Differences in Gut Microbiota Profiles and Microbiota Steroid Hormone Biosynthesis in Men with and Without Prostate Cancer.

Background: Although prostate cancer (PCa) is the most common cancer in men in Western countries, there is significant variability in geographical incidence. This might result from genetic factors, discrepancies in screening policies, or differences in lifestyle. Gut microbiota has recently been associated with cancer progression, but its role in PCa is unclear. Objective: Characterization of the gut microbiota and its functions associated with PCa. Design setting and participants: In a prospective multicenter clinical trial (NCT02241122), the gut microbiota profiles of 181 men with a clinical suspicion of PCa were assessed utilizing 16S rRNA sequencing. Outcome measurements and statistical analysis: Sequences were assigned to operational taxonomic units, differential abundance analysis, and α- and ß-diversities, and predictive functional analyses were performed. Plasma steroid hormone levels corresponding to the predicted microbiota steroid hormone biosynthesis profiles were investigated. Results and limitations: Of 364 patients, 181 were analyzed, 60% of whom were diagnosed with PCa. Microbiota composition and diversity were significantly different in PCa, partially affected by Prevotella 9, the most abundant genus of the cohort, and significantly higher in PCa patients. Predictive functional analyses revealed higher 5-α-reductase, copper absorption, and retinol metabolism in the PCa-associated microbiome. Plasma testosterone was associated negatively with the predicted microbial 5-α-reductase level. Conclusions: Gut microbiota of the PCa patients differed significantly compared with benign individuals. Microbial 5-α-reductase, copper absorption, and retinol metabolism are potential mechanisms of action. These findings support the observed association of lifestyle, geography, and PCa incidence. Patient summary: In this report, we found that several microbes and potential functions of the gut microbiota are altered in prostate cancer compared with benign cases. These findings suggest that gut microbiota could be the link between environmental factors and prostate cancer.

Individualised non-contrast MRI-based risk estimation and shared decision-making in men with a suspicion of prostate cancer: protocol for multicentre randomised controlled trial (multi-IMPROD V.2.0).

INTRODUCTION: European Association of Urology and UK National Institute for Health and Care Excellence guidelines recommend that all men with suspicions of prostate cancer should undergo prebiopsy contrast enhanced, that is, multiparametric prostate MRI. Subsequent prostate biopsies should also be performed if MRI is positive, that is, Prostate Imaging-Reporting and Data System (PI-RADS) scores 3-5. However, several retrospective post hoc analyses have shown that this approach still leads to many unnecessary biopsy procedures. For example, 88%-96% of men with PI-RADS, three findings are still diagnosed with clinically non-significant prostate cancer or no cancer at all. METHODS AND ANALYSIS: This is a prospective, randomised, controlled, multicentre trial, being conducted in Finland, to demonstrate non-inferiority in clinically significant cancer detection rates among men undergoing prostate biopsies post-MRI and men undergoing prostate biopsies post-MRI only after a shared decision based on individualised risk estimation. Men without previous diagnosis of prostate cancer and with abnormal digital rectal examination findings and/or prostate-specific antigen between 2.5 ug/L and 20.0 ug/L are included. We aim to recruit 830 men who are randomised at a 1:1 ratio into control (all undergo biopsies after MRI) and intervention arms (the decision to perform biopsies is based on risk estimation and shared decision-making). The primary outcome of the study is the proportion of men with clinically significant prostate cancer (Gleason 4+3 prostate cancer or higher). We will also compare the overall biopsy rate, benign biopsy rate and the detection of non-significant prostate cancer between the two study groups. ETHICS AND DISSEMINATION: The study (protocol V.2.0, 4 January 2021) was approved by the Ethics Committee of the Hospital District of Southwest Finland (IORG number: 0001744, IBR number: 00002216; trial number: 99/1801/2019). Participants are required to provide written informed consent. Full reports of this study will be submitted to peer-reviewed journals, mainly urology and radiology. TRIAL REGISTRATION NUMBER: NCT04287088; the study is registered at ClinicalTrials.gov.

Detection of Prostate Cancer Using Biparametric Prostate MRI, Radiomics, and Kallikreins: A Retrospective Multicenter Study of Men With a Clinical Suspicion of Prostate Cancer.

BACKGROUND: Accurate detection of clinically significant prostate cancer (csPCa), Gleason Grade Group ≥ 2, remains a challenge. Prostate MRI radiomics and blood kallikreins have been proposed as tools to improve the performance of biparametric MRI (bpMRI). PURPOSE: To develop and validate radiomics and kallikrein models for the detection of csPCa. STUDY TYPE: Retrospective. POPULATION: A total of 543 men with a clinical suspicion of csPCa, 411 (76%, 411/543) had kallikreins available and 360 (88%, 360/411) did not take 5-alpha-reductase inhibitors. Two data splits into training, validation (split 1: single center, n = 72; split 2: random 50% of pooled datasets from all four centers), and testing (split 1: 4 centers, n = 288; split 2: remaining 50%) were evaluated. FIELD STRENGTH/SEQUENCE: A 3 T/1.5 T, TSE T2-weighted imaging, 3x SE DWI. ASSESSMENT: In total, 20,363 radiomic features calculated from manually delineated whole gland (WG) and bpMRI suspicion lesion masks were evaluated in addition to clinical parameters, prostate-specific antigen, four kallikreins, MRI-based qualitative (PI-RADSv2.1/IMPROD bpMRI Likert) scores. STATISTICAL TESTS: For the detection of csPCa, area under receiver operating curve (AUC) was calculated using the DeLong's method. A multivariate analysis was conducted to determine the predictive power of combining variables. The values of P-value < 0.05 were considered significant. RESULTS: The highest prediction performance was achieved by IMPROD bpMRI Likert and PI-RADSv2.1 score with AUC = 0.85 and 0.85 in split 1, 0.85 and 0.83 in split 2, respectively. bpMRI WG and/or kallikreins demonstrated AUCs ranging from 0.62 to 0.73 in split 1 and from 0.68 to 0.76 in split 2. AUC of bpMRI lesion-derived radiomics model was not statistically different to IMPROD bpMRI Likert score (split 1: AUC = 0.83, P-value = 0.306; split 2: AUC = 0.83, P-value = 0.488). DATA CONCLUSION: The use of radiomics and kallikreins failed to outperform PI-RADSv2.1/IMPROD bpMRI Likert and their combination did not lead to further performance gains. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

How to read biparametric MRI in men with a clinical suspicious of prostate cancer: Pictorial review for beginners with public access to imaging, clinical and histopathological database.

Prostate Magnetic Resonance Imaging (MRI) is increasingly being used in men with a clinical suspicion of prostate cancer (PCa). Performing prostate MRI without the use of an intravenous contrast (IV) agent in men with a clinical suspicion of PCa can lead to reduced MRI scan time. Enabling a large array of different medical providers (from mid-level to specialized radiologists) to evaluate and potentially report prostate MRI in men with a clinical suspicion of PCa with a high accuracy could be one way to enable wide adoption of prostate MRI in men with a clinical suspicion of PCa. The aim of this pictorial review is to provide an insight into acquisition, quality control and reporting of prostate MRI performed without IV contrast agent in men with a clinical suspicion of PCa, aimed specifically at radiologists starting reporting prostate MRI, urologists, urology/radiology residents and mid-level medical providers without experience in reporting prostate MRI. Free public access (http://petiv.utu.fi/improd/and http://petiv.utu.fi/multiimprod/) to complete datasets of 161 and 338 men is provided. The imaging datasets are accompanied by clinical, laboratory and histopathological findings. Several topics are simplified in order to provide a solid base for the development of skills needed for an unsupervised review and potential reporting of prostate MRI in men with a clinical suspicion of PCa. The current review represents the first step towards enabling a large array of different medical providers to review and report accurately prostate MRI performed without IV contrast agent in men with a clinical suspicion of PCa.

Added value of systematic biopsy in men with a clinical suspicion of prostate cancer undergoing biparametric MRI-targeted biopsy: multi-institutional external validation study.

PURPOSE: We aimed to develop and externally validate a nomogram based on MRI volumetric parameters and clinical information for deciding when SBx should be performed in addition to TBx in man with suspicious prostate MRI. MATERIALS AND METHODS: Retrospective analyses of single (IMPROD, NCT01864135) and multi-institution (MULTI-IMPROD, NCT02241122) clinical trials. All men underwent a unique rapid biparametric magnetic resonance imaging (IMPROD bpMRI) consisting of T2-weighted imaging and three separate DWI acquisitions. Men with IMPROD bpMRI Likert scores of 3-5 were included. Logistic regression models were developed using IMPROD trial (n = 122) and validated using MULTI-IMPROD trial (n = 262) data. The model's performance was evaluated in the terms of PCa detection with Gleason Grade Group 1 (clinically insignificant prostate cancer, iPCa) and > 1 (clinically significant prostate cancer, csPCa). Net benefits and decision curve analyses (DCA) were compared. Combined biopsies were used for reference. RESULTS: The developed nomogram included age, PSA, prostate volume, MRI suspicion score (IMPROD bpMRI Likert or PIRADsv2.1 score), MRI-suspicion lesion volume percentage, and lesion location. All these variables were significant predictors of csPCa in SBx in multivariable analysis. In the validation cohort (n = 262) using different nomogram cutoffs, 19-43% of men would have avoided SBx while missing 1-4% of csPCa and avoiding detection of 9-20% of iPCa. Similar performance was found for nomograms using IMPROD bpMRI Likert score or v2.1. CONCLUSIONS: The developed nomogram demonstrated potential to select men with a clinical suspicion of PCa who would benefit from performing SBx in addition to TBx. Public access to the nomogram is provided at: https://petiv.utu.fi/multiimprod/ .

Negative Predictive Value of Biparametric Prostate Magnetic Resonance Imaging in Excluding Significant Prostate Cancer: A Pooled Data Analysis Based on Clinical Data from Four Prospective, Registered Studies.

BACKGROUND: Multiparametric prostate magnetic resonance imaging (mpMRI) can be considered the gold standard in prostate magnetic resonance imaging (MRI). Biparametric prostate MRI (bpMRI) is faster and could be a feasible alternative to mpMRI. OBJECTIVE: To determine the negative predictive value (NPV) of Improved Prostate Cancer Diagnosis (IMPROD) bpMRI as a whole and in clinical subgroups in primary diagnostics of clinically significant prostate cancer (CSPCa). DESIGN, SETTING, AND PARTICIPANTS: This is a pooled data analysis of four prospective, registered clinical trials investigating prebiopsy IMPROD bpMRI. Men with a clinical suspicion of prostate cancer (PCa) were included. INTERVENTION: Prebiopsy IMPROD bpMRI was performed, and an IMPROD bpMRI Likert scoring system was used. If suspicious lesions (IMPROD bpMRI Likert score 3-5) were visible, targeted biopsies in addition to systematic biopsies were taken. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Performance measures of IMPROD bpMRI in CSPCa diagnostics were evaluated. NPV was also evaluated in clinical subgroups. Gleason grade ≥3 + 4 in any biopsy core taken was defined as CSPCa. RESULTS AND LIMITATIONS: A total of 639 men were included in the analysis. The mean age was 64 yr, mean prostate-specific antigen level was 8.9 ng/ml, and CSPCa prevalence was 48%. NPVs of IMPROD bpMRI Likert scores 3-5 and 4-5 for CSPCa were 0.932 and 0.909, respectively, and the corresponding positive predictive values were 0.589 and 0.720. Only nine of 132 (7%) men with IMPROD bpMRI Likert score 1-2 had CSPCa and none with Gleason score >7. Thus, 132 of 639 (21%) study patients could have avoided biopsies without missing a single Gleason >7 cancer in the study biopsies. In the subgroup analysis, no clear outlier was present. The limitation is uncertainty of the true CSPCa prevalence. CONCLUSIONS: IMPROD bpMRI demonstrated a high NPV to rule out CSPCa. IMPROD bpMRI Likert score 1-2 excludes Gleason >7 PCa in the study biopsies. PATIENT SUMMARY: We investigated the feasibility of prostate magnetic resonance imaging (MRI) with the Improved Prostate Cancer Diagnosis (IMPROD) biparametric MRI (bpMRI) protocol in excluding significant prostate cancer. In this study, highly aggressive prostate cancer was excluded using the publicly available IMPROD bpMRI protocol (http://petiv.utu.fi/multiimprod/).

Clinical markers of morbidity, mortality and survival in bladder cancer patients treated with radical cystectomy. A systematic review.

Context: Radical cystectomy and pelvic lymph node dissection (RC and PLND) are an essential part of the treatment paradigm in high risk bladder cancer. However, these patients have high rates of morbidity and mortality related both to the treatment and to the disease.Objective: To provide overview of current literature about clinical markers that can be used to predict and improve BC-patient outcomes at the time of RC and PLND and to study if they are properly validated.Evidence acquisition: A systematic literature search was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria between January 1990 and October 2018 to identify English written original and review articles relevant to this topic. Prospective and retrospective studies were included.Evidence synthesis: There are several risk factors identified from non-randomised trials that can be improved before surgery to reduce perioperative mortality and morbidity. These include poor nutritional status, anaemia, renal function and smoking. Preoperative nomograms have also been developed to help decision-making and to inform patients about the risks of surgery. They can be used to estimate risk of postoperative mortality after RC and PLND with accuracy varying from 70 to 86%. These nomograms are largely based on retrospective data. Likewise, nomograms developed to calculate estimates about patient's overall and cancer specific survival have the same limitations.Conclusion: Clinical markers to predict morbidity, mortality and survival in patients with bladder cancer treated with RC and PLND may help to improve patient outcomes and treatment decision-making, but available data come from small retrospective trials and have not been properly validated. Prospective, multi-centre studies are needed to implement and disseminate predictive clinical markers and nomograms such that they can be utilised in treatment decision-making in daily practice.

Impact of biparametric prebiopsy prostate magnetic resonance imaging on the diagnostics of clinically significant prostate cancer in biopsy naïve men.

Background: The objective of this study was to compare the prevalence of clinically significant prostate cancer (CSPCa) in men with biparametric prebiopsy prostate magnetic resonance imaging (MRI) and lesion-targeted biopsies (TBs) to the group of men without prebiopsy MRI in an initial biopsy session.Methods: The MRI group consists of men enrolled into four prospective clinical trials investigating a biparametric MRI (bpMRI) and TB while the non-MRI group was a retrospective cohort of men collected from an era prior to a clinical use of a prostate MRI. All men had standard biopsies (SBs). In the MRI group, men had additional TBs from potential cancer-suspicious lesions. CSPCa was defined as Gleason score ≥3 + 4 in any biopsy core taken. All the patients were prostate biopsy naïve.Results: The MRI group consists of 507 while the non-MRI group 379 men. Mean age and prostate specific antigen (PSA) level differed significantly (p < 0.05) between the groups: In the MRI group, 64 years and 7.6 ng/ml, respectively, and in the non-MRI group 68 years and 8.2 ng/ml, respectively. Significantly (p < 0.05) more CSPCa was diagnosed with initial biopsies in the MRI group (48%) compared to non-MRI group (34%). In men with no CSPCa diagnosed during the initial biopsies, significantly fewer (p < 0.05) men had upgrading re-biopsies in the MRI group (5%) than in the non-MRI group (19%) during the follow up.Conclusions: Prebiopsy bpMRI with TBs combined with SBs could lead to earlier diagnoses of CSPCa compared with men without prebiopsy prostate MRI used in initial PCa diagnostics.

Decreased forced expiratory volume in first second is associated with erectile dysfunction in apparently healthy men. A preliminary study.

Although it has been evaluated that even 76% of men with chronic obstructive pulmonary disease suffer from erectile dysfunction, the association has been poorly characterised. The aim of the study was to describe the association between forced expiratory volume in first second and erectile dysfunction in apparently healthy men. All together 331 men aged 45-70 years old were randomly drawn from a cross-sectional population-based study conducted in 2005 in Finland. Decreased forced expiratory volume was defined by performing mini-spirometry and erectile dysfunction by International Index of Erectile Function short form questionnaire. After adjustment for age and depressive symptoms predicted forced expiratory volume (FEV1 < 65%) was associated with 2.66 (95% CI, 1.18-5.99) increased risk of moderate to severe erectile dysfunction (International Index of Erectile Function short form score < 17). Therefore, the authors highlight the importance of erectile and sexual health evaluation and treatment, if necessary, in men with decreased lung function.

Prostate Cancer Risk Stratification in Men With a Clinical Suspicion of Prostate Cancer Using a Unique Biparametric MRI and Expression of 11 Genes in Apparently Benign Tissue: Evaluation Using Machine-Learning Techniques.

BACKGROUND: Accurate risk stratification of men with a clinical suspicion of prostate cancer (cSPCa) remains challenging despite the increasing use of MRI. PURPOSE: To evaluate the diagnostic accuracy of a unique biparametric MRI protocol (IMPROD bpMRI) combined with clinical and molecular markers in men with cSPCa. STUDY TYPE: Prospective single-institutional clinical trial (NCT01864135). SUBJECTS: Eighty men with cSPCa. FIELD STRENGTH/SEQUENCE: 3T, surface array coils. Two T2 -weighted and three diffusion-weighted imaging (DWI) acquisitions: 1) b-values 0, 100, 200, 300, 500 s/mm2 ; 2) b-values 0,1500 s/mm2 ; 3) b-values 0, 2000 s/mm2 . ASSESSMENT: IMPROD bpMRI examinations were qualitatively (IMPROD bpMRI Likert score) and quantitatively (DWI-based Gleason grade score) prospectively reported. Men with IMPROD bpMRI Likert 3-5 had two targeted biopsies followed by 12-core systematic biopsies (SB); those with IMPROD bpMRI Likert 1-2 had only SB. Additionally, 2-core from normal-appearing prostate areas were obtained for the mRNA expression of ACSM1, AMACR, CACNA1D, DLX1, PCA3, PLA2G7, RHOU, SPINK1, SPON2, TMPRSS2-ERG, and TDRD1 measured by quantitative reverse-transcription polymerase chain reaction. STATISTICAL TESTS: Univariate and multivariate analysis using regularized least-squares, feature selection and tournament leave-pair-out cross-validation (TLPOCV), as well as 10 random splits of the data in training-testing sets, were used to evaluate the mRNA, clinical and IMPROD bpMRI parameters in detecting clinically significant prostate cancer (SPCa) defined as Gleason score ≥ 3 + 4. The evaluation metric was the area under the curve (AUC). RESULTS: IMPROD bpMRI Likert demonstrated the highest TLPOCV AUC of 0.92. The tested clinical variables had AUC 0.56-0.73, while the mRNA and additional IMPROD bpMRI parameters had AUC 0.50-0.67 and 0.65-0.89 respectively. The combination of clinical and mRNA biomarkers produced TLPOCV AUC of 0.87, the highest TLPOCV performance without including IMPROD bpMRI Likert. DATA CONCLUSION: The qualitative IMPROD bpMRI Likert score demonstrated the highest accuracy for SPCa detection compared with the tested clinical variables and mRNA biomarkers. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1540-1553.

Qualitative and Quantitative Reporting of a Unique Biparametric MRI: Towards Biparametric MRI-Based Nomograms for Prediction of Prostate Biopsy Outcome in Men With a Clinical Suspicion of Prostate Cancer (IMPROD and MULTI-IMPROD Trials).

BACKGROUND: Multiparametric MRI of the prostate has been shown to improve the risk stratification of men with an elevated prostate-specific antigen (PSA). However, long acquisition time, high cost, and inter-center/reader variability of a routine prostate multiparametric MRI limit its wider adoption. PURPOSE: To develop and validate nomograms based on unique rapid biparametric MRI (bpMRI) qualitative and quantitative derived variables for prediction of clinically significant cancer (SPCa). STUDY TYPE: Retrospective analyses of single (IMPROD, NCT01864135) and multiinstitution trials (MULTI-IMPROD, NCT02241122). POPULATION: 161 and 338 prospectively enrolled men who completed the IMPROD and MULTI-IMPROD trials, respectively. FIELD STRENGTH/SEQUENCE: IMPROD bpMRI: 3T/1.5T, T2 -weighted imaging, three separate diffusion-weighted imaging (DWI) acquisitions: 1) b-values 0, 100, 200, 300, 500 s/mm2 ; 2) b values 0, 1500 s/mm2 ; 3) values 0, 2000 s/mm2 . ASSESSMENT: The primary endpoint of the combined trial analysis was the diagnostic accuracy of the combination of IMPROD bpMRI and clinical variables for detection of SPCa. STATISTICAL TESTS: Logistic regression models were developed using IMPROD trial data and validated using MULTI-IMPROD trial data. The model's performance was expressed as the area under the curve (AUC) values for the detection of SPCa, defined as ISUP Gleason Grade Group ≥2. RESULTS: A model incorporating clinical variables had an AUC (95% confidence interval) of 0.83 (0.77-0.89) and 0.80 (0.75-0.85) in the development and validation cohorts, respectively. The corresponding values for a model using IMPROD bpMRI findings were 0.93 (0.89-0.97), and 0.88 (0.84-0.92), respectively. Further addition of the quantitative DWI-based score did not improve AUC values (P < 0.05). DATA CONCLUSION: A prediction model using qualitative IMPROD bpMRI findings demonstrated high accuracy for predicting SPCa in men with an elevated PSA. Online risk calculator: http://petiv.utu.fi/multiimprod/ Level of Evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1556-1567.

Prebiopsy IMPROD Biparametric Magnetic Resonance Imaging Combined with Prostate-Specific Antigen Density in the Diagnosis of Prostate Cancer: An External Validation Study.

BACKGROUND: Biparametric magnetic resonance imaging (bpMRI) combined with prostate-specific antigen density (PSAd) may be an effective strategy for selecting men for prostate biopsy. It has been shown that performing biopsy only for men with bpMRI Likert scores of 4-5 or PSAd ≥0.15 ng/ml/cm3 is the most efficient strategy. OBJECTIVE: To externally validate previously published biopsy strategies using two prospective bpMRI trial cohorts. DESIGN, SETTING, AND PARTICIPANTS: After IMPROD bpMRI, 499 men had systematic transrectal prostate biopsies and men with IMPROD bpMRI Likert scores of 3-5 had an additional two to four targeted biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Various IMPROD bpMRI Likert score and PSAd thresholds were assessed using detection rates for significant prostate cancer (sPCa; Gleason score ≥3 + 4), predictive values, and proportion of biopsies avoided. Net benefits and decision curve analyses (DCA) were compared with the aim of finding an optimal strategy for sPCa detection. Combined biopsies were used for reference. RESULTS AND LIMITATIONS: The negative predictive value (NPV) for sPCa in IMPROD bpMRI Likert 3-5 and 4-5 score groups was 93% and 92%, respectively, while the corresponding positive predictive value (PPV) was 57% and 72%, respectively. In DCA, the optimal combination was IMPROD bpMRI Likert score 4-5 or Likert 3 with PSAd ≥0.20 ng/ml/cm3, which had NPV of 93% and PPV of 67%. Using this combination, 35% of the study patients would have avoided biopsies and 13 sPCas (6%, 13/229, of all sPCas diagnosed) would have been missed. CONCLUSIONS: IMPROD bpMRI demonstrated a good NPV for sPCa. PSAd improved the NPV mainly among men with equivocal suspicion on IMPROD bpMRI. However, the additional value of PSAd was marginal: the NPV and PPV for IMPROD bpMRI Likert 4-5 score group were 92% and 72%, respectively, while the corresponding values for the best combination strategy were 93% and 67%. PATIENT SUMMARY: We investigated a rapid prostate magnetic resonance imaging protocol (IMPROD bpMRI) combined with prostate-specific antigen (PSA) density for detection of significant prostate cancer. Our results show that IMPROD bpMRI is a good diagnostic tool, but the additional value provided by PSA density is marginal.

Prediction of complication related death after radical cystectomy for bladder cancer with machine learning methodology.

Purpose: To create a pre-operatively usable tool to identify patients at high risk of early death (within 90 days post-operatively) after radical cystectomy and to assess potential risk factors for post-operative and surgery related mortality.Materials and methods: Material consists of 1099 consecutive radical cystectomy (RC) patients operated at 16 different hospitals in Finland 2005-2014. Machine learning methodology was utilized. For model building and testing, the data was randomly divided into training data (n = 733, 66.7%) and independent testing data (n = 366, 33.3%). To predict the risk of early death after RC from baseline variables, a binary classifier was constructed using logistic regression with lasso regularization. Finally, a user-friendly risk table was constructed for practical use.Results: The model resulted in an area under the receiver operating characteristic curve (AUROC) of 0.73 (95% CI = 0.59-0.87). The strongest risk factors were: American Society of Anesthesiologists physical status classification (ASA), congestive heart failure (CHF), age adjusted Charlson comorbidity index (ACCI) and chronic pulmonary disease.Conclusion: This study with a novel methodological approach adds CHF and chronic pulmonary disease to previously known independent prognostic risk factors for early death after RC. Importantly, the risk prediction tool uses purely pre-operative data and can be used before surgery.

Validation of IMPROD biparametric MRI in men with clinically suspected prostate cancer: A prospective multi-institutional trial.

BACKGROUND: Magnetic resonance imaging (MRI) combined with targeted biopsy (TB) is increasingly used in men with clinically suspected prostate cancer (PCa), but the long acquisition times, high costs, and inter-center/reader variability of routine multiparametric prostate MRI limit its wider adoption. METHODS AND FINDINGS: The aim was to validate a previously developed unique MRI acquisition and reporting protocol, IMPROD biparametric MRI (bpMRI) (NCT01864135), in men with a clinical suspicion of PCa in a multi-institutional trial (NCT02241122). IMPROD bpMRI has average acquisition time of 15 minutes (no endorectal coil, no intravenous contrast use) and consists of T2-weighted imaging and 3 separate diffusion-weighed imaging acquisitions. Between February 1, 2015, and March 31, 2017, 364 men with a clinical suspicion of PCa were enrolled at 4 institutions in Finland. Men with an equivocal to high suspicion (IMPROD bpMRI Likert score 3-5) of PCa had 2 TBs of up to 2 lesions followed by a systematic biopsy (SB). Men with a low to very low suspicion (IMPROD bpMRI Likert score 1-2) had only SB. All data and protocols are freely available. The primary outcome of the trial was diagnostic accuracy-including overall accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value-of IMPROD bpMRI for clinically significant PCa (SPCa), which was defined as a Gleason score ≥ 3 + 4 (Gleason grade group 2 or higher). In total, 338 (338/364, 93%) prospectively enrolled men completed the trial. The accuracy and NPV of IMPROD bpMRI for SPCa were 70% (113/161) and 95% (71/75) (95% CI 87%-98%), respectively. Restricting the biopsy to men with equivocal to highly suspicious IMPROD bpMRI findings would have resulted in a 22% (75/338) reduction in the number of men undergoing biopsy while missing 4 (3%, 4/146) men with SPCa. The main limitation is uncertainty about the true PCa prevalence in the study cohort, since some of the men may have PCa despite having negative biopsy findings. CONCLUSIONS: IMPROD bpMRI demonstrated a high NPV for SPCa in men with a clinical suspicion of PCa in this prospective multi-institutional clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT02241122.

Update on novel imaging techniques for the detection of lymph node metastases in bladder cancer.

Staging of muscle-invasive bladder cancer (MIBC) remains a challenge. It is generally acknowledged that the most commonly used imaging techniques have a trend to either upstage or downstage the disease. The aim of this review article is to evaluate the currently available scientific evidence for the use of imaging modalities in preoperative bladder cancer staging with special attention to the detection of lymph node metastasis (LNM). A non-systematic literature search utilizing PubMed database with terms MIBC and LN and MRI or PET or CT was performed with the search limited to articles published between 2010 and 2015. Magnetic resonance imaging (MRI) has shown potential for local tumor detection and staging in multiple studies, but the accuracy for LNM detection remains disappointingly low. The LN staging accuracy is improved with the use of ultra-small super-paramagnetic particles of iron oxide (USPIO). This experimental method, however, is not commercially available at the moment. Positron emission tomography (PET), a functional imaging technique most commonly accompanied with computed tomography (PET-CT), may also have a role in the detection of bladder cancer LNM in the future. According to the currently available scientific evidence, the following could be recommended for MIBC staging: 1. use of pelvic MRI for primary tumor evaluation and local LNM detection acknowledging limited nodal imaging accuracy; 2. pelvic/abdominal/chest CT for evaluation of distant metastasis. The scientific evidence does not support the routine use of PET-CT (18F-FDG, 18F/11C-choline, 11C-acetate) in bladder cancer staging or in LNM detection.

Erectile dysfunction cannot be used in primary screening of pre-diabetes.

We hypothesized that erectile dysfunction is associated with impaired fasting glucose and impaired glucose tolerance and could be used in primary screening of pre-diabetes. Although erectile dysfunction is known to be closely associated with diabetes, we demonstrate that it is not associated with pre-diabetes in 926 apparently healthy men.

Role of ultrasensitive prostate-specific antigen in the follow-up of prostate cancer after radical prostatectomy.

OBJECTIVE: Prostate-specific antigen (PSA) is an important tool in the follow-up of prostate cancer after radical prostatectomy (RP). However, the relevance of ultrasensitive PSA (uPSA) after RP is not well defined. The aim of this study was to investigate the value of uPSA in follow-up after RP and to determine whether ultrasensitive PSA doubling time (uDT) correlates with traditional PSA doubling time (tDT). PATIENTS AND METHODS: In total, 604 consecutive patients undergoing open RP and pelvic lymphadenectomy between 2004 and 2008 (minimum 5y of follow-up) were studied. To evaluate the postsurgical uPSA level, scatter plot statistics were used. To correlate uDT and tDT in patients with a biochemical recurrence (PSA ≥0.2ng/ml), at least 2 uPSA and 2 PSA measurements without salvage treatment were required and a weighted Cohen kappa statistic and receiver operating characteristic curve were used to test agreement across the categories. RESULTS: There were 229 patients without biochemical recurrence who did not have 3 rising PSA values after nadir within ultrasensitive area. Their highest uPSA value was between 0.003 and 0.1ng/ml. In 97.4% of patients, the highest uPSA value was less than 0.03ng/ml, and in 89% of these patients, the values were less than 0.02ng/ml. The median uDT and tDT were 10.2 and 11.4 months, respectively. The weighted Cohen kappa statistic between these 2 groups was 0.30 (95% CI:-0.09 to 0.50), demonstrating a poor agreement of PSA doubling time across categories. The predictive capability of uDT was tested with tDT <9 months. A receiver operating characteristic curve area under the curve value was 0.737 (95% CI:-0.577 to 0.897) demonstrating a fair agreement between the groups. CONCLUSIONS: uPSA values>0.03ng/ml seems to be valid and can be used in a clinical setting. There was a poor to fair agreement between tDT and uDT. The accuracy of uDT improves when it approaches the traditional PSA threshold of 0.1ng/ml. Also according to our results, there is no prognostic benefit of uDT calculation.

High-intensity physical activity, stable relationship, and high education level associate with decreasing risk of erectile dysfunction in 1,000 apparently healthy cardiovascular risk subjects.

INTRODUCTION: Erectile dysfunction (ED) is especially common in men with cardiovascular diseases (CVDs). However, the data are scarce concerning populations without manifested CVD. AIM: The aim of this study was to describe factors associated with ED, especially those associated with decreasing risk of ED, in men with cardiovascular risk factors but without CVD, diabetes, or chronic renal disease. METHODS: In 2004 to 2007, a cross-sectional population-based sample of men 45 to 70 years old in two rural towns in Finland was collected. Men with previously diagnosed CVD, diabetes, or kidney disease were not invited to the study. In total 1,000 eligible men with cardiovascular risk factors, i.e., central obesity, high scores in the Finnish Diabetes Risk Score, high blood pressure, antihypertensive medication, or family history of coronary heart disease, myocardial infarction, or stroke, were included in the analysis. Questionnaires, clinical measurements, and laboratory tests were obtained. The prevalence of ED was studied comparing the means, and risk factors were studied using multivariate logistic regression analysis. MAIN OUTCOME MEASURES: The rate of ED was defined by the International Index of Erectile Function short form (IIEF-5) and by two questions (2Q) about the ability to achieve and to maintain an erection. RESULTS: The prevalence of ED was 57% or 68% using IIEF-5 or 2Q, respectively. Age (odds ratio [OR]: up to 9.16; 95% confidence interval [CI], 5.00-16.79; P < 0.001), smoking (OR: 1.41; 95% CI, 1.04-1.91; P = 0.028), depressive symptoms (OR: 4.04 for moderate and severe; 95% CI,1.22-13.45; P = 0.001), high-intensity physical activity (OR: 0.50; 95% CI, 0.29-0.86; P = 0.045), high education (OR: 0.52; 95% CI, 0.33-0.83; P = 0.013), and stable relationship (OR: 0.43; 95% CI, 0.21-0.88; P = 0.046) were associated with ED. CONCLUSIONS: In apparently healthy men with cardiovascular risk factors, decreasing risk of ED is associated with high-intensity physical activity, stable relationship, and high education level.

Bulbourethral gland adenocarcinoma in a 25-year-old man without comorbidities: radical resection of proximal urethrae with Mitrofanoff-type appendicovesicostomy.

Adenocarcinoma of the paraurethral gland is a rare tumour with no published prevalence in male patients. This report presents a case of bulbourethral gland adenocarcinoma in a 25-year-old man without comorbidities. After resection of the proximal urethra, sphincter and prostate, Mitrofanoff-type appendicovesicostomy was performed. In this case, chemotherapy or radiation was not included in the treatment as the surgery was estimated to be radical. The patient achieved good surgical and quality of life results. This case shows that macroscopic haematuria should be examined even in young age groups without comorbidities.

Ankle-brachial index is lower in hypertensive than in normotensive individuals in a cardiovascular risk population.

BACKGROUND: Hypertension is an established risk factor for peripheral arterial disease (PAD), but the prevalence of this condition in hypertensive patients without comorbidities is unknown. METHODS: In this study, we assess the prevalence and factors associated with PAD, and the usefulness of ankle-brachial index (ABI) in evaluating cardiovascular risk in hypertensive patients without cardiovascular or renal disease or previously known diabetes mellitus. We measured ABI in 972 nonclaudicant patients with hypertension, newly diagnosed glucose disorders, metabolic syndrome, obesity or a 10-year risk of cardiovascular disease death of 5% or more according to the Systematic Coronary Risk Evaluation System. RESULTS: The prevalence of PAD (defined as ABI < or =0.90) and borderline PAD (defined as ABI 0.91-1.00) in hypertensive patients was 7.3% (39/532) and 23.7% (126/532), respectively. In a multivariate model, hypertension remained an independent factor associated with PAD (adjusted odds ratio 3.20; 95% confidence interval 1.56-6.58). There was no association between PAD and metabolic risk factors. SBP and pulse pressure increased linearly across subgroups of ABI (normal 0.91-1.00 and < or =0.90) in hypertensive patients (P < 0.001). CONCLUSION: Subclinical PAD is common in hypertensive patients even without comorbidities. The measurement of ABI is an efficient method to identify patients with increased cardiovascular risk and worth performing to hypertensive patients, particularly those with pulse pressure above 65 mmHg. Uniform criterions of defining PAD and borderline PAD would aid physicians in clinical decision-making.