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ProBio is the first outcome-adaptive platform trial in prostate cancer utilizing a Bayesian framework to evaluate efficacy within predefined biomarker signatures across systemic treatments. Prospective circulating tumor DNA and germline DNA analysis was performed in patients with metastatic castration-resistant prostate cancer before randomization to androgen receptor pathway inhibitors (ARPIs), taxanes or a physician's choice control arm. The primary endpoint was the time to no longer clinically benefitting (NLCB). Secondary endpoints included overall survival and (serious) adverse events. Upon reaching the time to NLCB, patients could be re-randomized. The primary endpoint was met after 218 randomizations. ARPIs demonstrated ~50% longer time to NLCB compared to taxanes (median, 11.1 versus 6.9 months) and the physician's choice arm (median, 11.1 versus 7.4 months) in the biomarker-unselected or 'all' patient population. ARPIs demonstrated longer overall survival (median, 38.7 versus 21.7 and 21.8 months for taxanes and physician's choice, respectively). Biomarker signature findings suggest that the largest increase in time to NLCB was observed in AR (single-nucleotide variant/genomic structural rearrangement)-negative and TP53 wild-type patients and TMPRSS2-ERG fusion-positive patients, whereas no difference between ARPIs and taxanes was observed in TP53-altered patients. In summary, ARPIs outperform taxanes and physician's choice treatment in patients with metastatic castration-resistant prostate cancer with detectable circulating tumor DNA. ClinicalTrials.gov registration: NCT03903835 ., Competing Interests: Competing interests A.C., A.D., B.L., M.P., S.J., S.D., M.B., A.K., C.S., J.V.W., M.H.E., L.P., E.J., J.S., P.S., M.N.V., M.O., S.V.B., M.A., I.V., E.E., J.D., D.L., M.S. and J.O. declare no competing interests. The following authors declare having received honoraria (privately or to institution/employer) from the following companies: MSD/Merck (B.S. and G.E.); Janssen-Cilag (B.S., B.D.L., A.M., C.T.K. and J.L.); AstraZeneca (B.D.L., C.T.K. and J.L.); ESMO (B.D.L.); Astellas (B.Y.A.); Pfizer (B.Y.A., H.G. and J.L.); BMS (BY.A. and W.D.R.); Ipsen (B.Y.A.); Johnson & Johnson Innovative Medicine (W.D.R.); Gilead (G.E.); Roche (G.E.); Pierre Fabre (G.E.); and Amgen (C.T.K.). The following authors declare having performed consulting or advisory roles for the following companies: Astellas (BS., A.U., D.D.M. and H.G.); Janssen-Cilag (B.S., P.O., A.U., H.G. and D.D.M.); BMS (B.S.); MSD/Merck (B.S., A.U., D.D.M. and P.O.); Bayer (B.S., P.O., H.G., A.M. and D.D.M.); AAA (P.O.); Novartis (P.O.); Pierre Fabre (A.U.); Pfizer (A.U. and D.D.M.); Roche (A.U.); Gilead (G.E.); Elicera Therapeutics (G.E).; XNK Therapeutics AB (G.E.); Sprint Bioscience AB (G.E.); Accord (H.G.); and AstraZeneca (H.G., D.D.M. and J.L.). The following authors declare having received research grants or sponsoring of trials from the following companaies: Bayer (P.O,. A.U. and N.L.); Janssen-Cilag (H.G.); AstraZeneca (H.G.); Merck (A.U. and W.D.R.); Pierre Fabre (A.U.); Ipsen (W.D.R. and N.L.); Johnson & Johnson Innovative Medicine (W.D.R.); and Roche Diagnostics (D.D.M.). The following authors declare having an unpaid membership in a (non-)governmental organization or advocacy organization: COMPERMED (B.D.L.); PSA Vlaanderen vzw (B.D.L. and C.G.); Swiss Urology (A.M.); Swedish Cancer Society (G.E.); and EAU Guidelines Urethral Stricture Panel (N.L.). The following authors declare having stock ownership or board membership: A3P AB (H.G. and M.E.); ClinSight AB (M.E.); Lighthouse Precision Oncology AB (B.D.L., J.L., M.M., R.B. and V.C.). The following authors declare having patents: J.L. and M.M. have filed a Swedish Patent Application (no. 2350786-6), ‘Method of identifying and adjusting for systematic variability in DNA abundance measurements’, which is applied in the current study to identify copy number alterations. However, the method will be made freely available under a GPL 3.0 license (https://github.com/ClinSeq/jumble/)., (© 2024. The Author(s).)

Background: Quality control indicators (QCIs) can be used to objectively evaluate guideline adherence and benchmark quality among urologists and centers., Objective: To assess six QCIs for non-muscle-invasive bladder cancer (NMIBC) using a prospective registry of transurethral resection of bladder tumor (TURBT) procedures., Design, Setting, and Participants: Clinical data for TURBT cases were prospectively collected using electronic case report forms (eCRFs) embedded in the electronic medical record in three centers during 2013-2017. Pathological data were collected retrospectively. Patients with T0 disease or prior T2 disease were excluded., Outcome Measurements and Statistical Analysis: We assessed six QCIs: complete resection (CR) status, presence of detrusor muscle (DM), re-TURBT, single instillation of mitomycin C (MMC), start of bacillus Calmette-Guérin (BCG) therapy, and therapy ≤6 wk after diagnosis. We assessed the quality of reporting on QCIs and compliance with QCIs, compared compliance between centers and over time, and investigated correlation between compliance and recurrence-free survival (RFS)., Results and Limitations: Data for 1350 TURBT procedures were collected, of which 1151 were included for 907 unique patients. The distribution of European Association of Urology risk categories after TURBT was 271 with low risk, 464 with intermediate risk, and 416 with high risk. The quality of reporting for two QCIs was suboptimal, at 35% for DM and 51% for BCG. QCI compliance was 97% for CR, 31% for DM, 65% for MMC, 33% for re-TURBT, 39% for BCG, and 88% for therapy ≤6 wk after diagnosis. Compliance with all QCIs differed significantly among centers. Compliance with MMC and re-TURBT increased significantly over time, which could be attributed to one center. Compliance with MMC was significantly correlated with RFS. The main study limitation is the retrospective collection of pathology data., Conclusions: A TURBT registry consisting of eCRFs to collect pathology and outcome data allowed assessment of QCIs for NMIBC. Our study illustrates the feasibility of this approach in a real-life setting. Differences in performance on QCIs among centers can motivate urologists to improve their day-to-day care for patients with NMIBC, and can thus improve clinical outcomes., Patient Summary: Our study demonstrates that quality control indicators for treatment of bladder cancer not invading the bladder muscle can be evaluated using electronic medical records. We assessed results for 1151 procedures in 907 individual patients to remove bladder tumors between 2013 and 2017 at three centers in Belgium. Compliance with the quality control indicators differed between centers, increased over time, and was correlated with recurrence of disease., (Copyright © 2022. Published by Elsevier B.V.)

Lutetium-177 prostate-specific membrane antigen radioligands ( 177 Lu-PSMA) are new therapeutic agents for the treatment of metastatic castration-resistant prostate cancer (mCRPC). We evaluated the prognostic value of circulating tumour DNA (ctDNA) profiling in patients with mCRPC starting treatment with 177 Lu-PSMA I&T. Between January 2020 and October 2022, patients with late-stage mCRPC ( n  = 57) were enrolled in a single-centre observational cohort study. Genomic alterations in the AR gene, PI3K signalling pathway, TP53, and TMPRSS2-ERG were associated with progression-free survival (PFS) on Kaplan-Meier and multivariable Cox regression analyses. Median PFS of 3.84 mo (95% confidence interval [CI] 3.3-5.4) was observed, and 21/56 (37.5%) evaluable patients experienced a prostate-specific antigen response of ≥50% during treatment. Among 46 patients who provided a blood sample for profiling before 177 Lu-PSMA treatment. ctDNA was detected in 39 (84.8%); higher ctDNA was correlated with shorter PFS. Genomic structural rearrangements in the AR gene (hazard ratio [HR] 9.74, 95% confidence interval [CI] 2.4-39.5; p  = 0.001) and alterations in the PI3K signalling pathway (HR 3.58, 95% CI 1.41-9.08; p  = 0.007) were independently associated with poor 177 Lu-PSMA prognosis on multivariable Cox regression. Prospective evaluation of these associations in biomarker-driven trials is warranted., Patient Summary: We examined cell-free DNA in blood samples from patients with advanced metastatic prostate cancer who started treatment with lutetium-177-PSMA, a new radioligand therapy. We found that patients with genetic alterations in the androgen receptor gene or PI3K pathway genes did not experience a lasting benefit from lutetium-177-PSMA., (© 2023 The Author(s).)

Niraparib (NIRA) is a highly selective inhibitor of poly (adenosine diphosphate-ribose) polymerase, PARP1 and PARP2, which play a role in DNA repair. The phase II QUEST study evaluated NIRA combinations in patients with metastatic castration-resistant prostate cancer who were positive for homologous recombination repair gene alterations and had progressed on 1 prior line of novel androgen receptor-targeted therapy. Results from the combination of NIRA with abiraterone acetate plus prednisone, which disrupts androgen axis signaling through inhibition of CYP17, showed promising efficacy and a manageable safety profile in this patient population., (© The Author(s) 2023. Published by Oxford University Press.)

Purpose: We hypothesized that two-tier re-classification of the "M" (metastasis) domain of the Tumor-Node-Metastasis (TNM) staging of Renal Cell Carcinoma (RCC) may improve staging accuracy than the current monolithic classification, as advancements in the understanding of tumor biology have led to increased recognition of the heterogeneous potential of metastatic RCC (mRCC)., Methods: Multicenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. Patients were stratified by number of metastases into two groups, M1 (≤3, "Oligometastatic") and M2 (>3, "Polymetastatic"). Primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS). Cox-regression and Kaplan-Meier (KMA) analysis were utilized for outcomes, and receiver operating characteristic analysis (ROC) was utilized to assess diagnostic accuracy compared to current "M" staging., Results: 429 patients were stratified into proposed M1 and M2 groups (M1 = 286/M2 = 143; median follow-up 19.2 months). Cox-regression revealed M2 classification as an independent risk factor for worsened all-cause mortality (HR=1.67, p=0.001) and cancer-specific mortality (HR=1.74, p<0.001). Comparing M1-oligometastatic vs. M2-polymetastatic groups, KMA revealed significantly higher 5-year OS (36% vs. 21%, p<0.001) and 5-year CSS (39% vs. 17%, p<0.001). ROC analyses comparing OS and CSS, for M1/M2 reclassification versus unitary M designation currently in use demonstrated improved c-index for OS (M1/M2 0.635 vs. unitary M 0.500) and CSS (M1/M2 0.627 vs. unitary M 0.500)., Conclusion: Subclassification of Stage "M" domain of mRCC into two clinical substage categories based on metastatic burden corresponds to distinctive tumor groups whose oncological potential varies significantly and result in improved predictive capability compared to current staging., 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 © 2023 Meagher, Mir, Minervini, Kriegmair, Heck, Porpiglia, Van Bruwaene, Linares, Hevia, D’Anna, Veccia, Roussel, Claps, Palumbo, Marchioni, Afari, Saitta, Liu, Rubio, Campi, Mari, Amiel, Checcucci, Musquera, Guruli, Pavan, Albersen, Antonelli, Klatte, Autorino, McKay and Derweesh.)

Background: The optimal treatment for patients with pathological node-positive (pN1) prostate cancer (PCa) is unclear., Objective: To evaluate whether whole-pelvis radiotherapy (WPRT) improves clinical relapse-free survival (cRFS) in comparison to prostate-only radiotherapy (PORT) in pN1 PCa., Design, Setting, and Participants: PROPER was a phase 3 trial randomizing patients to WPRT or PORT. All patients had pN1cM0 PCa with fewer than five lymph nodes involved., Intervention: All patients underwent pelvic lymph node dissection followed by radical prostatectomy/primary radiotherapy + 2 yr of androgen deprivation therapy (ADT). Patients were randomized to PORT (arm A) or WPRT (arm B)., Outcome Measurements and Statistical Analysis: The primary outcome was cRFS. The secondary endpoints were overall survival (OS), biochemical relapse-free survival (bRFS), and toxicity. The study was stopped because of poor accrual in June 2021 after the inclusion of 69 patients. We report on OS, bRFS, cRFS, and acute and late toxicity., Results and Limitations: The median follow-up was 30 mo in arm A (n = 33) and 36 mo in arm B (n = 31). The 3-yr OS rate was 92% ± 5% in arm A and 93% ± 5% in arm B (p = 0.61). None of the patients died of PCa. The 3-yr bRFS was 79% ± 9% in arm A and 92% ± 5% in arm B (p = 0.08). The 3-yr cRFS rate was 88% ± 6% in arm A and 92% ± 5% in arm B (p = 0.31). No pelvic recurrence was observed in arm B. Acute grade 2 gastrointestinal toxicity was higher with WPRT (15% in arm A vs 45% in arm B; p = 0.03). Limitations are the early closure because of poor accrual and the limited follow-up., Conclusions: The results of our trial are hypothesis-generating but add evidence supporting the recommendation to offer WPRT to patients with pN1 PCa. However, WPRT is associated with more acute gastrointestinal toxicity., Patient Summary: We looked at the impact of radiotherapy to the whole pelvis (WPRT) for patients with prostate cancer that had spread to the lymph nodes. Although the trial was closed early because of poor enrolment, we found that WPRT improves survival free from relapse, and no recurrences were observed in the pelvis. WPRT is associated with more acute side effects on the gastrointestinal system in comparison to radiotherapy to just the prostate., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Abiraterone acetate + prednisone (AAP) and docetaxel have proven their efficacy in the treatment of patients with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) in clinical trials. However, real-world data are scarce. The goal of this study is to evaluate real-world data on the efficacy and safety of these therapies in mHSPC patients., Patients and Methods: Records of 93 patients from 21 different centres were retrospectively reviewed. Primary and secondary endpoints were radiographic and PSA progression-free survival (RPFS - PSA-PFS) and cancer specific and overall survival (CSS - OS), respectively. Adverse events (AEs) were evaluated according to the Common Terminology Criteria for Adverse Events version 5.0. Differences in oncological outcome and AEs were evaluated between three treatment groups: ADT only (N=26) - ADT + AAP (N=48) - ADT + docetaxel (N=19). Survival analysis was performed using Kaplan-Meier statistics., Results: Median RPFS was 13 months (95% confidence interval [CI]: 9-17) for ADT only, 21 months (95% CI: 19-23) for ADT + AAP and 12 months (95% CI: 11-14) for ADT + docetaxel (p = 0.004). The 1-year PSA-PFS, CSS and OS were 73.5%, 90.7% and 88.7%, respectively, with no significant differences between the three groups. Adverse events of grade 3 or higher were not observed more frequently., Conclusion: Retrospective real-world data show a significantly longer RPFS for mHSPC patients treated with ADT + AAP compared to ADT only or ADT + docetaxel at short-term follow-up. This can aid in counselling of mHSPC patients in daily clinical practice.

Background: Treatment paradigms for management of metastatic renal cell carcinoma (mRCC) are evolving. We examined impact of surgical metastasectomy on survival across in mRCC stratified by risk-group., Methods: Multicenter retrospective analysis from the Registry of Metastatic RCC database. The cohort was subdivided utilizing Motzer criteria (favorable-, intermediate-, high-risk). Primary outcome was all-cause mortality (ACM)/overall survival (OS); secondary outcome was cancer-specific mortality (CSM)/cancer-specific survival (CSS). Impact of metastasectomy was analyzed via Cox-Regression analysis adjusting for potential prognostic variables and Kaplan-Meier analysis (KMA) within each risk-group., Results: Four hundred thirty-one patients (59 favorable-risk, 274 intermediate-risk, 98 high-risk; median follow-up 27.2 months) were analyzed. Metastasectomy was performed in 22 (37%), 66 (24%), and 32 (16%) of favorable-, intermediate- and high-risk groups (P = .012). Median number of metastases at diagnosis differed significantly (favorable-risk 2, intermediate-risk 3.4, high-risk 5.1, P < .001). On Cox-regression, high-risk (HR = 1.72, P = .002) was associated with worsened ACM, while metastasectomy was associated with improved ACM (HR = 0.56, P = .005). On KMA, median OS (months) was longer with metastasectomy in favorable- (92.7 vs. 25.8, P = .003) and intermediate-risk (26.3 vs. 20.1, P = .038), but not high-risk (P = .911) groups. Metastasectomy was associated with longer CSS in favorable- (76.1 vs. 32.8, P = .004) but not intermediate- (P = .06) and high-risk (P = .595) groups., Conclusions: Metastasectomy was independently associated with improved ACM and CSM, as well as improved CSS and OS in favorable- and intermediate-risk mRCC patients. Metastasectomy may be considered as component of multimodal management strategy in favorable and intermediate-risk subgroups. In high-risk patients, metastasectomy should be deferred except in select circumstances., (Copyright © 2022. Published by Elsevier Inc.)

Background: Selection of patients for upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) has to be improved., Objective: To evaluate a new scoring system for the prediction of overall mortality (OM) in mRCC patients undergoing CN., Design, Setting, and Participants: We identified a total of 519 patients with synchronous mRCC undergoing CN between 2005 and 2019 from a multi-institutional registry (Registry for Metastatic RCC [REMARCC])., Outcome Measurements and Statistical Analysis: Cox proportional hazard regression was used to test the main predictors of OM. Restricted mean survival time was estimated as a measure of the average overall survival time up to 36 mo of follow-up. The concordance index (C-index) was used to determine the model's discrimination. Decision curve analyses were used to compare the net benefit from the REMARCC model with International mRCC Database Consortium (IMDC) or Memorial Sloan Kettering Cancer Center (MSKCC) risk scores., Results and Limitations: The median follow-up period was 18 mo (interquartile range: 5.9-39.7). Our models showed lower mortality rates in obese patients (p = 0.007). Higher OM rates were recorded in those with bone (p = 0.010), liver (p = 0.002), and lung metastases (p < 0.001). Those with poor performance status (<80%) and those with more than three metastases had also higher OM rates (p = 0.026 and 0.040, respectively). The C-index of the REMARCC model was higher than that of the MSKCC and IMDC models (66.4% vs 60.4% vs 60.3%). After stratification, 113 (22.0%) patients were classified to have a favorable (no risk factors), 202 (39.5%) an intermediate (one or two risk factors), and 197 (38.5%) a poor (more than two risk factors) prognosis. Moreover, 72 (17.2%) and 51 (13.9%) patients classified as having an intermediate and a poor prognosis according to MSKCC and IMDC categories, respectively, would be reclassified as having a good prognosis according to the REMARCC score., Conclusions: Our findings confirm the relevance of tumor and patient features for the risk stratification of mRCC patients and clinical decision-making regarding CN. Further prospective external validations are required for the scoring system proposed herein., Patient Summary: Current stratification systems for selecting patients for kidney removal when metastatic disease is shown are controversial. We suggest a system that includes tumor and patient features besides the systems already in use, which are based on blood tests., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Cytoreductive nephrectomy (CN) plays an important role in the treatment of a subgroup of metastatic renal cell carcinoma (mRCC) patients., Objective: We aimed to evaluate morbidity associated with this procedure and identify potential predictors thereof to aid patient selection for this procedure and potentially improve patient outcomes., Design, Setting, and Participants: Data from 736 mRCC patients undergoing CN at 14 institutions were retrospectively recorded in the Registry for Metastatic RCC (REMARCC)., Outcome Measurements and Statistical Analysis: Logistic regression analysis was used to identify predictors for intraoperative, any-grade (AGCs), low-grade, and high-grade (HGCs) postoperative complications (according to the Clavien-Dindo classification) as well as 30-d readmission rates., Results and Limitations: Intraoperative complications were observed in 69 patients (10.9%). Thrombectomy (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.08-1.75, p = 0.009) and adjacent organ removal (OR 2.7, 95% CI 1.38-5.30) were significant predictors of intraoperative complications at multivariable analysis. Two hundred seventeen patients (29.5%) encountered AGCs, while 45 (6.1%) encountered an HGC, of whom 10 (1.4%) died. Twenty-four (3.3%) patients had multiple postoperative complications. Estimated blood loss (EBL; OR 1.49, 95% CI 1.08-2.05, p = 0.01) was a significant predictor of AGCs at multivariable analysis. CN case load (OR 0.13, 95% CI 0.03-0.59, p = 0.009) and EBL (OR 2.93, 95% CI 1.20-7.15, p = 0.02) were significant predictors solely for HGCs at multivariable analysis. Forty-one patients (11.5%) were readmitted within 30 d of surgery. No significant predictors were identified. Results were confirmed in a subanalysis focusing solely on patients treated in the contemporary targeted therapy era., Conclusions: Morbidity associated with CN is not negligible. Predictors of high-grade postoperative morbidity are predominantly indicators of complex surgery. EBL is a strong predictor of postoperative complications. CN case load correlates with lower high-grade morbidity and highlights the benefit of centralization of complex surgery. However, risks and benefits should be balanced when considering CN in mRCC patients., Patient Summary: We studied patients with metastatic renal cancer to evaluate the outcomes associated with the surgical removal of the primary kidney tumor. We found that this procedure is often complex and adverse events are not uncommon. High intraoperative blood loss and a small number of cases performed at the treating center are associated with a higher rate of postoperative complications., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: The REWIND study sought to describe the real-world clinical and prescribing practices for the management of urinary tract infection (UTI) in Italy, Belgium, Russia and Brazil in order to compare current practices with international, European and national guidelines., Methods: An integrated mixed-methods approach was adopted that used information from primary care electronic medical records in longitudinal patient databases available in Italy and Belgium, and surveys of physicians in Russia (general practitioners) and Brazil (gynaecologists)., Results: In total, 49 548 female patients were included in the study. Antibiotics were the most common management option for UTI in Italy (71.1%, n=27 600), Belgium (92.4%, n=7703), Russia (81.9%, n=1231) and Brazil (82.4%, n=740). Fosfomycin trometamol was the first-choice antibiotic for the treatment of UTI in all countries. Ciprofloxacin was also commonly prescribed in Italy (24.6%, n=6796), Belgium (17.8%, n=1373), Russia (14.9%, n=184) and Brazil (9.6%, n=71), while prescription of nitrofurantoin was common in Belgium (24.5%, n=1890) alone., Conclusions: Despite differences in study designs and data sources, fosfomycin trometamol was found to be the most commonly prescribed treatment for UTI in all participating countries. In Belgium, real-world prescribing practices for UTI adhered more closely to European guidelines than national guidelines. Although not recommended in international and European guidelines for lower UTI management, the use of fluoroquinolones was still widespread., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: The internet has resulted in huge efficiency gains in health care, the ability to deal with massive data accumulation and better manage patient data. However, potential and real pitfalls exist, including breeches in security of data and patient confidentiality, data storage issues, errors, and user interface issues., Methods: A MEDLINE review was performed using MeSH terms "health care" and "information technology." Cross-referencing was used to explore the different opportunities and challenges the internet has to offer., Results: As health professionals, we are fast adopting technologies at our fingertips, such as WhatsApp and video capabilities, into our clinical practice to increase productivity and improve patient care. However, the potential security breaches are significant for the health professional and health service. Further, electronic medical records have theoretical advantages to improve patient care, reduce medication errors, and expedite referrals. The downside is a less personalized approach to patient care, as well as the potential for these systems to be even more cumbersome. In regard to the acquisition of knowledge, there is no doubt the internet is our friend. Health care professionals as well as patients have unlimited resources for learning, including podcasts videos, apps, simulators, and wearable devices. Unfortunately, this comes with a risk of misinformation and poorly referenced data with little to no regulation of content., Conclusion: In this increasing digital world, it is our task as health care providers to embrace these new technologies but develop guidelines and control systems to minimize the pitfalls.

Purpose: We sought to expand current prediction tools for lymph node invasion in patients with prostate cancer using current state-of-the-art available tumor information, including multiparametric magnetic resonance imaging based tumor stage and detailed biopsy information., Materials and Methods: We selected patients with prostate cancer for study who had available registered information on ISUP (International Society of Urological Pathology) based biopsy grading and multiparametric magnetic resonance imaging, and who had undergone radical prostatectomy with extended pelvic lymph node dissection. We developed a lymph node invasion prediction tool in 420 patients and externally validated it in 187. A concordance index was estimated to quantify the discriminative performance of the model., Results: In the development cohort a median of 21 lymph nodes were removed per patient and 71 patients (16.9%) were diagnosed with lymph node invasion. Statistically significant predictors of lymph node invasion were the initial prostate specific antigen value, multiparametric magnetic resonance imaging based T stage, maximum tumor length in 1 core in mm and ISUP grade group corresponding to the maximum tumor involvement in 1 core. The predictive accuracy of this lymph node invasion prediction tool was 79.7% after fivefold internal cross validation and 72.5% after external validation., Conclusions: We report a contemporary, externally validated prediction tool for lymph node invasion in patients with prostate cancer. This prediction tool is a response to the paradigm shift from systematic to targeted biopsies by incorporating additional core specific biopsy information instead of the percent of positive cores. This new tool will also overcome stage migration, which is a potential risk when multiparametric magnetic resonance imaging information is used in digital rectal examination based nomograms.

Purpose: To develop a prospective non-muscle-invasive bladder cancer (NMIBC) data registry by generating NMIBC-specific electronic case report forms (eCRFs) in our institution's electronic patient file system, and to report on the development and implementation of a prospective multicentric registry. Methods: Templates for data collection, including clinical outcome parameters and quality indicators, were developed in InfoPath™ as an eCRF and were incorporated in our hospital's electronic patient file system. Quality parameters for managing NMIBC patients that were identified by comprehensive literature review were included in the eCRFs. Three separate eCRFs were developed for the management of NMIBC patients: surgery report, bladder instillation form, and multidisciplinary team form. Results: In August 2013, we started a Flemish prospective clinical and pathological data registry for all patients undergoing transurethral resection of bladder tumor (TURBT) for NMIBC in four participating hospitals, three of which continued using this to date. Three more hospitals started enrolling in 2017, 2018, and 2019, respectively. Written reports of the registered clinical actions are automatically generated within the electronic medical file. When urologists complete these eCRFs, an automated ready-to-send letter to the general practitioner is generated. Up till May 2019, 2,756 TURBTs in 2,419 patients are included in the dataset. Currently, we are recruiting over 600 TURBTs every year. Conclusions: Easy-to-use eCRFs were developed and included in the electronic patient file system. This registration tool was implemented in 7 hospitals, 6 of which are still using it today. The register harvests important clinical data, while performing routine clinical practice. The data will be used to analyze real-life data of NMIBC patients, to challenge the existing guidelines, to create novel risk stratification tools, and to develop, monitor and validate quality parameters for NMIBC management., (Copyright © 2019 Akand, Muilwijk, Cornelissen, Van Bruwaene, Vander Eeckt, Baekelandt, Mattelaer, Van Reusel, Van Cleynenbreugel, Joniau and Van Der Aa.)

Purpose: Surgical innovation is necessary to ensure continued improvement in patient care. However, several challenges unique to the surgical craft are encountered during the development and validation of such new technology. This article highlights some of these challenges and gives an overview of existing solutions., Methods: A Pubmed review was performed about the "introduction of new technology" to identify challenges. Cross-referencing was used to explore the possible solutions per challenge., Results: Several characteristics of the surgical craft itself limit our ability to establish randomised controlled trials and hence provide clear categorical evidence. Existing certification bodies for new technology often use unstructured regulations and allow fast-track bypassing systems. Consequently the IDEAL framework (innovation, development, exploration, assessment, long-term follow-up) proposes an objective scientific approach whilst defining stakeholder responsibilities. The selection of which new modality to implement is heavily influenced by third parties unrelated to the best patient outcomes and thus professional organisations can aid in this decision-making. Appropriate training of surgeons and their teams until proficiency is achieved is essential prior to credentialling. Finally long-term surveillance of outcomes in the form of registries is an increasing responsibility of the urological community to maintain our role in directing the adoption or rejection of these innovations., Conclusion: Urological innovation is a dynamic and challenging process. Increasing efforts are identified within the urological community to render the process more reliable and transparent.

Background: In Belgium, bladder cancer (BC) is the fifth most common cancer in men. The per-patient lifetime cost is high. Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of BC. We therefore hypothesised that selenium may be suitable for chemoprevention of recurrence of BC., Method: The Selenium and Bladder Cancer Trial (SELEBLAT) was an academic phase III placebo-controlled, double-blind, randomised clinical trial designed to determine the effect of selenium on recurrence of non-invasive urothelial carcinoma conducted in 14 Belgian hospitals. Patients were randomly assigned by a computer program to oral selenium yeast 200 μg once a day or placebo for three years, in addition to standard care. All study personnel and participants were blinded to treatment assignment for the duration of the study. All randomised patients were included in the intention to treat (ITT) and safety analyses. Per protocol analyses (PPAs) included all patients in the study three months after start date., Results: Between September 18, 2009 and April 18, 2013, 151 and 141 patients were randomised in the selenium and placebo group. Patients were followed until December 31, 2015. The ITT analysis resulted in 43 (28%; 95% CI, 0.21-0.35) and 45 (32%; 95% CI, 0.24-0.40) recurrences in the selenium and placebo group. The hazard ratio (HR) was 0.85 (95% CI, 0.56-1.29; p = 0.44) while the HR for the PPA resulted in 42 and 39 (28%; 95% CI, 0.20-0.35) recurrences in the selenium and placebo group (HR = 0.96 [95% CI, 0.62-1.48]; p = 0.93)., Conclusion: Selenium supplementation does not lower the probability of recurrence in BC patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Surgical simulation is becoming increasingly important in surgical education. However, the method of simulation to be incorporated into a surgical curriculum is unclear. We compared the effectiveness of a proficiency-based preclinical simulation training in laparoscopy with conventional surgical training and conventional surgical training interspersed with standard simulation sessions., Materials and Methods: In this prospective single-blinded trial, 30 final-year medical students were randomized into three groups, which differed in the way they were exposed to laparoscopic simulation training. The control group received only clinical training during residency, whereas the interval group received clinical training in combination with simulation training. The Center for Surgical Technologies Preclinical Training Program (CST PTP) group received a proficiency-based preclinical simulation course during the final year of medical school but was not exposed to any extra simulation training during surgical residency. After 6 months of surgical residency, the influence on the learning curve while performing five consecutive human laparoscopic cholecystectomies was evaluated with motion tracking, time, Global Operative Assessment of Laparoscopic Skills, and number of adverse events (perforation of gall bladder, bleeding, and damage to liver tissue)., Results: The odds of adverse events were 4.5 (95% confidence interval 1.3-15.3) and 3.9 (95% confidence interval 1.5-9.7) times lower for the CST PTP group compared with the control and interval groups. For raw time, corrected time, movements, path length, and Global Operative Assessment of Laparoscopic Skills, the CST PTP trainees nearly always started at a better level and were never outperformed by the other trainees., Conclusion: Proficiency-based preclinical training has a positive impact on the learning curve of a laparoscopic cholecystectomy and diminishes adverse events.

Introduction: Lymph node (LN) positive bladder cancer is a serious disease associated with a poor prognosis. Nevertheless even after radical cystectomy and lymph node dissection alone long-term oncologic control has been reported in a subset of these patients. Efforts have been made to stratify LN-positive patients according to various prognostic factors to make more individualized risk estimations. This review attempts to summarize the existing data on prognostic determinants in node-positive bladder cancer., Evidence Acquisition: A literature search of the English literature was performed in October 2015 on PubMed using the search terms "bladder cancer", "node-positive" and "prognosis/outcome". Papers were only selected when separate information on the node-positive subpopulation was available. Data from prospective studies, meta-analysis or multi-institutional were selected primarily., Evidence Synthesis: Current 2010 TNM classification of nodal disease seems to have limited prognostic value. Several other nodal parameters such as number of positive nodes, number of resected nodes, LN density and extracapsular extension have been extensively evaluated and show potential in distinguishing prognostic subgroups. Although node-positive bladder cancer is often seen as systemic disease local tumor characteristics such as T stage and histological variants seem to remain important. Molecular markers are promising in stratifying patients with bladder cancer but need further validation in a specific node-positive subgroup. Neo-adjuvant chemotherapy seems to improve the prognosis of clinical node-positive patients and evaluation of response could help in selecting patients who benefit from consolidating surgery. Although retrospective studies convincingly suggest improved clinical outcome with adjuvant chemotherapy for pathological node-positive patients, these findings are not consistently confirmed in recent prospective studies., Conclusions: Future research should aim at the incorporation of prognostic variables into clinically applicable nomograms and identification of the subgroup of patients who will benefit from adjuvant treatments.

Purpose: A Robotic Prostatectomy Care Pathway ("Robocare"), aiming to prepare men for robotic-assisted radical prostatectomy (RARP) and manage side-effects and long-term follow-up in a multidisciplinary fashion was established. The pathway enhances patient care by providing adequate information and support and optimizes efficiency by reducing length of stay and minimizing hospital visits. Our study assesses the pathway for patient satisfaction, co-ordination of care between disciplines, length of stay and readmission rates., Method: We analysed our database of all patients undergoing RARP with Robocare between July 2012 and December 2013 at Peter MacCallum Cancer Centre, Australia (PMCC). Compliance, Length of Stay and Postoperative Course were analysed. Patient satisfaction was assessed., Results: Overall 124 patients underwent RARP with 105 (85%) being discharged day 1 post-op (mean 1.3 days). Post-operative support phone calls were received by >95% of patients. Thereafter, 74 patients (60%) were followed in the long-term follow-up phone clinic. Twenty-nine complications were identified of which 19 (66%) were resolved by the nurse specialist. Eighteen patients had psychologist, 44 sexual health and 44 physiotherapist referral. Patient satisfaction in 74 (60%) returned surveys revealed 71 (96%) being well/very well supported., Conclusions: The Robocare pathway is safe with high patient satisfaction. It contributes to reducing post-operative length of stay and readmission rates as well as the outpatient follow-up. A true multidisciplinary approach that is nurse-led likely improves care and outcomes for RARP patients and may lower impact on hospital resources., (Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.)