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Objectives: To compare Uromonitor® (U-Monitor Lda, Porto, Portugal), a multitarget DNA assay that detects mutated proto-oncogenes (telomerase reverse transcriptase [TERT], fibroblast growth factor receptor 3 [FGFR-3], Kirsten rat sarcoma viral oncogene homologue [KRAS]), with urine cytology in the urine-based diagnosis of urothelial carcinoma of the bladder (UCB) within a multicentre real-world setting., Patients and Methods: This multicentre, prospective, double-blind study was conducted across four German urological centres from 2019 to 2024. We evaluated the diagnostic performance of Uromonitor compared to urine cytology in a cohort of patients with UCB and in healthy controls within a real-world setting. Sensitivity, specificity, positive-predictive value (PPV), negative-predictive value (NPV), and accuracy of the tests were measured, in addition to multivariate analyses to assess the ability of individual proto-oncogene mutations in detecting UCB. The biometric sample size was designed to achieve a 10% difference in sensitivity., Results: Patients with UCB comprised 63.7% (339/532) of the study group. Uromonitor showed a sensitivity, specificity, PPV, NPV, accuracy, and an area-under-the-curve of 49.3%, 93.3%, 92.8%, 51.1%, 65.2%, and 0.713%, respectively. These metrics did not demonstrate statistical superiority over urine cytology in terms of sensitivity (44.6%; P = 0.316). Moreover, the comparison of additional test parameters, as well as the comparison within various sensitivity analyses, yielded no significant disparity between the two urinary tests. Multivariate logistic regression underscored the significant predictive value of a positive Uromonitor for detecting UCB (odds ratio [OR] 9.03; P < 0.001). Furthermore, mutations in TERT and FGFR-3 were independently associated with high odds of UCB detection (OR 13.30 and 7.04, respectively), while KRAS mutations did not exhibit predictive capability., Conclusion: Despite its innovative approach, Uromonitor fell short of confirming the superior results anticipated from previous studies in this real-world setting. The search for an optimal urine-based biomarker for detecting and monitoring UCB remains ongoing. Results from this study highlight the complexity of developing non-invasive diagnostic tools and emphasise the importance of continued research efforts to refine these technologies., (© 2024 BJU International.)

The advent of micro-physiological systems (MPS) in biomedical research has enabled the introduction of more complex and relevant physiological into in vitro models. The recreation of complex morphological features in three-dimensional environments can recapitulate otherwise absent dynamic interactions in conventional models. In this study we developed an advanced in vitro Renal Cell Carcinoma (RCC) that mimics the interplay between healthy and malignant renal tissue. Based on the TissUse Humimic platform our model combines healthy renal proximal tubule epithelial cells (RPTEC) and RCC. Co-culturing reconstructed RPTEC tubules with RCC spheroids in a closed micro-perfused circuit resulted in significant phenotypical changes to the tubules. Expression of immune factors revealed that interleukin-8 (IL-8) and tumor necrosis factor-alfa (TNF-α) were upregulated in the non-malignant cells while neutrophil gelatinase-associated lipocalin (NGAL) was downregulated in both RCC and RPTEC. Metabolic analysis showed that RCC prompted a shift in the energy production of RPTEC tubules, inducing glycolysis, in a metabolic adaptation that likely supports RCC growth and immunogenicity. In contrast, RCC maintained stable metabolic activity, emphasizing their resilience to external factors. RNA-seq and biological process analysis of primary RTPTEC tubules demonstrated that the 3D tubular architecture and MPS conditions reverted cells to a predominant oxidative phosphorylate state, a departure from the glycolytic metabolism observed in 2D culture. This dynamic RCC co-culture model, approximates the physiology of healthy renal tubules to that of RCC, providing new insights into tumor-host interactions. Our approach can show that an RCC-MPS can expand the complexity and scope of pathophysiology and biomarker studies in kidney cancer research., (© 2024. The Author(s).)

Optimal urine-based diagnostic tests (UBDT) minimize unnecessary follow-up cystoscopies in patients with non-muscle-invasive bladder-cancer (NMIBC), while accurately detecting high-grade bladder-cancer without false-negative results. Such UBDTs have not been comprehensively described upon a broad, validated dataset, resulting in cautious guideline recommendations. Uromonitor ® , a urine-based DNA-assay detecting hotspot alterations in TERT, FGFR3, and KRAS, shows promising initial results. However, a systematic review merging all available data is lacking. Studies investigating the diagnostic performance of Uromonitor ® in NMIBC until November 2023 were identified in PubMed, Embase, Web-of-Science, Cochrane, Scopus, and medRxiv databases. Within aggregated analyses, test performance and area under the curve/AUC were calculated. This project fully implemented the PRISMA statement. Four qualifying studies comprised a total of 1190 urinary tests (bladder-cancer prevalence: 14.9%). Based on comprehensive analyses, sensitivity, specificity, positive-predictive value/PPV, negative-predictive value/NPV, and test accuracy of Uromonitor ® were 80.2%, 96.9%, 82.1%, 96.6%, and 94.5%, respectively, with an AUC of 0.886 (95%-CI: 0.851-0.921). In a meta-analysis of two studies comparing test performance with urinary cytology, Uromonitor ® significantly outperformed urinary cytology in sensitivity, PPV, and test accuracy, while no significant differences were observed for specificity and NPV. This systematic review supports the use of Uromonitor ® considering its favorable diagnostic performance. In a cohort of 1000 patients with a bladder-cancer prevalence of ~15%, this UBDT would avert 825 unnecessary cystoscopies (true-negatives) while missing 30 bladder-cancer cases (false-negatives). Due to currently limited aggregated data from only four studies with heterogeneous quality, confirmatory studies are needed.

Background: Research on penile cancer (PeCa) is predominantly conducted in countries with centralized treatment of PeCa-patients. In Germany and Austria (G + A), no state-regulated centralization is established, and no information is available on how PeCa-research is organized., Methods: Current research competence in PeCa was assessed by a 36-item questionnaire sent to all chairholders of urological academic centers in G + A. Based on PubMed records, all scientific PeCa-articles of 2012-2022 from G + A were identified. Current research trends were assessed by dividing the literature search into two periods (P1: 2012-2017, P2: 2018-2022). A bibliometric analysis was supplemented., Results: Response rate of the questionnaire was 75%, a median of 13 (IQR: 9-26) PeCa-patients/center was observed in 2021. Retrospective case series were conducted by 38.9% of participating clinics, while involvement in randomized-controlled trials was stated in 8.3% and in basic/fundamental research in 19.4%. 77.8% declared an interest in future multicenter projects. 205 PeCa-articles were identified [median impact factor: 2.77 (IQR: 0.90-4.37)]. Compared to P1, P2 showed a significant increase in the median annual publication count (29 (IQR: 13-17) vs. 15 (IQR: 19-29), p < 0.001), in multicenter studies (79.1% vs. 63.6%, p = 0.018), and in multinational studies (53% vs. 28.9%, p < 0.001); the proportion of basic/fundamental research articles significantly declined (16.5% vs. 28.9%, p = 0.041). Four of the top-5 institutions publishing PeCa-articles are academic centers. Bibliometric analyses revealed author networks, primary research areas in PeCa, and dominant journals for publications., Conclusions: Given the lack of centralization in G + A, this analysis highlights the need for research coordination within multicenter PeCa-projects. The decline in basic/fundamental research should be effectively addressed by the allocation of funded research projects., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Context: Symptomatic lymphocele (sLC) occurs at a frequency of 2-10% after robot-assisted radical prostatectomy (RARP) with pelvic lymph node dissection (PLND). Construction of bilateral peritoneal interposition flaps (PIFs) subsequent to completion of RARP + PLND has been introduced to reduce the risk of lymphocele, and was initially evaluated on the basis of retrospective studies., Objective: To conduct a systematic review and meta-analysis of only randomized controlled trials (RCTs) evaluating the impact of PIF on the rate of sLC (primary endpoint) and of overall lymphocele (oLC) and Clavien-Dindo grade ≥3 complications (secondary endpoints) to provide the best available evidence., Evidence Acquisition: In accordance with the Preferred Reporting Items for Meta-Analyses statement for observational studies in epidemiology, a systematic literature search using the MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE databases up to February 3, 2023 was performed to identify RCTs. The risk of bias (RoB) was assessed using the revised Cochrane RoB tool for randomized trials. Meta-analysis used random-effect models to examine the impact of PIF on the primary and secondary endpoints., Evidence Synthesis: Four RCTs comparing outcomes for patients undergoing RARP + PLND with or without PIF were identified: PIANOFORTE, PerFix, ProLy, and PLUS. PIF was associated with odds ratios of 0.46 (95% confidence interval [CI] 0.23-0.93) for sLC, 0.51 (95% CI 0.38-0.68) for oLC, and 0.41 (95% CI 0.21-0.83) for Clavien-Dindo grade ≥3 complications. Functional impairment resulting from PIF construction was not observed. Heterogeneity was low to moderate, and RoB was low., Conclusions: PIF should be performed in patients undergoing RARP and simultaneous PLND to prevent or reduce postoperative sLC., Patient Summary: A significant proportion of patients undergoing prostate cancer surgery have regional lymph nodes removed. This part of the surgery is associated with a risk of postoperative lymph collections (lymphocele). The risk of lymphocele can be halved via a complication-free surgical modification called a peritoneal interposition flap., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)