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Gunter De Win,1,2 Siska Van Bruwaene,3,4 Jyotsna Kulkarni,5 Ben Van Calster,6 Rajesh Aggarwal,7,8 Christopher Allen,9 Ann Lissens,4 Dirk De Ridder,3 Marc Miserez4,10 1Department of Urology, Antwerp University Hospital, 2Faculty of Health Sciences, University of Antwerp, Antwerp, 3Department of Urology, University Hospitals of KU Leuven, 4Centre for Surgical Technologies, KU Leuven, Leuven, Belgium; 5Kulkarni Endo Surgery Institute, Pune, India; 6Department of Development and Regeneration, KU Leuven, Leuven, Belgium; 7Department of Surgery, Faculty of Medicine, 8Steinberg Centre for Simulation and Interactive Learning, Faculty of Medicine, McGill University, Montreal, QC, Canada; 9School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA; 10Department of Abdominal Surgery, University Hospitals Leuven, Leuven, Belgium 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. Keywords: laparoscopy, simulation, learning curve, transfer of skills

Gunter De Win,1,2 Siska Van Bruwaene,1 Christopher Allen,3 Dirk De Ridder2 1Centre for Surgical Technologies, 2Department of Urology, University Hospitals, KU Leuven, Leuven, Belgium; 3School of Arts and Sciences, University of Pennsylvania, PA, USA Background: Surgical simulation is becoming increasingly important in surgical education. Despite the important work done on simulators, simulator model development, and simulator assessment methodologies, there is a need for development of integrated simulators in the curriculum. In this paper, we describe the design of our evidence-based preclinical training program for medical students applying for a surgical career at the Centre for Surgical Technologies. Methods: Twenty-two students participated in this training program. During their final months as medical students, they received structured, proficiency-based endoscopy training. The total amount of mentored training was 18 hours and the training was organized into three training blocks. The first block focused on psychomotor training, the second block focused on laparoscopic stitching and suturing, and the third block on laparoscopic dissection techniques and hemostasis. Deliberate practice was allowed and students had to show proficiency before proceeding to the next training block. Students’ psychomotor abilities were tested before the course and after each training block. At the beginning of their careers as surgical registrars, their performance on a laparoscopic suturing task was compared with that of registrars from the previous year who did not have this training course. Student opinions about this course were evaluated using a visual analog scale. Results: All students rated the training course as useful and their psychomotor abilities improved markedly. All students performed deliberate practice, and those who participated in this course scored significantly (P < 0.0001) better on the laparoscopic suturing task than first year registrars who did not participate in this course. Conclusion: Organization of a structured preclinical training program in laparoscopy for final year medical students is feasible, attractive, and successful. Keywords: laparoscopy training, proficiency based, surgical skill evaluation, curriculum development

Abstract Background In Belgium, bladder cancer is the fifth most common cancer in males (5.2%) and the sixth most frequent cause of death from cancer in males (3.8%). Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. This suggests that selenium may also be suitable for chemoprevention of recurrence. Method The SELEBLAT study opened in September 2009 and is still recruiting all patients with non-invasive transitional cell carcinoma of the bladder on TURB operation in 15 Belgian hospitals. Recruitment progress can be monitored live at http://www.seleblat.org. Patients are randomly assigned to selenium yeast (200 μg/day) supplementation for 3 years or matching placebo, in addition to standard care. The objective is to determine the effect of selenium on the recurrence of bladder cancer. Randomization is stratified by treatment centre. A computerized algorithm randomly assigns the patients to a treatment arm. All study personnel and participants are blinded to treatment assignment for the duration of the study. Design The SELEnium and BLAdder cancer Trial (SELEBLAT) is a phase III randomized, placebo-controlled, academic, double-blind superior trial. Discussion This is the first report on a selenium randomized trial in bladder cancer patients. Trial registration ClinicalTrials.gov identifier: NCT00729287

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.)