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Objectives: To provide a contemporary statement on focal therapy (FT) for localised prostate cancer (PCa) from an international and diverse group of physicians treating localised PCa, with the aim of overcoming the limitations of previous consensus statements, which were restricted to early adopters, and to offer direction regarding the various aspects of FT application that are currently not well defined., Materials and Methods: The FocAL therapy CONsensus (FALCON) project began with a 154-item online survey, developed following a steering committee discussion and literature search. Invitations to participate were extended to a large, diverse group of professionals experienced in PCa management. From 2022 to 2023, a Delphi consensus study consisting of three online rounds was conducted using the Modified Delphi method. A 1-9 Likert scale was used for the survey, which was followed by an in-person expert meeting. The threshold for achieving consensus was set at 70% agreement/disagreement. Six main aspects of FT were covered: (i) patient selection; (ii) energy source selection; (iii) treatment approach; (iv) treatment evaluation and follow-up; (v) treatment cost and accessibility; and (vi) future perspectives., Results: Of 246 initial participants, 148 (60%) completed all three rounds. Based on participant feedback, 27 new statements were added in the second round, and 33 questions related to personal expertise, for which consensus was not necessary, were excluded. After the third and final round, consensus had not been reached for 69 items. These items were discussed at the in-person meeting, resulting in a consensus of 57 additional items. Consensus was finally not reached on 12 items. Given the volume of data, the voting outcomes are summarised in this article, with a detailed breakdown presented in the form of figures and tables., Conclusions: The FALCON project delivered a significant consensus on the approach to FT for localised PCa. Additionally, it highlighted gaps in our knowledge that may provide guidance for future research., (© 2025 BJU International.)

Background and Objective: Biparametric magnetic resonance imaging (bpMRI), excluding dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), is a potential replacement for multiparametric MRI (mpMRI) in diagnosing clinically significant prostate cancer (csPCa). An extensive international multireader multicase observer study was conducted to assess the noninferiority of bpMRI to mpMRI in csPCa diagnosis., Methods: An observer study was conducted with 400 mpMRI examinations from four European centers, excluding examinations with prior prostate treatment or csPCa (Gleason grade [GG] ≥2) findings. Readers assessed bpMRI and mpMRI sequentially, assigning lesion-specific Prostate Imaging Reporting and Data System (PI-RADS) scores (3-5) and a patient-level suspicion score (0-100). The noninferiority of patient-level bpMRI versus mpMRI csPCa diagnosis was evaluated using the area under the receiver operating curve (AUROC) alongside the sensitivity and specificity at PI-RADS ≥3 with a 5% margin. The secondary outcomes included insignificant prostate cancer (GG1) diagnosis, diagnostic evaluations at alternative risk thresholds, decision curve analyses (DCAs), and subgroup analyses considering reader expertise. Histopathology and ≥3 yr of follow-up were used for the reference standard., Key Findings and Limitations: Sixty-two readers (45 centers and 20 countries) participated. The prevalence of csPCa was 33% (133/400); bpMRI and mpMRI showed similar AUROC values of 0.853 (95% confidence interval [CI], 0.819-0.887) and 0.859 (95% CI, 0.826-0.893), respectively, with a noninferior difference of -0.6% (95% CI, -1.2% to 0.1%, p < 0.001). At PI-RADS ≥3, bpMRI and mpMRI had sensitivities of 88.6% (95% CI, 84.8-92.3%) and 89.4% (95% CI, 85.8-93.1%), respectively, with a noninferior difference of -0.9% (95% CI, -1.7% to 0.0%, p < 0.001), and specificities of 58.6% (95% CI, 52.3-63.1%) and 57.7% (95% CI, 52.3-63.1%), respectively, with a noninferior difference of 0.9% (95% CI, 0.0-1.8%, p < 0.001). At alternative risk thresholds, mpMRI increased sensitivity at the expense of reduced specificity. DCA demonstrated the highest net benefit for an mpMRI pathway in cancer-averse scenarios, whereas a bpMRI pathway showed greater benefit for biopsy-averse scenarios. A subgroup analysis indicated limited additional benefit of DCE MRI for nonexperts. Limitations included that biopsies were conducted based on mpMRI imaging, and reading was performed in a sequential order., Conclusions and Clinical Implications: It has been found that bpMRI is noninferior to mpMRI in csPCa diagnosis at AUROC, along with the sensitivity and specificity at PI-RADS ≥3, showing its value in individuals without prior csPCa findings and prostate treatment. Additional randomized prospective studies are required to investigate the generalizability of outcomes., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To determine the surgical and oncologic outcomes of salvage radical prostatectomy (sRP) after FT failure., Materials and Methods: Patients who consecutively underwent primary RP or sRP after FT failure between 2008 and 2022 were retrospectively selected. Primary or sRP were performed with either a robot-assisted or open approach. All surgeries were performed by surgeons with experience of ≥ 500 cases. Biochemical recurrence-free survival (BFS), intra- and postoperative surgical and functional outcomes were assessed. To evaluate the impact of surgical setting, propensity score (PS) matching was performed., Results: 80 patients received sRP. Outcomes were analyzed using PS-matched cohorts (203 RPs vs. 68 sRPs). After a median follow-up of 25.4 months, sRP and RP had equal BFS (24mo-BFS: 72.4% vs. 76.0% (p = 0.8)). No statistically significant differences were found between sRP and RP in terms of median operative time (OT) (171 min vs. 168 min), estimated blood loss (EBL) (500 ml vs. 500 ml), length of hospital stay (LOS) (7 days vs. 7 days) and time to catheter removal (11 days vs. 11 days) and 1-year continence rates (all standardized mean differences ≤ 0.1). The main limitation is the retrospective study design., Conclusion: In the hands of experienced surgeons, sRP after FT offered comparable surgical and oncologic outcomes as RP in a primary setting., Competing Interests: Declaration. Conflict of interest: The authors declare that they have no conflict of interest., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Multiparametric MRI is the optimal primary investigation when prostate cancer is suspected, and its ability to rule in and rule out clinically significant disease relies on high-quality anatomical and functional images. Avenues for achieving consistent high-quality acquisitions include meticulous patient preparation, scanner setup, optimised pulse sequences, personnel training, and artificial intelligence systems. The impact of these interventions on the final images needs to be quantified. The prostate imaging quality (PI-QUAL) scoring system was the first standardised quantification method that demonstrated the potential for clinical benefit by relating image quality to cancer detection ability by MRI. We present the updated version of PI-QUAL (PI-QUAL v2) which applies to prostate MRI performed with or without intravenous contrast medium using a simplified 3-point scale focused on critical technical and qualitative image parameters. CLINICAL RELEVANCE STATEMENT: High image quality is crucial for prostate MRI, and the updated version of the PI-QUAL score (PI-QUAL v2) aims to address the limitations of version 1. It is now applicable to both multiparametric MRI and MRI without intravenous contrast medium. KEY POINTS: High-quality images are essential for prostate cancer diagnosis and management using MRI. PI-QUAL v2 simplifies image assessment and expands its applicability to prostate MRI without contrast medium. PI-QUAL v2 focuses on critical technical and qualitative image parameters and emphasises T2-WI and DWI., (© 2024. The Author(s).)

Background: Despite the evidence supporting the use of focal therapy (FT) in patients with localized prostate cancer (PCa), considerable variability exists in the patient selection criteria across current studies. This study aims to review the most recent evidence concerning the optimal approach to patient selection for FT in PCa., Methods: PubMed database was systematically queried for studies reporting patient selection criteria in FT for PCa before December 31, 2023. After excluding non-relevant articles and a quality assessment, data were extracted, and results were described qualitatively., Results: There is no level I evidence regarding the best patient selection approach for FT in patients with PCa. Current international multidisciplinary consensus statements recommend multiparametric magnetic resonance imaging (mpMRI) followed by MRI-targeted and systematic biopsy for all candidates. FT may be considered in clinically localized, intermediate risk (Gleason 3 + 4 and 4 + 3), and preferably unifocal disease. Patients should have an acceptable life expectancy. Those with prostate volume >50 ml and erectile dysfunction should not be excluded from FT. Prostate-specific antigen (PSA) level of < 20 (ideally < 10) ng/mL is recommended. However, the utility of other molecular and genomic biomarkers in patient selection for FT remains unknown., Conclusions: FT may be considered in well-selected patients with localized PCa. This review provides a comprehensive insight regarding the optimal approach for patient selection in FT., (© 2024. The Author(s).)

Background/Objectives : Progression to metastatic castration-resistant prostate cancer (mCRPC) is defined either biochemically, radiographically or both. Moreover, staging for mCRPC can be performed either conventionally or with molecular imaging such as prostate-specific membrane antigen computer tomography (PSMA-PET/CT). Methods : We relied on the Frankfurt Metastatic Cancer Database of the Prostate (FRAMCAP) database to compare progression-free (PFS) and overall survival (OS) outcomes regarding the cause of castration resistance and the staging modality used. Results : Overall, 35% progressed to mCRPC biochemically vs. 23% radiographically vs. 42% biochemically + radiographically. The PSA nadir in mHSPC (1.4 vs. 0.4 vs. 0.8 ng/mL) and PSA level at mCRPC progression (15 vs. 2 vs. 21 ng/mL, both p ≤ 0.01) were significantly higher for biochemical vs. radiographic vs. both progressed patients. In PFS and OS analyses, no significant differences were observed among all three compared groups. In the comparison of the staging used for progression to mCRPC, 67% received conventional vs. 33% PSMA-PET/CT, with higher metastatic burden in mHSPC and osseous lesions in mCRPC for conventionally staged patients (both p < 0.01). In PFS (15.3 vs. 10.1 months, hazard ratio [HR]: 0.75) and OS analyses (52.6 vs. 34.3 months, HR: 0.61, both p < 0.05), PSMA-PET/CT harbored better prognosis; however, this did not hold after multivariable adjustment. Similar results were observed for further analyses in second- and third-line mCRPC or patients with a PSA level of ≥2 ng/mL. Conclusions : The cause of progression to mCRPC seems not to influence cancer-control outcomes, despite important baseline tumor characteristic differences. The PSMA-PET/CT staging modality might be associated with better PFS and OS outcomes, possibly due to its more sensitive detection of progression or new metastatic lesions.

Background: Artificial intelligence (AI) systems can potentially aid the diagnostic pathway of prostate cancer by alleviating the increasing workload, preventing overdiagnosis, and reducing the dependence on experienced radiologists. We aimed to investigate the performance of AI systems at detecting clinically significant prostate cancer on MRI in comparison with radiologists using the Prostate Imaging-Reporting and Data System version 2.1 (PI-RADS 2.1) and the standard of care in multidisciplinary routine practice at scale., Methods: In this international, paired, non-inferiority, confirmatory study, we trained and externally validated an AI system (developed within an international consortium) for detecting Gleason grade group 2 or greater cancers using a retrospective cohort of 10 207 MRI examinations from 9129 patients. Of these examinations, 9207 cases from three centres (11 sites) based in the Netherlands were used for training and tuning, and 1000 cases from four centres (12 sites) based in the Netherlands and Norway were used for testing. In parallel, we facilitated a multireader, multicase observer study with 62 radiologists (45 centres in 20 countries; median 7 [IQR 5-10] years of experience in reading prostate MRI) using PI-RADS (2.1) on 400 paired MRI examinations from the testing cohort. Primary endpoints were the sensitivity, specificity, and the area under the receiver operating characteristic curve (AUROC) of the AI system in comparison with that of all readers using PI-RADS (2.1) and in comparison with that of the historical radiology readings made during multidisciplinary routine practice (ie, the standard of care with the aid of patient history and peer consultation). Histopathology and at least 3 years (median 5 [IQR 4-6] years) of follow-up were used to establish the reference standard. The statistical analysis plan was prespecified with a primary hypothesis of non-inferiority (considering a margin of 0·05) and a secondary hypothesis of superiority towards the AI system, if non-inferiority was confirmed. This study was registered at ClinicalTrials.gov, NCT05489341., Findings: Of the 10 207 examinations included from Jan 1, 2012, through Dec 31, 2021, 2440 cases had histologically confirmed Gleason grade group 2 or greater prostate cancer. In the subset of 400 testing cases in which the AI system was compared with the radiologists participating in the reader study, the AI system showed a statistically superior and non-inferior AUROC of 0·91 (95% CI 0·87-0·94; p<0·0001), in comparison to the pool of 62 radiologists with an AUROC of 0·86 (0·83-0·89), with a lower boundary of the two-sided 95% Wald CI for the difference in AUROC of 0·02. At the mean PI-RADS 3 or greater operating point of all readers, the AI system detected 6·8% more cases with Gleason grade group 2 or greater cancers at the same specificity (57·7%, 95% CI 51·6-63·3), or 50·4% fewer false-positive results and 20·0% fewer cases with Gleason grade group 1 cancers at the same sensitivity (89·4%, 95% CI 85·3-92·9). In all 1000 testing cases where the AI system was compared with the radiology readings made during multidisciplinary practice, non-inferiority was not confirmed, as the AI system showed lower specificity (68·9% [95% CI 65·3-72·4] vs 69·0% [65·5-72·5]) at the same sensitivity (96·1%, 94·0-98·2) as the PI-RADS 3 or greater operating point. The lower boundary of the two-sided 95% Wald CI for the difference in specificity (-0·04) was greater than the non-inferiority margin (-0·05) and a p value below the significance threshold was reached (p<0·001)., Interpretation: An AI system was superior to radiologists using PI-RADS (2.1), on average, at detecting clinically significant prostate cancer and comparable to the standard of care. Such a system shows the potential to be a supportive tool within a primary diagnostic setting, with several associated benefits for patients and radiologists. Prospective validation is needed to test clinical applicability of this system., Funding: Health~Holland and EU Horizon 2020., Competing Interests: Declaration of interests NAO provides statistical consultation to Siemens Healthineers, Takeda, and Qure, and serves as a committee member of the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network, the Tomosynthesis Mammographic Imaging Screening Trial, and the National Cancer Institute's Clinical Imaging Steering Committee (Bethesda, MD, USA). AB has been a consultant and advisor for Astellas and Bayer; board membership, officer, and trustee for Glactone Pharma, and LIDDS Pharma; has received lecture honoraria for Accord, Astellas, AstraZeneca, Bayer, Ipsen, Janssen, and Merck; has participated in trials run by Astellas, Ferring, and Janssen; and holds stock in Glactone Pharma, LIDDS Pharma, Noviga, and WntResearch. BvG holds stocks in and is a founder of Thirona. JKC has received research funding from GE Healthcare and Genentech and is the co-inventor of software that has been licensed to Siloam Vision. JKC has equity ownership in Siloam Vision. GS has been an advisory board member of Exact Imaging and Angiogenesis and has received lecture honorarium from Hitachi. OR has received funding for travel expenses from Philips Medical Systems. ARP has received research funding from Siemens Healthineers, holds stocks in Lucida Medical, and has received lecture honoraria for Siemens Healthineers and Bayer. HH has received research funding from Siemens Healthineers and Canon Medical Systems. GV has been a clinical advisory board member of AGFA Healthcare. VK has received lecture honoraria on prostate cancer diagnosis from the European Association of Urology and Singapore Urology Association and has received research funding from Prostate Cancer UK and the John Black Charitable Foundation. DB has received lecture honorarium from Bayer Vital and holds stocks in NVIDIA, Microsoft, and MSCI-World ETF. RvdB has been an advisory board member for Janssen; has received lecture honoraria from Amgen, Astellas, Ipsen, Janssen, and MSD; has received research support from Astellas and Janssen; and has participated in trials run by Janssen. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: To evaluate the long-term oncological outcomes and functional results of the neurovascular structure-adjacent frozen-section examination (NeuroSAFE) during nerve-sparing (NS) radical prostatectomy (RP)., Materials and Methods: A 10-yr survival analysis on 11069 RPs performed with or without the NeuroSAFE, between January 2002 to June 2011 was carried out. In the NeuroSAFE cohort, the neurovascular structure-adjacent prostatic margins are removed and stained for cryo-sectioning during RP. In case of a PSM, partial or full removal of the neurovascular bundle was performed. The impact of NeuroSAFE on biochemical recurrence-free survival (BFS), salvage radiation therapy-free survival, metastasis-free survival, and prostate cancer-specific survival at 10 years was analyzed. 1-year (1-yr) erectile function (EF), 1-yr, and 2-yr continence rates were assessed in propensity score-based matched cohorts., Results: Median follow-up was 121 (IQR: 73, 156) months. No differences in BFS between NeuroSAFE and non-NeuroSAFE were recorded (10-yr BFS: NeuroSAFE vs non-Neurosafe, pT2: 81% vs 84%, p = 0.06; pT3a: 58% vs. 63%, p = 0.6; ≥pT3b: 22% vs. 27%, p = 0.99). No differences were found between the two groups in terms of sRFS (pT2: p = 0.1; pT3a: p = 0.4; ≥pT3b: p = 0.4) (Fig. 1B, Table 2), and MTS (pT2: p = 0.3; pT3a: p = 0.6; ≥pT3b: p = 0.9). The NeuroSAFE-navigated patients reported a better 1-yr EF than non-NeuroSAFE (68% vs. 58%, p = 0.02) and no differences in 1-yr and 2-yr continence rates (92.4% vs. 91.8%, and 93.4% vs. 93%, respectively). The main limitation is the retrospective study design., Conclusions: While the NeuroSAFE approach did not show significant improvements in long-term oncologic or continence outcomes, it did provide an opportunity for a higher proportion of patients to improve postoperative functional results, possibly through increased nerve-sparing procedures., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To analyze outcomes and complications of cytoreductive prostatectomy (CRP) for oligometastatic prostate cancer (PCa) in order to elucidate its role in this space., Methods: We performed a systematic literature search using three databases (Medline, Scopus, and Web of Science). The primary endpoints were oncologic outcomes. The secondary endpoints were complication rates and functional results., Results: In all studies, overall survival was better or at least comparable variable in the groups with CRP compared to no local treatment. The greatest benefit from CRP in 5-year overall survival in one study was 67.4% for CRP versus 22.5% for no local treatment. Cancer-specific survival (CSS) showed the same trend. Several authors found significant benefits from CSS in the CRP group: from 79% vs . 46% to 100% vs . 61%. CRP was a predictor of better CSS (hazard ratio 0.264, p =0.004). Positive surgical margin rates differed widely from 28.6% to 100.0%. Urinary continence in CRP versus RP for localized PCa was significantly lower (57.4% vs. 90.8%, p <0.0001). Severe incontinence occurred seldom (2.5%-18.6%). Total complication rates after CRP differed widely, from 7.0% to 43.6%. Rates of grades 1 and 2 events prevailed. Patients on ADT alone also showed a considerable number of complications varying from 5.9% to 57.7%., Conclusion: CRP improves medium-term cancer control in patients with oligometastatic PCa. The morbidity and complication rates of this surgery are comparable with other approaches, but postoperative incontinence rate is higher compared with RP for localized disease., (© 2024 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier B.V.)

Purpose: To compare oncological, functional, and surgical outcomes of a large cohort of patients who underwent open retropubic radical prostatectomy (ORP) or robot-assisted radical prostatectomy (RARP)., Materials and Methods: Data from 18,805 RPs performed with either the open or the robot-assisted approaches at a single tertiary referral center between 2008 and 2022 were analyzed. The impact of surgical approach on biochemical recurrence-free survival, salvage radiotherapy-free survival, and metastasis-free survival was analyzed by log-rank test and Kaplan-Meier analysis in a propensity score (PS)-based matched cohort. Intraoperative and postoperative surgical outcomes were assessed. One-week, 3-month, and 12-month continence rates and 12-month erectile function (EF) were analyzed., Results: No statistically significant differences in oncological outcomes were found between ORP and RARP. A slight statistically significant difference in favor of RARP was noted in urinary continence at 3 months (RARP vs. ORP: 81% vs. 77%, p = 0.007) and 12 months (91% vs. 89.3%, p = 0.008), respectively. The rate of EF was statistically significantly higher (60%) after RARP than after ORP (45%, p < 0.001)., Conclusion: Both RARP and ORP yielded similar oncological outcomes. RARP offered a slight advantage in terms of continence recovery, but its clinical significance may be less meaningful. RARP resulted in significantly improved postoperative EF, suggesting a potential influence of both surgical experience and minimally invasive approach., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Myocarditis is an inflammation of the heart muscle most often caused by an immune response to viral infections. Sex differences in the immune response during myocarditis have been well described but upstream mechanisms in the heart that might influence sex differences in disease are not completely understood., Methods: Male and female BALB/c wild type mice received an intraperitoneal injection of heart-passaged coxsackievirus B3 (CVB3) or vehicle control. Bulk-tissue RNA-sequencing was conducted to better understand sex differences in CVB3 myocarditis. We performed enrichment analysis to understand sex differences in the transcriptional landscape of myocarditis and identify candidate transcription factors that might drive sex differences in myocarditis., Results: The hearts of male and female mice with myocarditis were significantly enriched for pathways related to an innate and adaptive immune response compared to uninfected controls. When comparing females to males with myocarditis, males were enriched for inflammatory pathways and gene changes that suggested worse mitochondrial transcriptional support (e.g., mitochondrial electron transport genes). In contrast, females were enriched for pathways related to mitochondrial respiration and bioenergetics, which were confirmed by higher transcript levels of master regulators of mitochondrial function including peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1α), nuclear respiratory factor 1 (NRF1) and estrogen-related receptor alpha (ERRα). TRANSFAC analysis identified ERRa as a transcription factor that may mediate sex differences in mitochondrial function during myocarditis., Conclusions: Master regulators of mitochondrial function were elevated in females with myocarditis compared to males and may promote sex differences in mitochondrial respiratory transcript expression during viral myocarditis resulting in less severe myocarditis in females following viral infection., Competing Interests: Competing Interests The authors declare that they have no competing interests.

Context: Whole-gland ablation is a feasible and effective minimally invasive treatment for localized prostate cancer (PCa). Previous systematic reviews supported evidence for favorable functional outcomes, but oncological outcomes were inconclusive owing to limited follow-up., Objective: To evaluate the real-world data on the mid- to long-term oncological and functional outcomes of whole-gland cryoablation and high-intensity focused ultrasound (HIFU) in patients with clinically localized PCa, and to provide expert recommendations and commentary on these findings., Evidence Acquisition: We performed a systematic review of PubMed, Embase, and Cochrane Library publications through February 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. As endpoints, baseline clinical characteristics, and oncological and functional outcomes were assessed. To estimate the pooled prevalence of oncological, functional, and toxicity outcomes, and to quantify and explain the heterogeneity, random-effect meta-analyses and meta-regression analyses were performed., Evidence Synthesis: Twenty-nine studies were identified, including 14 on cryoablation and 15 on HIFU with a median follow-up of 72 mo. Most of the studies were retrospective (n = 23), with IDEAL (idea, development, exploration, assessment, and long-term study) stage 2b (n = 20) being most common. Biochemical recurrence-free survival, cancer-specific survival, overall survival, recurrence-free survival, and metastasis-free survival rates at 10 yr were 58%, 96%, 63%, 71-79%, and 84%, respectively. Erectile function was preserved in 37% of cases, and overall pad-free continence was achieved in 96% of cases, with a 1-yr rate of 97.4-98.8%. The rates of stricture, urinary retention, urinary tract infection, rectourethral fistula, and sepsis were observed to be 11%, 9.5%, 8%, 0.7%, and 0.8%, respectively., Conclusions: The mid- to long-term real-world data, and the safety profiles of cryoablation and HIFU are sound to support and be offered as primary treatment for appropriate patients with localized PCa. When compared with other existing treatment modalities for PCa, these ablative therapies provide nearly equivalent intermediate- to long-term oncological and toxicity outcomes, as well as excellent pad-free continence rates in the primary setting. This real-world clinical evidence provides long-term oncological and functional outcomes that enhance shared decision-making when balancing risks and expected outcomes that reflect patient preferences and values., Patient Summary: Cryoablation and high-intensity focused ultrasound are minimally invasive treatments available to selectively treat localized prostate cancer, considering their nearly comparable intermediate- to long term cancer control and preservation of urinary continence to other radical treatments in the primary setting. However, a well-informed decision should be made based on one's values and preferences., (Published by Elsevier B.V.)

The transformation pathways between low-energy naphthalene isomers are studied by investigating the topology of the energy landscape of this astrophysically relevant molecule. The threshold algorithm is used to identify the minima basins of the isomers on the potential energy surface of the system and to evaluate the probability flows between them. The transition pathways between the different basins and the associated probabilities were investigated for several lid energies up to 11 eV, this value being close to the highest photon energy in the interstellar medium (13.6 eV). More than a hundred isomers were identified and a set of 23 minima was selected among them, on the basis of their energy and probability of occurrence. The return probabilities of these 23 minima and the transition probabilities between them were computed for several lid energies up to 11 eV. The first connection appeared at 3.5 eV while all minima were found to be connected at 9.5 eV. The local density of state was also sampled inside their respective basins. This work gives insight into both energy and entropic barriers separating the different basins, which also provides information about the transition regions of the energy landscape.

Introduction: A Doppler ultrasound (US) of the scrotum is commonly used to improve the diagnostic confidence for testicular torsion in an emergency setting. However, the sensitivity of this investigation to identify torsion varies largely. This is due, in part, to a lack of guidelines on how-to perform the US and therefore training is necessary., Evidence Acquisition: The Scrotal and Penile Imaging Working Group of the European Society of Urogenital Radiology (ESUR-SPIWG) and the Section of Urological Imaging of the European Association of Urology (ESUI) established a joint panel of experts to standardize Doppler US investigation of patients with testicular torsion. The panel reviewed the available literature, identified accumulated knowledge and limitations, and released recommendations on how-to perform Doppler US in patients with acute scrotal pain., Evidence Synthesis: Diagnosis of testicular torsion is based on clinical evaluation and investigation of the cord, the testis, and the paratesticular structures. A preliminary clinical evaluation, including history and palpation, is necessary. Grey scale US, color Doppler US and spectral analysis must be performed by a sonologist with at least level 2 competence. Modern equipment with adequate grey-scale and Doppler capabilities are required., Conclusions: Standardization of Doppler US in suspicious testicular torsion is presented, with the aim to obtain comparable results among different centres, prevent unnecessary operations, and improve patient management.

Purpose: To describe the national-level patterns of care for local ablative therapy among men with PCa and identify patient- and hospital-level factors associated with the receipt of these techniques., Methods: We retrospectively interrogated the National Cancer Database (NCDB) for men with clinically localized PCa between 2010 and 2017. The main outcome was receipt of local tumor ablation with either cryo- or laser-ablation, and "other method of local tumor destruction including high-intensity focused ultrasound (HIFU)". Patient level, hospital level, and demographic variables were collected. Mixed effect logistic regression models were fitted to identify separately patient- and hospital-level predictors of receipt of local ablative therapy., Results: Overall, 11,278 patients received ablative therapy, of whom 78.8% had cryotherapy, 15.6% had laser, and 5.7% had another method including HIFU. At the patient level, men with intermediate-risk PCa were more likely to be treated with local ablative therapy (OR 1.05; 95% CI 1.00-1.11; p = 0.05), as were men with Charlson Comorbidity Index > 1 (OR 1.36; 95% CI 1.29-1.43; p < 0.01), men between 71 and 80 years (OR 3.70; 95% CI 3.43-3.99; p < 0.01), men with Medicare insurance (OR 1.38; 95% 1.31-1.46; p < 0.01), and an income < $47,999 (OR 1.16; 95% CI 1.06-1.21; p < 0.01). At the hospital-level, local ablative therapy was less likely to be performed in academic/research facilities (OR 0.45; 95% CI 0.32-0.64; p < 0.01)., Conclusions: Local ablative therapy for PCa treatment is more commonly offered among older and comorbid patients. Future studies should investigate the uptake of these technologies in non-hospital-based settings and in light of recent changes in insurance coverage., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Prostate cancer (PCa) detection is usually achieved by PSA measurement and, if indicated, further diagnostics. The recent EAU guidelines recommend a first PSA test at the age of 50 years, if no family history of PCa or BRCA2 mutation exists. However, some men might harbor significant PCa at younger age; thus we evaluated the histopathological results of men treated with radical prostatectomy (RP) in their 40 s at our institution., Materials and Methods: We relied on the data of all patients who underwent RP in our institution between 1992 and 2020 and were younger than 50 years at the time of surgery. The histopathological results are descriptively presented. Moreover, we tested the effect of a positive family history on the descriptive results., Results: Overall, 1225 patients younger than 50 years underwent RP at our institution. Median age was 47 years. Most patients showed favorable histopathological characteristics. However, 20% of patients had extraprostatic disease (≥ pT3a), 15% had ISUP Gleason grade group ≥ 3, and 7% had positive lymph nodes (pN1). Patients with a known positive family history did not have a higher rate of adverse disease as their counterparts with a negative family history., Discussion: Our data show that the majority of patients who were diagnosed with PCa at a very young age had favorable histopathological RP characteristics. However, a non-negligible proportion of patients already showed locally advanced disease and would have probably benefited from earlier PCa detection. This should be kept in mind when PCa screening recommendations are proposed., (© 2023. The Author(s).)

Surfactants are long-chain compounds comprising a hydrophobic tail and a hydrophilic head, lending them the ability to act as a “bridge” between oil and water. Their detergent, foaming and other properties prove useful in a number of settings, including home and workplace sanitation, cosmetics (rinse and no-rinse cleansers) and medicine. When used on skin, surfactants reduce the superficial surface tension of proteins and lipids on the stratum corneum. This helps to eliminate skin debris such as sebum, oils and dirt, but also presents a risk of damage to the skin barrier. The irritation potential of surfactants has long been common knowledge, but with the development and deployment of novel compounds, notably to replace first-generation, mostly sodium-lauryl-sulphate-based products, their potential to cause allergic contact dermatitis has come to light. Knowledge about this allergic potential and the associated dermatitises must also become commonplace so that contact allergies are considered in the presence of surfactant exposure.

Background: Focal therapy (FT) for prostate cancer (PCa) is promising. However, long-term oncological results are awaited and there is no consensus on follow-up strategies. Molecular biomarkers (MB) may be useful in selecting, treating and following up men undergoing FT, though there is limited evidence in this field to guide practice. We aimed to conduct a consensus meeting, endorsed by the Focal Therapy Society, amongst a large group of experts, to understand the potential utility of MB in FT for localized PCa., Methods: A 38-item questionnaire was built following a literature search. The authors then performed three rounds of a Delphi Consensus using DelphiManager, using the GRADE grid scoring system, followed by a face-to-face expert meeting. Three areas of interest were identified and covered concerning MB for FT, 1) the current/present role; 2) the potential/future role; 3) the recommended features for future studies. Consensus was defined using a 70% agreement threshold., Results: Of 95 invited experts, 42 (44.2%) completed the three Delphi rounds. Twenty-four items reached a consensus and they were then approved at the meeting involving (N.=15) experts. Fourteen items reached a consensus on uncertainty, or they did not reach a consensus. They were re-discussed, resulting in a consensus (N.=3), a consensus on a partial agreement (N.=1), and a consensus on uncertainty (N.=10). A final list of statements were derived from the approved and discussed items, with the addition of three generated statements, to provide guidance regarding MB in the context of FT for localized PCa. Research efforts in this field should be considered a priority., Conclusions: The present study detailed an initial consensus on the use of MB in FT for PCa. This is until evidence becomes available on the subject.

Topology in quantum many-body systems has profoundly changed our understanding of quantum phases of matter. The model that has played an instrumental role in elucidating these effects is the antiferromagnetic spin-1 Haldane chain 1,2 . Its ground state is a disordered state, with symmetry-protected fourfold-degenerate edge states due to fractional spin excitations. In the bulk, it is characterized by vanishing two-point spin correlations, gapped excitations and a characteristic non-local order parameter 3,4 . More recently it has been understood that the Haldane chain forms a specific example of a more general classification scheme of symmetry-protected topological phases of matter, which is based on ideas connected to quantum information and entanglement 5-7 . Here, we realize a finite-temperature version of such a topological Haldane phase with Fermi-Hubbard ladders in an ultracold-atom quantum simulator. We directly reveal both edge and bulk properties of the system through the use of single-site and particle-resolved measurements, as well as non-local correlation functions. Continuously changing the Hubbard interaction strength of the system enables us to investigate the robustness of the phase to charge (density) fluctuations far from the regime of the Heisenberg model, using a novel correlator., (© 2022. The Author(s).)

Purpose: To investigate the concordance of biopsy and pathologic International Society of Urological Pathology (ISUP) grading in salvage radical prostatectomy (SRP) patients for recurrent prostate cancer., Methods: Within a high-volume center database, we identified patients who underwent SRP for recurrent prostate cancer (PCa) between 2004 and 2020. Upgrading, downgrading, concordance, and any discordance between posttreatment biopsy ISUP and ISUP at SRP were tested. Logistic regression models were used to predict ISUP upgrading and ISUP discordance. Models were adjusted for prostatic specific antigen before SRP, age at surgery, initial prostatic specific antigen (PSA), type of primary treatment, time from primary PCa diagnosis to SRP, number of positive cores at biopsy, and original Gleason score., Results: Overall, 184 patients with available biopsy and pathologic ISUP grading were identified. Of those, 17.4% (n = 32), 40.8% (n = 75), 19.6% (n = 36), and 22.2% (n = 41) harbored biopsy ISUP 1, ISUP 2, ISUP 3, and ISUP 4-5 grading, respectively. Pathologic ISUP 1, ISUP 2, ISUP 3, and ISUP 4-5 grading was recorded in 6.0% (n = 11), 40.8% (n = 75), 32.1% (n = 59), and 21.2% (n = 39), respectively. Median PSA before SRP was 5.5 ng/ml (interquartile range [IQR]: 3.1-8.1 ng/ml), median age at SRP was 65.1 years (IQR:60.7-69.4 years) and median time from original PCa diagnosis to SRP was 47 months (IQR: 27.3-85.2 months). Concordance of biopsy and pathologic ISUP was identified in 45.1% (n = 83). Conversely, any ISUP discordance, upgrading and downgrading of at least one ISUP group was identified in 54.9% (n = 101), 35.3% (n = 65), and 19.6% (n = 36). In logistic models, none of the preoperative characteristics was associated with upgrading or ISUP discordance (all p > 0.1)., Conclusion: Discordance between biopsy and pathologic ISUP grading is common at SRP. However, in 45% of SRP cases biopsy ISUP is capable to predict pathologic ISUP. Further studies are necessary to identify characteristics for ISUP upgrading at SRP., (© 2021 The Authors. The Prostate published by Wiley Periodicals LLC.)

Objective: The objective of this study is to evaluate prostate-specific membrane antigen positron emission tomography-computed tomography (PSMA PET/CT)-based primary staging in exclusively D'Amico intermediate-risk prostate cancer (PCa) patients., Patients and Methods: We relied on the Braunschweig institutional database and retrospectively identified D'Amico intermediate-risk PCa patients who were administered to 68Ga-PSMA PET/CT-based primary staging prior to consecutive radical prostatectomy and extended lymph node dissection. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the detection of lymph node metastases were analyzed per-patient (n = 39), per-pelvic side (n = 78), and per-anatomic-region (external iliac artery and vein left/right vs. obturator fossa left/right vs. internal iliac artery left/right) (n = 203), respectively., Results: Sensitivity, specificity, PPV, and NPV per-patient were 20.0, 94.1, 33.3, and 88.9%, respectively. Sensitivity, specificity, PPV, and NPV per-pelvic-side were 16.7, 97.2, 33.3, and 93.3%, respectively. Sensitivity, specificity, PPV, and NPV per-anatomic-region were 16.7, 99.0, 33.3, and 97.5%, respectively., Conclusions: We recorded high rates of specificity and NPV for 68Ga-PSMA PET/CT-based primary staging in D'Amico intermediate-risk PCa patients. Conversely, the sensitivity and PPV were lower than anticipated. Larger and favorably prospective trials are needed to verify our results and to unravel possible bias from such smaller studies., (© 2021 S. Karger AG, Basel.)

Background: Micro-ultrasound (microUS) is a novel ultrasound-based imaging modality which has demonstrated the ability to visualize prostate cancer. Multiparametric MRI/ultrasound (mpMRI/US) fusion has recognized advantages for the performance of prostate biopsy, however, it encompasses additional cost, time and technical expertise to performing prostate biopsy in comparison to conventional trans-rectal ultrasound biopsy. MicroUS may simplify and optimize this pathway., Methods: OPTIMUM is a 3-arm randomized controlled trial comparing microUS guided biopsy with MRI/US fusion and MRI/MicroUS "contour-less" fusion. This trial will investigate whether microUS alone, or in combination with mpMRI, provides effective guidance during prostate biopsy for the detection of clinically significant prostate cancer (csPCa) for biopsy naïve subjects. 1200 subjects will be randomized. The economic impact will be evaluated., Results: The rate of csPCa (defined as Grade Group 2 and above) in each arm will be compared. The primary hypothesis is non-inferiority of csPCa rate between the MRI/US fusion arm and the microUS-only arm (including the blinded microUS-only portion of the MRI/MicroUS arm). As a secondary objective, the csPCa rate between MRI/MicroUS fusion and MRI/US fusion arms will also be compared. Other secondary objectives include the increase in rate of patients diagnosed with csPCa due to each type of sample (mpMRI targeted, microUS targeted, systematic), the negative predictive value of each imaging modality, and a health economic analysis of the procedures in each arm., Conclusions: OPTIMUM will determine whether microUS can be used as an alternative to MRI/US fusion biopsy. The trial will also evaluate the efficacy of the simplified "contour-less" MRI/MicroUS fusion procedure. The adoption of the microUS technique will increase the proportion of men who can benefit from modern imaging-centric diagnostic strategies, and may help reduce variability, complexity, waiting time and cost within the diagnostic pathway., (Copyright © 2021. Published by Elsevier Inc.)

Background: Imaging techniques are used to identify local recurrence of prostate cancer (PCa) for salvage therapy and to exclude metastases that should be addressed with systemic therapy. For magnetic resonance imaging (MRI), a reduction in the variability of acquisition, interpretation, and reporting is required to detect local PCa recurrence in men with biochemical relapse after local treatment with curative intent., Objective: To propose a standardised method for image acquisition and assessment of PCa local recurrence using MRI after radiation therapy (RP) and radical prostatectomy (RT)., Evidence Acquisition: Prostate Imaging for Recurrence Reporting (PI-RR) was formulated using the existing literature. An international panel of experts conducted a nonsystematic review of the literature. The PI-RR system was created via consensus through a combination of face-to-face and online discussions., Evidence Synthesis: Similar to with PI-RADS, based on the best available evidence and expert opinion, the minimum acceptable MRI parameters for detection of recurrence after radiation therapy and radical prostatectomy are set. Also, a simplified and standardised terminology and content of the reports that use five assessment categories to summarise the suspicion of local recurrence (PI-RR) are designed. PI-RR scores of 1 and 2 are assigned to lesions with a very low and low likelihood of recurrence, respectively. PI-RR 3 is assigned if the presence of recurrence is uncertain. PI-RR 4 and 5 are assigned for a high and very high likelihood of recurrence, respectively. PI-RR is intended to be used in routine clinical practice and to facilitate data collection and outcome monitoring for research., Conclusions: This paper provides a structured reporting system (PI-RR) for MRI evaluation of local recurrence of PCa after RT and RP., Patient Summary: A new method called PI-RR was developed to promote standardisation and reduce variations in the acquisition, interpretation, and reporting of magnetic resonance imaging for evaluating local recurrence of prostate cancer and guiding therapy., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Artificial intelligence developments are essential to the successful deployment of community-wide, MRI-driven prostate cancer diagnosis. AI systems should ensure that the main benefits of biopsy avoidance are delivered while maintaining consistent high specificities, at a range of disease prevalences. Since all current artificial intelligence / computer-aided detection systems for prostate cancer detection are experimental, multiple developmental efforts are still needed to bring the vision to fruition. Initial work needs to focus on developing systems as diagnostic supporting aids so their results can be integrated into the radiologists' workflow including gland and target outlining tasks for fusion biopsies. Developing AI systems as clinical decision-making tools will require greater efforts. The latter encompass larger multicentric, multivendor datasets where the different needs of patients stratified by diagnostic settings, disease prevalence, patient preference, and clinical setting are considered. AI-based, robust, standard operating procedures will increase the confidence of patients and payers, thus enabling the wider adoption of the MRI-directed approach for prostate cancer diagnosis. KEY POINTS: • AI systems need to ensure that the benefits of biopsy avoidance are delivered with consistent high specificities, at a range of disease prevalence. • Initial work has focused on developing systems as diagnostic supporting aids for outlining tasks, so they can be integrated into the radiologists' workflow to support MRI-directed biopsies. • Decision support tools require a larger body of work including multicentric, multivendor studies where the clinical needs, disease prevalence, patient preferences, and clinical setting are additionally defined., (© 2021. The Author(s).)

Competing Interests: The authors have no funding or conflicts of interest to declare.

Context: The value of Histoscanning™ (HS) in prostate cancer (PCa) imaging is much debated, although it has been used in clinical practice for more than 10 years now., Objective: To summarize the data on HS from various PCa diagnostic perspectives to determine its potential., Materials and Methods: We performed a systematic search using 2 databases (Medline and Scopus) on the query "Histoscan*". The primary endpoint was HS accuracy. The secondary endpoints were: correlation of lesion volume by HS and histology, ability of HS to predict extracapsular extension or seminal vesicle invasion., Results: HS improved cancer detection rate "per core", OR = 16.37 (95% CI 13.2; 20.3), p < 0.0001, I 2  = 98% and "per patient", OR = 1.83 (95% CI 1.51; 2.21), p < 0.0001, I 2  = 95%. The pooled accuracy was markedly low: sensitivity - 0.2 (95% CI 0.19-0.21), specificity - 0.12 (0.11-0.13), AUC 0.12. 8 of 10 studiers showed no additional value for HS. The pooled accuracy with histology after RP was relatively better, yet still very low: sensitivity - 0.56 (95% CI 0.5-0.63), specificity - 0.23 (0.18-0.28), AUC 0.4. 9 of 12 studies did not show any benefit of HS., Conclusion: This meta-analysis does not see the incremental value in comparing prostate Histoscanning with conventional TRUS in prostate cancer screening and targeted biopsy. HS proved to be slightly more accurate in predicting extracapsular extension on RP, but the available data does not allow us to draw any conclusions on its effectiveness in practice. Histoscanning is a modification of ultrasound for prostate cancer visualization. The available data suggest its low accuracy in screening and detecting of prostate cancer., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The competition between antiferromagnetism and hole motion in two-dimensional Mott insulators lies at the heart of a doping-dependent transition from an anomalous metal to a conventional Fermi liquid. We observe such a crossover in Fermi-Hubbard systems on a cold-atom quantum simulator and reveal the transformation of multipoint correlations between spins and holes upon increasing doping at temperatures around the superexchange energy. Conventional observables, such as spin susceptibility, are furthermore computed from the microscopic snapshots of the system. Starting from a magnetic polaron regime, we find the system evolves into a Fermi liquid featuring incommensurate magnetic fluctuations and fundamentally altered correlations. The crossover is completed for hole dopings around 30%. Our work benchmarks theoretical approaches and discusses possible connections to lower-temperature phenomena.

Introduction: We provide a systematic analysis of nerve-sparing surgery (NSS) to assess and summarize the risks and benefits of NSS in high-risk prostate cancer (PCa)., Evidence Acquisition: We have undertaken a systematic search of original articles using 3 databases: Medline/PubMed, Scopus, and Web of Science. Original articles in English containing outcomes of nerve-sparing radical prostatectomy (RP) for high-risk PCa were included. The primary outcomes were oncological results: the rate of positive surgical margins and biochemical relapse. The secondary outcomes were functional results: erectile function (EF) and urinary continence., Evidence Synthesis: The rate of positive surgical margins differed considerably, from zero to 47%. The majority of authors found no correlation between NSS and a positive surgical margin rate. The rate of biochemical relapse ranged from 9.3% to 61%. Most of the articles lacked data on odds ratio (OR) for positive margin and biochemical relapse. The presented results showed no effect of nerve sparing (NS) on positive margin (OR=0.81, 0.6-1.09) or biochemical relapse (hazard ratio [HR]=0.93, 0.52-1.64). A strong association between NSS and potency rate was observed. Without NSS, between 0% and 42% of patients were potent, with unilateral 79-80%, with bilateral - up to 90-100%. Urinary continence was not strongly associated with NSS and was relatively good in both patients with and without NSS., Conclusions: NSS may provide benefits for patients with urinary continence and significantly improves EF in high-risk patients. Moreover, it is not associated with an increased risk of relapse in short- and middle-term follow-up. However, the advantages of using such a surgical technique are unclear.

Maladaptive Daydreaming (MD) is a newly proposed mental disorder characterized by excessive, vivid fantasy activity impairing functioning. There is a high comorbidity of MD with Obsessive-Compulsive Spectrum Symptoms (OCSS), yet the mechanisms responsible for this relationship are still unclear. The present study set out to explore the relationship between MD and OCSS by: (1) examining dissociation, trauma, sense of control, and mind-wandering as potential mediators; (2) exploring whether MD is more strongly related to obsessions or compulsions; and (3) identifying patterns of specific obsessions and/or compulsions common in an MD sample. A group of 510 participants with self-identified MD completed a battery of online questionnaires. Dissociation and sense of control significantly mediated the MD-OCSS association. MD was moderately related to both obsessions and compulsions but was significantly more strongly related to the former. Frequently endorsed obsessions and compulsions among MD participants included checking and repetition compulsions, intrusive obsessions, and body-related obsessions and compulsions. We conclude that dissociative mechanisms, including dissociative absorption, play a major role in the relationship between MD and OCSS and may lead to consequent checking when transitioning back to reality, altered embodiment, intrusive images, and thoughts, and an impaired sense of mental control. Clinicians working with OCSS should be aware of the possible role of MD in the development or maintenance of symptoms. Future work should develop useful interventions for this type of shared psychopathology., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To compare the detection rate of clinically significant cancer (CSCa) by magnetic resonance imaging-targeted biopsy (MRI-TB) with that by standard systematic biopsy (SB) and to evaluate the role of MRI-TB as a replacement from SB in men at clinical risk of prostate cancer., Methods: The non-systematic literature was searched for peer-reviewed English-language articles using PubMed, including the prospective paired studies, where the index test was MRI-TB and the comparator text was SB. Also the randomized clinical trials (RCTs) are included if one arm was MRI-TB and another arm was SB., Results: Eighteen prospective studies used both MRI-TB and TRUS-SB, and eight RCT received one of the tests for prostate cancer detection. In most prospective trials to compare MRI-TB vs. SB, there was no significant difference in any cancer detection rate; however, MRI-TB detected more men with CSCa and fewer men with CISCa than SB., Conclusion: MRI-TB is superior to SB in detection of CSCa. Since some significant cancer was detected by SB only, a combination of SB with the TB technique would avoid the underdiagnosis of CSCa.

Introduction and Objectives: Knowledge about the significance of sarcopenia (muscle loss) in prostate cancer (PCa) patients is limited. The aim of this study was to determine the influence of skeletal muscle index (SMI) on early functional and pathological outcome in patients undergoing radical prostatectomy (RP). Materials and Methods: One hundred randomly chosen patients who received RP between November 2016 and April 2017 at Martini-Klinik (Hamburg, Germany) were retrospectively assessed. SMI (skeletal muscle mass cross-sectional area at L3/m 2 ) was measured by preoperative staging computed tomography scans at L3 level. Cox regression analysis was applied to determine the impact of SMI on post-operative outcome. Follow-up was 12 months. Continence was defined as no more than one safety pad per day. Results: Mean age of the cohort was 63.6 years. Mean SMI was 54.06 cm 2 /m 2 (range, 40.65-74.58 cm 2 /m 2 ). Of the patients, 41.4% had pT2, 28.7% had pT3a, and 29.9% had pT3b or pT4 PCa. SMI revealed to be without significant correlation on tumor stage. Follow-up data of 55 patients were available for early functional outcome analysis. SMI showed no significant influence on erectile function in multivariable Cox regression analysis. In multivariable Cox regression analysis, SMI turned out to have no influence on continence rates 6 weeks after surgery. Conclusion: The present study shows that patients undergoing RP have a wide range of SMI. Unlike in other urological malignancies, there was no significant impact of SMI on early functional outcome and pathological outcome. A larger cohort is needed to confirm these results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Angerer, Salomon, Beyersdorff, Fisch, Graefen and Rosenbaum.)

Background: Although recent advances in multiparametric magnetic resonance imaging (MRI) led to an increase in MRI-transrectal ultrasound (TRUS) fusion prostate biopsies, these are time consuming, laborious, and costly. Introduction of deep-learning approach would improve prostate segmentation., Objective: To exploit deep learning to perform automatic, real-time prostate (zone) segmentation on TRUS images from different scanners., Design, Setting, and Participants: Three datasets with TRUS images were collected at different institutions, using an iU22 (Philips Healthcare, Bothell, WA, USA), a Pro Focus 2202a (BK Medical), and an Aixplorer (SuperSonic Imagine, Aix-en-Provence, France) ultrasound scanner. The datasets contained 436 images from 181 men., Outcome Measurements and Statistical Analysis: Manual delineations from an expert panel were used as ground truth. The (zonal) segmentation performance was evaluated in terms of the pixel-wise accuracy, Jaccard index, and Hausdorff distance., Results and Limitations: The developed deep-learning approach was demonstrated to significantly improve prostate segmentation compared with a conventional automated technique, reaching median accuracy of 98% (95% confidence interval 95-99%), a Jaccard index of 0.93 (0.80-0.96), and a Hausdorff distance of 3.0 (1.3-8.7) mm. Zonal segmentation yielded pixel-wise accuracy of 97% (95-99%) and 98% (96-99%) for the peripheral and transition zones, respectively. Supervised domain adaptation resulted in retainment of high performance when applied to images from different ultrasound scanners (p > 0.05). Moreover, the algorithm's assessment of its own segmentation performance showed a strong correlation with the actual segmentation performance (Pearson's correlation 0.72, p < 0.001), indicating that possible incorrect segmentations can be identified swiftly., Conclusions: Fusion-guided prostate biopsies, targeting suspicious lesions on MRI using TRUS are increasingly performed. The requirement for (semi)manual prostate delineation places a substantial burden on clinicians. Deep learning provides a means for fast and accurate (zonal) prostate segmentation of TRUS images that translates to different scanners., Patient Summary: Artificial intelligence for automatic delineation of the prostate on ultrasound was shown to be reliable and applicable to different scanners. This method can, for example, be applied to speed up, and possibly improve, guided prostate biopsies using magnetic resonance imaging-transrectal ultrasound fusion., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To investigate the predictors of recurrence and of de novo incontinence in patients treated by transurethral incision or resection for vesico-urethral anastomotic stenosis (VUAS) after radical prostatectomy., Material and Methods: All patients undergoing endoscopic treatment for VUAS between March 2009 and October 2016 were identified in our multi-institutional database. Digital chart reviews were performed and patients contacted for follow-up. Recurrence was defined as any need for further instrumentation or surgery, and de-novo-incontinence as patient-reported outcome., Results: Of 103 patients undergoing endoscopic VUAS treatment, 67 (65%) underwent transurethral resection (TR) and 36 (35%) transurethral incision (TI). TI was performed more frequently as primary treatment compared to TR (58% vs. 37%; p = 0.041). Primary and repeated treatment was performed in 46 (45%) and 57 patients (55%), respectively. Overall, 38 patients (37%) had a history of radiation therapy. There was no difference in time to recurrence for primary vs repeat VUAS treatment, previous vs no radiation, TR compared to TI (all p > 0.08). Regarding treatment success, no difference was found for primary vs. repeat VUAS treatment (50% vs. 37%), previous radiation vs. no radiation (42% vs. 43%), and TR vs. TI (37% vs. 53%; all p ≥ 0.1). Postoperative de novo incontinence was more common after TI vs. TR (31% vs. 12%; p = 0.032), no difference was observed for previous radiation therapy vs. no radiation therapy (18% vs. 18%; p > 0.9) or primary vs. repeat VUAS treatment (22% vs. 16%; p = 0.5)., Conclusion: VUAS recurrence after endoscopic treatment is not predictable. Endoscopic treatment with TI showed a higher risk for de novo incontinence than TR, and previous irradiation and the number of treatments do not influence incontinence.

Background: The prognostic value of circulating tumor cells (CTCs) in patients with hormone-naïve oligometastatic prostate cancer (HNoMPC) undergoing cytoreductive radical prostatectomy (CRP) is unknown., Objective: To determine the pre- and postoperative prognostic value of CTC enumeration in patients undergoing CRP., Design, Setting, and Participants: Thirty-three patients with HNoMPC from the prospective, single-arm ProMPT trial who underwent CRP between 2014 and 2015 at the Martini-Klinik were evaluated. Follow-up visits for all patients were conducted every 6 mo up to 36 mo after CRP and included serial detection of CTCs in 7.5 ml blood samples using the CellSearch system., Intervention: CRP., Outcome Measurements and Statistical Analysis: CTC enumerations before and after CRP, and their prognostic value on metastatic castration-resistant prostate cancer-free survival and overall survival (OS) were analyzed using Kaplan-Meier plots and univariable Cox-regression analysis., Results and Limitations: Sixteen patients (48.5%) had positive CTCs prior to CRP. A CTC count of ≥2 before or 6 mo after CRP was a prognostic factor for worse oncologic outcome. Compared with other biomarkers (prostate-specific antigen, lactate dehydrogenase, and bone-specific alkaline phosphatase), the prognostic value of CTCs was highest using Harrell's C for OS (0.69), while the highest C-index could be achieved for a combination of conventional markers and CTC count (0.74). After progression to metastatic castration-resistant prostate cancer, CTC enumeration of ≥5 was prognostic for OS. The main limitation is the small sample size., Conclusions: CTC enumeration contributes to prognostic information, which might help select HNoMPC patients who might benefit most from CRP., Patient Summary: In this report, we looked at the value of circulating tumor cell (CTC) determination in patients undergoing radical prostatectomy for oligometastatic prostate cancer. We could show that the number of CTCs was a prognostic factor at all analyzed time points and was more closely associated with prognosis than other biomarkers commonly used in daily clinical practice., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Shear-wave elastography (SWE) permits local estimation of tissue elasticity, an important imaging marker in biomedicine. This recently developed, advanced technique assesses the speed of a laterally traveling shear wave after an acoustic radiation force "push" to estimate local Young's moduli in an operator-independent fashion. In this work, we show how synthetic SWE (sSWE) images can be generated based on conventional B-mode imaging through deep learning. Using side-by-side-view B-mode/SWE images collected in 50 patients with prostate cancer, we show that sSWE images with a pixel-wise mean absolute error of 4.5 ± 0.96 kPa with regard to the original SWE can be generated. Visualization of high-level feature levels through t -distributed stochastic neighbor embedding reveals substantial overlap between data from two different scanners. Qualitatively, we examined the use of the sSWE methodology for B-mode images obtained with a scanner without SWE functionality. We also examined the use of this type of network in elasticity imaging in the thyroid. Limitations of the technique reside in the fact that networks have to be retrained for different organs, and that the method requires standardization of the imaging settings and procedure. Future research will be aimed at the development of sSWE as an elasticity-related tissue typing strategy that is solely based on B-mode ultrasound acquisition, and the examination of its clinical utility.

Objectives: This study aims to define consensus-based criteria for acquiring and reporting prostate MRI and establishing prerequisites for image quality., Methods: A total of 44 leading urologists and urogenital radiologists who are experts in prostate cancer imaging from the European Society of Urogenital Radiology (ESUR) and EAU Section of Urologic Imaging (ESUI) participated in a Delphi consensus process. Panellists completed two rounds of questionnaires with 55 items under three headings: image quality assessment, interpretation and reporting, and radiologists' experience plus training centres. Of 55 questions, 31 were rated for agreement on a 9-point scale, and 24 were multiple-choice or open. For agreement items, there was consensus agreement with an agreement ≥ 70% (score 7-9) and disagreement of ≤ 15% of the panellists. For the other questions, a consensus was considered with ≥ 50% of votes., Results: Twenty-four out of 31 of agreement items and 11/16 of other questions reached consensus. Agreement statements were (1) reporting of image quality should be performed and implemented into clinical practice; (2) for interpretation performance, radiologists should use self-performance tests with histopathology feedback, compare their interpretation with expert-reading and use external performance assessments; and (3) radiologists must attend theoretical and hands-on courses before interpreting prostate MRI. Limitations are that the results are expert opinions and not based on systematic reviews or meta-analyses. There was no consensus on outcomes statements of prostate MRI assessment as quality marker., Conclusions: An ESUR and ESUI expert panel showed high agreement (74%) on issues improving prostate MRI quality. Checking and reporting of image quality are mandatory. Prostate radiologists should attend theoretical and hands-on courses, followed by supervised education, and must perform regular performance assessments., Key Points: • Multi-parametric MRI in the diagnostic pathway of prostate cancer has a well-established upfront role in the recently updated European Association of Urology guideline and American Urological Association recommendations. • Suboptimal image acquisition and reporting at an individual level will result in clinicians losing confidence in the technique and returning to the (non-MRI) systematic biopsy pathway. Therefore, it is crucial to establish quality criteria for the acquisition and reporting of mpMRI. • To ensure high-quality prostate MRI, experts consider checking and reporting of image quality mandatory. Prostate radiologists must attend theoretical and hands-on courses, followed by supervised education, and must perform regular self- and external performance assessments.

Purpose: To assess the efficacy of dual-energy CT (DECT) in predicting the composition of urinary stones with a single index (dual energy ratio [DER]) and five indices. Methods: Patients undergoing DECT before active urolithiasis treatment were prospectively enrolled in the study. Predictions of stone composition were made based on discriminant analysis with a single index (DER) and five indices (stone density at 80 and 135 kV, Zeff [the effective atomic number of the absorbent material] of the stone, DER, dual-energy index [DEI] and dual-energy difference [DED]). After extraction, stone composition was evaluated by means of physicochemical analyses (X-ray phase analysis, electron microscopy, wet chemistry techniques, and infrared spectroscopy). Results : A total of 91 patients were included. For calcium oxalate monohydrate (COM) stones, the sensitivity, specificity, and overall accuracy of DECT with one index (DER) were 83.3%, 89.8%, and 86.8%, respectively; for calcium oxalate dihydrate (COD) and calcium phosphate stones-88.2%, 92.9%, and 91.2%, respectively; for uric acid stones-0%, 98.8% and 97.8%, respectively; for struvite stones-60%, 95.3%, and 93.4%, respectively. Discriminant analysis with five indices yielded the following sensitivity, specificity, and overall accuracy: 95.2%, 89.8%, and 92.3% for COM stones, 85.3%, 96.4%, and 92.3% for COD stones, and 100% in all three categories for both uric acid and struvite stones. Conclusions: DECT is a promising tool for stone composition assessment. It allowed for evaluation of chemical composition of all stone types with specificity and accuracy ranging from 85% to 100%. Five DECT indices have shown much better diagnostic accuracy compared to a single DECT index.

Blind source separation (BSS) refers to a number of signal processing techniques that decompose a signal into several "source" signals. In recent years, BSS is increasingly employed for the suppression of clutter and noise in ultrasonic imaging. In particular, its ability to separate sources based on measures of independence rather than their temporal or spatial frequency content makes BSS a powerful filtering tool for data in which the desired and undesired signals overlap in the spectral domain. The purpose of this work was to review the existing BSS methods and their potential in ultrasound imaging. Furthermore, we tested and compared the effectiveness of these techniques in the field of contrast-ultrasound super-resolution, contrast quantification, and speckle tracking. For all applications, this was done in silico, in vitro, and in vivo. We found that the critical step in BSS filtering is the identification of components containing the desired signal and highlighted the value of a priori domain knowledge to define effective criteria for signal component selection.

Quantum gas microscopy has emerged as a powerful new way to probe quantum many-body systems at the microscopic level. However, layered or efficient spin-resolved readout methods have remained scarce as they impose strong demands on the specific atomic species and constrain the simulated lattice geometry and size. Here we present a novel high-fidelity bilayer readout, which can be used for full spin- and density-resolved quantum gas microscopy of two-dimensional systems with arbitrary geometry. Our technique makes use of an initial Stern-Gerlach splitting into adjacent layers of a highly stable vertical superlattice and subsequent charge pumping to separate the layers by 21  μm. This separation enables independent high-resolution images of each layer. We benchmark our method by spin- and density-resolving two-dimensional Fermi-Hubbard systems. Our technique furthermore enables the access to advanced entropy engineering schemes, spectroscopic methods, or the realization of tunable bilayer systems.

Background: Updates in the eighth edition of the AJCC prostate cancer staging manual include removal of the organ-confined (pT2) substages., Methods: Retrospective analyses of 12,028 pT2 patients that underwent radical prostatectomy between 2003 and 2016 and did not receive neo- or adjuvant treatments. Kaplan-Meier curves as well as multivariable Cox-regression analyses compared biochemical recurrence (BCR), metastatic progression (MP) and overall mortality (OM) between the 3 subcategories (pT2a, pT2b and pT2c)., Results: After surgery, 1,441 patients were classified as pT2a, 126 as pT2b and 10.495 as pT2c. Five-year BFS rates for pT2a, pT2b and pT2c were 92.0% vs. 97.4% vs. 88.0%. For the same groups, 5-year MP-FS rates were 99.5% vs. 100% vs. 99.0% and 5-year OS rates were 98.0% vs. 98.2% vs. 97.7%. In multivariable analyses pT2 substratification did not reach independent predictor status for biochemical recurrence, MP or overall mortality., Conclusions: Substratification of pT2 prostate cancer was not predictive for further disease progression. Therefore, removing the substages simplifies the staging system without loss of important information., (Copyright © 2020. Published by Elsevier Inc.)

Context: There is a lack of comprehensive data regarding the factors that influence the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) to detect and localize clinically significant prostate cancer (csPCa)., Objective: To systematically review the current literature assessing the factors influencing the variability of mpMRI performance in csPCa diagnosis., Evidence Acquisition: A computerized bibliographic search of Medline/PubMed database was performed for all studies assessing magnetic field strength, use of an endorectal coil, assessment system used by radiologists and inter-reader variability, experience of radiologists and urologists, use of a contrast agent, and use of computer-aided diagnosis (CAD) tools in relation to mpMRI diagnostic accuracy., Evidence Synthesis: A total of 77 articles were included. Both radiologists' reading experience and urologists'/radiologists' biopsy experience were the main factors that influenced diagnostic accuracy. Therefore, it is mandatory to indicate the experience of the interpreting radiologists and biopsy-performing urologists to support the reliability of the findings. The most recent Prostate Imaging Reporting and Data System (PI-RADS) guidelines are recommended for use as the main assessment system for csPCa, given the simplified and standardized approach as well as its particular added value for less experienced radiologists. Biparametric MRI had similar accuracy to mpMRI; however, biparametric MRI performed better with experienced readers. The limited data available suggest that the combination of CAD and radiologist readings may influence diagnostic accuracy positively., Conclusions: Multiple factors affect the accuracy of mpMRI and MRI-targeted biopsy to detect and localize csPCa. The high heterogeneity across the studies underlines the need to define the experience of radiologists and urologists, implement quality control, and adhere to the most recent PI-RADS assessment guidelines. Further research is needed to clarify which factors impact the accuracy of the MRI pathway and how., Patient Summary: We systematically reported the factors influencing the accuracy of multiparametric magnetic resonance imaging (mpMRI) in detecting clinically significant prostate cancer (csPCa). These factors are significantly related to each other, with the experience of the radiologists being the dominating factor. In order to deliver the benefits of mpMRI to diagnose csPCa, it is necessary to develop expertise for both radiologists and urologists, implement quality control, and adhere to the most recent Prostate Imaging Reporting and Data System assessment guidelines., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: The aim of this survey was to obtain an overview of current European standards in the endoscopic visualization and management of bladder tumors. Methods: An online survey was launched in July 2018 for a duration of 4 months. It was distributed to all members of the European Association of Urology (EAU) and included 23 questions divided into 3 thematic sections: general information, white light cystoscopy (WLC) and imaging, and transurethral resection of bladder tumor (TURBT) techniques. Results: Responses of 222 participants were included for analysis. The majority of physicians were between 30 and 40 years of age (48.2%, n  = 107) and performed over 50 TURBT per year (52.2%, n  = 115). Overall, 52.3% ( n  = 116) reported WLC findings in written form only, 23.8% ( n  = 53) added endoscopic footage, and 79.2% ( n  = 176) considered preliminary WLC/TURBT reports before performing a subsequent bladder intervention. About half of the participants (50.5%, n  = 104) used additional tumor visualization methods (aTVMs), but aTVMs were utilized by a greater proportion of physicians from Western countries (58.1%, n  = 90) compared with developing countries (20.0%, n  = 7). Photodynamic diagnosis was the predominant aTVM technique employed (43.8%, n  = 60). Bipolar current was the most common technique for TURBT (46.6%, n  = 149). Most urologists in this study occasionally utilized techniques like resections in fractions (80%, n  = 161) or en bloc resection (87.2%, n  = 182). A repeated TURBT was performed when no muscle was found in the specimen (70.6%, n  = 149) and/or if the tumor was stage pT1 (72.0%, n  = 152) or high grade (63.0%, n  = 133). Conclusion: Implementation of resection techniques or repeated TURBT within EAU guidelines is promising, but it can be further challenged. For example, WLC/TURBT reporting should be improved since urologists consistently consider previous documentation. Given the moderate application rate of aTVMs, an attempt to increase its utilization would lead to a better assessment of its potential benefit.

Objectives: The aim of this study was to assess the potential of machine learning based on B-mode, shear-wave elastography (SWE), and dynamic contrast-enhanced ultrasound (DCE-US) radiomics for the localization of prostate cancer (PCa) lesions using transrectal ultrasound., Methods: This study was approved by the institutional review board and comprised 50 men with biopsy-confirmed PCa that were referred for radical prostatectomy. Prior to surgery, patients received transrectal ultrasound (TRUS), SWE, and DCE-US for three imaging planes. The images were automatically segmented and registered. First, model-based features related to contrast perfusion and dispersion were extracted from the DCE-US videos. Subsequently, radiomics were retrieved from all modalities. Machine learning was applied through a random forest classification algorithm, using the co-registered histopathology from the radical prostatectomy specimens as a reference to draw benign and malignant regions of interest. To avoid overfitting, the performance of the multiparametric classifier was assessed through leave-one-patient-out cross-validation., Results: The multiparametric classifier reached a region-wise area under the receiver operating characteristics curve (ROC-AUC) of 0.75 and 0.90 for PCa and Gleason > 3 + 4 significant PCa, respectively, thereby outperforming the best-performing single parameter (i.e., contrast velocity) yielding ROC-AUCs of 0.69 and 0.76, respectively. Machine learning revealed that combinations between perfusion-, dispersion-, and elasticity-related features were favored., Conclusions: In this paper, technical feasibility of multiparametric machine learning to improve upon single US modalities for the localization of PCa has been demonstrated. Extended datasets for training and testing may establish the clinical value of automatic multiparametric US classification in the early diagnosis of PCa., Key Points: • Combination of B-mode ultrasound, shear-wave elastography, and contrast ultrasound radiomics through machine learning is technically feasible. • Multiparametric ultrasound demonstrated a higher prostate cancer localization ability than single ultrasound modalities. • Computer-aided multiparametric ultrasound could help clinicians in biopsy targeting.

Elementary particles carry several quantum numbers, such as charge and spin. However, in an ensemble of strongly interacting particles, the emerging degrees of freedom can fundamentally differ from those of the individual constituents. For example, one-dimensional systems are described by independent quasiparticles carrying either spin (spinon) or charge (holon). Here, we report on the dynamical deconfinement of spin and charge excitations in real space after the removal of a particle in Fermi-Hubbard chains of ultracold atoms. Using space- and time-resolved quantum gas microscopy, we tracked the evolution of the excitations through their signatures in spin and charge correlations. By evaluating multipoint correlators, we quantified the spatial separation of the excitations in the context of fractionalization into single spinons and holons at finite temperatures., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)