BACKGROUND:The long-term prevalence of clinically significant prostate cancer (csPCa) in patients with initial negative prostate biopsy is unknown. PURPOSE:To investigate the rate of csPCa of men with initial negative biopsy. STUDY TYPE:Retrospective analysis of prospectively collected data. POPULATION:A total of 197 men (mean age 63 years [SD ±6.98, range 29-79]) without csPCa on initial biopsy and available baseline biparametric prostate MRI (bpMRI). FIELD STRENGTH/SEQUENCE:3.0 T, turbo spin-echo T2-weighted (axial and sagittal) and three sets of diffusion-weighted imaging using single-shot spin-echo planar imaging (5 b-values 0-500 seconds/mm2; 2 b-values 0 and 1500 seconds/mm2, and 2 b-values 0 and 2000 seconds/mm2). ASSESSMENT:BpMRI was read using Prostate Imaging Reporting Data System (PI-RADS) v2.1. Systematic or targeted biopsy results served as reference standard. STATISTICAL TESTS:Continuous variables were compared using Kruskal-Wallis rank sum test. Categorical variables were compared using either Fisher's exact test or Pearson's chi-square test. Uni- and multivariate regression odds ratios (95% confidence interval) were used to study factors affecting csPCa being diagnosed during follow-up. Time to diagnosis of csPCa is calculated using the Kaplan-Meier method. RESULTS:Of 197 men, 74 (38%), 57 (29%), and 66 (34%) presented with PI-RADS 1-2, 3, and 4-5 findings in the baseline bpMRI. During the median follow-up of 52 months, 8.1%, 5.3%, and 18.2% of these men were diagnosed with csPCa, respectively. Baseline PI-RADS finding was the only factor that associated with csPCa found during the follow-up. DATA CONCLUSION:Baseline bpMRI with PI-RADS scores 1-3 and initial biopsies negative of csPCa had low rate of csPCa during follow-up, which supports more conservative follow-up for them but further research with longer follow-up is warranted. LEVEL OF EVIDENCE:3 TECHNICAL EFFICACY: Stage 2.

BackgroundAlthough 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.ObjectiveCharacterization of the gut microbiota and its functions associated with PCa.Design, setting, and participantsIn 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 analysisSequences were assigned to operational taxonomic units, differential abundance analysis, and α- and β-diversities, and predictive functional analyses were performed. Plasma steroid hormone levels corresponding to the predicted microbiota steroid hormone biosynthesis profiles were investigated.Results and limitationsOf 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.ConclusionsGut 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 summaryIn 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.

BackgroundAccurate 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).PurposeTo develop and validate radiomics and kallikrein models for the detection of csPCa.Study TypeRetrospective.PopulationA 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/SequenceA 3 T/1.5 T, TSE T2‐weighted imaging, 3x SE DWI.AssessmentIn 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 TestsFor 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.ResultsThe 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 ConclusionThe 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 Evidence1Technical EfficacyStage 2

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.

Background: Prostate cancer (PC) is the most common cancer in men worldwide. The incidence of PC varies significantly geographically, which might result e.g. from genetic factors and local discrepancies in screening policies, but also from differences in lifestyle such as diet. Novel environmental factor, namely gut microbiota (GM) has been recently associated with many pathological processes including tumor progression within human body but its role in PC is disputable. Methods: Within a clinical prospective single center trial, the GM profiles were assessed from 181 men with clinical suspicion of PC utilizing 16S rRNA gene sequencing (Illumina). Sequences were assigned to operational taxonomic units (OTUs) after which differential abundance analysis, - and {beta}-diversities, and predictive functional (PICRUST) analysis were performed. Further, plasma steroid hormone levels correlated to predicted microbiota functions. Results: PC was diagnosed in 60% (108/181). Apart for less smoking among subjects with PC, there were no life-style differences between the groups. The GM profiles of men with PC differed significantly from those without cancer, e.g. Prevotella 9, members of family Erysipelotrichaceae and potentially pathogenic Escherichia-Shigella were increased, and e.g. Jonquetella, Moryella, Anaeroglobus, Corynebacterium and CAG-352 were reduced in PC cases. Predictive functional analyses revealed increased 5--reductase activity (5-AR), copper absorption and retinal metabolism as functional results of different microbiota. Plasma testosterone negatively correlated with predicted microbial 5-AR activity (Wilcoxon rank sum p=0.057) and in a subgroup of men taking 5-AR inhibitors (n=17), plasma estrone 3 (p=0.027), and estradiol (p=0.054) levels were higher in men with predicted increased microbial 5-AR function. Conclusions: Certain bacterial and functional features within GM composition are associated with PC risk and altered androgen, copper and retinol metabolism are potential mechanisms. Findings could explain the previously reported association of life-style effects and geographical differences observed in PC.

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.

ABSTRACT Purpose Although prostate cancer 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 been recently associated with cancer progression, but its role in prostate cancer is unclear. Methods In a prospective multicenter clinical trial ( NCT02241122 ), the gut microbiota profiles of 181 men with a clinical suspicion of prostate cancer were assessed utilizing 16S rRNA gene sequencing. Sequences were assigned to operational taxonomic units, and differential abundance analysis, α- and β-diversities, and predictive functional (PICRUSt) analyses were performed. Additionally, plasma steroid hormone levels were correlated with the predicted microbiota functions. Results Several differences in the gut microbiota between the subjects with and without prostate cancer were noted. Prevotella 9 , members of the Erysipelotrichaceae family and Escherichia-Shigella were higher, and Jonquetella, Moryella, Anaeroglobus, Corynebacterium and CAG-352 were lower in the cancer group. Predictive functional analyses revealed higher 5-α-reductase, copper absorption, and retinal metabolism in the prostate cancer associated microbiome. Plasma testosterone associated negatively with the microbial 5-α-reductase activity (p=0.030). In a subgroup of men taking 5-α-reductase inhibitors (n=17), plasma estrone (p=0.027) and estradiol (p=0.059) levels were lower in men with predicted elevation of the microbial 5-α-reductase function. Conclusions Gut microbiota of the prostate cancer patients differed significantly compared to benign subjects. Microbial 5-α-reductase, copper absorption and retinol metabolism are potential mechanisms of action. These findings could explain the observed association of lifestyle, geography, and prostate cancer incidence.

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 naive. 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.

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 T-2-weighted and three diffusion-weighted imaging (DWI) acquisitions: 1) b-values 0, 100, 200, 300, 500 s/mm(2); 2) b-values 0,1500 s/mm(2); 3) b-values 0, 2000 s/mm(2). 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. Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1540-1553.

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/).

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/ .

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.

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.

BackgroundProstate MRI is increasingly being used in men with a clinical suspicion of prostate cancer (PCa). However, development and validation of methods for focal therapy planning are still lagging.PurposeTo evaluate the diagnostic accuracy on lesion, region‐of‐interest (ROI), and voxel level of IMPROD biparametric prostate MRI (bpMRI) for PCa detection in men with a clinical suspicion of PCa who subsequently underwent radical prostatectomy.Study TypeProspective single‐institution clinical trial (NCT01864135).PopulationSixty‐four men who underwent radical prostatectomy after IMPROD bpMRI performed in prebiopsy settings.Field Strength/SequenceIMPROD bpMRI consisted of T2‐weighted imaging (T2w) and three separate diffusion‐weighted imaging acquisitions with an average acquisition time of 15 minutes.AssessmentThe diagnostic accuracy of prospectively reported manual cancer delineations and regions increased with 3D dilation were evaluated on the voxel level (volume of 1.17 mm3, 1 mm3, 125 mm3) as well as the 36 ROI level. Only PCa lesions with a diameter ≥ 5 mm or any Gleason Grade 4 were analyzed. All data and protocols are freely available at: http://petiv.utu.fi/improdStatistical TestsSensitivity, specificity, accuracy.ResultsIn total, 99 PCa lesions were identified. Forty (40%, 40/99) had a Gleason score (GS) of >3 + 4. Twenty‐eight PCa lesions (28%, 28/99) were missed by IMPROD bpMRI, three (7.5%, 3/40) with GS >3 + 4. 3D dilation of manual cancer delineations in all directions by ~10–12 mm (corresponding to the Hausdorff distance) was needed to achieve sensitivity approaching 100% on a voxel level.Data ConclusionIMPROD bpMRI had a high sensitivity on lesion level for PCa with GS >3 + 4. Increasing 3D lesion delineations by ~10–12 mm (corresponding to the Hausdorff distance) was needed to achieve high sensitivity on the voxel level. Such information may help in planning ablation therapies.Level of Evidence: 1Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2019;50:1641–1650.

Background: Transrectal ultrasound-guided prostate biopsy (TRUS-Bx) is typically considered a safe procedure. However, infectious complications have been increasing. Objective: To determine the contemporary rate of biopsy-related infectious and noninfectious complications after TRUS-Bx, and identify potential risk factors associated with the complications. Design, setting, and participants: This was a prospective multicenter study and a substudy of a trial investigating the role of magnetic resonance imaging (MRI) in prostate cancer diagnosis (multi-IMPROD, NCT02241122). Intervention: TRUS-Bx was performed for all patients included in the study. Ciprofloxacin, levofloxacin, or fosfomycin was administered for antibiotic prophylaxis. Outcome measurements and statistical analysis: On inclusion, patients completed a detailed questionnaire and underwent MRI scanning. Antibiotic prophylaxis was prospectively recorded. After collection of a rectal swab, TRUS-Bx (total of 14-18 biopsy cores) was performed and. The rectal swabs were cultured and the antimicrobial susceptibility profile of Escherichia coli strains was analyzed. Biopsy complications leading to a visit to a health care unit were recorded and potential risk factors for complications were analyzed. Results and limitations: Twelve of the 294 patients (4.1%) had a biopsy-related complication, of which two (0.7%) were infectious and managed in the outpatient setting. Some 11% of the patients had an E. coli strain resistant to the prophylactic antibiotic administered. Conclusions: The risk of an infectious or noninfectious complication after TRUS-Bx is very low, although the FQ resistance rate in the study population was significant. Accordingly, the present TRUS-Bx procedure and antibiotic prophylaxis are efficient in guarding against biopsy complications, but regional resistance rates may affect the generalizability of the results. Patient summary: We examined the rate of complications after prostate biopsies in 294 patients. The risk of having a biopsy-related complication was low (4.1%). The rate of infectious complications was reasonably low (0.7%) although antibiotic resistance to the prophylactic antibiotic regimen was significant (11%). (c) 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Abstract 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.

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.

PURPOSE: Neoadjuvant chemotherapy (NAC) improves survival in muscle invasive bladder cancer (MIBC). Rate of adverse events (AE) have been reported only in randomized clinical trials (RCT). Purpose was to evaluate incidence, type, and risk factors of AEs during NAC treatment in a population-based setting. MATERIAL AND METHODS: The Finnish national cystectomy database covering years 2008-2014 was utilized. NAC associated AEs were reported by Common Terminology Criteria for Adverse Events (CTCAE) v.5.0. AEs during NAC in five-tier severity scale was the outcome measure. Spearman correlation between AEs and 22 clinical variables were calculated. P-values were corrected for multiple testing by controlling false discovery rate (FDR) with Benjamini-Hochberg method. RESULTS: Thirty-one percent of MIBC patients were assigned to NAC. Final analysis included 229 NAC patients representing 30% of radical cystectomy (RC) population. Majority (88%) received cisplatin-gemcitabine. 105 patients (46%) had no AEs. 124 patients (54%) had 168 AEs in total. Severe events (CTCAE grade 3-5) were documented in 31% of patients and one (0.4%) died. In five patients (2.1%) RC was not performed due to the AE. Of the severe AEs, hematological were most common, followed with cardiac, vascular and urinary tract as most commonly affected organ systems. The number of chemotherapy cycles was the only variable significantly associated with AEs. Severe AEs occurred already during or after the first cycle of NAC leading to early termination. CONCLUSION: NAC is generally well tolerated, but poses a considerable risk for adverse events. This is the first study to evaluate AEs caused by NAC in real life scenario on population level.

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.