deprivation therapy (ADT) is castration-resistant prostate... (Meta-Analysis)
Meta-Analysis Review
Prostate cancer ranks as the second most common malignancy in males. Prostate cancer progressing on androgen deprivation therapy (ADT) is castration-resistant prostate cancer (CRPC). Poly-ADP ribose polymerase (PARP) inhibitors (PARPis) have been at the forefront of the treatment of CRPC. We aim to better characterize the progression-free survival (PFS) and overall survival (OS) in metastatic CRPC patients treated with PARPis. A systemic review search was conducted using National Clinical Trial (NCT), PubMed, Embase, Scopus, and Central Cochrane Registry. The improvement in overall survival was statistically significant, favoring PARPis (hazard ratio (HR) 0.855; 95% confidence interval (CI) 0.752-0.974; = 0.018). The improvement in progression-free survival was also statistically significant, with results favoring PARPis (HR 0.626; 95%CI 0.566-0.692; = 0.000). In a subgroup analysis, similar results were observed where the efficacy of PARPis was evaluated in a subgroup of patients without homologous recombination repair (HRR) gene mutation, which showed improvement in PFS favoring PARPis (HR 0.747; 95%CI 0.0.637-0.877; = 0.000). Our meta-analysis of seven RCTs showed that PARPis significantly increased PFS and OS when used with or without antihormonal agents like abiraterone or enzalutamide.
Topics: Humans; Male; Androgen Antagonists; Poly(ADP-ribose) Polymerase Inhibitors; Progression-Free Survival; Prostatic Neoplasms, Castration-Resistant; Randomized Controlled Trials as Topic
PubMed: 37887569
DOI: 10.3390/curroncol30100669 -
European Urology Dec 2015Given the highly variable behavior and clinical course of prostate cancer (PCa) and the multiple available treatment options, a personalized approach to oncologic risk... (Review)
Review
CONTEXT
Given the highly variable behavior and clinical course of prostate cancer (PCa) and the multiple available treatment options, a personalized approach to oncologic risk stratification is important. Novel genetic approaches offer additional information to improve clinical decision making.
OBJECTIVE
To review the use of genomic biomarkers in the prognostication of PCa outcome and prediction of therapeutic response.
EVIDENCE ACQUISITION
Systematic literature review focused on human clinical studies reporting outcome measures with external validation. The literature search included all Medline, Embase, and Scopus articles from inception through July 2014.
EVIDENCE SYNTHESIS
An improved understanding of the genetic basis of prostate carcinogenesis has produced an increasing number of potential prognostic and predictive tools, such as transmembrane protease, serine2:v-ets avian erythroblastosis virus E26 oncogene homolog (TMPRSS2:ERG) gene fusion status, loss of the phosphatase and tensin homolog (PTEN) gene, and gene expression signatures utilizing messenger RNA from tumor tissue. Several commercially available gene panels with external validation are now available, although most have yet to be widely used. The most studied commercially available gene panels, Prolaris, Oncotype DX Genomic Prostate Score, and Decipher, may be used to estimate disease outcome in addition to clinical parameters or clinical nomograms. ConfirmMDx is an epigenetic test used to predict the results of repeat prostate biopsy after an initial negative biopsy. Additional future strategies include using genetic information from circulating tumor cells in the peripheral blood to guide treatment decisions at the initial diagnosis and at subsequent decision points.
CONCLUSIONS
Major advances have been made in our understanding of PCa biology in recent years. Our field is currently exploring the early stages of a personalized approach to augment traditional clinical decision making using commercially available genomic tools. A more comprehensive appreciation of value, limitations, and cost is important.
PATIENT SUMMARY
We summarized current advances in genomic testing in prostate cancer with a special focus on the estimation of disease outcome. Several commercial tests are currently available, but further understanding is needed to appreciate the potential benefits and limitations of these novel tests.
Topics: Genomics; Humans; Male; Prognosis; Prostatic Neoplasms; Treatment Outcome
PubMed: 25913390
DOI: 10.1016/j.eururo.2015.04.008 -
European Urology Jul 2021Castration-resistant prostate cancer (CRPC) treatment is an evolving challenge. Prostate-specific membrane antigen (PSMA)-targeted endoradiotherapy/radioligand therapy... (Meta-Analysis)
Meta-Analysis
A Systematic Review and Meta-analysis of the Effectiveness and Toxicities of Lutetium-177-labeled Prostate-specific Membrane Antigen-targeted Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer.
CONTEXT
Castration-resistant prostate cancer (CRPC) treatment is an evolving challenge. Prostate-specific membrane antigen (PSMA)-targeted endoradiotherapy/radioligand therapy (PRLT) with small-molecule, urea-based agents labeled with the β-particle-emitting radionuclide lutetium-177 (Lu) is a promising new approach.
OBJECTIVE
In this systematic review and meta-analysis, we evaluated the efficacy and toxicity of PRLT.
EVIDENCE ACQUISITION
A systematic search was performed in PubMed/Medline (last updated February 18, 2019). A total of 250 studies were reviewed, and 24 studies with 1192 patients were included in the analysis. Proportions of patients with ≥50% serum prostate-specific antigen (PSA) decrease, any PSA decrease, and any PSA increase were extracted. Proportions of patients showing any grade toxicity and those with grade 3/4 toxicities based on Common Terminology Criteria for Adverse Events (CTCAE) grading were extracted from manuscripts. Overall survival and progression-free survival were evaluated. A meta-analysis of single proportions was carried out. Furthermore, we compared the two most common PRLT agents, Lu-PSMA with Lu-PSMA-I&T, for effectiveness and toxicity.
EVIDENCE SYNTHESIS
Among the 24 included studies, 20 included data on Lu-PSMA-617, three included data on Lu-PSMA-I&T, and one study had aggregated data for Lu-PSMA-617 and Lu-PSMA-I&T. The estimated proportion of Lu-PSMA-617-treated patients who showed a serum PSA decrease of ≥50% with at least an 8-wk interval between therapy and PSA measurement was 0.44 (0.39; 0.50). Therapy with Lu-PSMA-I&T demonstrated an estimated proportion of patients with ≥50% PSA reduction to be 0.36 (0.26; 0.47). The aggregate results for men treated with more than one cycle of any kind of PRLT showed an estimated proportion of 0.46 (0.41; 0.51) for PSA response ≥50%. Regarding aggregate data from all of the PRLT agents, we found that grade 3 and 4 toxicities were uncommon, with estimated proportions from 0.01 (0.00;0.04) for nausea, fatigue, diarrhea, and elevated aspartate transaminase up to 0.08 (0.05; 0.12) for anemia. There was considerable heterogeneity among the studies in the "any-grade toxicity" groups. Meta-regression showed that more than one cycle of PRLT is associated with a greater proportion of patients with ≥50% PSA reduction. Overall survival according to pooled hazard ratios (HRs) for any PSA decline was 0.29 (0.18; 0.46), and for >50% PSA reduction was 0.67 (0.43; 1.07). Progression-free survival according to a pooled HR of >50% PSA reduction was 0.53 (0.32; 0.86).
CONCLUSIONS
The relatively high number of PSA responders alongside the low rate of severe toxicity reflects the potentially promising role of PRLT in treating CRPC. The ultimate utility of this treatment modality will become clearer as multiple prospective studies continue to accrue. In the interim, this systematic review and meta-analysis can serve as a compendium of effectiveness and adverse events associated with PRLT for treating clinicians.
PATIENT SUMMARY
Prostate-specific membrane antigen-targeted endoradiotherapy/radioligand therapy (PRLT) is associated with ≥50% reduction in prostate-specific antigen level in a large number of patients and a low rate of toxicity, reflecting its potential in treating castration-resistant prostate cancer. This systematic review and meta-analysis presents as a compendium of the effectiveness and adverse events related to PRLT for treating clinicians.
Topics: Dipeptides; Heterocyclic Compounds, 1-Ring; Humans; Lutetium; Male; Prospective Studies; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radioisotopes; Treatment Outcome
PubMed: 33840558
DOI: 10.1016/j.eururo.2021.03.004 -
Minerva Urologica E Nefrologica = the... Feb 2018To evaluate the available evidence on the standard diagnosis and management of men with metastatic castration resistant prostate cancer (mCRPC), and providing the timely... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
To evaluate the available evidence on the standard diagnosis and management of men with metastatic castration resistant prostate cancer (mCRPC), and providing the timely update on new pharmacological treatments.
EVIDENCE ACQUISITION
A systematic literature search from from January 2000 until March 2017 was performed by combining the following MESH terms: castrate resistant prostate cancer, abiraterone, enzalutamide, 223radium, sipuleucel-T, docetaxel, cabazitaxel, resistance mechanisms, resistance to androgen deprivation, androgen receptor (AR) mutations, amplifications, splice variants, and AR alterations. We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA).
EVIDENCE SYNTHESIS
In the few last years the introduction of new treatment modalities as abiraterone or enzalutamide have significantly change our prospective in mCRPC management increasing patients survival and quality of life. The standard imaging modalities to define the presence of regional or distant metastasis or the different resistant mechanisms to the available treatments are still an issue of debate, however several studies are ongoing to define the standard of care and to reduce treatments' resistance. Data from ongoing phase III trials are awaited to introduce in clinical new effective treatments that can be used in patients resistant to abiraterone/enzalutamide or more probably in a different phase of the disease.
CONCLUSIONS
Castration resistant prostate cancer is now the key issue in prostate cancer management and research. Our challenge in the near future will be to identify the right treatment or better the right combination and sequencing of treatments that should be used in patients with mCRPC or even with advanced prostate cancer.
Topics: Humans; Male; Prostatic Neoplasms, Castration-Resistant; Quality of Life
PubMed: 28707844
DOI: 10.23736/S0393-2249.17.02976-9 -
Minerva Urologica E Nefrologica = the... Dec 2017The aim of our work was to evaluate the role of multi-parametric magnetic resonance imaging (mpMRI) in detection and management of prostate cancer (PC); specifically... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The aim of our work was to evaluate the role of multi-parametric magnetic resonance imaging (mpMRI) in detection and management of prostate cancer (PC); specifically investigating the efficacy of mpMRI-based biopsy techniques in terms of diagnostic yield of significant prostate neoplasm and the improved management of patients who choose conservative treatments or active surveillance.
EVIDENCE ACQUISITION
A systematic and critical analysis through Medline, Embase, Scopus and Web of Science databases was carried out in March 2016, following the PRISMA ("Preferred Reporting Items for Systematic Reviews and Meta-Analyses") statement. The search was conducted using the following key words: "MRI/TRUS-fusion biopsy," "PIRADS," "prostate cancer," "magnetic resonance imaging (MRI)," "multiparametric MRI (mpMRI)," "systematic prostate biopsy (SB)," "targeted prostate biopsy (TPB)." English language articles were reviewed for inclusion ability.
EVIDENCE SYNTHESIS
Sixty-six studies were selected in order to evaluate the characteristics and limitations of traditional sample biopsy, the role of mpMRI in detection of PC, specifically the increased degree of diagnostic accuracy of targeted prostate biopsy compared to systematic biopsy (12 cores), and to transperineal saturation biopsies with trans-rectal ultrasound (TRUS) only. MpMRI can detect index lesions in approximately 90% of cases when compared to prostatectomy specimen. The diagnostic performance of biparametric MRI (T2w + DWI) is not inferior to mpMRI, offering valid options to diminish cost- and time-consumption. Since approximately 10% of significant lesions are still MRI-invisible, systematic cores biopsy seem to still be necessary. The analysis of the different techniques shows that in-bore MRI-guided biopsy and MRI/TRUS-fusion-guided biopsy are superior in detection of significant PC compared to visual estimation alone. MpMRI proved to be very effective in active surveillance, as it prevents underdetection of significant PC and it assesses low-risk disease accurately. In higher-risk disease, presurgical MRI may change the clinically-based surgical plan in up to a third of cases.
CONCLUSIONS
Targeted prostate biopsy, guided by mpMRI, is able to improve diagnostic accuracy and to reduce the detection of insignificant PC. Since the negative predictive value (NPV) of mpMRI is still imperfect, systematic cores biopsy should not be omitted for optimal staging of disease. A process of a progressive and periodic evolution in the detection and radiological classification of prostate lesions (such as PIRADS), is still needed in patients in active surveillance and in radical prostatectomy planning.
Topics: Humans; Image-Guided Biopsy; Magnetic Resonance Imaging; Male; Neoplasm Staging; Prostatic Neoplasms
PubMed: 28488844
DOI: 10.23736/S0393-2249.17.02819-3