Diagnosis of prostate cancer with magnetic resonance imaging in men treated with 5-alpha-reductase inhibitors.

PURPOSE: The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade ≥ 2). METHODS: This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients. RESULTS: 705 patients (9%) were treated with 5-ARIs [median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72] and 6913 were 5-ARIs naïve (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1-2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (p < 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG ≥ 3) was higher in treated patients (23% vs 19%, p = 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS ≥ 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively. CONCLUSIONS: Exposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions. TRIAL REGISTRATION: The present study was registered at ClinicalTrials.gov number: NCT05078359.

Nationwide analysis of survival after radical cystectomy for bladder cancer in Finland.

BACKGROUND: Population-based survival results after radical cystectomy (RC) are limited. Our objective was to report short and long-term survival results after RC for bladder cancer from Finland in a population-based setting. MATERIALS AND METHODS: The Finnish National Cystectomy Database containing retrospectively collected essential RC data covering the years 2005-2017 was combined with the survival data from the Finnish Cancer Registry. Kaplan-Meier plots were used to estimate survival and the survival graphs were illustrated according to the final pathological staging. Centers were divided according to operational volume, and the results were then compared using Pearsons's Chi-squared test. RESULTS: A total of 2047 patients were included in the study. 30-, and 90-day mortality was 1.3%, and 3.8%, respectively. The OS of the entire RC population at 5- and 10 years was 66% and 55%, and CSS was 74% and 72%, respectively. Center volume did not significantly associate with surgical mortality or long-term survival. The 5- and 10-year OS according to pT-category was 87% and 74% for pT0, 85% and 69% for pTa-pTis-pT1, 70% and 58% for pT2, 50% and 42% for pT3 and 41% and 30% for pT4. The corresponding 5- and 10-year CSS rates were 96% and 93% for pT0, 91% and 90% for pTa-pTis-pT1, 78% and 75% for pT2, 56% and 55% for pT3 and 47% and 44% for pT4. The 5- and 10-year OS rates in patients with no lymph node metastases (pN-) were 74% and 62%, and CSS 82% and 80%, respectively. If lymph nodes were positive (pN+), the corresponding OS rates were 44% and 34% and CSS 49% and 48%, respectively. CONCLUSION: RC survival results have improved in contemporary series and are associated with the pTNM-status. The nationwide results from Finland demonstrate outcome comparable to high volume single-center series.

Estrés, burnout y emociones en personal de salud ante la emergencia por COVID-19 / Stress, burnout and emotions in health workers´ emergency conditions due to the COVID-19

La situación epidemiológica originada por la COVID-19 provocó nuevas demandas a las ya existentes en el personal de salud. Objetivos: Describir las dimensiones del síndrome de burnout: agotamiento emocional, despersonalización y falta de realización profesional en el personal del área de salud, determinar los niveles de estrés, explorar el ambiente emocional en sus dimensiones de afectividad positiva y negativa y delimitar la relación entre estas variables. Estudio cuantitativo con un diseño descriptivo de corte transversal, en un Policlínico durante el mes de diciembre del 2021. En personal médico (n=23) y de enfermería (n=16), se aplica el Inventario de burnout de Maslach, la Escala sintomática de estrés y la Escala de afectividad positiva y negativa. Resultados: Se obtiene agotamiento emocional alto en el 30,8%, medio en 33,3%; despersonalización, en un sujeto fue alto, y en 6 medio; la eficacia profesional en 9 sujetos fue medio y en 1 bajo; el nivel de estrés fue patológico en 41%, la afectividad positiva es alta en 53,8%, la negativa en el 5,1%. No existen diferencias respecto al sexo, ocupación y haber padecido o no COVID-19, se constata relación inversa entre la despersonalización y la edad. Conclusiones: La relación directa entre el estrés, agotamiento emocional y afectividad negativa son expresión de un desgaste producto de las respuestas fisiológicas y emocionales a situaciones mantenidas de movilización de recursos en el entorno laboral, lo cual se manifiesta en el grupo estudiado. Se recomiendan acciones dirigidas a intervenir de modo participativo y prevenir el ambiente emocional negativo(AU)

The epidemiological situation originated by COVID-19 caused new demands to those already existing in health personnel. Objectives: Describe the dimensions of the burnout syndrome, determine the levels of stress explore the emotional environment in its positive and negative affectivity dimensions and define the relationship between these variables. Quantitative study with crosssectional design, in a polyclinic during the month of December 2021. In medical (n=23) and nursing (n=16) staff the Scale of Positive and Negative Affect -PANAS- the Symptomatic Scales of Stress and the Maslach Burnout Inventory were applied. Measures of central tendency, absolutes and relative frequencies, measures of association and correlation coefficients with a reliability of 95% were used. Results: High emotional exhaustion is obtained in 30.8%, medium in 33.3%, depersonalization in one subject was high and in 6 medium, professional efficacy in 9 subjects was medium and in 1 low; the level of pathological stress in 41%, the positive affectivity is high in 53,8%, the negative in the 5.1%. There are no differences regarding sex, occupation and having suffered or not COVID-19. An inverse relationship between depersonalization and age is verified. Conclusions: The direct relationship between stress, emotional exhaustion and negative affectivity are expressions of a wear due to the physiological and emotional response to chronic situations of mobilization of resource at work. Actions aimed at intervening in a participatory way and preventing the negative emotional environment is recommended(AU)

Predicting the Need for Biopsy to Detect Clinically Significant Prostate Cancer in Patients with a Magnetic Resonance Imaging-detected Prostate Imaging Reporting and Data System/Likert ≥3 Lesion: Development and Multinational External Validation of the Imperial Rapid Access to Prostate Imaging and Diagnosis Risk Score.

BACKGROUND: Although multiparametric magnetic resonance imaging (MRI) has high sensitivity, its lower specificity leads to a high prevalence of false-positive lesions requiring biopsy. OBJECTIVE: To develop and externally validate a scoring system for MRI-detected Prostate Imaging Reporting and Data System (PIRADS)/Likert ≥3 lesions containing clinically significant prostate cancer (csPCa). DESIGN, SETTING, AND PARTICIPANTS: The multicentre Rapid Access to Prostate Imaging and Diagnosis (RAPID) pathway included 1189 patients referred to urology due to elevated age-specific prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE); April 27, 2017 to October 25, 2019. INTERVENTION: Visual-registration or image-fusion targeted and systematic transperineal biopsies for an MRI score of ≥4 or 3 + PSA density ≥0.12 ng/ml/ml. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Fourteen variables were used in multivariable logistic regression for Gleason ≥3 + 4 (primary) and Gleason ≥4 + 3, and PROMIS definition 1 (any ≥4 + 3 or ≥6 mm any grade; secondary). Nomograms were created and a decision curve analysis (DCA) was performed. Models with varying complexity were externally validated in 2374 patients from six international cohorts. RESULTS AND LIMITATIONS: The five-item Imperial RAPID risk score used age, PSA density, prior negative biopsy, prostate volume, and highest MRI score (corrected c-index for Gleason ≥3 + 4 of 0.82 and 0.80-0.86 externally). Incorporating family history, DRE, and Black ethnicity within the eight-item Imperial RAPID risk score provided similar outcomes. The DCA showed similar superiority of all models, with net benefit differences increasing in higher threshold probabilities. At 20%, 30%, and 40% of predicted Gleason ≥3 + 4 prostate cancer, the RAPID risk score was able to reduce, respectively, 11%, 21%, and 31% of biopsies against 1.8%, 6.2%, and 14% of missed csPCa (or 9.6%, 17%, and 26% of foregone biopsies, respectively). CONCLUSIONS: The Imperial RAPID risk score provides a standardised tool for the prediction of csPCa in patients with an MRI-detected PIRADS/Likert ≥3 lesion and can support the decision for prostate biopsy. PATIENT SUMMARY: In this multinational study, we developed a scoring system incorporating clinical and magnetic resonance imaging characteristics to predict which patients have prostate cancer requiring treatment and which patients can safely forego an invasive prostate biopsy. This model was validated in several other countries.

The Mount Sinai Prebiopsy Risk Calculator for Predicting any Prostate Cancer and Clinically Significant Prostate Cancer: Development of a Risk Predictive Tool and Validation with Advanced Neural Networking, Prostate Magnetic Resonance Imaging Outcome Database, and European Randomized Study of Screening for Prostate Cancer Risk Calculator.

Background: The European Association of Urology guidelines recommend the use of imaging, biomarkers, and risk calculators in men at risk of prostate cancer. Risk predictive calculators that combine multiparametric magnetic resonance imaging with prebiopsy variables aid as an individualized decision-making tool for patients at risk of prostate cancer, and advanced neural networking increases reliability of these tools. Objective: To develop a comprehensive risk predictive online web-based tool using magnetic resonance imaging (MRI) and clinical data, to predict the risk of any prostate cancer (PCa) and clinically significant PCa (csPCa) applicable to biopsy-naïve men, men with a prior negative biopsy, men with prior positive low-grade cancer, and men with negative MRI. Design setting and participants: Institutional review board-approved prospective data of 1902 men undergoing biopsy from October 2013 to September 2021 at Mount Sinai were collected. Outcome measurements and statistical analysis: Univariable and multivariable analyses were used to evaluate clinical variables such as age, race, digital rectal examination, family history, prostate-specific antigen (PSA), biopsy status, Prostate Imaging Reporting and Data System score, and prostate volume, which emerged as predictors for any PCa and csPCa. Binary logistic regression was performed to study the probability. Validation was performed with advanced neural networking (ANN), multi-institutional European cohort (Prostate MRI Outcome Database [PROMOD]), and European Randomized Study of Screening for Prostate Cancer Risk Calculator (ERSPC RC) 3/4. Results and limitations: Overall, 2363 biopsies had complete clinical information, with 57.98% any cancer and 31.40% csPCa. The prediction model was significantly associated with both any PCa and csPCa having an area under the curve (AUC) of 81.9% including clinical data. The AUC for external validation was calculated in PROMOD, ERSPC RC, and ANN for any PCa (0.82 vs 0.70 vs 0.90) and csPCa (0.82 vs 0.78 vs 0.92), respectively. This study is limited by its retrospective design and overestimation of csPCa in the PROMOD cohort. Conclusions: The Mount Sinai Prebiopsy Risk Calculator combines PSA, imaging and clinical data to predict the risk of any PCa and csPCa for all patient settings. With accurate validation results in a large European cohort, ERSPC RC, and ANN, it exhibits its efficiency and applicability in a more generalized population. This calculator is available online in the form of a free web-based tool that can aid clinicians in better patients counseling and treatment decision-making. Patient summary: We developed the Mount Sinai Prebiopsy Risk Calculator (MSP-RC) to assess the likelihood of any prostate cancer and clinically significant disease based on a combination of clinical and imaging characteristics. MSP-RC is applicable to all patient settings and accessible online.

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.

Awareness of Smoking as a Risk Factor in Bladder Cancer: Results from the Prospective FinnBladder 9 Trial.

BACKGROUND: Data regarding patient education and smoking habits among bladder cancer patients are scarce. OBJECTIVE: To investigate awareness of smoking as a risk factor for bladder cancer among bladder cancer patients. DESIGN, SETTING, AND PARTICIPANTS: This is a substudy of a prospective, randomized, multicenter phase 3 trial (FinnBladder 9, NCT01675219). The data were collected at baseline and after 12 mo of follow-up between 2012 and 2020. INTERVENTION: Patients completed a comprehensive nonvalidated questionnaire on smoking in relation to bladder cancer. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcomes measured were patient-reported awareness of smoking as a risk factor for bladder cancer, and the effect of smoking on bladder cancer-related recurrence, progression, and death. Parametric data were compared using Student's t test and proportions using Fischer's exact test. Factors affecting baseline awareness of the effect of smoking cessation on bladder cancer were studied using logistic regression. RESULTS AND LIMITATIONS: Of the 411 patients randomized, 370 completed the baseline questionnaire and were included in the analysis. At baseline, 44% of patients were uncertain if smoking was a risk factor for bladder cancer. Patient awareness of the fact that smoking cessation reduces the risk of bladder cancer recurrence increased from 86% to 92% after 12 mo of follow-up (p = 0.038). Older patients and patients with recurrent bladder cancer had significantly less knowledge about the effect of smoking on bladder cancer recurrence, progression, and mortality. A major limitation is that the response rate was lower at the 12-mo follow-up visit than at baseline. CONCLUSIONS: Awareness of smoking as a bladder cancer risk factor is low. Older patients and patients with recurrent bladder cancer may need special attention regarding education. PATIENT SUMMARY: We looked at outcomes for smoking-related patient education on bladder cancer in a Finnish population. We conclude that older patients and patients with recurrent bladder cancer may need to be educated on this subject.

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/).

Combined Use of Prostate-specific Antigen Density and Magnetic Resonance Imaging for Prostate Biopsy Decision Planning: A Retrospective Multi-institutional Study Using the Prostate Magnetic Resonance Imaging Outcome Database (PROMOD).

BACKGROUND: Previous studies suggested that prostate-specific antigen (PSA) density (PSAd) combined with magnetic resonance imaging (MRI) may help avoid unnecessary prostate biopsy (PB) with a limited risk of missing clinically significant prostate cancer (csPCa; Gleason grade group [GGG] >1). OBJECTIVE: To define optimal diagnostic strategies based on the combined use of PSAd and MRI in patients at risk of prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of the international multicenter Prostate MRI Outcome Database (PROMOD), including 2512 men having undergone PSAd and prostate MRI before PB between 2013 and 2019, was performed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Rates of avoided PB, missed GGG 1, and csPCa according to 10 strategies based on PSAd values and MRI reporting scores (Prostate Imaging Reporting and Data System [PI-RADS]/Likert/IMPROD biparametric prostate MRI Likert). Decision curve analysis (DCA) was used to statistically compare the net benefit of each strategy. Combined systematic and targeted biopsies were used for reference. RESULTS AND LIMITATIONS: According to DCA, the best strategy in biopsy-naive patients was #7 (PI-RADS/Likert 4-5 or PI-RADS/Likert 3 if PSAd >0.2), which avoided 41.2% PBs while missed 44% of GGG 1 and 10.9% of csPCa cases. From a clinical standpoint, however, strategies with a lower risk of missing csPCa included #10 (PI-RADS/Likert 4-5 or PI-RADS 3 if PSAd >0.10 or PSAd >0.2), which avoided 27% PBs while missing 24.4% GGG 1 and 4% csPCa cases, or #5 (PI-RADS/Likert 3-5 or PSAd>0.15), which avoided 14.7% PBs while missing 9.3% GGG 1 and 1.7% csPCa cases. Similar results were found in patients with a previous negative biopsy. This study is limited by its retrospective nature, and no central review of MRI and histopathological findings. CONCLUSIONS: Combined PSAd and MRI findings allows individualization of the decision to perform PB on the basis of the risk of missing PCa that both patients and clinicians are ready to accept to avoid this procedure. PATIENT SUMMARY: We compared several biopsy strategies based on a combination of prostate magnetic resonance imaging findings and prostate-specific antigen density, providing a readily available tool for each center and practicing urologist to counsel patients about their individual risk of significant prostate cancer.

Portafolio de evaluación: una experiencia novedosa en la asignatura Introducción a la Medicina General Integral / Assessment portfolio: a novel experience in the Introduction to Comprehensive General Medicine course

RESUMEN Se hace referencia a la novedosa aplicación del portafolio en la asignatura Introducción a la Medicina General Integral en primer año de la carrera de Medicina para la evaluación de las actividades de educación en el trabajo. El portafolio representa un nuevo escenario para la evaluación, es una técnica que informa sobre las competencias que el estudiante puede demostrar, así como la naturaleza y el aprovechamiento del proceso de aprendizaje, permite acumular evidencias e incluye la evaluación de los aspectos educativos en vínculo indisoluble a lo instructivo. Por su pertinencia y novedad, los autores consideran oportuno compartir sus experiencias sobre esta modalidad de evaluación a través de la presente comunicación.

ABSTRACT Reference is made to the novel application of the portfolio in the Introduction to Comprehensive General Medicine subject in the first year of the Medicine degree for the evaluation of the in-service training activities. The portfolio represents a new scenario for evaluation, it is a technique that informs about the competences that the student can demonstrate, as well as the nature and use of the learning process, allows the accumulation of evidence and includes the evaluation of educational aspects in an indissoluble link to the instructive. Due to its relevance and novelty, the authors consider it appropriate to share their experiences on this type of evaluation through this research paper.

Prediction of prostate cancer aggressiveness using 18F-Fluciclovine (FACBC) PET and multisequence multiparametric MRI.

The aim of this prospective single-institution clinical trial (NCT02002455) was to evaluate the potential of advanced post-processing methods for 18F-Fluciclovine PET and multisequence multiparametric MRI in the prediction of prostate cancer (PCa) aggressiveness, defined by Gleason Grade Group (GGG). 21 patients with PCa underwent PET/CT, PET/MRI and MRI before prostatectomy. DWI was post-processed using kurtosis (ADCk, K), mono- (ADCm), and biexponential functions (f, Dp, Df) while Logan plots were used to calculate volume of distribution (VT). In total, 16 unique PET (VT, SUV) and MRI derived quantitative parameters were evaluated. Univariate and multivariate analysis were carried out to estimate the potential of the quantitative parameters and their combinations to predict GGG 1 vs >1, using logistic regression with a nested leave-pair out cross validation (LPOCV) scheme and recursive feature elimination technique applied for feature selection. The second order rotating frame imaging (RAFF), monoexponential and kurtosis derived parameters had LPOCV AUC in the range of 0.72 to 0.92 while the corresponding value for VT was 0.85. The best performance for GGG prediction was achieved by K parameter of kurtosis function followed by quantitative parameters based on DWI, RAFF and 18F-FACBC PET. No major improvement was achieved using parameter combinations with or without feature selection. Addition of 18F-FACBC PET derived parameters (VT, SUV) to DWI and RAFF derived parameters did not improve LPOCV AUC.

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.

Symptoms and diagnostic delays in bladder cancer with high risk of recurrence: results from a prospective FinnBladder 9 trial.

PURPOSE: To investigate the symptoms and delays in the clinical pathway of bladder cancer (BC). METHODS: This is a substudy of a prospective, randomized, multicenter phase III study (FinnBladder 9, NCT01675219) where the efficacy of photodynamic diagnosis and 6 weekly optimized mitomycin C instillations are studied in pTa bladder cancer with high risk for recurrence. The data of presenting symptoms and critical time points were prospectively collected, and the effect of factors on delays was analyzed. RESULTS: At the time of analysis, 245 patients were randomized. Analysis included 131 patients with primary bladder cancer and their complete data. Sixty-nine percent had smoking history and 67% presented with macroscopic hematuria. Median patient delay (from symptoms to health-care contact) was 7 days. The median general practice delay (from health-care contact to urology referral) was 8 days. Median time from urology referral to cystoscopy was 23 days and from cystoscopy to TUR-BT 21 days. Total time used in the clinical pathway (from symptom to TUR-BT) was 78 days. Current and former smokers had non-significantly shorter patient-related and general practice delays compared to never smokers. TUR-BT delay was significantly shorter in patients with malignant cytology (16 days) compared to patients with benign cytology (21 days, p = 0.03). CONCLUSIONS: Patient-derived delay was short and most of the delay occurred in the referral centers. The majority had macroscopic hematuria as the initial symptom. Surprisingly, current and past smokers were more prone to contact the health-care system compared to never smokers.

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 biochemical recurrence in prostate cancer patients who underwent prostatectomy using routine clinical prostate multiparametric MRI and decipher genomic score.

BACKGROUND: Biochemical recurrence (BCR) affects a significant proportion of patients who undergo robotic-assisted laparoscopic prostatectomy (RALP). PURPOSE: To evaluate the performance of a routine clinical prostate multiparametric magnetic resonance imaging (mpMRI) and Decipher genomic classifier score for prediction of biochemical recurrence in patients who underwent RALP. STUDY TYPE: Retrospective cohort study. SUBJECTS: Ninety-one patients who underwent RALP performed by a single surgeon, had mpMRI before RALP, Decipher taken from RALP samples, and prostate specific antigen (PSA) follow-up for >3 years or BCR within 3 years, defined as PSA >0.2 mg/ml. FIELD STRENGTH/SEQUENCE: mpMRI was performed at 27 different institutions using 1.5T (n = 10) or 3T scanners and included T2 w, diffusion-weighted imaging (DWI), or dynamic contrast-enhanced (DCE) MRI. ASSESSMENT: All mpMRI studies were reported by one reader using Prostate Imaging Reporting and Data System v. 2.1 (PI-RADsv2.1) without knowledge of other findings. Eighteen (20%) randomly selected cases were re-reported by reader B to evaluate interreader variability. STATISTICAL TESTS: Univariate and multivariate analysis using greedy feature selection and tournament leave-pair-out cross-validation (TLPOCV) were used to evaluate the performance of various variables for prediction of BCR, which included clinical (three), systematic biopsy (three), surgical (six: RALP Gleason Grade Group [GGG], extracapsular extension, seminal vesicle invasion, intraoperative surgical margins [PSM], final PSM, pTNM), Decipher (two: Decipher score, Decipher risk category), and mpMRI (eight: prostate volume, PSA density, PI-RADv2.1 score, MRI largest lesion size, summed MRI lesions' volume and relative volume [MRI-lesion-percentage], mpMRI ECE, mpMRI seminal vesicle invasion [SVI]) variables. The evaluation metric was the area under the curve (AUC). RESULTS: Forty-eight (53%) patients developed BCR. The best-performing individual features with TLPOCV AUC of 0.73 (95% confidence interval [CI] 0.64-0.82) were RALP GGG, MRI-lesion-percentage followed by biopsy GGG (0.72, 0.62-0.82), and Decipher score (0.71, 0.60-0.82). The best performance was achieved by feature selection of Decipher+Surgery and MRI + Surgery variables with TLPOCV AUC of 0.82 and 0.81, respectively DATA CONCLUSION: Relative lesion volume measured on a routine clinical mpMRI failed to outperform Decipher score in BCR prediction. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:1075-1085.

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.