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Background/Aim: To evaluate the long-term oncological outcomes in men with intermediate risk prostate cancer (PCa) enrolled in active surveillance (AS). Patients and Methods: From April 2015 to December 2022, 30 men with Gleason score 3+4/ISUP Grade Group2 (GG2), greatest percentage of cancer (GPC) ≤50%, Gleason pattern 4 ≤10%, ≤3 positive biopsy cores were enrolled in AS. All patients underwent confirmatory transperineal saturation biopsy (SPBx: 20 cores) 12 months from diagnosis plus multiparametric magnetic resonance (mpMRI) evaluation. At the last follow-up, 68Ga prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) was added: lesions with PIRADS score ≥3 and/or standardized uptake value (SUVmax) >5 were submitted to four targeted cores. Results: Three out of 30 (10%) men with GG2 PCa were reclassified at confirmatory biopsy. At the last follow-up (median 5.2 years), only 2 of 27 (7.4%) men were reclassified and 23/30 (76.6%) continued AS. Conclusion: Men with favorable GG2 PCa enrolled in AS have good long-term oncological results. The use of selective criteria (i.e., SPBx, mpMRI, PSMA PET/CT) reduces the risk of reclassification. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases (CVDs) are a prominent cause of mortality in prostate cancer patients. However, it has been reported that patients with preexisting CVDs are at greater risk. Literature on the magnitude of this problem in Saudi Arabia is lacking. Objectives: To measure the prevalence of prostate cancer patients with preexisting CVDs in our population and to elucidate the possible risk factors of new cardiovascular events (CVEs) in patients who received androgen deprivation therapy (ADT). Materials and Methods: This retrospective study included all patients newly diagnosed with prostate cancer at a tertiary hospital in the Eastern Province of Saudi Arabia from October 2008 to January 2019. The prevalence of preexisting cardiovascular diseases in these patients were determined. In addition, the incidence of new CVEs after initiating ADT was determined along with the risk factors for the same. Results: The prevalence of preexisting CVD in our cohort was 16%. About 6% of the patients who received ADT had CVEs after a median follow-up of 39 months (IQR: 11-49 months). In the univariate analysis, hyperlipidemia (P = 0.002), stroke (P = 0.001), peripheral vascular disease (P = <0.001), cardiac patients with stents (P = <0.001), and cardiac patients without stent (P = <0.001) were significant risk factors of new CVEs after initiating ADT. However, in the multivariate regression analysis, only history of stroke and CVD (with or without stent) were found to be significant risk factors of new CVEs after initiating ADT (P = 0.01). Conclusion: About one-fifth of the prostate cancer patients had preexisting CVDs. This study also found that luteinizing hormone-releasing hormone agonist could be a risk factor for new CVEs. [ABSTRACT FROM AUTHOR]

Background Image-guided approaches improve the diagnostic yield of prostate biopsy and frequently modify estimates of clinical risk. To better understand the impact of magnetic resonance imaging–ultrasound fusion targeted biopsy (MRF-TB) on risk assessment, we compared the distribution of National Comprehensive Cancer Network (NCCN) risk groupings, as calculated from MRF-TB vs systematic biopsy alone. Methods We performed a retrospective analysis of 713 patients who underwent MRF-TB from January 2017 to July 2021. The primary study objective was to compare the distribution of National Comprehensive Cancer Network risk groupings obtained using MRF-TB (systematic + targeted) vs systematic biopsy. Results Systematic biopsy alone classified 10% of samples as very low risk and 18.7% of samples as low risk, while MRF-TB classified 10.5% of samples as very low risk and 16.1% of samples as low risk. Among patients with benign findings, low-risk disease, and favorable/intermediate-risk disease on systematic biopsy alone, 4.6% of biopsies were reclassified as high risk or very high risk on MRF-TB. Of 207 patients choosing active surveillance, 64 (31%), 91 (44%), 42 (20.2%), and 10 (4.8%) patients were classified as having very low-risk, low-risk, and favorable/intermediate-risk and unfavorable/intermediate-risk criteria, respectively. When using systematic biopsy alone, 204 patients (28.7%) were classified as having either very low-risk and low-risk disease per NCCN guidelines, while 190 men (26.6%) received this classification when using MRF-TB. Conclusion The addition of MRF-TB to systematic biopsy may change eligibility for active surveillance in only a small proportion of patients with prostate cancer. Our findings support the need for routine use of quantitative risk assessment over risk groupings to promote more nuanced decision making for localized cancer. [ABSTRACT FROM AUTHOR]

Purpose: Germline mutations in DNA damage repair (DDR) genes such as BRCA2 have been associated with prostate cancer (PC) risk but has not been thoroughly evaluated for metastatic prostate cancer (mPC) in Asian men. This study attempts to evaluate frequency of DDR mutations in the largest cohort of Koreans. Materials and Methods: We recruited 340 patients with mPC unselected for family history of cancer and compared to 495 controls. Whole genome sequencing was applied to assess germline pathogenic/likely pathogenic variants (PV/LPVs) in 26 DDR genes and HOXB13, including 7 genes (ATM, BRCA1/2, CHEK2, BRIP1, PALB2, and NBN) associated with hereditary PC. Comparisons to published Caucasian and Japanese cohorts were performed. Results: Total of 28 PV/LPVs were identified in 30 (8.8%) patients; mutations were found in 13 genes, including BRCA2 (15 men [4.41%]), ATM (2 men [0.59%]), NBN (2 men [0.59%], and BRIP1 (2 men [0.59%]). Only one patient had HOXB13 mutation (0.29%). A lower rate of overall germline variant frequency was observed in Korean mPC compared to Caucasians (8.8% vs. 11.8%), but individual variants notably differed from Caucasian and geographically similar Japanese cohorts. PV/ LPVs in DDR genes tended to increase gradually with higher Gleason scores (GS 7, 7.1%; GS 8, 7.5%; GS 9–10, 9.9%). Conclusions: BRCA2 was the most frequently mutated gene common to different cohorts supporting its importance, but differences in variant distribution in Korean mPC underscore the need for ethnic-specific genetic models. Future ethnic-specific analyses are warranted to verify our findings. [ABSTRACT FROM AUTHOR]

Background/Aim: Prostate cancer patients undergoing radiotherapy (RT) may experience distress. This study evaluated the course of distress during RT. Patients and Methods: Four distress characteristics were analyzed for change of distress in 136 patients irradiated for prostate cancer, including age, Karnofsky performance score, intent of RT, and previous RT. Results: Mean distress scores were 4.3 (±2.9) at baseline and 4.2 (±2.7) at the end of RT. Associations with increased distress were found for KPS >80 (p<0.001) and curative intent RT (p=0.072). When evaluating increased distress as binary variable (yes vs. no), KPS >80 was significant on univariable (p<0.001) and multivariable (p=0.016) analyses. In patients with baseline scores ≤5 points, KPS >80 was associated with mean change of distress (p=0.009) and increased distress (p=0.029). Conclusion: Many patients receiving RT for prostate cancer do not experience increased distress during their treatment course. Patients at higher risk of increased distress may require early psychological assistance. [ABSTRACT FROM AUTHOR]

Introduction and purpose: Prostate cancer is the second most frequent malignancy in men worldwide. The aim of this study is to analyze the key modifiable and non-modifiable risk factors associated with the development of prostate cancer and to discuss existing prevention strategies. Materials and methods: A literature review was conducted using the "PubMed" database with the keywords "prostate cancer", "prostate cancer risk factors", "prostate cancer prevention”. State of knowledge: Prostate cancer risk factors can be divided into two groups: modifiable and non-modifiable. Modifiable risk factors include: diet, infections and alcohol use. Non-modifiable risk factors include: age, race, genetic factors, and family history. Chemoprevention plays an important role in the prevention of prostate cancer. Summary: Despite the fact that prostate cancer remains a significant challenge for current medicine, the development of preventive methods in recent years gives hope for reducing mortality associated with the disease. Research is still being conducted to identify prostate cancer risk factors and to improve methods of primary and secondary prevention.

Introduction The aim of this study was to assess the association between the type and number of D'Amico high-risk criteria (DHRCs) with rates of pathologically non-organ-confined (NOC) prostate cancer in patients treated with radical prostatectomy (RP) and pelvic lymphadenectomy (PLND). Material and methods In the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 12961 RP and PLDN patients with at least one DHRC. We relied on descriptive statistics and multivariable logistic regression models. Results Of 12 961 patients, 6135 (47%) exclusively harboured biopsy Gleason score (GS) 8-10, 3526 (27%) had clinical stage ≥T2c, and 1234 (9.5%) had prostate-specific antigen (PSA) >20 ng/mL. Only 1886 (15%) harboured any combination of 2 DHRCs. Finally, all 3 DHRCs were present in 180 (1.4%) patients. NOC rates increased from 32% for clinical T stage ≥T2c to 49% for either GS 8-10 only or PSA >20 ng/mL only and to 66-68% for any combination of 2 DHRCs, and to 84% for respectively all 3 DHRCs, which resulted in a multivariable logistic regression OR of 1.00, 2.01 (95% CI 1.85-2.19; p <0.001), 4.16 (95% CI 3.69-4.68; p <0.001), and 10.83 (95% CI 7.35-16.52; p <0.001), respectively. Conclusions Our study indicates a stimulus-response effect according to the type and number of DHRCs. Hence, a formal risk-stratification within high-risk prostate cancer patients should be considered in clinical decision-making. [ABSTRACT FROM AUTHOR]

Genetic alterations are one of the important known risk factors of prostate cancer. The family predisposition of breast and ovarian cancers may cause the severe progression of familial prostate cancer in some men. The association of germline mutations in BRCA1 and BRCA2 genes can cause breast cancer in almost 35% of women and 9% of men. Carriers of these pathogenic variants have a higher risk of causing prostate cancer. This study focused on the analysis of mutations causing prostate cancer around the world, associated with breast cancer susceptibility genes. [ABSTRACT FROM AUTHOR]

The authors reviewed and sumarised the literature about active surveillance in prostate cancer. It provides a useful reference on patient selection criteria, surveillence investigations, barriers and enablers of active surveillence and evolving technologies that will be used in the future. The use of PSA screening has led to downstaging and downgrading of prostate cancer at diagnosis, increasing detection of indolent disease. Active surveillance aims to reduce over-treatment by delaying or avoiding radical treatment and its associated morbidity. However, there is not a consensus on the selection cr iter ia and monitoring schedules that should be used. This article aims to summarize the evidence supporting the safety of active surveillance, the current selection cr iter ia recommended and in use, the incidence of active surveillance, barriers existing to its uptake and future developments in patient selection. [ABSTRACT FROM AUTHOR]

DNA damage repair (DDR) pathways hold prognostic information in high-risk prostate cancer. Here, we investigated DDR in low-risk prostate cancer and demonstrated that high DDR is associated with poor clinical outcome and a distinct molecular subtype. Introduction: Understanding if divergent molecular profiles of DNA damage and repair (DDR) pathway activity, a biomarker of disease progression, exist in prostate tumors with favorable-risk features is an unmet need, which this study aim to unearth. Materials and Methods: This was a multicenter registry genome-wide expression profiling study of prospectively collected radical prostatectomy (RP) tumor samples from 2014 to 2016. DDR activity was calculated from average expression of 372 DDR genes. Consensus hierarchical clustering was used to arrive at a robust clustering solution based on DDR gene expression patterns. Genome-wide differential expression between clusters was performed, and outcomes were evaluated across expression patterns. Results: Of 5239 patients from the prospective registry, 376 had favorable-risk disease (Grade group [GG] 1 to 2, PSA prior to RP < 10ng/ml, pT2 or less). DDR activity score was correlated with prognostic genomic signatures that predict for metastatic risk (r = 0.37, P < 2e -16) and high grade groups (P < .001). High DDR activity (top-quartile) was observed in 28% of patients with favorablerisk disease. In favorable-risk disease, 3 distinct clusters with varied DDR activity emerged with consensus clustering. Cluster I (compared with cluster II-III and GG3-GG5 disease) had the highest expression of all DDR sub-pathways, MYC, PAPR1, AR, and AR activity (P < .001 for all). Furthermore, cluster I was associated with poorer metastasis-free survival (MFS) and Overall survival (OS) compared with other clusters (MFS; HR: 2.43, 95%CI, [1.22-4.83], P = .01; OS; HR: 2.77, 95%CI, [1.18-6.5], P = .01). Conclusions: Cluster I is a novel subgroup of favorable-risk disease with high DDR activity, AR activity, PARP1 and chr8q/MYC expression, and poorer MFS and OS. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the most frequently occurring type of malignant tumor and a leading cause of oncological death in men. PCa is very heterogeneous in terms of grade, phenotypes, and genetics, displaying complex features. This tumor often has indolent growth, not compromising the patient's quality of life, while its more aggressive forms can manifest rapid growth with progression to adjacent organs and spread to lymph nodes and bones. Nevertheless, the overtreatment of PCa patients leads to important physical, mental, and economic burdens, which can be avoided with careful monitoring. Early detection, even in the cases of locally advanced and metastatic tumors, provides a higher chance of cure, and patients can thus go through less aggressive treatments with fewer side effects. Furthermore, it is important to offer knowledge about how modifiable risk factors can be an effective method for reducing cancer risk. Innovations in PCa diagnostics and therapy are still required to overcome some of the limitations of the current screening techniques, in terms of specificity and sensitivity. In this context, this review provides a brief overview of PCa statistics, reporting its incidence and mortality rates worldwide, risk factors, and emerging screening strategies. [ABSTRACT FROM AUTHOR]

Purpose: Prostate cancer (PCa) is the most commonly diagnosed cancer in men, resulting in a large cancer burden given a relatively higher 5-year survival rate of patients after cancer diagnosis. The underlying etiology of prostate cancer is not well understood. Chronic inflammation plays a significant role in carcinogenesis overall and may be involved in the development of PCa, but immune-related biomarker studies in prostate cancer are limited. Methods: The associations of serum concentrations of cytokines, systemic immune biomarkers, with risk of PCa were assessed in a randomly selected sub-cohort (n = 798, mean age = 73 years) of the Osteoporotic Fractures in Men (MrOS) study, a prospective cohort of older men. At baseline, we measured serum interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), soluble receptors (SR) of IL-6 (IL-6SR) and TNF (TNFαSR1 and TNFαSR2), and IL-10. The risk of PCa was calculated for higher tertile levels of measured individual cytokines relative to the lowest tertile using Cox proportional hazards regression models. Results: After an average 6 years of follow-up, 59 men developed incident PCa. Men in the middle or highest tertile of IL-10 had a statistically significant 50% lower risk of PCa compared to the lowest tertile (hazard ratio = 0.50, 95% confidence interval = 0.30–0.84). There was no significant association between any of the other cytokines measured and PCa risk. Conclusion: IL-10, an anti-inflammatory cytokine, was associated with lower risk of PCa. Further research of IL-10 and inflammation in relation to PCa development is warranted. [ABSTRACT FROM AUTHOR]

We examined the independent and combined effects of body mass index/obesity and diabetes mellitus in relation to the NCCN prostate cancer (PCa) risk groups in a racially-diverse cohort of men from an urban medical center. We found that obesity and diabetes were associated with high-risk PCa; however, most of the association was driven by obesity. Introduction: Obesity and diabetes mellitus (DM) have been associated with prostate cancer (PCa) risk, but data examining their combined effects on aggressive PCa are sparse, particularly among non-Hispanic Black and Hispanic men. We investigated the associations of obesity and DM in relation to National Comprehensive Cancer Network (NCCN) PCa risk groups in a racially-diverse patient population. Patients and Methods: We abstracted demographic and clinical data from men who underwent radical prostatectomy at our institution between 2005 and 2019. Patients were classified into three NCCN PCa risk-groups: low, intermediate and high-risk. Logistic regression models were used to examine the independent and combined associations of body mass index (BMI)/obesity and DM with risks of intermediate and high-risk PCa, adjusting for age and race/ethnicity. Results: A total of 1303 men with PCa (average age 60 ± 6.9 years) were analyzed. The majority were non-Hispanic Black (N = 493, 38%) or Hispanic (N = 407, 31%). The prevalence of obesity (BMI = 30 kg/m 2) and DM was 29.3% (N = 382) and 28.3% (N = 369), respectively. In multivariate analyses, obesity was independently associated with an odds ratio (OR) = 2.21 of high-risk PCa (95% CI: 1.28-3.81), while DM was associated with an OR = 1.49 (95% CI: 1.05-2.11) of intermediate-risk PCa. Compared to non-obese men without diabetes, men with BMI = 30 and DM had increased risks of both intermediate (OR = 1.93; 95% CI 1.12-3.43) and high-risk PCa (OR = 2.40; 95% CI 1.22-4.73). Interestingly, most of the association of highrisk PCa was driven by obesity. Conclusion: In this multiethnic population both obesity and DM were independently associated with intermediate- and high-risk PCa; however, most of the association for high-risk cancer was driven by obesity. Our results corroborate findings that obesity increases the risk of aggressive PCa; however, results regarding DM need to be confirmed in other large multiethnic populations. [ABSTRACT FROM AUTHOR]

The article discusses a research study on the detection and treatment of prostate cancer. Topics mentioned include the risk factors associated with prostate cancer, the common symptoms of prostate cancer, a description of various medical examinations for early detection of prostate cancer, the relation of age and the incidence of prostate cancer, and the benefit of prostate-specific antigen testing.

Prostate cancer, constituting a substantial portion of global cancer incidence and mortality, prompts a critical examination of potential modifiers, notably ejaculation frequency. This narrative review explores the complex relationship between ejaculation frequency and prostate cancer risk, addressing the paucity of consensus and the intricate interplay of factors. The evidence drawn from eleven studies with diverse methodologies reveals a complex understanding of this association. While some studies suggest an inverse correlation between ejaculation frequency and prostate cancer risk, signifying a potential protective effect, others present conflicting findings, necessitating a comprehensive exploration. Evidence synthesis underscores the importance of considering age, urinary health, and lifestyle factors in elucidating the ejaculation frequency-prostate cancer relationship. Notably, technological advancements, including machine learning models and genetic markers, enhance the precision of patient counselling and individualized care. In a clinical context, the findings emphasize the clinical relevance of incorporating sexual behavior into preventive strategies. Public health campaigns emerge as influential tools, breaking taboos, raising awareness, and empowering men to prioritize their well-being. The paradigm shift in prostate cancer understanding, fueled by technology and personalized medicine, holds promise for more accurate risk assessments. Liquid biopsies, multiparametric MRI, and considerations of the gut microbiome present avenues for tailored preventive strategies. However, methodological challenges and study variations necessitate further research, emphasizing consistency, exploring underlying mechanisms, and a life course perspective. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) infects a wide range of human cells, resulting in both benign and malignant tumors. In the last few decades, proteins and/or nucleic acids of the virus were found to be often highly expressed in in patients with basal cell hyperplasia and prostatic neoplasia. This research aimed to unravel the rate of HCMV infections among prostatic tissue subsets from Iraqi patients with adenocarcinoma and benign hyperplasia. One hundred, formalin-fixed and paraffin embedded prostatic tissues were obtained from 40 tissue samples collected from different grades of prostate carcinoma; 40 from benign prostatic hyperplasia and 20 from apparently healthy prostatic tissues. These tissue specimens were collected from the archives of different public and private histopathological laboratories in Baghdad. Detection of HCMV-DNA was achieved by a highly sensitive version of chromogenic in situ hybridization technique. The signals of chromogenic in situ hybridization reactions for HCMV-DNA detection in prostatic adenocarcinoma tissues were found in 65% (26 out of 40) of the tissues, whereas in BPH (Benign Prostatic Hyperplasia), HCMV-DNA was detected in 57.5% (23 out of 40) of the tissues, and in the healthy control group in 25% (5 out of 20) of the tissues. The highest percentage of positive- HCMV- DNACISH reactions (57.5%) was found in prostatic adenocarcinomatous tissues that showed poor differentiation. Our results could show that HCMV might contribute to the development of the studied subsets of prostatic adenocarcinoma and benign prostatic hyperplasia. [ABSTRACT FROM AUTHOR]

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MicroRNAs (miRNAs) of urine exosomes have emerged as biomarkers for urological cancers, owing to their high stability. MiRNAs have been linked to factors associated with aggressive prostate cancer such as biochemical recurrence (BCR) and metastasis. In this study, we aimed to identify urinary exosomal miRNAs as prognostic markers associated with BCR in intermediate-risk prostate cancer. We profiled the expression levels of miRNAs via next generation sequencing in urinary exosomes from 21 non-BCR patients and 6 BCR patients of intermediate-risk prostate cancer. A total of 21 urinary exosomal miRNAs were found to be differentially expressed (> twofold) in BCR patients compared to non-BCR patients. For external validation, we validated these results using quantitative reverse transcription PCR in an independent cohort of 28 non-BCR patients and 26 BCR patients. A validation analysis revealed that three miRNAs (miR-26a-5p, miR-532-5p, and miR-99b-3p) were upregulated in exosomes from BCR patients. The univariate and multivariate Cox regression analyses showed that miR-532-5p was an important predictive factor for BCR of intermediate-risk prostate cancer. In conclusion, miR-532-5p in urine exosomes might be a potential biomarker for predicting BCR, which is a poor prognosis in patients with intermediate-risk prostate cancer. Further research is needed on the biological functions and mechanisms of this miRNA. [ABSTRACT FROM AUTHOR]

Diabetic men have decreased risk for prostate cancer (PCa) overall and lower PSA compared to non-diabetics. This may affect the outcomes of PSA-based screening. We investigated the effect of PSA-based screening at 4-year intervals on PCa incidence and mortality separately among users and non-users of antidiabetic medication with the hypothesis that screening would detect less low-grade cancer and more high-grade cancer in diabetic men. A cohort of 80,458 men from the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) were linked to national prescription database to obtain information on antidiabetic medication purchases. PCa risk and mortality were compared between the FinRSPC screening arm (SA) and the control arm (CA) separately among users and non-users of antidiabetic medication. Among antidiabetic medication users median PSA was lower than in non-users (0.93 and 1.09 ng/ml, respectively, P for difference = 0.001). Screening increased overall PCa incidence compared to CA after the first screen both among medication users and non-users (HR 1.31, 95% CI 1.08–1.60 and HR 1.55, 95% CI 1.44–1.66, respectively). On the second and third screen the difference between SA and CA attenuated only among medication users. Detection of Gleason 6 tumors was lower among medication users, whereas no difference was observed in detection of Gleason 8–10 cancers. Concordantly, screening affected PCa mortality similarly regardless of antidiabetic medication use (HR 0.38, 95% CI 0.14–1.07 and HR 0.19, 95% CI 0.11–0.33 among users and non-users after three screens, respectively. P for difference = 0.18). Median PSA is lower in men using antidiabetic drugs than among non-users. Systematic PSA screening detects less low-risk tumors among medication users, whereas detection of high-risk tumors and mortality effects are similar regardless of medication use. This suggests that antidiabetic medication users may form a suitable target group for PCa screening, with less screening-related overdiagnosis of indolent tumors. [ABSTRACT FROM AUTHOR]

To analyze the clinical characteristics of patients with negative biparametric magnetic resonance imaging (bpMRI) who didn't need prostate biopsies (PBs). A total of 1,012 male patients who underwent PBs in the First Affiliated Hospital of Nanjing Medical University from March 2018 to November 2019, of 225 had prebiopsy negative bpMRI (defined as Prostate Imaging Reporting and Data System (PI-RADS 2.1) score less than 3). The detection efficiency of clinically significant prostate cancer (CSPCa) was assessed according to age, digital rectal examination (DRE), prostate volume (PV) on bpMRI, prostate-specific antigen (PSA) and PSA density (PSAD). The definition of CSPCa for Gleason score > 6. Univariate and multivariable logistic regression analysis were used to identify predictive factors of absent CSPCa on PBs. Moreover, absent CSPCa contained clinically insignificant prostate cancer (CIPCa) and benign result. The detection rates of present prostate cancer (PCa) and CSPCa were 27.11% and 16.44%, respectively. Patients who were diagnosed as CSPCa had an older age (P < 0.001), suspicious DRE (P < 0.001), a smaller PV (P < 0.001), higher PSA value (P = 0.008) and higher PSAD (P < 0.001) compared to the CIPCa group and benign result group. PSAD < 0.15 ng/ml/cm3 (P = 0.004) and suspicious DRE (P < 0.001) were independent predictors of absent CSPCa on BPs. The negative forecast value of bpMRI for BP detection of CSPCa increased with decreasing PSAD, mainly in patients with naive PB (P < 0.001) but not in prior negative PB patients. 25.33% of the men had the combination of negative bpMRI, PSAD < 0.15 ng/ml/cm3 and PB naive, and none had CSPCa on repeat PBs. The incidence of PB was determined, CSPCa was 1.59%, 0% and 16.67% in patients with negative bpMRI and PSAD < 0.15 ng/ml/cm3, patients with negative bpMRI, PSAD < 0.15 ng/ml/cm3 and biopsy naive and patients with negative bpMRI, PSAD < 0.15 ng/ml/cm3 and prior negative PB, separately. We found that a part of patients with negative bpMRI, a younger age, no suspicious DRE and PSAD < 0.15 ng/ml/cm3 may securely avoid PBs. Conversely PB should be considered in patients regardless of negative bpMRI, especially who with a greater age, obviously suspicious DRE, significantly increased PSA value, a significantly small PV on MRI and PSAD > 0.15 ng/ml/cm3. [ABSTRACT FROM AUTHOR]

Multiparametric prostate magnetic resonance imaging (mpMRI) is widely used as a triage test for men at a risk of prostate cancer. However, the traditional role of mpMRI was confined to prostate cancer staging. Radiomics is the quantitative extraction and analysis of minable data from medical images; it is emerging as a promising tool to detect and categorize prostate lesions. In this paper we review the role of radiomics applied to prostate mpMRI in detection and localization of prostate cancer, prediction of Gleason score and PI-RADS classification, prediction of extracapsular extension and of biochemical recurrence. We also provide a future perspective of artificial intelligence (machine learning and deep learning) applied to the field of prostate cancer. [ABSTRACT FROM AUTHOR]

Obesity is associated with an increased risk of advanced, recurrent and fatal prostate cancer. Adipokines may mediate this relationship. We conducted a systematic review and meta-analysis of associations of leptin and adiponectin with overall and aggressive prostate cancer. Bibliographic databases were systematically searched up to 1st April 2017. Log Odds Ratios (ORs) per 2.5 unit increase in adiponectin or leptin levels were derived and pooled. All analyses were stratified by study type (cross-sectional/prospective). 746 papers were retrieved, 34 eligible studies identified, 31 of these could be included in the meta-analysis. Leptin was not consistently associated with overall prostate cancer (pooled OR 1.00, 95%CI 0.98–1.02, per 2.5 ng/ml increase, prospective study OR 0.97, 95%CI 0.95–0.99, cross-sectional study OR 1.19, 95%CI 1.13–1.26) and there was weak evidence of a positive association with aggressive disease (OR 1.03, 95%CI 1.00–1.06). There was also weak evidence of a small inverse association of adiponectin with overall prostate cancer (OR 0.96, 95%CI 0.93–0.99, per 2.5 µg/ml increase), but less evidence of an association with aggressive disease (OR 0.98, 95%CI 0.94–1.01). The magnitude of any effects are small, therefore levels of circulating adiponectin or leptin alone are unlikely to be useful biomarkers of risk or prognosis. [ABSTRACT FROM AUTHOR]

Background and objectives Several hundred inherited genetic variants or SNPs that alter the risk of cancer have been identified through genome-wide association studies. In populations of European ancestry, these variants are mostly present at relatively high frequencies. To gain insight into evolutionary origins, we screened a series of genes and SNPs linked to breast or prostate cancer for signatures of historical positive selection. Methodology We took advantage of the availability of the 1000 genome data and we performed genomic scans for positive selection in five different Caucasian populations as well as one African reference population. We then used prostate organoid cultures to provide a possible functional explanation for the interplay between the action of evolutionary forces and the disease risk association. Results Variants in only one gene showed genomic signatures of positive, evolutionary selection within Caucasian populations melanophilin (MLPH). Functional depletion of MLPH in prostate organoids, by CRISPR/Cas9 mutation, impacted lineage commitment of progenitor cells promoting luminal versus basal cell differentiation and on resistance to androgen deprivation. Conclusions and implications The MLPH variants influencing prostate cancer risk may have been historically selected for their adaptive benefit on skin pigmentation but MLPH is highly expressed in the prostate and the derivative, positively selected, alleles decrease the risk of prostate cancer. Our study suggests a potential functional mechanism via which MLPH and its genetic variants could influence risk of prostate cancer, as a serendipitous consequence of prior evolutionary benefits to another tissue. Lay Summary We screened a limited series of genomic variants associated with breast and prostate cancer risk for signatures of historical positive selection. Variants within the melanophilin (MLPH) gene fell into this category. Depletion of MLPH in prostate organoid cultures, suggested a potential functional mechanism for impacting on cancer risk, as a serendipitous consequence of prior evolutionary benefits to another tissue. [ABSTRACT FROM AUTHOR]

The intermediate-risk (IR) prostate cancer (PCa) group is heterogeneous in terms of prognosis. For unfavorable or favorable IR PCa treated by radiotherapy, the optimal strategy remains to be defined. In routine practice, the physician's decision to propose hormonal therapy (HT) is controversial. The PROACT survey aimed to evaluate pattern and preferences of daily practice in France in this IR population. A web questionnaire was distributed to French radiotherapy members of 91 centers of the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG). The questionnaire included four sections concerning: (i) the specialists who prescribe treatments and multidisciplinary decisions (MTD) validation; (ii) the definition of IR subsets of patients; (iii) radiotherapy parameters; (iv) the pattern of practice regarding cardiovascular (CV) and (iv) metabolic evaluation. A descriptive presentation of the results was used. Among the 82 responses (90% of the centers), HT schedules and irradiation techniques were validated by specific board meetings in 54% and 45% of the centers, respectively. Three-fourths (76%) of the centers identified a subset of IR patients for a dedicated strategy. The majority of centers consider PSA > 15 (77%) and/or Gleason 7 (4 + 3) (87%) for an unfavorable IR definition. Overall, 41% of the centers performed systematically a CV evaluation before HT prescription while 61% consider only CV history/status in defining the type of HT. LHRH agonists are more frequently prescribed in both favorable (70%) and unfavorable (98%) IR patients. Finally, weight (80%), metabolic profile (70%) and CV status (77%) of patients are considered for follow-up under HT. To the best of our knowledge, this is the first survey on HT practice in IR PCa. The PROACT survey indicates that three-quarters of the respondents identify subsets of IR-patients in tailoring therapy. The CV status of the patient is considered in guiding the HT decision, its duration and type of drug. [ABSTRACT FROM AUTHOR]

The prostate, an adjacent gland of the male urogenital tract, is located behind the pubic symphysis, below the bladder and anteriorly of the rectum, surrounding the first part of the urethra and its smooth sphincter (Fig.1). It is a glandular organ, has the shape of a flattened chestnut, according to Winslow, having an average length of 3 cm, width 4 cm, thickness between 2-5 cm and a weight of 20-25 g, the size increasing with age. The prostate contains 30-35 small glands, secreting prostate fluid that does not allow the destruction of sperm (7, 35). Neoplastic lesions of the prostate are common in men aged 50-70 years and are often diagnosed late (35). Prostate carcinoma is part of the group of osteophilic and lymphophilic cancers. Recent studies have reported that the intestinal microbiome contributes to the tumorigenesis of some viscera, in this case the adnexal gland of the genital apparatus-prostate. Prostate dysbiosis has been associated with prostate cancer, and although there are not enough studies, researchers support the hypothesis that the gastrointestinal microbiome may be significantly different in men with this condition. These differences may play a role in the pathology of prostate cancer. Moreover, high estrogens levels have been implicated in the development of prostate cancer, thus supporting the hypothesis that estroboloma has an important contribution to the development of prostate cancer. Inflammation of the prostate may increase the risk of prostate cancer. However, the precise association between the urinary microbiome, the content of seminal liquid and of prostate secretions with prostate neoplasm is unclear. This review paper aims to develop current information on the relationship between the human microbiota and prostate cancer; most studies have focused on direct interactions, including the influence of prostate infections on the risk of cancer and, more recently, on the correlation between urinary microbiome composition and prostate cancer. [ABSTRACT FROM AUTHOR]

Background: The prostate cancer remains one of the most widespread and least understood of all human malignancies. Pathologic evidence suggests that neoplastic changes of the prostate epithelium begin early in man's adult life, but do not become clinically evident or relevant until decades later. The lifetime risk of a man diagnosed with PC is estimated to be 1 in 9. Global cancer incidence shows that the PC become the fifth most common cancer in the world and second most common cancer in men. Thus, better understanding of its risk factors, will eventually lead to improve the control measures and more safe health outcomes. This study aimed to investigate the impact of different medical characteristics and some behavioral factors on the development of PC in men. Results: The bivariate analysis of study revealed that age of > 55 years and positive family history were found to increase the risk of developing prostate cancer by more than two and three times (OR= 2.28, and 3.05) respectively (P<0.05). Furthermore, the active smoking, alcohol consumption and obesity (BMI of >30) were also notable as potential risk factors associated with increased risk of developing prostate cancer by 8.01, 3.79 and 5.26 times respectively (P< 0.05). The study showed that a negative association between exercise and prostate cancer (0R=043). No significant associations were found between psychological upset, dietary habits and prostate cancer (P>0.05). Conclusion: Age of 55+ years, positive family history, active smoking, alcohol consumption and obesity all appeared to be a potential risk factors for development of prostate cancer. In contrast, regular exercise, found to be significant protective factor against development of such a disease. [ABSTRACT FROM AUTHOR]

We had six cases of patients who were treated with long-term testosterone replacement therapy (TRT) after high dose-rate (HDR) brachytherapy and androgen deprivation therapy for high-risk prostate cancer. All patients were given testosterone enanthate by intramuscular injection every 3 to 4 weeks. Blood biochemistry including prostate specific antigen (PSA) level was evaluated every 3 to 6 months after TRT, and radiological imaging was performed every 12 months. All patients had slight increases in PSA within the normal range and not indicative of biochemical recurrence. A sudden increase in PSA was observed in one patient, but it finally decreased. Aging male symptoms scale and various metabolic factors were improved by TRT in all of cases. Although adverse events included polycythemia in one patient, no patients experienced disease recurrence or progression during TRT. Our results suggest TRT for high risk-patients with HDR brachytherapy for prostate cancer may be beneficial and safe. [ABSTRACT FROM AUTHOR]

Copyright of Jornal Brasileiro de Patologia e Medicina Laboratorial is the property of Sociedade Brasileira de Patologia Clinica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Reconstructive Urology is the property of Turkiye Klinikleri and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To study the prostate cancer detection rates upon transrectal ultrasound (TRUS) guided biopsy in relation to prostatespecific antigen (PSA) and digital rectal examination (DRE) included risk factors for prostate cancer diagnosis. Materials and Methods: 1,176 patients who underwent TRUS prostate biopsy between 2002 to 2008 were enrolled to the study. The prostate cancer detection rates with reference to PSA level and DRE finding were investigated. Logistic regression analysis was performed on age at biopsy, clinical symptoms, prostate-specific antigen (PSA), and DRE findings to identify significant risk factors. The correlation of DRE findings in combination with PSA value was also analyzed. Results: Referring to patients with normal DRE, the cancer detection rates were 10.8%, 12.9%, 21.3%, 42.6% and 77.8% in patients with PSA <4, 4 to 10, 10.01 to 20, 20.01 to 50 and >50 ng/ml, respectively. According to patients with abnormal DRE, the cancer detection rates were 15.0%, 20.7%, 41.2%, 60.5% and 84.8% in patients with PSA <4, 4 to 10, 10.01 to 20, 20.01 to 50 and >50 ng/ml, respectively. Additionally, the age at biopsy, PSA level and DRE finding were the significant risk factors for prostate cancer diagnosis while clinical symptom was not. The data revealed that normal DRE finding in combination with PSA level was statistically significant when PSA level was above 20 ng/ml. Similarly, the abnormal DRE finding in combination with PSA level was statistically significant when PSA level was above 10 ng/ml. Conclusion: Thai men appeared to have lower prostate cancer detection rate when compared to the Western population. The age at biopsy, PSA level and DRE finding were the significant risk factors for prostate cancer. Besides, the combination of DRE and PSA level increased the accuracy and were the best tool for prostate cancer screening. [ABSTRACT FROM AUTHOR]

Purpose: Research on the association between physical activity and the risk of prostate cancer is inconsistent. The aim of this study was to investigate whether the timing, intensity, and type of recreational physical activity influence prostate cancer risk.Methods: A population-based case-control study was conducted in Western Australia in 2001-2002. Data were collected on lifetime recreational physical activity from a self-reported questionnaire. The estimated effects of recreational physical activity on prostate cancer risk were analyzed using logistic regression, adjusting for demographic and lifestyle factors. This analysis included 569 incident cases and 443 controls.Results: There was a significant, inverse dose-response relationship between vigorous-intensity recreational physical activity between the ages 19 and 34 years and the risk of prostate cancer (pTrend = 0.013). Participants in the most active quartile of vigorous-intensity physical activity in this age period had a 33% lower risk of prostate cancer than participants in the least active quartile (Adjusted Odds Ratio = 0.67, 95% confidence interval = 0.45-1.01). Moderate-intensity recreational physical activity was not associated with the risk of prostate cancer. Recreational physical activity performed over the lifetime showed no association with prostate cancer risk. Weight training performed from early adulthood onwards showed a non-significant but consistent inverse association with prostate cancer risk. There was no strong evidence that physical activity was differentially associated with the risks of low-grade and medium-to-high grade prostate cancers.Conclusions: A high level of vigorous recreational physical activity in early adulthood may be required to reduce the risk of prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Studies have suggested that rapid age‐related declines of testosterone (T) level may play a critical role in the development of prostate cancer (PCa), and family history of PCa is another well‐established risk factor of PCa, which have been reported to be associated with androgen metabolism‐related genes. However, few studies have ever investigated whether a family history of PCa influences the risk of PCa via regulating the age‐related trend of T level among males over the life course. Objectives: To examine the association between family history of PCa and age‐related trend of T levels. Materials and Methods: We used National Health and Nutrition Examination Survey (NHANES) data from 2003 to 2004 (n = 322) to compare the age‐specific T levels in males with a family history of PCa and those without. Results: We found that between two younger age groups (ages 20–39 and 40–59), there was a more pronounced drop‐off in T levels among men with a family history of PCa compared to men without a family history. Discussion and Conclusion: This preliminary analysis suggested that men with a family history of PCa may experience a sharper decline in T level over the life course as compared to males without a family history. However, no conclusions can be made due to small sample sizes. Further longitudinal studies with large sample sizes are needed. [ABSTRACT FROM AUTHOR]

Introduction: Previous Canadian epidemiologic studies have identified associations between occupations and prostate cancer risk, though evidence is limited. However, there are no well-established preventable risk factors for prostate cancer, which warrants the need for further investigation into occupational factors to strengthen existing evidence. This study uses occupation and prostate cancer information from a large surveillance cohort in Ontario that linked workers' compensation claim data to administrative health databases. Methods: Occupations were examined using the Occupational Disease Surveillance System (ODSS). ODSS included 1 231 177 male workers for the 1983 to 2015 period, whose records were linked to the Ontario Cancer Registry (OCR) in order to identify and follow up on prostate cancer diagnoses. Cox proportional hazard models were used to calculate age-adjusted hazard ratios and 95% CI to estimate the risk of prostate cancer by occupation group. Results: A total of 34 997 prostate cancer cases were diagnosed among workers in ODSS. Overall, elevated prostate cancer risk was observed for men employed in management/administration (HR 2.17, 95% CI = 1.98-2.38), teaching (HR 1.99, 95% CI = 1.79-2.21), transportation (HR 1.20, 95% CI = 1.16-1.24), construction (HR 1.09, 95% CI = 1.06-1.12), firefighting (HR 1.62, 95% CI = 1.47-1.78), and police work (HR 1.20, 95% CI = 1.10-1.32). Inconsistent findings were observed for clerical and farming occupations. Conclusion: Associations observed in white collar, construction, transportation, and protective services occupations were consistent with previous Canadian studies. Findings emphasize the need to assess job-specific exposures, sedentary behaviour, psychological stress, and shift work. Understanding specific occupational risk factors can lead to better understanding of prostate cancer etiology and improve prevention strategies. [ABSTRACT FROM AUTHOR]

In this gendered autoethnography, I critically analyze my personal thoughts on how my Christian faith informs my advocacy-oriented practice for African American men at risk for prostate cancer in Louisiana. This autoethnographic narrative will utilize the theoretical framework of Critical Race Theory (CRT) and intersectionality to explore the author's lived experience as a researcher-practitioner problematizing the intersection of race and racism, health, and faith among African American men over the age of 50 at risk for prostate cancer. A review of the literature suggests research that examines the experiences and intersectional identities of Louisiana Black men at risk for prostate cancer is limited. By inquiring through an autoethnographic approach, Christian social work practitioners can become more aware of oppressive policies and practices in contemporary American society which negatively African American men at risk for prostate cancer in Louisiana. [ABSTRACT FROM AUTHOR]

Abstract Objective To analyze the performance of two mobile phone apps—the Rotterdam prostate cancer risk app and the Coral app—in a cohort of patients undergoing prostate biopsies. Methods A consecutive series of men undergoing prostate biopsies were enrolled in two centers. Indications for prostate biopsy included abnormal prostate-specific antigen levels (PSA >4 ng/mL) and/or an abnormal digital rectal examination (DRE). Prostate cancer risk and high-grade prostate cancer risk were assessed using the Rotterdam prostate cancer risk app (iOS) and the Coral app (iOS). The usability of the apps was also assessed and compared using the Post-Study System Usability Questionnaire (PSSUQ) developed by IBM. Results Overall, 1682 patients with a median age of 68 (62–73) years were enrolled. The Rotterdam app outperformed the Coral app in the prediction of prostate cancer (AUC: 0.70 versus 0.631, p = 0.001) and of high-grade prostate cancer (0.75 versus 0.69, p = 0.001) (Fig. 1). PSSUQ data revealed that both Rotterdam and Coral applications were comparable in terms of usefulness (87% versus 83%, p = 0.708), information quality (74% versus 72%, p = 0.349), interface quality (79% versus 74%, p = 0.216) and satisfaction (76% versus 76%, p = 0.935), respectively. In terms of preferences, 26/50 (54%) preferred the Rotterdam app, while 24/50 (46%) preferred the Coral app. Conclusion In our experience the Rotterdam App outperformed the Coral App for the prediction of prostate cancer or high-grade cancer diagnosis. In particular we confirmed, using the Rotterdam app, that only one out of ten patients with a low Rotterdam score will harbor high-grade prostate cancer on biopsy. [ABSTRACT FROM AUTHOR]

Background: Disrupted sleep rhythms may lead to cancer development. We conducted a population-based cohort study to evaluate the incidence and risk of prostate cancer in patients with sleep disorders (SDs).Methods: Patients newly diagnosed with SDs between 2000 and 2010 were enrolled from the Taiwan Longitudinal Health Insurance Database. A non-SD cohort age-matched (5-y intervals), comorbidities, and medications was randomly sampled from the general population at a 1:1 ratio. The follow-up period extended from the index date of SDs to the diagnosis of prostate cancer, censoring, or the end of 2013. We used Cox proportional hazards models to calculate the risk of prostate cancer.Results: In total, 41,444 patients were enrolled in each cohort. The mean age of the SD cohort was 48.0 years and that of the non-SD cohort was 47.8 years, with 58.2% of both cohorts aged younger than 50 years. The incidence of prostate cancer increased with age. The overall incidence of prostate cancer was higher in the SD cohort than in the non-SD cohort (9.56 vs 6.36 per 10,000 person-y), with an adjusted hazard ratio of 1.42 (95% CI = 1.20-1.69). Age-specific analysis revealed a 1.35-fold increased risk of prostate cancer in the patients aged ≥65 years in the SD cohort compared with the non-SD counterparts (95% CI = 1.10-1.65).Conclusions: Patients with SDs are associated with increased risk of prostate cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Alkylphenolic compounds are chemicals with endocrine disrupting properties that have been widely used in industry with important changes in their usage over time. Few epidemiologic studies have evaluated the effect of alkylphenolic compounds on human health. Objectives We investigated whether occupational exposure to alkylphenolic compounds is associated with breast and prostate cancer. Methods We carried out a population-based case–control study including 1513 incident cases of breast cancer, 1095 of prostate cancer, and 3055 controls, frequency matched by sex, age and region. Occupational exposure to alkylphenolic compounds was estimated using a recently developed job-exposure matrix, which considered different scenarios of exposure and different subtypes of alkylphenolic compounds. Results History of occupational exposure to alkylphenolic compounds was modestly associated with breast cancer (OR = 1.23; 95% CI = 1.01–1.48). Within the different scenarios, the occupational use of domestic tensioactives was positively associated with breast cancer (OR = 1.28; 95% CI = 1.02–1.60), while occupational exposure in other scenarios showed mostly a suggestion of a similar positive associations. Exposure to nonylphenol ethoxylates was positively associated with breast cancer (OR = 1.21; 95% CI = 1.00–1.47), while exposure to other compounds was uncommon. In general, we did not observe associations between alkylphenolic compounds and prostate cancer, except for a positive association among men occupationally exposed to cosmetic, hair and personal hygiene products. Conclusions Our findings suggest a modest association between breast cancer risk and occupational exposure to alkylphenolic compounds, and no associations between these compounds and prostate cancer risk. These findings warrant further corroboration in other studies. Highlights • This is the largest study examining occupational exposure to alkylphenolic compounds and breast and prostate cancer risk. • We observed a modest association between breast cancer risk and occupational exposure to alkylphenolic compounds. • Our findings suggest no significant associations for prostate cancer and these compounds. • Among women, nonylphenol ethoxylates were the most frequent compound, which was positively associated to breast cancer. • The elucidation of the role of these compounds should shed a light on the etiology of those diseases and help informing public health decisions. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to examine the relationship between proinflammatory diet and prostate cancer risk.Methods: Energy-adjusted Dietary Inflammatory Index (E-DII) scores were computed among 40,161 participants in the California Men's Health Study. Over 9.7 ± 3.8 years of follow-up, 2707 incident prostate cancer cases were diagnosed and categorized as low-, intermediate-, or high-risk, based on disease grade and stage. Accelerated failure-time models assessed time to diagnosis of prostate cancer. Cox proportional hazard models estimated hazard ratios (HR) and 95% confidence intervals (95% CI). Nonlinear effects of E-DII were modeled as third-order polynomials.Results: Time to prostate cancer diagnosis did not differ by E-DII quartile. The HR for high-risk prostate cancer increased in the third E-DII quartile (HRQ3 vs. Q1 = 1.36; 95% CI: 1.04-1.76), but not in the fourth (HRQ4 vs. Q1 = 0.99; 95% CI: 0.74-1.32, Ptrend = .74), suggesting a nonlinear dose-response. HR curves for prostate cancer increased exponentially above an E-DII threshold of ≈+3.0. HR curves for high-risk prostate cancer had a much steeper incline above an E-DII threshold of ≈+2.5. Curves were higher among Blacks and Whites relative to other races and among overweight or obese men. No relationship was observed between E-DII scores and intermediate- or low-risk disease.Conclusions: Relationships between proinflammatory diet and prostate cancer risk may be nonlinear, with an increased risk above an E-DII threshold of ≈+2.5. [ABSTRACT FROM AUTHOR]

Introduction: The main purpose of this work is to study prostate cancer and stroke in the United States during the years 2007-2017 and to find not only statistically significant predictors for cancer, but also a possible association between prostate cancer and stroke. Material and methods: The statistical methods used to derive the results of this work are c2 test and one-way analysis of variance (ANOVA), in order to check the statistical significance of prostate cancer in relation to socio-economic factors of patients. In addition, a multivariate logistic regression analysis was used with the odds ratio (OR) to find statistically significant prognostic factors for both prostate cancer and stroke. Results: According to multiple logistic regression analysis, males who are unemployed but have worked previously have 16 times higher risk of developing prostate cancer, while widowed men have five times higher risk for the occurrence of this type of cancer. In addition, marital status and employment proved to be also prognostic risk factors for stroke. Conclusions: Our results describe for the first time the importance of deprivation (of work and partner) as a primary prognostic risk factor for cancer. Moreover, the same factor proved to be the primary prognostic risk factor for stroke as well as for prostate cancer, a fact that implies a possible link between cancer and stroke. [ABSTRACT FROM AUTHOR]

Abstract Malfunction of apoptosis plays a key role in carcinogenesis. Previous studies have reported that polymorphisms in caspase genes could lead to poor apoptotic signaling, thus facilitating the onset of several human cancers. The aim of this study was to evaluate the association between three polymorphisms (rs1049216, rs2705897 and rs4647603) of the CASP3 gene and the risk of prostate cancer (PCa) in Galicia (NW Spain).The relationship between these single nucleotide polymorphisms (SNPs) and PCa in European populations has yet to be studied. To test this hypothesis, we carried out a case-control study on a total of 243 patients with PCa and 191 healthy individuals, genotyping all polymorphisms using the matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) method. Overall, none of the polymorphisms were clearly associated with the risk of PCa. Nevertheless, the results drawn from this study suggest that genetic variability in the CASP3 gene, in combination with lifestyle and environmental factors may influence the predisposition to develop PCa in the Galician population. Specifically, the results of study seem to hint at a higher risk of PCa in smokers of up to 20 pack-years (PY) and carriers of both the CASP3 -rs1049216 GG genotype and the G allele (OR = 3.61, p = 0.044; OR = 1.71; p = 0.018). In addition, the GG and AG genotypes showed increased predisposition to PCa in overweight individuals (OR = 4.43, p = 0.040; OR = 2.00; p = 0.022). Finally, the CASP3- rs4647603 CT genotype and T allele were associated with a higher susceptibility to PCa in obese individuals (OR CT/TT = 4.30, p = 0.003; OR T/C = 3.58, p = 0.004). Further replication studies in other populations are required to assess these findings. Highlights • We investigate the association between polymorphisms in CASP3 and prostate cancer. • GG genotype (rs1049216) elevates the risk of PCa in smokers (<20PY) individuals. • GG/AG genotypes (rs1049216) in overweight subjects exhibit an increased risk to PCa. • T allele (rs4647603) shows a greater susceptibility to PCa in obese persons. [ABSTRACT FROM AUTHOR]

Introduction: The question of whether pioglitazone, an antidiabetic drug, increases the risk of cancer has been debated for some time. Recent studies have shown that pioglitazone use can increase the risk of prostate cancer as well as pancreatic cancer. However, it is unclear whether pioglitazone is a causal risk factor for these cancers.Methods: In this study, we aimed to explore the direct targets of pioglitazone and genes associated with this drug by querying open platforms in order to construct a biological function network, and then to further evaluate the relationships of pioglitazone with prostate cancer and pancreatic cancer.Results: We first tested our hypothesis using DrugBank and STRING. We identified four direct targets of pioglitazone and 50 pioglitazone-associated genes, which were then selected for KEGG pathway analysis using STRING and WebGestalt. This analysis generated the top 25 KEGG pathways, among which four pathways were related to site-specific cancers, including prostate cancer and pancreatic cancer. Finally, a genomic study using cBioPortal indicated that genomic alterations of two gene sets related to the prostate cancer and pancreatic cancer pathways, respectively, are associated with the acceleration of carcinogenesis.Conclusions: Pioglitazone is likely to be a causal risk factor for prostate cancer and pancreatic cancer, so this drug should be used with caution. The present research also demonstrates the use of biological function network analysis to effectively explore drug interactions and drug safety profiles. [ABSTRACT FROM AUTHOR]

The development of hemoblastosis is often associated with the influence of various genotoxic unfavorable factors, in particular, with the effect of ionizing radiation. This article presents a case report of acute myeloid leukemia (AML) in a patient who was involved in the 1986 accident at the Chernobyl Nuclear Power Plant and suffered an acute radiation syndrome of degree II severity. Based on clinical and cytogenetic dosimetry, the average absorbed radiation dose to the whole body was estimated to be 4.3 Gy. During long-term clinical follow-up (27 years), moderate transient instability of hematological parameters was observed: lymphocytosis, leukopenia and thrombocytopenia, which was associated with chronic viral hepatitis C. Further cytogenetic investigations demonstrated a very high frequency of translocations, up to 50 times background values, that persisted over 3 decades. In 2014, the patient was diagnosed and operated on for prostate cancer and received a course of radiotherapy (total fractionated local dose of 35 Gy) in May 2015. From December 2015 through April 2016, the patient experienced general weakness and developed progressive cytopenia. A diagnosis of AML, resulting from a myelodysplastic syndrome, was confirmed by abnormal complex clones detected in 38% of metaphases by the mFISH-method, along with other chromosomal rearrangements. The patient underwent several chemotherapy treatments for AML but eventually died of bilateral pneumonia in March 2017. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies regarding the relationship between acne and prostate cancer risk have reported inconsistent results. We performed the present meta-analysis of observational studies to summarize the evidence on this association. Methods: A comprehensive literature search up to March 2018 was performed in PubMed, Scopus, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) databases. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were estimated with a random effects model. The Q statistic and the I2 index were used to evaluate the heterogeneity across the studies. Results: Eight studies were ultimately included in this meta-analysis. In the overall analysis, no significant association was found between acne and prostate cancer risk (OR = 1.08, 95% CI 0.93–1.25). A significant heterogeneity was observed across studies (P = 0.006, I2 = 64.5%). In the subgroup analysis by study design, a significant association was observed in the cohort studies (OR = 1.51, 95% CI 1.19–1.93) but not in the case-control studies (OR = 0.98, 95% CI 0.86–1.12). Conclusions: In summary, this meta-analysis did not find an association between acne in adolescence and prostate cancer risk. However, because there was some heterogeneity in the overall analysis and a significant association was observed in the meta-analysis of the cohort studies, further well-designed large prospective studies are warranted to confirm our results. [ABSTRACT FROM AUTHOR]

Abstract Prostate cancer is one of the leading causes of cancer-related mortality among men living in developed countries, making the development of safe, practical approaches to prostate cancer risk reduction a high research priority. The relationship between prostate cancer risk and selenium, an essential nutrient required for a number of metabolically important enzymes including glutathione peroxidases, has been investigated, but a satisfactory integration of results has proven elusive. Dogs, like men, naturally develop prostate cancer during aging, providing an appropriate context to study the effects of selenium supplementation on the dysregulation of homeostasis that drives cancer development within the aging prostate. In this paper, we summarize the translational significance of research results gained from dog studies on selenium and prostate cancer risk. Our discovery of a U-shaped dose-response between toenail selenium concentration and prostatic DNA damage in dogs remarkably parallels data on the relationship between selenium status and prostate cancer risk in men. Notably, the dog U-curve provides a plausible explanation for the unanticipated increase in prostate cancer incidence among men with highest baseline selenium who received selenium supplementation in the largest-ever prostate cancer prevention trial (SELECT). Moreover, the dog U-curve guided the discovery of a non-antioxidant, anti-carcinogenic mechanism of organic selenium — the preferential triggering of apoptosis in DNA damaged cells, which we have termed "homeostatic housecleaning". Taken together, the data from dogs and men indicate that increasing selenium status will not necessarily be associated with prostate cancer risk reduction. Landing in the trough of the U — achieving mid-range selenium status — is better than being too low or too high. Personalizing health promotion in a more-is-not-necessarily-better world poses distinctive challenges. Dog studies can be relied upon to contribute important insights into dose-dependent and form-dependent effects — two critical aspects of selenium biology that will have to be disentangled if the burgeoning science of selenium is to be translated into effective strategies for human disease prevention. Beyond contributing to understanding the role of selenium in biology, our work situates the concept of U-shaped thinking at the core of personalized medicine and precision nutrition. Graphical abstract fx1 Highlights • A U-shaped dose response informs more selenium is not always better for risk reduction. • Dog studies can integrate results of human studies and guide discovery of mechanisms. • A dog U-curve provides a map for interpreting the results of men studied in SELECT. • The critical hypothesis regarding selenium and prostate cancer risk remains untested. • U-shaped thinking is an essential element of personalized (precision) medicine. [ABSTRACT FROM AUTHOR]

Abstract Purpose Although external beam radiation therapy (EBRT) plus a brachytherapy boost (BB) offers a 20% improvement in biochemical progression-free survival compared with dose-escalated EBRT alone for men with intermediate and high-risk prostate cancer, population studies show a concerning decline in BB utilization. Methods We modified our clinical pathway (CP) in January 2016 to indicate EBRT with BB as first-choice modality for high-risk prostate cancer, based on preliminary findings of Androgen Suppression Combined with Elective Nodal and Dose-Escalated Radiation Therapy. A retrospective review was performed on 659 patients with high-risk prostate cancer treated with definitive intent EBRT ± BB within a network of 19 sites between December 2011 and July 2017. χ 2 test was used to determine changes in practice pattern before vs. after CP modification. Results Before CP modification, 25.2% of patients were planned for BB, compared with 45.4% afterward (p < 0.001). Among 23 nonbrachytherapist physicians, utilization of BB increased from 3.4% to 14.8% (p < 0.001) after CP modification. Among nine brachytherapists, utilization increased from 46.4% to 55.6% (p = 0.120). Among patients treated by a nonbrachytherapist who did not receive BB, the reason was physician preference in 59.7%, patient preference in 19.9%, and other in 20.4%. Conclusion Based on recent evidence suggesting improved biochemical progression-free survival with use of BB for high-risk prostate cancer, we modified our CP, after which we observed increased use of a BB across a network, especially among physicians who do not perform brachytherapy. However, physician preference remains the most significant factor in the nonutilization of BB. New mechanisms are needed to overcome this barrier. [ABSTRACT FROM AUTHOR]

Abstract Purpose The available data demonstrating that superiority of LDR brachytherapy (LDR-BT) boost in high-risk prostate cancer patients under represents patients with extracapsular extension (T3a) and/or seminal vesicle invasion (T3b) have been limited. We report long-term clinical outcomes data for patients with cT3a/b disease receiving LDR-BT. Methods and Materials Ninety-nine men (median age: 69.4 years) with cT3a/bN0M0 high-risk prostate adenocarcinoma received definitive LDR-BT or LDR-BT boost after external beam radiation therapy (EBRT) at a single institution between 1998 and 2007. About 86% of patients received androgen deprivation therapy. Freedom from biochemical failure (FFBF), prostate cancer–specific survival (PCSS), and overall survival (OS) was calculated using the Kaplan–Meier method with the Phoenix definition used as definition of failure. Cox regression analysis was used to compare outcomes between clinical stage, initial PSA, Gleason Score, and percent core positive rate. Results With a median followup of 7 years, 7-year rate of FFBF, PCSS, and OS for the entire cohort was 65.2% (±5.6%), 90.1% (±3.6%), and 77.9% (±4.7%), respectively. LDR-BT boost patients achieved a 7-year FFBF rate of 73.5 (±6.5%). No significant difference in outcomes was present between T3a or T3b disease, Gleason score, iPSA stratification and percent core positive rates. Conclusions LDR-BT, primarily as a boost in conjunction with ADT and EBRT, is not only feasible, but also highly effective in men with cT3a and cT3b high-risk prostate cancer resulting in excellent biochemical control and survival outcomes. LDR-BT boost implantation of patients should be strongly considered for cT3 patients given the merits of trimodality care. [ABSTRACT FROM AUTHOR]

Abstract Background Experimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting. Objective To examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer. Design, setting, and participants Analysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group. Outcome measurements and statistical analysis Odds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration. Results and limitations Men in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR = 0.77, 95% confidence interval [CI] 0.69–0.86; p < 0.001) compared with men with higher concentrations (2nd–10th tenths of the distribution). Heterogeneity was present by tumour grade (p het = 0.01), with a lower risk of low-grade disease (OR = 0.76, 95% CI 0.67–0.88) and a nonsignificantly higher risk of high-grade disease (OR = 1.56, 95% CI 0.95–2.57). There was no evidence of heterogeneity by tumour stage. The observational design is a limitation. Conclusions Men with low circulating free testosterone may have a lower risk of overall prostate cancer; this may be due to a direct biological effect, or detection bias. Further research is needed to explore the apparent differential association by tumour grade. Patient summary In this study, we looked at circulating testosterone levels and risk of developing prostate cancer, finding that men with low testosterone had a lower risk of prostate cancer. Take Home Message We found that men with low circulating free testosterone had a 23% reduced risk of overall prostate cancer, but there was some evidence that these men had an increased risk of developing high-grade disease. [ABSTRACT FROM AUTHOR]

Abstract Background The fecal microbiome is associated with prostate cancer risk factors (obesity, inflammation) and can metabolize and produce various products that may influence cancer but have yet to be defined in prostate cancer. Objective To investigate gut bacterial diversity, identify specific metabolic pathways associated with disease, and develop a microbiome risk profile for prostate cancer. Design, setting, and participants After prospective collection of 133 rectal swab samples 2 wk before the transrectal prostate biopsy, we perform 16S rRNA amplicon sequencing on 105 samples (64 with cancer, 41 without cancer). Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was applied to infer functional categories associated with taxonomic composition. The p values were adjusted using the false discovery rate. The α- and β-diversity analyses were performed using QIIME. The Mann-Whitney U test was employed to evaluate the statistical significance of β-diversity distances within and between groups of interest, and least absolute shrinkage and selection operator (LASSO) regression analysis was used to determine pathway significance. Outcome measurements and statistical analysis The detection of prostate cancer on transrectal prostate needle biopsy and 16s microbiome profile. Results and limitations We identified significant associations between total community composition and cancer/non-cancer status (Bray-Curtis distance metric, p < 0.01). We identified significant differences in enrichments of Bacteroides and Streptococcus species in cancer (all p < 0.04). Folate (LDA 3.8) and arginine (LDA 4.1) were the most significantly altered pathways. We formed a novel microbiome–derived risk factor for prostate cancer based on 10 aberrant metabolic pathways (area under curve = 0.64, p = 0.02). Conclusions Microbiome analyses on men undergoing prostate biopsy noted mostly similar bacterial species diversity among men diagnosed with and without prostate cancer. The microbiome may have subtle influences on prostate cancer but are likely patient-specific and would require paired analysis and precise manipulation, such as improvement of natural bacterial folate production. Patient summary Microbiome evaluation may provide patients with personalized data regarding the presence or absence of particular bacteria that have metabolic functions and implications regarding prostate cancer risk. The study provides a basis to investigate the manipulation of aberrant microbiomes to reduce prostate cancer risk. Take Home Message We note minimal differences in the microbiome profiles between men diagnosed with and without prostate cancer. While a global microbiome profile is unlikely to predict prostate cancer, bacteria associated with a specific metabolic pathway, such as B vitamins, do seem to have an association with prostate cancer and warrant further investigation. [ABSTRACT FROM AUTHOR]