Introduction: The entrance of Generation Z into professional life, including the practice of medicine, marks a transformational shift in priorities and values. This also applies for urology. Consequently, we conducted a pilot survey among European leaders in urology to conduct first insights on generational change and its implications for clinical practice, education and healthcare systems. Methods: Between August and October 2025, a survey containing seven open-ended questions was sent out to 11 European leaders in urology. The results are presented in an only descriptive manner. Results: Answers from all experts were received. We summarized the results in four take home messages: 1. Generation Z is capable and expects modern training environments. 2. Structural and legal frameworks drive most observed changes. 3. Reduced clinical presence affects surgical exposure and continuity of care. 4. Traditional apprenticeship models no longer fit current conditions. National and European urological societies, training committees and educational bodies were repeatedly referenced as key platforms for coordinating and implementing such adaptations. Conclusion: We provide first key factors as hypothesis for further discussion and evaluation of educational programs in urology in the future and therefore, improving patient care.

Gesundheit und ökologische Nachhaltigkeit hängen eng miteinander zusammen: Einerseits wird die (urologische) Gesundheit durch die Klimakrise gefährdet, andererseits erzeugt die Gesundheitsversorgung erhebliche Emissionen. Bisher fehlen konkrete Zahlen zum aktuellen Status, möglichen Potentialen und Barrieren aber auch Erwartungen hinsichtlich Nachhaltigkeit unter deutschen Urologinnen und Urologen. Um dies zu ermitteln, wurde eine Umfrage unter Mitgliedern der Deutschen Gesellschaft für Urologie e. V. (DGU) durchgeführt. Die 339 Studienteilnehmerinnen und -teilnehmer sehen Nachhaltigkeit als relevant an, beobachten jedoch keine praktische Umsetzung in der täglichen Arbeit. Nachhaltige Urologie wird mit Ressourceneffizienz, Kostenreduktion und einem Beitrag zu gesellschaftlicher Verantwortung assoziiert. In der Realität jedoch mangelt es an Priorisierung, Klarheit und personellen sowie finanziellen Ressourcen. Die DGU-Mitglieder, die an der Umfrage teilgenommen haben, wünschen sich Unterstützung vonseiten der Fachgesellschaft, Industrie, Politik und Forschung zur Fortbildung, Strategieentwicklung, Implementierung und Finanzierung von Nachhaltigkeit in der Urologie.

Abstract Prostate cancer (PCa), the second most common cancer, is still a major cause of morbidity and mortality among men worldwide. A particularly aggressive group of PCa, where prognostic biomarkers are still needed, are clinically defined high-risk PCa. We had previously shown that the survival and proliferation factor progranulin (GP88) is a prognostic marker for primary PCa. We aimed in this study to characterize GP88 protein expression in high-risk PCa by immunohistochemistry and to examine its association with prognosis. Immunohistochemical staining for GP88 was performed with TMA of samples from 94 high-risk PCa patients using an H-score. GP88 staining was in a range of 3.69 to 252.51 (median: 109.28). The association of GP88 staining with prognosis was examined by survival analyses (Kaplan–Meier, multivariate Cox’s regression analysis). Elevated GP88 expression was associated with a shorter clinical progression-free survival (CPFS) in all PCa patients (P = 0.043), and in the following patient subgroups: Elder PCa patients (> 67 years; P = 0.020), patients with pT3 tumors (P = 0.008), with Gleason scores GS5 and GS6 (P = 0.033 and P = 0.030), and patients without radiation therapy (P = 0.009) at considering that only four patients received an adjuvant radiation therapy. In a multivariate Cox’s regression analysis, increased GP88 protein expression (RR = 2.98; P = 0.049) and the preoperative PSA level (RR = 5.29; P = 0.030) appeared as independent prognostic factors for clinical progression. Interestingly, lower GP88 staining in corresponding low Gleason lesions was correlated with the presence of immune cells, suggesting an immune cell suppressive effect of GP88. Altogether, Progranulin (GP88) protein positivity appears very likely to be an independent prognostic factor for clinical progression in high-risk PCa patients.

Initiation and sustainment of oncogenic signaling is a hallmark of cancer evolution and progression. In renal clear cell carcinoma, loss of von Hippel-Lindau protein causes stabilization of hypoxia-inducible transcription factors (HIF) evoking a pseudo-hypoxic response, perturbing epithelial homeostasis and leading to cancer development. Although genetic polymorphisms link the EPAS1 oncogene (coding for HIF-2α) to renal cancer and anti-HIF-2 compounds emerge as renal tumor therapies, little is known about transcriptional dysregulation of this factor in renal malignancies. We use genetic, epigenetic and transcriptomic data from large patient cohorts and cell models to dissect mechanisms of augmented EPAS1 transcription in clear cell renal cell carcinoma. We define an oncogenic enhancer of EPAS1 which operates depending on the presence of HIF and renal lineage-specific factors, thereby providing evidence for an auto-regulatory feed-forward circuit of HIF-2α regulation which promotes renal cancer growth.

BACKGROUND AND OBJECTIVE:The Food and Drug Administration and the European Medicine Agency approved erdafitinib for patients with FGFR3-altered metastatic urothelial carcinoma (mUC), highlighting the central role of tumor molecular profiling for patients with mUC. Although different studies described the molecular landscape of muscle-invasive bladder cancer (MIBC) using publicly-available data, a dedicated evaluation of real-world actionable alterations, with evidence-based therapeutic recommendations according to current Molecular Tumor Board (MTB) guidelines, is still lacking. DESIGN, SETTING, AND PARTICIPANTS:We characterized actionable genetic alterations in a retrospective cohort of 233 patients with MIBC/mUC (Muscle-Invasive Erlangen [MIER] cohort) using targeted sequencing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Clinically relevant variants were assessed through a custom bioinformatics workflow and expert medical review. To validate their clinical relevance in a real-world setting, we examined actionable alterations and associated therapy recommendations in a cohort of 40 patients with MIBC/mUC undergoing routine diagnostics (MTB cohort). RESULTS AND LIMITATIONS:In the MIER cohort, 95% of patients (n = 226/233; 95% confidence interval [CI], 94-99) harbored at least one pathogenic/likely pathogenic variant. Therapeutically relevant FGFR3 alterations were identified in 11% of patients (n = 26/233; 95% CI, 7.4-16). Additionally, 40% of patients (95% CI, 34-47) showed alterations in 24 biomarkers for FDA-approved therapies. In the MTB cohort, 55% of patients received either on-label (5.0%) or off-label (50%) therapy recommendations. Notably, the recommendation was implemented in only one patient, who achieved stable disease for 4 mo with off-label alpelisib. Retrospectively, similar on-label and off-label indications could have applied to 10% and 70% of patients in the MIER cohort, respectively. CONCLUSIONS:Overall, evidence-based indications for on-label and off-label therapies were observed for the majority of patients with MIBC/mUC. However, our results also revealed a significant gap between the high prevalence of actionable findings and the actual implementation of MTB-guided treatments in clinical practice, suggesting a need for enhanced therapy access and physician adherence to MTB recommendations.

Penile squamous cell carcinoma (PSCC) is rare, but a biologically aggressive malignancy. Recent comprehensive genomic profiling (CPG) efforts revealed the underlying genomic landscape of PSCC, identifying TP53, TERT, CDKN2A, PIK3CA, NOTCH1, and FAT1 as frequently altered genes with potential roles in penile oncogenesis. In addition, recurrent mutations encoded in the GPS1 gene have been observed in 7.4% of cases in a particular PSCC cohort. Functional studies demonstrated loss of function due to GPS1 Exon 9 missense mutations, proposing a possible role for these alterations as oncogenic driver events in PSCC. However, no other study confirmed the occurrence of GPS1 gene mutations in PSCC. To elucidate the biological function of GPS1 exon 9 mutations in PSCC pathogenesis, we utilized a comprehensive in-house cohort of 106 PSCC cases to explore their frequency and occurrence. Albeit, the previously reported GPS1 mutations p.D382H and p.M384I were not observed in this large cohort of PSCC cases; this analysis, however, revealed two novel GPS1 alterations in exon 9 in two (1.9%) of the analyzed cases: p.S372F (c.1115C>T) and p.A375D (c.1124C>A). This observation suggests that GPS1 exon 9 sequence is a target of genetic alteration during PSCC pathogenesis. However, the non-recurrent nature of these alterations indicates that they are unlikely to represent oncogenic drivers in this disease.

Healthcare is closely linked to climate change: on the one hand, climate change has negative effects on (urological) health; on the other hand, resource intensive patient care has negative effects on global warming. Currently, there is a lack of data on current status, potential benefits, barriers, and expectations regarding environmental sustainability among urologists practicing in Germany. Thus, a survey was conducted among members of the German Society of Urology (Deutsche Gesellschaft für Urologie e. V., DGU). The 339 participants consider sustainability to be relevant. While sustainable urology is associated with more efficient use of resources, cost reductions, and a stronger contribution to societal responsibility, the main barriers identified are low prioritization in daily practice, lack of clarity regarding ecological effects of individual measures, and insufficient personnel and financial resources. Members of the DGU who took part in the survey consider sustainability to be an important area of action that has seen little practical implementation to date. They call for support from professional associations, industry, politics, and research in terms of education, strategies, prioritization, and financing for sustainable action in urology.

The prognostic value of histopathological grade in muscle-invasive urothelial carcinoma (MIBC) to predict disease-specific survival (DSS) is understudied. While grading systems like WHO1973 and WHO2004 are established in non-muscle-invasive bladder cancer (NMIBC), their relevance in MIBC remains controversial. This study assessed the prognostic impact of histopathological grade on DSS in a multicenter cohort. We included 1,123 cN0M0 MIBC patients treated with upfront radical cystectomy (1987–2020) at nine centers. Tumors were graded using WHO1973 (G1 + G2 combined as G1/2 due to low numbers vs. G3), WHO2004 (low-grade [LG] vs. high-grade [HG]), and a hybrid three-tier system. Slides were locally reviewed by uro-pathologists. DSS was analyzed using Kaplan-Meier and Cox models, adjusting for age, stage, lympho-vascular invasion, surgical margins, lymph-node status, adjuvant chemotherapy, treatment center, and era of cystectomy. Among all cases, 74 (6.6

This study aimed to develop and evaluate a non-invasive XGBoost-based machine learning model using radiomic features extracted from pre-treatment CT images to differentiate grade 4 renal cell carcinoma (RCC) from lower-grade tumours. A total of 102 RCC patients who underwent contrast-enhanced CT scans were included in the analysis. Radiomic features were extracted, and a two-step feature selection methodology was applied to identify the most relevant features for classification. The XGBoost model demonstrated high performance in both training (AUC = 0.87) and testing (AUC = 0.92) sets, with no significant difference between the two (p = 0.521). The model also exhibited high sensitivity, specificity, positive predictive value, and negative predictive value. The selected radiomic features captured both the distribution of intensity values and spatial relationships, which may provide valuable insights for personalized treatment decision-making. Our findings suggest that the XGBoost model has the potential to be integrated into clinical workflows to facilitate personalized adjuvant immunotherapy decision-making, ultimately improving patient outcomes. Further research is needed to validate the model in larger, multicentre cohorts and explore the potential of combining radiomic features with other clinical and molecular data.

Introduction Clean intermittent catheterization (CIC) has significant advantages over indwelling catheters. To facilitate CIC, a continent catheterizable channel (CCC) to the bladder is required in some cases. The Mitrofanoff appendicovesicostomy (APV) is considered the gold standard for pediatric CCC creation. However, when the appendix is unavailable or unsuitable for the creation of a CCC alternatives are required. Objective This study aims to share our single-center experience with using a spare ureter as a CCC in pediatric patients and compare its advantages and complications to those of APV and the use of bowel segments. Study Design A retrospective review of the medical records of all pediatric patients who underwent CCC creation between 2001 and 2023 was performed. The inclusion criteria were age younger than 18 years at surgery and the use of an appendix, ileal segment, or ureter for CCC creation. Results A total of 108 pediatric patients underwent CCC creation. Of these, 90 had an APV, 5 had an ileal segment CCC, and 13 had a ureteral CCC. Operating times were not significantly different among the groups. The median follow-up was 78 months for the ureter group, 66 months for the APV groups and 13 months for the ileal group. The stomal continence rates were 92% for the ureter group, 97% for the APV group, and 100% for the ileal group. Stomal complications occurred in 15.4% of ureter CCCs, 25.6% of APVs, and 40% of ileal CCCs. No significant differences in complication rates were observed among the groups. Discussion Our findings demonstrate that ureteral CCCs have acceptable complication rates and functional outcomes comparable to those of APVs and ileal CCCs. The limitations of this study include its retrospective design and small sample size, especially in the ureteral and ileal groups. Future prospective studies with larger cohorts are recommended to further validate these findings. Conclusion Our study indicates that the utilizazion of a spare ureter for CCC creation is a feasible and effective alternative in pediatric patients with a nonfunctioning kidney.

Alterations in Homologous Recombination Repair (HRR) Pathway genes have been found to be associated with HR‐Deficiency (HRD), which is an approved biomarker for PARP Inhibitor (PARPi) treatment. The aim of a Molecular Tumor Board (MTB) is to identify molecular alterations in cancer patients with advanced tumors that may suggest off‐label treatment options. So far, few studies have analyzed the presence of HRR gene mutations and their association with HRD outside of clinical studies. Currently, no data on HRD testing in the setting of a MTB have been published. For the present study, a cohort of 237 patients encompassing 24 different tumor entities was collected from the MTB of the Comprehensive Cancer Center Erlangen‐EMN. We show that an elevated Genomic Instability Score (GIS ≥42) can occur in samples with and without mutations in HRR‐related genes. Overall, 38.1% of cancer samples with BRCA1/2 mutations, 10.9% of tumors with alterations in HRR genes other than BRCA1/2 , and 4.3% of cancer samples without HRR gene mutations harbored an elevated GIS. Notably, our data show that various inactivating BRCA1/2 mutations are not associated with an elevated GIS. Taken together, panCancer assessment of HRD in addition to BRCA1/2 and other HRR gene mutational analysis is recommended to guide decisions regarding PARPi treatment. Further studies are needed to establish thresholds for GIS in non‐ovarian cancer entities. Finally, HRD can be observed in 4.3% of BRCA1/2 and other HRR gene wildtype cancer samples, and may emerge as an independent biomarker for PARPi in the future.

Occupational diseases and sequelae of accidents in the field of urology Urology and occupational medicine have a number of points of contact. A large table provides a compact overview for company doctors. In addition, reference is made to separate articles or a review in this issue, where applicable. Practice-relevant references are also cited.

Supplementary Figure 1. Expression of membranous NECTIN-4 in UC histology subtypes in PRIM (A) and MET (B). (C) depicts differential NECTIN-4 expression during metastatic spread. Intergroup comparison was calculated by non-parametric Kruskal-Wallis test.