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IntroductionProstate cancer hypoxia is a negative prognostic biomarker. A promising MRI-based tool to assess hypoxia is the ‘Consumption and Supply based Hypoxia’ (CSH) model based on diffusion-weighted imaging (DWI). The aim of the study was to validate the association between the CSH hypoxia fraction (HFDWI) with pathological Grade Group (pGG) and pathological T-staging (pTstage) in an external prostatectomy cohort.MethodsApparent diffusion coefficient (ADC) and fractional blood volume (fBV) maps were assessed from DWI data from 291 prostatectomies and combined by the CSH model. HFDWI was calculated for each lesion after median scaling of ADC and fBV to address differences in acquisition and analysis between centers. The absolute HFDWI values and the associations of HFDWI between pGG < 3 versus ≥ 3, and pTstage = 2 versus = 3 in the Netherlands Cancer Institute (NKI) cohort were compared to the obtained by original cohort (Oslo cohort). Statistical T- and Mann-Whitney tests (p

Hip-implants structured with anti-bacterial textures should show a low-friction coefficient and should not leach hazardous substances into the human body. The surface of a typical material used for hip-implants, namely Cobalt–Chrome–Molybdenum (CoCrMo) was textured with different types of laser-induced periodic surface structures (LIPSS)—i.e., low spatial frequency LIPSS (LSFL), hierarchical structures consisting of grooves superimposed with high spatial frequency LIPSS (HSFL) and Triangular shaped Nanopillars (TNP)—using a picosecond pulsed laser source. The effect of LIPSS on the wettability, friction, as well as wear of the structures, when slid against a polyethylene (PE) counter surface and biocompatibility was analyzed. Surfaces covered with LSFL show superhydrophobicity and grooves with superimposed HSFL, as well as TNP, show hydrophobic behavior. The coefficient of friction (CoF) of LIPSS against a polyethylene (PE) counter surface was found to be higher (ranging from 0.40 to 0.66) than the CoF of (polished) CoCrMo, which was found to equal 0.22. It was found that the samples release cobalt within biocompatible limits. Compared to polished reference surfaces, LIPSS cause higher friction of CoCrMo against PE contact. However, the wear of the PE counter surface only increased significantly for the LSFL textures. For these reasons, it is concluded that LIPSS are not suitable for a heavily loaded metal-on-plastic bearing contact.

Small and medium-sized enterprises (SMEs) often struggle with company innovation, compared to their larger counterparts. A university-business collaboration (UBC) programme in the north of the Netherlands attempts to increase the innovation capabilities of regional SMEs with the support of graduating bachelor students. The 18-months long Hanze Innovation Traineeship Programme (HITP) combines the graduation phase with a consecutive 12-months traineeship, during which students are meant to implement an innovation at the company. We measure the innovation capacity of the participating SMEs at the beginning of the programme and identify strong and weak points within the organisations. We discuss the outcomes of the HITP for SME innovation and further evaluate the programme’s suitability on the intended student learning outcomes.

Background and Objective: A meta-analysis of two randomized STAMPEDE platform trials revealed that 3 yr of abiraterone acetate in addition to androgen deprivation therapy and radiation therapy significantly improved metastasis-free and overall survival (OS) in high-risk nonmetastatic prostate cancer (PCa) and should be considered a new standard of care. The aim of our study was to assess long-term cancer-specific survival (CSS) and OS for surgically treated patients with newly diagnosed nonmetastatic node-negative PCa meeting the STAMPEDE criteria for high risk., Methods: This was a retrospective, multicenter cohort study of patients with European Association of Urology (EAU) high-risk PCa who underwent radical prostatectomy and extended pelvic lymph node dissection. CSS was assessed using cumulative incidence curves and the Kaplan-Meier method was used to evaluate OS. We used a Fine and Gray model to evaluate the prognostic value of STAMPEDE high-risk factors (SHRFs) for CSS, and a Cox proportional-hazards model to assess the association of SHRFs with OS., Key Findings and Limitations: A total of 2994 patients with EAU high-risk PCa were divided into groups with 0, 1, 2, or 3 SHRFs. The 10-yr survival estimates for patients with 0-1 versus 2-3 SHRFs were 95% versus 82% for CSS and 81% versus 64% for OS (both p < 0.0001). In comparison to patients with 0 SHRFs, hazard ratios were 1.2 (p = 0.5), 3.9 (p < 0.0001), and 5.5 (p < 0.0001) for CSS, and 1.1 (p = 0.4), 2.2 (p < 0.0001), and 2.5 (p = 0.0004) for OS for patients with 1, 2, and 3 SHRFs, respectively., Conclusions and Clinical Implications: Our results confirm that the STAMPEDE high-risk criteria identify a subgroup of patients with highly aggressive PCa features and adverse long-term oncological outcomes. This population is likely to benefit most from aggressive multimodal treatment. Nevertheless, we have shown for the first time that surgery remains a viable treatment option for patients with STAMPEDE high-risk PCa., Patient Summary: Prostate cancer that meets the high-risk definitions from the STAMPEDE trial is an aggressive type of cancer. Our results for long-term cancer control outcomes indicate that surgery is a viable option for the subgroup of patients with this type of prostate cancer., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background and Objective: Persistent prostatic specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP). However, the impact of persistent PSA on oncologic outcomes in patients undergoing salvage RP is unknown. To investigate the impact of persistent PSA after salvage RP on long-term oncologic outcomes., Material and Methods: Patients who underwent salvage RP for recurrent prostate cancer between 2000 and 2021 were identified from twelve high-volume centers. Only patients with available PSA after salvage RP were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of persistent PSA on biochemical recurrence (BCR), metastasis and any death after salvage RP. Persistent PSA was defined as a PSA-value ≥ 0.1 ng/ml, at first PSA-measurement after salvage RP., Results: Overall, 580 patients were identified. Of those, 42% (n = 242) harbored persistent PSA. Median follow-up after salvage RP was 38 months, median time to salvage RP was 64 months and median time to first PSA after salvage RP was 2.2 months. At 84 months after salvage RP, BCR-free, metastasis-free, and overall survival was 6.6 vs. 59%, 71 vs. 88% and 77 vs. 94% for patients with persistent vs. undetectable PSA after salvage RP (all p < 0.01). In multivariable Cox models persistent PSA was an independent predictor for BCR (HR: 5.47, p < 0.001) and death (HR: 3.07, p < 0.01)., Conclusion: Persistent PSA is common after salvage RP and represents an independent predictor for worse oncologic outcomes. Patients undergoing salvage RP should be closely monitored after surgery to identify those with persistent PSA., (© 2023. The Author(s).)

Phenotypic plasticity is a hallmark of cancer and increasingly realized as a mechanism of resistance to androgen receptor (AR)-targeted therapy. Now that many prostate cancer (PCa) patients are treated upfront with AR-targeted agents, it's critical to identify actionable mechanisms that drive phenotypic plasticity, to prevent the emergence of resistance. We showed that loss of tristetraprolin (TTP, gene ZFP36) increased NF-κB activation, and was associated with higher rates of aggressive disease and early recurrence in primary PCa. We also examined the clinical and biological impact of ZFP36 loss with co-loss of PTEN, a known driver of PCa. Analysis of multiple independent primary PCa cohorts demonstrated that PTEN and ZFP36 co-loss was associated with increased recurrence risk. Engineering prostate-specific Zfp36 deletion in vivo, induced prostatic intraepithelial neoplasia, and, with Pten co-deletion, resulted in rapid progression to castration-resistant adenocarcinoma. Zfp36 loss altered the cell state driven by Pten loss, demonstrated by enrichment of EMT, inflammation, TNFα/NF-κB, IL6-JAK/STAT3 gene sets. Additionally, our work revealed that ZFP36 loss also induced enrichment of multiple gene sets involved in mononuclear cell migration, chemotaxis, and proliferation. Use of the NF-κB inhibitor, dimethylaminoparthenolide (DMAPT) induced marked therapeutic responses in tumors with PTEN and ZFP36 co-loss and reversed castration resistance.

Purpose: To investigate functional, oncological and complication outcomes in women undergoing robot-assisted cystectomy (RARC) with intracorporeal orthotopic neobladder., Methods: From a multi-institutional database, we identified females with bladder cancer treated with RARC and intracorporeal orthotopic neobladder. We evaluated the continence rate, short-term oncological outcomes, and complication rates. Analyses were repeated and stratified by the status of preserving gynecological organs., Results: The study involved 146 patients with the median age 60 years (IQR, 51-66 years). Pelvic organ-preserving procedure (POP) was performed in 77 patients (53%). Overall daytime and nighttime continence rates were 54% and 53%, respectively. For POP, the continence rate was 58% for both daytime and nighttime continence. In the non-POP cohort, the continence rate was 50% for daytime and 49% for nighttime continence. Both groups had balanced positive surgical margin rates (5,3% for POP and 4,7% for non-POP). In the whole cohort, high-grade (Clavien-Dindo ≥3) early and late complication rate was 7,5% and 7,5%, respectively., Conclusions: Robot-assisted radical cystectomy with intracorporeal orthotopic neobladder in females demonstrate excellent functional and complication outcomes. Pelvic organ-preserving cystectomy enhances urinary continence rates without adversely affecting surgical margins. Orthotopic neobladder in selected women with bladder cancer, along with pelvic organ-preserving cystectomy may be used for improved functional outcomes without compromising oncological results., (© 2024. The Author(s).)

Purpose: Our study aimed to assess the oncological outcomes of sentinel node dissection during radical prostatectomy according to nodal location in comparison to extended pelvic lymph node dissection., Materials and Methods: Prospectively collected data of clinically node-negative patients who underwent prostatectomy and extended lymph node dissection with or without sentinel node from January 2013 to January 2023 were retrospectively analyzed. The primary end point was to assess oncological outcomes on the whole population. Kaplan-Meier curves were used to depict biochemical and clinical recurrence-free survival. Multivariable Cox regression models assessed the impact of nodal location on single-photon emission computed tomography on oncological outcomes. Adjustment for case mix included: pathological T stage, ISUP (International Society of Urological Pathology) grade group, initial PSA, nodal burden, age at surgery, and surgical margin status. Secondarily, a propensity score match was performed according to age at surgery, PSA, biopsy ISUP, clinical T stage, and Briganti risk of nodal invasion. Survival and regression analyses were also performed in the matched population., Results: Of the patients, 55.8% had at least 1 sentinel node outside of lymph node dissection template at single-photon emission computed tomography/CT. Log-rank test showed comparable 36-month biochemical ( P = .3) and clinical recurrence-free survival ( P = .6) among patients with sentinel node inside template, outside template, or extended pelvic lymph node dissection alone. At Cox regression, sentinel node location outside template was associated with lower hazard of metastases (HR 0.62; P = .04) in the overall cohort, while in the matched cohort benefits were observed only for biochemical recurrence (HR 0.57; P = .001)., Conclusions: Wider nodal resection boundaries outside the "classic" template, driven by sentinel node procedure, have a positive impact on oncological outcomes in selected patient.

Background and Objective: Different training programs have been developed to improve trainee outcomes in urology. However, evidence on the optimal training methodology is sparse. Our aim was to provide a comprehensive description of the training programs available for urological robotic surgery and endourology, assess their validity, and highlight the fundamental elements of future training pathways., Methods: We systematically reviewed the literature using PubMed/Medline, Embase, and Web of Science databases. The validity of each training model was assessed. The methodological quality of studies on metrics and curricula was graded using the MERSQI scale. The level of evidence (LoE) and level of recommendation for surgical curricula were awarded using the educational Oxford Centre for Evidence-Based Medicine classification., Key Findings and Limitations: A total of 75 studies were identified. Many simulators have been developed to aid trainees in mastering skills required for both robotic and endourology procedures, but only four demonstrated predictive validity. For assessment of trainee proficiency, we identified 18 in robotics training and six in endourology training; however, the majority are Likert-type scales. Although proficiency-based progression (PBP) curricula demonstrated superior outcomes to traditional training in preclinical settings, only four of six (67%) in robotics and three of nine (33%) in endourology are PBP-based. Among these, the Fundamentals of Robotic Surgery and the SIMULATE curricula have the highest LoE (level 1b). The lack of a quantitative synthesis is the main limitation of our study., Conclusions and Clinical Implications: Training curricula that integrate simulators and PBP methodology have been introduced to standardize trainee outcomes in robotics and endourology. However, evidence regarding their educational impact remains restricted to preclinical studies. Efforts should be made to expand these training programs to different surgical procedures and assess their clinical impact., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Prostate cancer hypoxia is a negative prognostic biomarker. A promising MRI-based tool to assess hypoxia is the 'Consumption and Supply based Hypoxia' (CSH) model based on diffusion-weighted imaging (DWI). The aim of the study was to validate the association between the CSH hypoxia fraction (HF DWI ) with pathological Grade Group (pGG) and pathological T-staging (pTstage) in an external prostatectomy cohort., Methods: Apparent diffusion coefficient (ADC) and fractional blood volume (fBV) maps were assessed from DWI data from 291 prostatectomies and combined by the CSH model. HF DWI was calculated for each lesion after median scaling of ADC and fBV to address differences in acquisition and analysis between centers. The absolute HF DWI values and the associations of HF DWI between pGG < 3 versus ≥ 3, and pTstage = 2 versus = 3 in the Netherlands Cancer Institute (NKI) cohort were compared to the obtained by original cohort (Oslo cohort). Statistical T- and Mann-Whitney tests ( p <0.05) were performed. Pearson correlation was determined between HF DWI and individual pGG groups., Results: The HF DWI showed comparable absolute values and similar metric performance as in the original published cohort. Higher HF DWI values were observed for higher pGG (Oslo: 0.27; NKI: 0.24) compared to lower pGG (Oslo: 0.11; NKI: 0.17). Similar results were obtained for pTstage. Furthermore, HF DWI demonstrated a significant positive correlation with pGG groups 1-5 (ρ = 0.41, p <0.001)., Conclusion: The CSH model exhibited sufficient robustness in the external cohort, suggesting a plausible reflection of true hypoxia and enabling the use of the HF DWI metric for further research into prostate cancer and hypoxia., 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 © 2024 Fernandez Salamanca, Hompland, Deręgowska-Cylke, Van der Poel, Bekers, Guimaraes, Lyng, Van der Heide, Schoots and Van Houdt.)

International Society of Urological Pathology grade group 1 (GG 1) prostate cancer (PCa) is generally considered insignificant, with recent suggestions that it should even be considered as "noncancerous". We evaluated outcomes for patients with GG 1 PCa on biopsy (bGG 1) and high-risk features (prostate-specific antigen [PSA] >20 ng/ml and/or cT3-4 stage) to challenge the hypothesis that every case of bGG 1 PCa has a benign disease course. We used the multi-institutional EMPaCT database, which includes data for 9508 patients with high-risk PCa undergoing surgery. We included patients with bGG 1 PCa ( n  = 848) in our analysis and divided them into three groups according to PSA >20 ng/ml, cT3-4 stage, or both. The estimated 10-yr cancer-specific survival (CSS) rate was 96% in the overall population, 88% in the group with both PSA >20 ng/ml and cT3-4 stage, 97% in the group with PSA >20 ng/ml alone, and 98% in the group with cT3-4 stage alone. Similar CSS outcomes were found in subgroups with GG 1 PCa on pathology ( n  = 502) and with GG 1 on biopsy diagnosed after 2005 ( n  = 253). Study limitations include the lack of magnetic resonance imaging (MRI) staging and MRI-targeted biopsies. In conclusion, patients with GG 1 and either PSA >20 ng/ml or cT3-4 stage have a low risk of dying from their cancer after surgery. However, patients with GG 1 PCa and both PSA >20 ng/ml and cT3-4 stage are at higher risk of cancer-specific mortality and active treatment should be discussed for this subgroup., Patient Summary: We assessed outcomes for patients diagnosed with low-grade prostate cancer on biopsy who also had one or two factors associated with high risk disease. Men with both of those risk factors had a higher risk of dying from their prostate cancer. Active treatment should be discussed for this subgroup of patients., (© 2024 The Author(s).)

Background: In a subset of patients with oligorecurrent prostate cancer (PCa), salvage surgery with prostate-specific membrane antigen (PSMA) radioguided surgery (PSMA-RGS) seems to be of value., Objective: To evaluate whether a lower level of postoperative prostate-specific antigen (PSA; <0.1 ng/ml) is predictive of therapy-free survival (TFS) following salvage PSMA-RGS., Design, Setting, and Participants: This cohort study evaluated patients with biochemical recurrence after radical prostatectomy and oligorecurrent PCa on PSMA positron emission tomography treated with PSMA-RGS in three tertiary care centers (2014-2022)., Intervention: PSMA-RGS., Outcome Measurements and Statistical Analysis: Postsalvage surgery PSA response was categorized as <0.1, 0.1-<0.2, or >0.2 ng/ml. Kaplan-Meier and multivariable Cox regression models evaluated TFS according to PSA response., Results and Limitations: Among 553 patients assessed, 522 (94%) had metastatic soft tissue lesions removed during PSMA-RGS. At 2-16 wk after PSMA-RGS, 192, 62, and 190 patients achieved PSA levels of <0.1, 0.1-<0.2, and >0.2 ng/ml, respectively. At 2 yr of follow-up, TFS rate was 81.1% versus 56.1% versus 43.1% (p < 0.001) for patients with PSA <0.1 versus 0.1-<0.2 versus >0.2 ng/ml. In multivariable analyses, PSA levels of 0.1-0.2 ng/ml (hazard ratio [HR]: 1.9, confidence interval [CI]: 1.1-3.1) and ≥0.2 ng/ml (HR: 3.2, CI: 2.2-4.6, p < 0.001) independently predicted the need for additional therapy after PSMA-RGS. The main limitation is the lack of a control group., Conclusions: For patients after salvage PSMA-RGS, a lower biochemical response (PSA <0.1 ng/ml) seems to predict longer TFS. This insight may help in counseling patients postoperatively as well as guiding the timely selection of additional therapy., Patient Summary: We studied what happened to prostate cancer patients in three European centers who had salvage surgery using a special method called prostate-specific membrane antigen-targeted radioguidance. We found that patients who had low prostate-specific antigen levels soon after surgery were less likely to need further treatment for a longer time., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

(1) Background: Somatic and germline alterations can be commonly found in prostate cancer (PCa) patients. The aim of our present study was to perform a comprehensive review of the current literature in order to examine the impact of BRCA mutations in the context of PCa as well as their significance as genetic biomarkers. (2) Methods: A narrative review of all the available literature was performed. Only "landmark" publications were included. (3) Results: Overall, the number of PCa patients who harbor a BRCA2 mutation range between 1.2% and 3.2%. However, BRCA2 and BRCA1 mutations are responsible for most cases of hereditary PCa, increasing the risk by 3-8.6 times and up to 4 times, respectively. These mutations are correlated with aggressive disease and poor prognosis. Gene testing should be offered to patients with metastatic PCa, those with 2-3 first-degree relatives with PCa, or those aged < 55 and with one close relative with breast (age ≤ 50 years) or invasive ovarian cancer. (4) Conclusions: The individualized assessment of BRCA mutations is an important tool for the risk stratification of PCa patients. It is also a population screening tool which can guide our risk assessment strategies and achieve better results for our patients and their families.

Purpose: This study aims to develop and externally validate a clinically plausible Bayesian network structure to predict one-year erectile dysfunction in prostate cancer patients by combining expert knowledge with evidence from data using clinical and Patient-reported outcome measures (PROMs) data. In addition, compare and contrast structures that stem from PROM information and routine clinical data., Summary of Background: For men with localized prostate cancer, choosing the optimal treatment can be challenging since each option comes with different side effects, such as erectile dysfunction, which negatively impacts their quality of life. Our previous findings demonstrate that logistic regression models are able to identify patients at high risk of erectile dysfunction. However, methods such as Bayesian networks may be more successful, as they intricately represent the causal relations between the variables., Patients and Methods: 946 prostate cancer patients from 65 Dutch hospitals were considered to develop the Bayesian network structure. Continuous variables were discretized before analysis based on expert opinions and literature. Patients with missing information and variables with more than 25% of missing information were excluded. Prostate cancer treating physicians first determined the relationships (arcs) between the available variables. The structures were then modified based on algorithmically derived structures using the hill-climbing algorithm. Structural Performance was evaluated based on the area under the curve (AUC) values and calibration plots on the training and test data., Results: BMI and prostate volume via MRI were excluded from this analysis due to their high percentage of missingness ( > 45 %). The final cohort was reduced to 505 and 216 after excluding 157 and 68 patients with missing information, respectively. The AUC of the PROM structure was better than the clinical structure in both the train and test data. The structure that combined both sources of information had an AUC value of 0.94 (0.92 - 0.96) and 0.84171 (0.77 91) in the train and test data, respectively., Conclusion: Bayesian network structures derived from PROM information by complimenting expert knowledge with evidence from the data produce a clinically plausible structure that is more performant than structures from clinical data. Our study supports the growing global recognition of incorporating the patient's perspective in outcomes research for better decision-making and optimal outcomes. However, a structure that combines both sources of information gives a more holistic view of the patient with actionable insights and improved discriminative power., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy & Oncology.)