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JAMA Oncology Jun 2024Prostate magnetic resonance imaging (MRI) is increasingly integrated within the prostate cancer (PCa) early detection pathway. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Prostate magnetic resonance imaging (MRI) is increasingly integrated within the prostate cancer (PCa) early detection pathway.
OBJECTIVE
To systematically evaluate the existing evidence regarding screening pathways incorporating MRI with targeted biopsy and assess their diagnostic value compared with prostate-specific antigen (PSA)-based screening with systematic biopsy strategies.
DATA SOURCES
PubMed/MEDLINE, Embase, Cochrane/Central, Scopus, and Web of Science (through May 2023).
STUDY SELECTION
Randomized clinical trials and prospective cohort studies were eligible if they reported data on the diagnostic utility of prostate MRI in the setting of PCa screening.
DATA EXTRACTION
Number of screened individuals, biopsy indications, biopsies performed, clinically significant PCa (csPCa) defined as International Society of Urological Pathology (ISUP) grade 2 or higher, and insignificant (ISUP1) PCas detected were extracted.
MAIN OUTCOMES AND MEASURES
The primary outcome was csPCa detection rate. Secondary outcomes included clinical insignificant PCa detection rate, biopsy indication rates, and the positive predictive value for the detection of csPCa.
DATA SYNTHESIS
The generalized mixed-effect approach with pooled odds ratios (ORs) and random-effect models was used to compare the MRI-based and PSA-only screening strategies. Separate analyses were performed based on the timing of MRI (primary/sequential after a PSA test) and cutoff (Prostate Imaging Reporting and Data System [PI-RADS] score ≥3 or ≥4) for biopsy indication.
RESULTS
Data were synthesized from 80 114 men from 12 studies. Compared with standard PSA-based screening, the MRI pathway (sequential screening, PI-RADS score ≥3 cutoff for biopsy) was associated with higher odds of csPCa when tests results were positive (OR, 4.15; 95% CI, 2.93-5.88; P ≤ .001), decreased odds of biopsies (OR, 0.28; 95% CI, 0.22-0.36; P ≤ .001), and insignificant cancers detected (OR, 0.34; 95% CI, 0.23-0.49; P = .002) without significant differences in the detection of csPCa (OR, 1.02; 95% CI, 0.75-1.37; P = .86). Implementing a PI-RADS score of 4 or greater threshold for biopsy selection was associated with a further reduction in the odds of detecting insignificant PCa (OR, 0.23; 95% CI, 0.05-0.97; P = .048) and biopsies performed (OR, 0.19; 95% CI, 0.09-0.38; P = .01) without differences in csPCa detection (OR, 0.85; 95% CI, 0.49-1.45; P = .22).
CONCLUSION AND RELEVANCE
The results of this systematic review and meta-analysis suggest that integrating MRI in PCa screening pathways is associated with a reduced number of unnecessary biopsies and overdiagnosis of insignificant PCa while maintaining csPCa detection as compared with PSA-only screening.
Topics: Humans; Male; Prostatic Neoplasms; Magnetic Resonance Imaging; Early Detection of Cancer; Prostate-Specific Antigen
PubMed: 38576242
DOI: 10.1001/jamaoncol.2024.0734 -
International Journal of Molecular... Aug 2020Prostate cancer is a major cause of death among men worldwide. Recent preclinical evidence implicates cannabinoids as powerful regulators of cell growth and... (Review)
Review
Prostate cancer is a major cause of death among men worldwide. Recent preclinical evidence implicates cannabinoids as powerful regulators of cell growth and differentiation, as well as potential anti-cancer agents. The aim of this review was to evaluate the effect of cannabinoids on in vivo prostate cancer models. The databases searched included PubMed, Embase, Scopus, and Web of Science from inception to August 2020. Articles reporting on the effect of cannabinoids on prostate cancer were deemed eligible. We identified six studies that were all found to be based on in vivo/xenograft animal models. Results: In PC3 and DU145 xenografts, WIN55,212-2 reduced cell proliferation in a dose-dependent manner. Furthermore, in LNCaP xenografts, WIN55,212-2 reduced cell proliferation by 66-69%. PM49, which is a synthetic cannabinoid quinone, was also found to result in a significant inhibition of tumor growth of up to 90% in xenograft models of LNCaP and 40% in xenograft models of PC3 cells, respectively. All studies have reported that the treatment of prostate cancers in in vivo/xenograft models with various cannabinoids decreased the size of the tumor, the outcomes of which depended on the dose and length of treatment. Within the limitation of these identified studies, cannabinoids were shown to reduce the size of prostate cancer tumors in animal models. However, further well-designed and controlled animal studies are warranted to confirm these findings.
Topics: Animals; Benzoxazines; Cannabinoids; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Humans; Male; Morpholines; Naphthalenes; PC-3 Cells; Prostatic Neoplasms; Tumor Burden; Xenograft Model Antitumor Assays
PubMed: 32872551
DOI: 10.3390/ijms21176265 -
BMC Public Health Jun 2023Association of cigarette smoking habits with the risk of prostate cancer is still a matter of debate. This systematic review and meta-analysis aimed to assess the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Association of cigarette smoking habits with the risk of prostate cancer is still a matter of debate. This systematic review and meta-analysis aimed to assess the association between cigarette smoking and prostate cancer risk.
METHODS
We conducted a systematic search on PubMed, Embase, Cochrane Library, and Web of Science without language or time restrictions on June 11, 2022. Literature search and study screening were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Prospective cohort studies that assessed the association between cigarette smoking habits and the risk of prostate cancer were included. Quality assessment was conducted using the Newcastle-Ottawa Scale. We used random-effects models to obtain pooled estimates and the corresponding 95% confidence intervals.
RESULTS
A total of 7296 publications were screened, of which 44 cohort studies were identified for qualitative analysis; 39 articles comprising 3 296 398 participants and 130 924 cases were selected for further meta-analysis. Current smoking had a significantly reduced risk of prostate cancer (RR, 0.74; 95% CI, 0.68-0.80; P < 0.001), especially in studies completed in the prostate-specific antigen screening era. Compared to former smokers, current smokers had a significant lower risk of PCa (RR, 0.70; 95% CI, 0.65-0.75; P < 0.001). Ever smoking showed no association with prostate cancer risk in overall analyses (RR, 0.96; 95% CI, 0.93-1.00; P = 0.074), but an increased risk of prostate cancer in the pre-prostate-specific antigen screening era (RR, 1.05; 95% CI, 1.00-1.10; P = 0.046) and a lower risk of prostate cancer in the prostate-specific antigen screening era (RR, 0.95; 95% CI, 0.91-0.99; P = 0.011) were observed. Former smoking did not show any association with the risk of prostate cancer.
CONCLUSIONS
The findings suggest that the lower risk of prostate cancer in smokers can probably be attributed to their poor adherence to cancer screening and the occurrence of deadly smoking-related diseases, and we should take measures to help smokers to be more compliant with early cancer screening and to quit smoking.
TRIAL REGISTRATION
This study was registered on PROSPERO (CRD42022326464).
Topics: Male; Humans; Cigarette Smoking; Prostate-Specific Antigen; Prospective Studies; Smoking; Prostatic Neoplasms; Habits
PubMed: 37316851
DOI: 10.1186/s12889-023-16085-w -
Seminars in Oncology Oct 2022Prostate cancer is the second most common cause of cancer-related mortality in men. In patients undergoing a failure after radical treatment, one of the therapeutic... (Meta-Analysis)
Meta-Analysis Review
Prostate cancer is the second most common cause of cancer-related mortality in men. In patients undergoing a failure after radical treatment, one of the therapeutic option is androgen deprivation: despite initial response rates, a progression to a state of castration resistance is observed in most of the patients. In the present article, we conducted a systematic review and meta-analysis of all clinical trials assessing treatment for nmCRPC with next-generation androgen receptor inhibitors. We performed a review and meta-analysis of phase III randomized controlled trials comparing new agents (apalutamide, enzalutamide, darolutamide) with placebo as control arm, in the setting of nmCRPC. Patients treated with next-generation ARIs had a 26% reduction in the risk of death compared with placebo; compared with other ARIs, darolutamide had the lowest rate of grade 3 and 4 AEs and the lowest therapy discontinuation rate due to any grade AEs. This meta-analysis shows that treatment with new ARIs is safe and significantly reduces the risk of death and of metastasis onset in nmCRPC patients. Under way studies on new biomarkers such as genomic classifiers will probably allow the stratification in more specific subsets of disease. New imaging modalities such as PSMA-PET have shown greater sensibility and specificity than conventional imaging in metastases detection. All patients were randomized in a 2:1 fashion, with a total of 2,694 who underwent next-generation ARIs (806 apalutamide, 955 darolutamide, 933 enzalutamide) and 1,423 in the placebo arm.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; Androgen Antagonists; Radiation Oncologists; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 36192243
DOI: 10.1053/j.seminoncol.2022.09.005 -
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 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 -
African Journal of Reproductive Health Dec 2020Male genital schistosomiasis (MGS) may result in eggs lodged in the prostate causing persistent inflammation that may play a major role in prostate carcinogenesis.... (Review)
Review
Male genital schistosomiasis (MGS) may result in eggs lodged in the prostate causing persistent inflammation that may play a major role in prostate carcinogenesis. Globally, prostate cancer (PCa) is one of the most common cancers and the global distribution of PCa overlaps with that of schistosomiasis infections, suggesting a probable causal relationship. Objectives of this review were to assess evidence of co-existence of schistosomiasis and PCa and possible causal association between the two diseases. Relevant literature published between 1950 and 2019 yielded 20 publications on schistosomiasis and PCa co-existence. Schistosoma (S.) haematobium and S. mansoni were associated with MGS manifestation and mostly prostate adenocarcinoma diagnosis. Effects of prostatic MGS infection progressed over time with high Schistosoma egg burden thought to contribute to the development of PCa. Causal association and mechanistic pathways of MGS on PCa development and the role of Schistosoma eggs on the development of PCa remains unestablished.
Topics: Adenocarcinoma; Animals; Humans; Male; Prostatic Neoplasms; Schistosoma haematobium; Schistosomiasis
PubMed: 34077083
DOI: 10.29063/ajrh2020/v24i4.19 -
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 -
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