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Background: Aging is the most important risk factor for prostate cancer (PC). Imaging techniques can be useful to measure age‐related changes associated with the transition to diverse pathological states. However, biomarkers of aging from prostate magnetic resonance imaging (MRI) remain to be explored. Purpose: To develop an aging biomarker from prostate MRI and to examine its relationship with clinically significant PC (csPC, Gleason score ≥7) risk occurrence. Study Type: Retrospective. Population: Four hundred and sixty‐eight (65.97 ± 6.91 years) biopsied males, contributing 7243 prostate MRI slices. A deep learning (DL) model was trained on 3223 MRI slices from 81 low‐grade PC (Gleason score ≤6) and 131 negative patients, defined as non‐csPC. The model was tested on 90 negative, 52 low‐grade (142 non‐csPC), and 114 csPC patients. Field Strength/Sequence: 3‐T, axial T2‐weighted spin sequence. Assessment: Chronological age was defined as the age of the participant at the time of the visit. Prostate‐specific antigen (PSA), prostate volume, Gleason, and Prostate Imaging‐Reporting and Data System (PI‐RADS) scores were also obtained. Manually annotated prostate masks were used to crop the MRI slices, and a DL model was trained with those from non‐csPC patients to estimate the age of the patients. Following, we obtained the prostate age gap (PAG) on previously unseen csPC and non‐csPC cropped MRI exams. PAG was defined as the estimated model age minus the patient's age. Finally, the relationship between PAG and csPC risk occurrence was assessed through an adjusted multivariate logistic regression by PSA levels, age, prostate volume, and PI‐RADS ≥ 3 score. Statistical Tests: T‐test, Mann–Whitney U test, permutation test, receiver operating characteristics (ROC), area under the curve (AUC), and odds ratio (OR). A P value <0.05 was considered statistically significant. Results: After adjusting, there was a significant difference in the odds of csPC (OR = 3.78, 95% confidence interval [CI]: 2.32–6.16). Further, PAG showed a significantly larger bootstrapped AUC to discriminate between csPC and non‐csPC than that of adjusted PI‐RADS ≥ 3 (AUC = 0.981, 95% CI: 0.975–0.987). Data Conclusion: PAG may be associated with the risk of csPC and could outperform other PC risk factors. Level of Evidence: 3 Technical Efficacy: Stage 3 [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the feasibility of AI-assisted reading of prostate magnetic resonance imaging (MRI) in Organized Prostate cancer Testing (OPT). Methods: Retrospective cohort study including 57 men with elevated prostate-specific antigen (PSA) levels =3 µg/L that performed bi-parametric MRI in OPT. The results of a CE-marked deep learning (DL) algorithm for prostate MRI lesion detection were compared with assessments performed by on-site radiologists and reference radiologists. Per patient PI-RADS (Prostate Imaging-Reporting and Data System)/Likert scores were cross-tabulated and compared with biopsy outcomes, if performed. Positive MRI was defined as PI-RADS/Likert =4. Reader variability was assessed with weighted kappa scores. Results: The number of positive MRIs was 13 (23%), 8 (14%), and 29 (51%) for the local radiologists, expert consensus, and DL, respectively. Kappa scores were moderate for local radiologists versus expert consensus 0.55 (95% confidence interval [CI]: 0.37-0.74), slight for local radiologists versus DL 0.12 (95% CI: -0.07 to 0.32), and slight for expert consensus versus DL 0.17 (95% CI: -0.01 to 0.35). Out of 10 cases with biopsy proven prostate cancer with Gleason =3+4 the DL scored 7 as Likert =4. Interpretation: The Dl-algorithm showed low agreement with both local and expert radiologists. Training and validation of DL-algorithms in specific screening cohorts is essential before introduction in organized testing. [ABSTRACT FROM AUTHOR]

Purpose: Tensor‐valued diffusion encoding provides more specific information than conventional diffusion‐weighted imaging (DWI), but has mainly been applied in neuroimaging studies. This study aimed to assess its potential for the imaging of prostate cancer (PCa). Methods: Seventeen patients with histologically proven PCa were enrolled. DWI of the prostate was performed with linear and spherical tensor encoding using a maximal b‐value of 1.5 ms/µm2 and a voxel size of 3 × 3 × 4 mm3. The gamma‐distribution model was used to estimate the mean diffusivity (MD), the isotropic kurtosis (MKI), and the anisotropic kurtosis (MKA). Regions of interest were placed in MR‐defined cancerous tissues, as well as in apparently healthy tissues in the peripheral and transitional zones (PZs and TZs). Results: DWI with linear and spherical encoding yielded different image contrasts at high b‐values, which enabled the estimation of MKA and MKI. Compared with healthy tissue (PZs and TZs combined) the cancers displayed a significantly lower MD (P <.05), higher MKI (P < 10−5), and lower MKA (P <.05). Compared with the TZ, tissue in the PZ showed lower MD (P < 10−3) and higher MKA (P < 10−3). No significant differences were found between cancers of different Gleason scores, possibly because of the limited sample size. Conclusion: Tensor‐valued diffusion encoding enabled mapping of MKA and MKI in the prostate. The elevated MKI in PCa compared with normal tissues suggests an elevated heterogeneity in the cancers. Increased in‐plane resolution could improve tumor delineation in future studies. [ABSTRACT FROM AUTHOR]

Background: High rates of overdiagnosis are a critical barrier to organized prostate cancer screening. Magnetic resonance imaging (MRI) with targeted biopsy has shown the potential to address this challenge, but the implications of its use in the context of organized prostate cancer screening are unknown.Methods: We conducted a population-based noninferiority trial of prostate cancer screening in which men 50 to 74 years of age from the general population were invited by mail to participate; participants with prostate-specific antigen (PSA) levels of 3 ng per milliliter or higher were randomly assigned, in a 2:3 ratio, to undergo a standard biopsy (standard biopsy group) or to undergo MRI, with targeted and standard biopsy if the MRI results suggested prostate cancer (experimental biopsy group). The primary outcome was the proportion of men in the intention-to-treat population in whom clinically significant cancer (Gleason score ≥7) was diagnosed. A key secondary outcome was the detection of clinically insignificant cancers (Gleason score 6).Results: Of 12,750 men enrolled, 1532 had PSA levels of 3 ng per milliliter or higher and were randomly assigned to undergo biopsy: 603 were assigned to the standard biopsy group and 929 to the experimental biopsy group. In the intention-to-treat analysis, clinically significant cancer was diagnosed in 192 men (21%) in the experimental biopsy group, as compared with 106 men (18%) in the standard biopsy group (difference, 3 percentage points; 95% confidence interval [CI], -1 to 7; P<0.001 for noninferiority). The percentage of clinically insignificant cancers was lower in the experimental biopsy group than in the standard biopsy group (4% [41 participants] vs. 12% [73 participants]; difference, -8 percentage points; 95% CI, -11 to -5).Conclusions: MRI with targeted and standard biopsy in men with MRI results suggestive of prostate cancer was noninferior to standard biopsy for detecting clinically significant prostate cancer in a population-based screening-by-invitation trial and resulted in less detection of clinically insignificant cancer. (Funded by the Swedish Research Council and others; STHLM3-MRI ClinicalTrials.gov number, NCT03377881.). [ABSTRACT FROM AUTHOR]

Background: Active surveillance (AS) for men with low-risk prostate cancer (PC) can lead to patient morbidity and healthcare overutilization. The aim of this study was to evaluate an AS protocol using the Stockholm3 test and magnetic resonance imaging (MRI) to reduce biopsy intensity.Methods: We conducted a prospective multicenter study of 280 invited men from a contemporary screening study (STHLM3), with Gleason Score (GS) 3 + 3 PC on a current AS protocol. Patients underwent prostate-MRI and blood sampling for analysis of the Stockholm3 test including protein biomarkers, genetic variants, and clinical variables to predict risk of GS ≥3 + 4 PC followed by systematic biopsies and targeted biopsies (for Prostate Imaging Reporting and Data System version 2 ≥3 lesions) in all men. Primary outcomes were reclassification to GS ≥3 + 4 PC and clinically significant PC (csPCa), including unfavorable intermediate risk PC or higher based on National Comprehensive Cancer Network guidelines.Results: Adding MRI-targeted biopsies to systematic biopsies increased sensitivity of GS ≥3 + 4 PC compared with systematic biopsies alone (relative sensitivity [RS] = 1.52, 95% confidence interval [CI] = 1.28 to 1.85). Performing biopsies in only MRI positive increased sensitivity of GS ≥3 + 4 PC (RS = 1.30, 95% CI = 1.04 to 1.67) and reduced number of biopsy procedures by 49.3% while missing 7.2% GS ≥3 + 4 PC and 1.4% csPCa. Excluding men with negative Stockholm3 test reduced the number of MRI investigations at follow-up by 22.5% and biopsies by 56.8% while missing 6.9% GS ≥3 + 4 PC and 1.3% csPCa.Conclusion: Including MRI and targeted/systematic biopsies in the follow-up for men on AS increased sensitivity of PC reclassification. Incorporation of risk prediction models including biomarkers may reduce the need for MRI use in men with low-risk PC. [ABSTRACT FROM AUTHOR]

To assess the value of a first MRI examination and image-fusion-guided biopsies in men with low-risk prostate cancer who have been on active surveillance (AS) for several years with no signs of progression. All 45 participants from two centers who had not previously had an MRI were included. They had been on AS for T1c Gleason score 6 prostate cancer for 2.6 to 6.7 years and had 2 to 5 sets of systematic biopsies with a total of 1640 cores. All underwent a bi-parametric MRI, PI-RADS ≥ 3 lesions were targeted with image-fusion-guided biopsies. Primary outcome measure: detection of Gleason score ≥7 cancer. Twenty-five of the 45 men (56%) had a total of 30 suspicious MRI lesions. The lesion with the highest score was a PI-RADS 3 in 18, a PI-RADS 4 in 5 and PI-RADS 5 in 3 men. Targeted biopsies from the 30 lesions detected Gleason score 7 cancer in 6 men. Of these six cancers, four were located in the apical and one in the anterior/apical part of the prostate. A Gleason score 7 cancer was detected in 3 of 5 men with PSA density >0.15 ng/ml/cm3. Even after several years of AS with stable PSA values and many sets of systematic biopsies, a first MRI and targeted biopsies lead to the detection of Gleason score 7 (ISUP 2 and ISUP 3) cancer in a significant proportion of men, particularly among those with a high PSA density. [ABSTRACT FROM AUTHOR]

The article discusses a novel model for integrated prostate cancer diagnostics that combines MRI, prostate biopsy, and pathology reports. Developed by a multi-professional group in Sweden, the model aims to streamline data collection, improve patient outcomes, and enhance quality assessment. The model was tested in a pilot study with positive feedback from urologists, radiologists, and pathologists, showing potential for widespread implementation and validation in clinical practice. The structured approach offers a concise summary of relevant information, benefiting both healthcare providers and patients. [Extracted from the article]

Introduction Prostate cancer is a leading cause of cancer death among men in the Western world. Early detection of prostate cancer has been shown to decrease mortality, but has limitations with low specificity leading to unnecessary biopsies and overdiagnosis of low-risk cancers. The STHLM3 trial has paved way for improved specificity in early detection of prostate cancer using the blood-based STHLM3 test for identifying men at increased risk of harbouring significant prostate cancer. Targeted prostate biopsies based on MRI images have shown noninferior sensitivity to detect significant prostate cancer and decrease the number of biopsies and non-significant cancers among men referred for prostate biopsy in clinical practice. The strategy of the STHLM3-MRI project is to study an improved diagnostic pathway including an improved blood-based test for identification of men with increased risk of prostate cancer and use of MRI to select men for diagnostic workup with targeted prostate biopsies. Methods This study compares prostate cancer detection using prostate-specific antigen (PSA) and systematic biopsies to the improved pathway for prostate cancer detection using the STHLM3 test and targeted biopsies in a screening context. The study will recruit 10 000 participants during 1 June 2018 to 1 June 2020 combining a paired and randomised design. Participants are grouped by PSA and Stockholm3 test level. Men with Stockholm3 ≥11% or PSA ≥3 ng/mL are randomised to systematic or MRI-targeted biopsies. This protocol follows SPIRIT guidelines. Endpoints include the number of detected prostate cancers, number of performed biopsy procedures and number of performed MRIs. Additional aims include to assess the health economic consequences and development of automated image-analysis. Ethics and dissemination The study is approved by the regional ethical review board in Stockholm (2017- 1280/31). The study findings will be published in peerreview journals. Findings will also be disseminated by conference/departmental presentations and by media. [ABSTRACT FROM AUTHOR]

Background: To investigate the reliability with which healthcare professionals with different levels of expertise are able to impart the exact location of prostate cancer (PCA) after (A) reading written magnetic resonance imaging (MRI) reports, (B) attending MRI presentations in multidisciplinary team meetings (MDT), and (C) examining 3D printed prostate models, which represents a new technology to describe the location of PCA lesions. Methods: We used three different PCA cases to assess the three information tools. Construct validation was performed using two healthcare groups with different levels of expertise: (1) Nine expert urologists in PCA, and (2) nine medical students. After each information tool, the study participants plotted the tumor location in a 2-dimensional prostate diagram. A scoring system was established to evaluate the drawings in terms of accuracy of plotting tumor position. Data are shown as median scores with interquartile range. Results: Within the expert group, no significant difference was seen in the overall scoring results between the information tools (p = 0.34). Medical students performed significantly worse with MDT information (p = 0.03). Experts performed better in all three information tools compared to students, resulting in a significantly 25% higher overall total score (25.0[22.3–26.7] vs. 20.0[15.0–24.0], p<0.001). The difference was largest after MDT information, with experts showing a 49% better scoring (p<0.001), and second largest with the 3D printed models, showing a 17% better scoring of the experts (p = 0.07). No difference was found in the written MRI report scoring results between experts and students. Conclusions: 3D printed models provided better orientation guide to medical students compared to MDT MRI presentations. This indicates that the 3D printed models might be easier to understand than the current gold standard MDT conferences. Therefore, 3D models may play an increasingly important role in providing guidance for orientation for less experienced individuals, such as surgical trainees. [ABSTRACT FROM AUTHOR]

Background: The evidence supporting the use of magnetic resonance imaging (MRI) in prostate cancer detection has been established, but its accuracy in local staging is questioned. Purpose: To investigate the additional value of multi-planar radial reconstructions of a three-dimensional (3D) T2-weighted (T2W) MRI sequence, intercepting the prostate capsule perpendicularly, for improving local staging of prostate cancer. Material and Methods: Preoperative, bi-parametric prostate MRI examinations in 94 patients operated between June 2014 and January 2015 where retrospectively reviewed by two experienced abdominal radiologists. Each patient was presented in two separate sets including diffusion-weighted imaging, without and with the 3D T2W set that included radial reconstructions. Each set was read at least two months apart. Extraprostatic tumor extension (EPE) was assessed according to a 5-point grading scale. Sensitivity and specificity for EPE was calculated and presented as receiver operating characteristics (ROC) with area under the curve (AUC), using histology from whole-mount prostate specimen as gold standard. Inter-rater agreement was calculated for the two different reading modes using Cohen's kappa. Results: The AUC for detection of EPE for Readers 1 and 2 in the two-dimensional (2D) set was 0.70 and 0.68, respectively, and for the 2D+3D set 0.62 and 0.65, respectively. Inter-rater agreement (Reader 1 vs. Reader 2) on EPE using Cohen's kappa for the 2D and 2D+3D set, respectively, was 0.42 and 0.17 (i.e. moderate and poor agreement, respectively). Conclusion: The addition of 3D T2W MRI with radial reconstructions did not improve local staging in prostate cancer. [ABSTRACT FROM AUTHOR]

Objectives To analyse oncological and functional outcomes 12 months after treatment of very-low-risk prostate cancer with radical prostatectomy in men who could have been candidates for active surveillance. Patients and Methods We conducted a prospective study of all men with very-low-risk prostate cancer who underwent radical prostatectomy at one of 14 participating centres. Validated patient questionnaires were collected at baseline and after 12 months by independent healthcare researchers. Biochemical recurrence ( BCR) was defined as prostate-specific antigen ( PSA) ≥0.25 ng/ mL or treatment with salvage radiotherapy or with hormones. Urinary continence was defined as <1 pad changed per 24 h. Erectile function was defined as ability to achieve erection hard enough for penetration more than half of the time after sexual stimulation. Changes in tumour grade and stage were obtained from pathology reports. We report descriptive frequencies and proportions of men who had each outcome in various subgroups. Fisher's exact test was used to assess differences between the age groups. Results Of the 4003 men in the LAPPRO cohort, 338 men fulfilled the preoperative national criteria for very-low-risk prostate cancer. Adverse pathology outcomes included upgrading, defined as pT3 or postoperative Gleason sum ≥7, which was present in 35% of the men (115/333) and positive surgical margins, which were present in 16% of the men (54/329). Only 2.1% of the men (7/329) had a PSA concentration >0.1 ng/ mL 6-12 weeks postoperatively. Erectile function and urinary continence were observed in 44% (98/222) and 84% of the men (264/315), respectively, 12 months postoperatively. The proportion of men achieving the trifecta, defined as preoperative potent and continent men who remained potent and continent with no BCR, was 38% (84/221 men) at 12 months. Conclusions Our prospective study of men with very-low-risk prostate cancer undergoing open or robot-assisted radical prostatectomy showed that there were favourable oncological outcomes in approximately two-thirds. Approximately 40% did not have surgically induced urinary incontinence or erectile dysfunction 12 months postoperatively. These results provide additional support for the use of active surveillance in men with very-low-risk prostate cancer; however, the number of men with risk of upgrading and upstaging is not negligible. Improved stratification is still urgently needed. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to create a preoperative prediction model predicting extraprostatic tumour growth in men with clinically organ-confined disease from a prospectively collected Swedish cohort.Materials and methods: The study used data from 3386 men in the prospective multi-centre Laparoscopic Prostatectomy Robot Open (LAPPRO) trial, with 14 participating urological departments. External validation was performed using a cohort of 634 men from the largest study centre with patients who underwent surgery before and after the inclusion period of the LAPPRO study. External validation of the updated Partin table was used for comparison. The prediction models were created by multivariable logistic regression. Nomogram prediction performance, internal, internal–external and external validation are presented as the area under the receiver operating characteristic curve (AUC).Results: The nomogram reached a prediction performance with an AUC of 0.741, with internal and external validation of 0.738 and 0.698, respectively. Internal–external validation showed great divergence between centres, with AUCs ranging from 0.476 to 0.892, indicating inconsistencies in pathological staging or one or more of the included variables in the regression model. When includingcentreas a variable in the multivariable model it was significantly associated with the outcome of pT3 (p < 0.001). AUC for external validation of the Partin table was 0.694.Conclusions: Accurate prediction tools in prostate cancer require consistent assessment of included variables, and local validation is needed before the use of such tools in clinical practice. [ABSTRACT FROM AUTHOR]

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Background and Objective: The use of blood-based risk prediction tools has been proposed to improve prostate cancer screening, but data on repeated screening are lacking. Our aim was to compare outcomes using the blood tests prostate-specific antigen (PSA) and Stockholm3 for repeat prostate cancer screening., Methods: In the population-based screening-by-invitation STHLM3-MRI trial, men aged 50-74 yr were invited to participate in screening. At 2-3 yr after the initial round, men with PSA ≥1.5 ng/ml at trial inclusion who were randomized to magnetic resonance imaging (MRI)-enhanced screening and were not diagnosed with prostate cancer after the initial round were invited for repeat screening involving analysis of PSA and Stockholm3. Biparametric 1.5-T MRI was performed in cases with PSA ≥3 ng/ml or Stockholm3 ≥0.11. Men with Prostate Imaging0Reporting and Data System ≥3 lesions were referred for targeted plus systematic biopsies. The primary outcome was Gleason ≥7 cancer. Secondary outcomes included the number of MRI scans and biopsy procedures, and detection of Gleason 6 and Gleason ≥4 + 3 cancer. Outcomes were compared using the relative positive fractions (RPF)., Key Findings and Limitations: Of 7609 men from the initial screening round, 2078 were eligible for repeat screening and 1500 (72%) participated. For detection of Gleason ≥7 prostate cancer, the area under the receiver operating characteristic curve was 0.765 (95% confidence interval [CI] 0.725-0.805) for Stockholm3 and 0.651 (95% CI 0.601-0.701) for PSA. Stockholm3 ≥0.15 was associated with 41% fewer MRI scans in comparison to PSA ≥3 ng/ml (RPF 0.59, 95%CI 0.54-0.64), while the detection of GS ≥4 + 3 cancers was similar (RPF 1.00, 95% CI 0.78-1.29). Stockholm3 ≥0.15 detected fewer Gleason ≥7 (RPF 0.75, 95% CI 0.59-0.95) and Gleason 6 (RPF 0.73, 95% CI 0.46-1.16) cancers. Stockholm3 ≥0.11 was associated with no decrease in the number of MRI scans, but an increase of the number of cancer cases detected. Limitations include the lack of long-term outcomes., Conclusions and Clinical Implications: Use of the Stockholm3 test for repeated prostate cancer screening could reduce the need for MRI while maintaining detection rates for high-risk cancer., Patient Summary: In this study, we invited men to a second round of prostate cancer screening. We found that use of a new blood test called Stockholm3 can make screening programs more efficient by using fewer resources while still detecting aggressive cancers., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Objective: The optimal biopsy strategy in prostate cancer screening is unknown. This study aims to assess the diagnostic effects of omitting systematic biopsies in a screening cohort., Methods: We used data from the STHLM3-MRI trial. A total of 7609 men aged 50-74 yr were randomised to undergo magnetic resonance imaging (MRI) if having an elevated risk of prostate cancer (prostate-specific antigen [PSA] ≥3 ng/ml or Stockholm3 ≥11%). Participants with Prostate Imaging Reporting and Data System (PI-RADS) ≥3 underwent targeted and systematic biopsies. Cancer detection rates from combined and targeted-only biopsies were presented as a risk ratio (RR). Subgroup analyses were stratified by age, PSA density (PSAd), and PI-RADS. Differences in reclassification rates at radical prostatectomy were calculated., Key Findings and Limitations: The median age of the participants was 66 yr (interquartile range: 61-71) and PSA 3.8 ng/ml (2.9-5.8). Out of 395 men undergoing combined biopsies, 52 (13.2%) had International Society of Urological Pathology (ISUP) grade group (GG) 1 and 230 (58%) had ISUP GG ≥2 prostate cancer. Omission of systematic biopsies reduced cancer detection rates (RR of ISUP GG 1: 0.83 [95% confidence interval 0.64-1.07]; ISUP GG ≥2: 0.85 [0.81-0.90]; and ISUP GG ≥3: 0.86 [0.79-0.95]). Each case of averted ISUP GG 1 cancer was associated with 3.8 cases of missed ISUP GG ≥2 and 1.1 case of ISUP GG ≥3 cancer. Detection of fewer ISUP GG ≥2 cases than the number of avoided ISUP 1 cancer cases was observed in all subgroups when systematic biopsies were omitted. Using PSAd ≥0.05 ng/ml 2 as a cut-off for a biopsy resulted in the same numbers of ISUP GG 1 tumours saved, with higher detection rates of ISUP GG ≥2 tumours. In 146 men undergoing radical prostatectomy, 46 (31.5%) versus 28 (19.2%) were upgraded following targeted biopsies versus a combined biopsy strategy (p < 0.05)., Conclusions and Clinical Implications: Complete omission of systematic biopsies in prostate cancer screening is associated with decreased detection of significant cancer, while reducing overdetection of insignificant cancer to a smaller extent. This strategy also increased the risk of histopathological misclassification., Patient Summary: In a prostate cancer screening setting, we examined the diagnostic effects of systematic biopsies in addition to targeted biopsies in men with suspicious magnetic resonance imaging lesions. We found that exclusion of systematic biopsies led to reduced detection of clinically significant prostate cancer. Our findings emphasise the importance of incorporating systematic biopsies alongside targeted biopsies for improved diagnostic outcomes., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent., Methods and Analysis: A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, ≤T2a, prostate-specific antigen (PSA) <15 ng/mL, PSA density ≤0.2 ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in <30% of cores on systematic biopsy and <10 mm cancer in one core on systematic or targeted biopsy are also eligible. Men diagnosed on systematic biopsy should have an MRI and targeted biopsies against Prostate Imaging and Reporting Data System V.2 3-5 lesions before inclusion. Identical follow-up in the two study arms: biannual PSA testing, yearly clinical examination and MRI every second year. In the experimental arm, standardised triggers based on MRI and PSA density elicit repeated biopsies. MRI and histopathological progression trigger radical treatment. Primary outcome measure is progression-free survival. Secondary outcome measures are cumulative incidence of metastatic disease, treatments with curative intent, pT3-4 at radical prostatectomy, switch to watchful waiting, prostate cancer mortality and quality of life. Inclusion started in October 2016 and in October 2018; 275 patients have been enrolled., Ethics and Dissemination: Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals., Trial Registration Number: NCT02914873., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Prostate cancer is a leading cause of cancer death among men in the Western world. Early detection of prostate cancer has been shown to decrease mortality, but has limitations with low specificity leading to unnecessary biopsies and overdiagnosis of low-risk cancers. The STHLM3 trial has paved way for improved specificity in early detection of prostate cancer using the blood-based STHLM3 test for identifying men at increased risk of harbouring significant prostate cancer. Targeted prostate biopsies based on MRI images have shown non-inferior sensitivity to detect significant prostate cancer and decrease the number of biopsies and non-significant cancers among men referred for prostate biopsy in clinical practice. The strategy of the STHLM3-MRI project is to study an improved diagnostic pathway including an improved blood-based test for identification of men with increased risk of prostate cancer and use of MRI to select men for diagnostic workup with targeted prostate biopsies., Methods: This study compares prostate cancer detection using prostate-specific antigen (PSA) and systematic biopsies to the improved pathway for prostate cancer detection using the STHLM3 test and targeted biopsies in a screening context. The study will recruit 10 000 participants during 1 June 2018 to 1 June 2020 combining a paired and randomised design. Participants are grouped by PSA and Stockholm3 test level. Men with Stockholm3 ≥11% or PSA ≥3 ng/mL are randomised to systematic or MRI-targeted biopsies. This protocol follows SPIRIT guidelines. Endpoints include the number of detected prostate cancers, number of performed biopsy procedures and number of performed MRIs. Additional aims include to assess the health economic consequences and development of automated image-analysis., Ethics and Dissemination: The study is approved by the regional ethical review board in Stockholm (2017-1280/31). The study findings will be published in peer-review journals. Findings will also be disseminated by conference/departmental presentations and by media., Trial Registration Number: NCT03377881; Pre-results., Competing Interests: Competing interests: HG has five prostate cancer diagnostic related patents pending, has patent applications licensed to Thermo Fisher Scientific and might receive royalties from sales related to these patents. ME is named on four of these five patent applications. Karolinska Institutet collaborates with Thermo Fisher Scientific in developing the technology for the Stockholm3 test., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

In 2009, vinflunine was introduced as a second-line treatment to be used after the failure of platinum therapy in patients with metastatic urothelial carcinoma (mUC). The present study investigated the administered vinflunine to patients with mUC in standard clinical practice with the aim of evaluating treatment patterns, response, survival parameters and side-effects. Data were collected retrospectively from the first 100 mUC patients treated with vinflunine at three Nordic cancer centers associated with the Nordic Urothelial Cancer Oncology Group. The overall response rate was 23% and complete response was observed in one patient. The median progression-free survival (mPFS) and median overall survival (mOS) were 2.8 (range, 0.5-34.3) and 6.3 (range, 0.3-39.7) months, respectively. An Eastern Cooperative Oncology Group performance status (ECOG PS) of 2 was present in 20% of the patients, and those patients exhibited significantly shorter mOS (4.1 vs. 7.0 months, P=0.001) and a significantly higher degree of grade 3/4 toxicity (P=0.026) compared with ECOG PS 0-1 patients. Furthermore, patients without visceral metastases had significantly longer mOS than patients with visceral metastases (10.6 vs. 6.0 months, P=0.008). The median number of cycles of vinflunine was 3 (range, 1-28). The current data confirms that vinflunine is an active agent for second-line treatment in an unselected clinical cohort of patients with mUC. ECOG PS and presence of visceral metastases were significant prognostic parameters. In particular, patients with ECOG PS 2 receiving vinflunine had a shorter mOS and a higher frequency of severe toxicity, and, thus, should be treated with caution. Furthermore, the present study observed large inter-individual differences in radiological response and OS, indicating the need for further development of improved patient selection tools to optimize vinflunine treatment in platinum-refractory mUC patients.