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Prostate Cancer and Prostatic Diseases Dec 2023Artificial intelligence (AI) is a promising tool in pathology, including cancer diagnosis, subtyping, grading, and prognostic prediction. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Artificial intelligence (AI) is a promising tool in pathology, including cancer diagnosis, subtyping, grading, and prognostic prediction.
METHODS
The aim of the study is to assess AI application in prostate cancer (PCa) histology. We carried out a systematic literature search in 3 databases. Primary outcome was AI accuracy in differentiating between PCa and benign hyperplasia. Secondary outcomes were AI accuracy in determining Gleason grade and agreement among AI and pathologists.
RESULTS
Our final sample consists of 24 studies conducted from 2007 to 2021. They aggregate data from roughly 8000 cases of prostate biopsy and 458 cases of radical prostatectomy (RP). Sensitivity for PCa diagnostic exceeded 90% and ranged from 87% to 100%, and specificity varied from 68% to 99%. Overall accuracy ranged from 83.7% to 98.3% with AUC reaching 0.99. The meta-analysis using the Mantel-Haenszel method showed pooled sensitivity of 0.96 with I = 80.7% and pooled specificity of 0.95 with I = 86.1%. Pooled positive likehood ratio was 15.3 with I = 87.3% and negative - was 0.04 with I = 78.6%. SROC (symmetric receiver operating characteristics) curve represents AUC = 0.99. For grading the accuracy of AI was lower: sensitivity for Gleason grading ranged from 77% to 87%, and specificity from 82% to 90%.
CONCLUSIONS
The accuracy of AI for PCa identification and grading is comparable to expert pathologists. This is a promising approach which has several possible clinical applications resulting in expedite and optimize pathology reports. AI introduction into common practice may be limited by difficult and time-consuming convolutional neural network training and tuning.
Topics: Male; Humans; Prostate; Prostatic Neoplasms; Artificial Intelligence; Prostatectomy; Prognosis; Neoplasm Grading
PubMed: 37185992
DOI: 10.1038/s41391-023-00673-3 -
Prostate Cancer and Prostatic Diseases Dec 2023The goal of precision medicine in prostate cancer (PCa) is to individualize the treatment according to the patient's germline mutation status. PCa has a very high rate... (Review)
Review
BACKGROUND
The goal of precision medicine in prostate cancer (PCa) is to individualize the treatment according to the patient's germline mutation status. PCa has a very high rate of genetic predisposition compared with other cancers in men, with an estimated rate of cancers ascribable to hereditary factors of 5-15%.
METHODS
A systematic search (PubMed, Web of Science, and ClinicalTrials.gov) of English literature from 2000 to 2022, using the keywords "prostate cancer", "germline mutations", "family history", and "inheritance" was conducted, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.
RESULTS
The search identified 980 publications. Of these, 200 papers were removed before screening (duplicates, non-English literature, and publication year before 2000) and 245 records were excluded after title/abstract screening. Finally, 50 articles were included in the final analysis. We analyze the latest evidence on the genetic basis of PCa predisposition and clinical implications for more personalized screening protocols and therapeutic management of this high-prevalent cancer.
DISCUSSION
Emerging data show that germline mutations in homologous recombination genes (BRCA1/2, ATM, CHECK2), in mismatch repair genes (MLH1, MLH2, MSH6), and other additional genes are associated with the development and aggressiveness of PCa. Germline testing and genetic counseling have increasingly important implications in cancer screening and therapeutic decisions making for patients affected by PCa. Patients with localized PCa and some gene mutations are more likely to develop aggressive cancer, so active treatment may be preferable to active surveillance for these patients. Moreover, in patients with metastatic PCa, these gene alterations may be useful biomarkers for predicting response to specific therapy such as PARP inhibitors, recently approved for the treatment of metastatic castration-resistant PCa. The evidence supports recent guidelines and recommendations considering germline genetic testing for patients with a positive family history of PCa or men with high risk or metastatic disease.
Topics: Male; Humans; Prostatic Neoplasms; Germ-Line Mutation; BRCA1 Protein; Precision Medicine; BRCA2 Protein
PubMed: 36434163
DOI: 10.1038/s41391-022-00609-3 -
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 -
Prostate Cancer and Prostatic Diseases Jun 2024Prostate cancer (PCa), one of the most prevalent malignancies affecting men, significantly contributes to increased mortality rates worldwide. While the causative death... (Review)
Review
BACKGROUND
Prostate cancer (PCa), one of the most prevalent malignancies affecting men, significantly contributes to increased mortality rates worldwide. While the causative death is due to advanced metastatic disease, this occurrence disproportionately impacts men of African descent compared to men of European descent. In this review, we describe potential mechanisms underlying PCa metastases disparities and current treatments for metastatic disease among these populations, differences in treatment outcomes, and survival rates, in hopes of highlighting a need to address disparities in PCa metastases.
METHODS
We reviewed existing literature using databases such as PubMed, Google Scholar, and Science Direct using the following keywords: "prostate cancer metastases", "metastatic prostate cancer disparity", "metastatic prostate cancer diagnosis and treatment", "prostate cancer genetic differences and mechanisms", "genetic differences and prostate tumor microenvironment", and "men of African descent and access to clinical treatments". The inclusion criteria for literature usage were original research articles and review articles.
RESULTS
Studies indicate unique genetic signatures and molecular mechanisms such as Epithelial-Mesenchymal Transition (EMT), inflammation, and growth hormone signaling involved in metastatic PCa disparities. Clinical studies also demonstrate differences in treatment outcomes that are race-specific, for example, patients of African descent have a better response to enzalutamide and immunotherapy yet have less access to these drugs as compared to patients of European descent.
CONCLUSIONS
Growing evidence suggests a connection between a patient's genetic profile, the prostate tumor microenvironment, and social determinants of health that contribute to the aggressiveness of metastatic disease and treatment outcomes. With several potential pathways highlighted, the limitations in current diagnostic and therapeutic applications that target disparity in PCa metastases warrant rigorous research attention.
Topics: Humans; Prostatic Neoplasms; Male; Neoplasm Metastasis; Tumor Microenvironment; Healthcare Disparities; Health Status Disparities; Epithelial-Mesenchymal Transition
PubMed: 37046071
DOI: 10.1038/s41391-023-00667-1 -
The Journal of Urology Sep 2023There are limited pooled data showing the impact of visceral metastasis on oncologic outcomes in metastatic prostate cancer patients treated with combination systemic... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
There are limited pooled data showing the impact of visceral metastasis on oncologic outcomes in metastatic prostate cancer patients treated with combination systemic therapies. We aimed to analyze and compare the efficacy of combination systemic therapies in metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer with or without visceral metastasis.
MATERIALS AND METHODS
Three databases were queried in July 2022 for randomized, controlled trials analyzing metastatic prostate cancer patients treated with combination systemic therapy (androgen receptor signaling inhibitor and/or docetaxel plus androgen deprivation therapy) to standard of care. We analyzed the association between presence of visceral metastases and efficacy of systemic therapies in metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer patients. The main and secondary outcomes of interest were overall survival and progression-free survival, respectively. Formal meta-analysis using fixed-effect model and network meta-analysis using random-effect model were conducted. We followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) and AMSTAR (A MeaSurement Tool to Assess systematic Reviews) guidelines.
RESULTS
Overall, 12 and 8 randomized, controlled trials were included for systematic review and meta-analyses/network meta-analyses, respectively. In metastatic hormone-sensitive prostate cancer patients, adding androgen receptor signaling inhibitor to standard of care improved overall survival in patients with visceral metastasis (pooled HR: 0.77, 95% CI: 0.64-0.94) as well as in those without (pooled HR: 0.66, 95% CI: 0.60-0.72; no differences in both across- and within-trial approach; = .13 and = .06, respectively). On the other hand, the progression-free survival benefit from androgen receptor signaling inhibitor + androgen deprivation therapy was significantly lower in patients with visceral metastasis using across-trial approach ( = .03), while it did not reach statistical significance using within-trial approach ( = .14). Analysis of treatment ranking in metastatic hormone-sensitive prostate cancer showed that darolutamide + docetaxel + androgen deprivation therapy had the highest likelihood of improved overall survival irrespective of visceral metastasis. In post-docetaxel metastatic castration-resistant prostate cancer patients, adding androgen receptor signaling inhibitor to androgen deprivation therapy significantly improved overall survival in both patients with visceral metastasis (pooled HR: 0.79, 95% CI: 0.63-0.98) and those without (pooled HR: 0.63, 95% CI: 0.55-0.72). No randomized, controlled trials reported the differential oncologic outcomes stratified by lung vs liver metastases.
CONCLUSIONS
Despite aggressive clinical behavior and worse trajectory of metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer with visceral metastasis, the effectiveness of novel systemic therapies is similar in both metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer patients with and without visceral metastasis. Further well-designed studies with detailed visceral metastatic sites and number will enrich the clinical decision-making.
Topics: Male; Humans; Prostatic Neoplasms; Docetaxel; Prostatic Neoplasms, Castration-Resistant; Network Meta-Analysis; Androgen Antagonists; Receptors, Androgen; Androgens; Androgen Receptor Antagonists; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Metastasis
PubMed: 37339479
DOI: 10.1097/JU.0000000000003594 -
Journal of Medical Internet Research Apr 2021Machine learning algorithms have been drawing attention at the joining of pathology and radiology in prostate cancer research. However, due to their algorithmic learning... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Machine learning algorithms have been drawing attention at the joining of pathology and radiology in prostate cancer research. However, due to their algorithmic learning complexity and the variability of their architecture, there is an ongoing need to analyze their performance.
OBJECTIVE
This study assesses the source of heterogeneity and the performance of machine learning applied to radiomic, genomic, and clinical biomarkers for the diagnosis of prostate cancer. One research focus of this study was on clearly identifying problems and issues related to the implementation of machine learning in clinical studies.
METHODS
Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) protocol, 816 titles were identified from the PubMed, Scopus, and OvidSP databases. Studies that used machine learning to detect prostate cancer and provided performance measures were included in our analysis. The quality of the eligible studies was assessed using the QUADAS-2 (quality assessment of diagnostic accuracy studies-version 2) tool. The hierarchical multivariate model was applied to the pooled data in a meta-analysis. To investigate the heterogeneity among studies, I statistics were performed along with visual evaluation of coupled forest plots. Due to the internal heterogeneity among machine learning algorithms, subgroup analysis was carried out to investigate the diagnostic capability of machine learning systems in clinical practice.
RESULTS
In the final analysis, 37 studies were included, of which 29 entered the meta-analysis pooling. The analysis of machine learning methods to detect prostate cancer reveals the limited usage of the methods and the lack of standards that hinder the implementation of machine learning in clinical applications.
CONCLUSIONS
The performance of machine learning for diagnosis of prostate cancer was considered satisfactory for several studies investigating the multiparametric magnetic resonance imaging and urine biomarkers; however, given the limitations indicated in our study, further studies are warranted to extend the potential use of machine learning to clinical settings. Recommendations on the use of machine learning techniques were also provided to help researchers to design robust studies to facilitate evidence generation from the use of radiomic and genomic biomarkers.
Topics: Algorithms; Genomics; Humans; Machine Learning; Male; Prostatic Neoplasms
PubMed: 33792552
DOI: 10.2196/22394 -
Chinese Medical Journal Dec 2017The optimal management strategy for prostate cancer (PCa) remains controversial. We performed a systemic review of current progress and controversies regarding the... (Review)
Review
OBJECTIVE
The optimal management strategy for prostate cancer (PCa) remains controversial. We performed a systemic review of current progress and controversies regarding the diagnosis and treatment of PCa.
DATA SOURCES
We searched PubMed for recently published articles up to July 2017 using the following key words: "prostate cancer," "progress," "controversy," "immunotherapy," and "prevention."
STUDY SELECTION
Articles were obtained and reviewed to provide a systematic review of the current progress and controversies regarding PCa management.
RESULTS
The value of serum prostate-specific antigen (PSA) screening remains controversial, but PSA screening is recommended to facilitate the early diagnosis of PCa in high-risk groups. Prostate biopsy via the transrectal or perineal approach has both advantages and disadvantages. There was a significant correlation between testosterone levels and PCa prognosis. The current research is focused on the mechanisms responsible for PCa. Active surveillance has been proposed as a management strategy for low-risk, localized PCa, but there is an urgent need for further clinical studies to establish the criteria for recommending this approach. The main complications of radical resection for PCa are urinary incontinence and erectile dysfunction, though three-dimensional laparoscopic and robot-assisted laparoscopic techniques have obvious advantages over radical surgery. Radiotherapy is also a therapeutic option for PCa, while immunotherapies may alter the prostate tumor microenvironment. Ongoing studies aim to provide guidance on effective sequential and combination strategies. Prevention remains an important strategy for reducing PCa morbidity and mortality.
CONCLUSIONS
The diagnosis, treatment, and prevention of PCa are complex issues, worthy of intensive study. Further studies are needed to improve the management of PCa.
Topics: Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy
PubMed: 29237932
DOI: 10.4103/0366-6999.220317 -
Advanced Biology Jul 2023Extracellular vesicles (EVs) are emerging as biomarker candidates for early detection of prostate cancer. Studies compare EV-microRNA (miRNA) expression in individuals...
Extracellular vesicles (EVs) are emerging as biomarker candidates for early detection of prostate cancer. Studies compare EV-microRNA (miRNA) expression in individuals with prostate cancer (PCa) with cancer-free samples for diagnostic purposes. The aim of this study is to review miRNA signatures to investigate the overlap between miRNAs enriched in PCa tissue and miRNAs enriched in EVs isolated from subjects with PCa biofluids (i.e., urine, serum, and plasma). Signatures dysregulated in EVs from PCa biofluids and tissue are potentially associated with the primary tumor site and might be more indicative of PCa at an early stage. A systematic review of EV-derived miRNAs and a reanalysis of PCa tissue miRNA sequencing data for comparison is presented. Articles in the literature are screened for validated miRNA dysregulation in PCa and compared with TCGA primary PCa tumor data using DESeq2. This resulted in 190 dysregulated miRNAs being identified. Thirty-one eligible studies are identified, indicating 39 dysregulated EV-derived miRNAs. The top ten markers identified as significantly dysregulated in the PCa tissue dataset TCGA (e.g., miR-30b-3p, miR-210-3p, miR-126-3p, and miR-196a-5p) have a significant expression change in EVs with the same directionality in one or several statistically significant results. This analysis highlights several less frequently studied miRNAs in PCa literature.
Topics: Male; Humans; MicroRNAs; Prostatic Neoplasms; Extracellular Vesicles
PubMed: 37300338
DOI: 10.1002/adbi.202200327 -
Cancer Treatment Reviews Nov 2018While a number of studies indicate tobacco smoking has a detrimental impact on survival and recurrence after a prostate cancer diagnosis, there has been no quantitative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
While a number of studies indicate tobacco smoking has a detrimental impact on survival and recurrence after a prostate cancer diagnosis, there has been no quantitative review of this literature and it is unclear whether tobacco smoking affects clinical populations differentially. We conducted a systematic review and meta-analysis to investigate the associations between tobacco smoking and overall (OM) and prostate cancer-specific (PSM) mortality and recurrence after a prostate cancer diagnosis.
METHODS
EMBASE and ISI Web of Science were searched for English-language studies, published up to August 17, 2017, which conducted a survival analysis to estimate the association between tobacco smoking and OM, PSM and/or recurrence. A random-effects meta-analysis was conducted to estimate the summary hazard ratios (HRs) for the associations between tobacco smoking and the three outcomes.
RESULTS
A total of 28 studies met the inclusion criteria. The results of the primary meta-analysis indicate current smokers have significantly poorer overall survival (Summary HR = 1.96, 95% CI = 1.69, 2.28), prostate cancer-specific survival (Summary HR = 1.79, 95% CI = 1.47, 2.20) and recurrence-free survival (Summary HR = 1.48, 95% CI = 1.28, 1.72) than never smokers. Similar results were found in population-based studies and in studies conducted in specific clinical populations.
CONCLUSIONS
The results of this systematic review and meta-analysis indicate that tobacco smoking at prostate cancer diagnosis is associated with a significantly increased risk of overall mortality, prostate-cancer specific mortality and recurrence. We recommend future studies collect more detailed information about tobacco smoking to further understanding of the association between tobacco smoking and PCa prognosis. In addition, further research should concentrate on the impact of smoking cessation post-diagnosis and post-treatment on prognosis, and the feasibility and effectiveness of smoking cessation programs.
Topics: Humans; Male; Neoplasm Recurrence, Local; Prognosis; Prostatic Neoplasms; Risk Factors; Survival Rate; Tobacco Smoking
PubMed: 30055462
DOI: 10.1016/j.ctrv.2018.07.001 -
Histopathology Sep 2023Cribriform architecture has been recognised as an independent parameter for prostate cancer outcome. Little is yet known on the added value of individual Gleason 5... (Review)
Review
Cribriform architecture has been recognised as an independent parameter for prostate cancer outcome. Little is yet known on the added value of individual Gleason 5 growth patterns. Comedonecrosis is assigned Gleason pattern 5 and can occur in both invasive and intraductal carcinoma. The aim of this study is to systematically review the literature for the prognostic value of comedonecrosis in prostate cancer. A systematic literature search of Medline, Web of Science, Cochrane library and Google scholar was performed according to the Preferred reporting items for systematic reviews and meta-analysis (PRISMA)guidelines. After identification and screening of all relevant studies published up to July 2022, 12 manuscripts were included. Clinicopathological data were extracted and the presence of comedonecrosis in either invasive, intraductal or ductal carcinoma was associated with at least one clinical outcome measure. No meta-analysis was performed. Eight of 11 studies showed that comedonecrosis was significantly associated with biochemical recurrence and two studies with metastasis or death. The only studies using metastasis-free and disease specific-free survival as an endpoint both found comedonecrosis to be an independent prognostic parameter in multivariate analysis. The studies were all retrospective and demonstrated considerable heterogeneity with regard to clinical specimen, tumour type, grade group, correction for confounding factors and endpoints. This systematic review demonstrates weak evidence for comedonecrosis to be associated with adverse prostate cancer outcome. Study heterogeneity and lack of correction for confounding factors prohibit drawing of definitive conclusions.
Topics: Male; Humans; Retrospective Studies; Prostatic Neoplasms; Prognosis; Neoplasm Grading; Carcinoma, Ductal, Breast; Breast Neoplasms
PubMed: 37195595
DOI: 10.1111/his.14945