This study aimed to externally validate the P-Score, a composite scoring system combining PI-RADS and PRIMARY score, for its diagnostic accuracy in detecting clinically significant (ISUP ≥ 2) and higher-grade (ISUP ≥ 3) prostate cancer (PCa). 230 biopsy-naïve men with suspected PCa were prospectively enrolled in the DEPROMP trial and underwent multiparametric MRI and [68Ga]Ga-DKFZ-PSMA-11 PET/CT. Lesions were assessed using PI-RADS v2.1, the PRIMARY score, and the derived P-Score. Targeted biopsies were guided by imaging findings, and histopathology served as the reference standard. Diagnostic performance was evaluated using receiver operating characteristic curve analyses and DeLong’s test to compare the area under the curve (AUC) between scoring systems. For clinically significant PCa (ISUP ≥ 2), no significant difference in diagnostic performance was observed between the P-Score (AUC 0.796) and PI-RADS (AUC 0.804; p = 0.72), whereas the P-Score significantly outperformed the PRIMARY score (AUC 0.730; p < 0.001). Similarly, for detection of ISUP ≥ 3 disease, no significant difference in diagnostic performance was observed between the P-Score (AUC 0.840) and PI-RADS (AUC 0.830; p = 0.66). In the PI-RADS 3 subgroup, diagnostic performance remained limited, with AUCs of 0.573 (95

Importance:Metastatic castration-resistant prostate cancer (mCRPC) is an incurable disease with a highly variable clinical course, necessitating robust prognostic tools to guide individualized patient management. Objective:To validate the prognostic ability of the Bellmunt Risk Score (BRS) for predicting survival in patients with mCRPC. Design, Setting, and Participants:For this prognostic study, a post hoc analysis was conducted of 2 international, multicenter, phase 3 randomized clinical trials of men (aged ≥18 years) with mCRPC (ACIS [first-line setting] and ELM-PC-5 [postdocetaxel setting]). The ACIS trial enrolled patients between December 2014 and August 2016. The ELM-PC-5 trial enrolled patients between October 2010 and February 2013. Data analyses were conducted between September 2024 and March 2025. Exposure:Baseline BRS (range, 0-3), calculated by assigning 1 point for each of 3 factors (Eastern Cooperative Oncology Group Performance Status score ≥1, hemoglobin level <10 g/dL, and liver metastases). Main Outcomes and Measures:The primary outcomes, overall survival (OS) and radiographic progression-free survival, were assessed via Kaplan-Meier and multivariable Cox proportional hazards regression analysis. Results:This analysis included 678 evaluable male participants from the ACIS trial (median age, 71 years [range, 48-92 years]) and 1078 from the ELM-PC-5 trial (median age, 70 years [range, 43-89 years]), for a total of 1756 participants. The median follow-up was 54.8 months (IQR, 51.5-58.4 months) in the ACIS trial and 10.7 months (IQR, 0.4-27.1 months) in the ELM-PC-5 trial. Having a higher BRS was consistently associated with unfavorable OS in both cohorts. In the ACIS trial, the median OS decreased from 42.2 months (95% CI, 35.7-46.7 months) for patients with a BRS of 0 to 9.1 months (95% CI, 3.7 months to not reached) for those with a BRS of 3. Adjusted hazard ratios (AHRs) for OS were 1.37 (95% CI, 1.12-1.67) for patients with a BRS of 1, 2.64 (95% CI, 1.89-3.69) for a BRS of 2, and 8.29 (95% CI, 2.57-26.78) for a BRS of 3 compared with those with a BRS of 0. In the ELM-PC-5 trial, the median OS decreased from 23.0 months (95% CI, 21.50 months to not reached) for patients with a BRS of 0 to 3.2 months (95% CI, 1.4-8.6 months) for those with a BRS of 3. AHRs for OS were 1.65 (95% CI, 1.31-2.07) for patients with a BRS of 1, 2.93 (95% CI, 2.22-3.87) for those with a BRS of 2, and 4.43 (95% CI, 2.65-7.40) for those with a BRS of 3 compared with those with a BRS of 0. The BRS remained a robust and independent prognostic factor for both outcomes in all multivariable models. Conclusions and Relevance:In this prognostic study of patients with mCRPC, the BRS was validated as a prognostic tool that provides clinically meaningful information across different treatment lines. Due to its simplicity, the BRS is a practical aid for guiding treatment decisions and facilitating prognostic discussions in routine clinical care.

BACKGROUND:Renal cyst formation, as observed in autosomal dominant polycystic kidney disease (ADPKD), is a life-threatening condition with no effective cure yet. The molecular mechanisms underlying primary cilia dysfunction, which causes cyst formation and disease development, are not well understood. Human kidney tubuloids offer a promising model system to investigate the disease mechanisms of PKD in physiologically relevant 3D structures. However, their inherent cystic morphology poses a challenge in effectively modelling kidney cystogenesis. Therefore, our study aims to refine the culture method of tubuloids and assess the efficacy of these modified cultures in modeling cyst formation and development. RESULTS:We developed human kidney tubuloid models derived from adult kidney tubular cells using different methods for 3D in-vitro cultures. Tubuloids cultured in suspension or an extracellular matrix scaffold manifested distinctly polarized epithelial structures. Bulk RNA sequencing and immunohistochemistry revealed differential transcriptional profiles, highlighting variations in cellular composition and cellular fate within the kidney epithelium between the two types of tubuloids. Notably, the experimental activation of chronic cAMP signalling promoted cyst formation in vitro, validating the suitability of these tubuloids for studying kidney cystogenesis. Furthermore, we demonstrate that tubuloids are amenable to genetic modification through recombinant adeno-associated virus transduction. CONCLUSIONS:Our study identifies different in-vitro tubuloid cultures as relevant model systems for examining the molecular and cellular changes involved in kidney cystogenesis in humans. These models will enhance our capability to discover novel pathogenetic mechanisms underlying ADPKD and validate candidate drugs for clinical application.

In a preceding monocentric study, serum liver enzymes (ALAT, ASAT, GGT) and lactate dehydrogenase (LDH) were identified as independent prognosticators for patients with metastatic renal cell cancer (mRCC) treated with immune-based first-line (1L) therapy. Here, we evaluated the prognostic potential of ALAT, ASAT, GGT and LDH in a larger multicentric real-world cohort. Baseline levels of ALAT, ASAT, GGT and LDH from 240 patients with mRCC undergoing immune-based 1L therapy were retrospectively investigated regarding progression-free survival (PFS), overall survival (OS) and response rates. Independent prognostic factors for PFS and OS were identified via multivariate Cox regression analyses. Although none of the serum parameters were markedly associated with therapy response, patients with low LDH showed a significantly longer PFS. Furthermore, patients with low GGT and LDH also exhibited a significantly prolonged OS. The combination of GGT and LDH risk groups enhanced the prognostic power. The concomitant elevation of both GGT and LDH was significantly associated with a higher progression rate and increased overall mortality and subsequently identified as independent prognosticator for PFS and OS. Overall, the prognostic potential of baseline GGT and LDH serum levels was substantiated in a larger multicentric cohort of patients with mRCC undergoing immune-based 1L therapy.

Objective: MicroRNAs (miRs) play a significant role in carcinogenesis and tumor progression, suggesting their potential as biomarkers. This study aimed to evaluate the diagnostic utility of four circulating miRs in patients with clear cell renal cell carcinoma (ccRCC). Methods: Serum expression levels of miR-193a-3p, miR-378-3p, miR-210-3p, and miR-362-3p were quantified in 30 patients with clear cell renal cell carcinoma (ccRCC) and 15 non-tumor controls using real-time polymerase chain reaction. Mann-Whitney U tests and Receiver Operating Characteristics with Area under the curve (AUC) calculations were employed to evaluate the association between miR expression levels and patient group (ccRCC versus controls). Results: Statistically significant differences in mean serum levels of miR-193a-3p and miR-378-3p were observed between ccRCC patients and controls. The median miR-193a-3p level was increased in ccRCC patients (median: 4.50 %, IQR: 1.38, 11.47) compared to controls (median: 2.57 %, IQR: 0.27, 3.87), p = 0.032; AUC for ccRCC detection was 0.70. Also, the median miR-378-3p level was higher in ccRCC patients (median: 2.01 %, IQR: 1.00, 3.33) compared to controls (median: 0.66 %, IQR: 0.44, 1.98), p = 0.049. AUC was 0.68. No significant differences were found for serum miR-362-3p and miR-210-3p expression in ccRCC patients and non-tumor controls (p = 0.547 for miR-362-3p and p = 0.791 for miR-210-3p). Conclusion: These findings suggest that miR-193a-3p and miR-378-3p may have limited potential as diagnostic biomarkers for ccRCC. The data do not support further investigation of miR-362-3p and miR-210-3p for this purpose.

Clear cell renal cell carcinoma (ccRCC) is characterized by marked histological heterogeneity, encompassing its vasculature. Here, we introduce PropSegNet, a learning-based algorithm that segments and classifies three distinct vascular patterns in CD31-stained tissue sections. Integrating transcriptomic features, our work identifies a trajectory from high- to low-branching vessel architecture that co-evolves with the loss of proximal tubular cell traits in tumor cells. Furthermore, low-branching vessels form niches enriched with T cells and antigen-presenting cells. Mechanistically, air-liquid-interface cultures of patient-derived tumor fragments confirm that low-branching vessel features associate with T cell infiltration resulting in reduced viability under IL-2 rich conditions. Post-hoc transcriptomic analyses from two phase III clinical trials demonstrate that patients with tumors exhibiting an inflamed, low-branching vascular phenotype benefit most from the addition of immune checkpoint inhibition to anti-angiogenic treatment. These findings provide a rationale for prospective evaluation of vascular patterns and vessel-immune cell niches as potential biomarkers in ccRCC. ### Competing Interest Statement VG: lectures: Bristol-Myers Squibb, Ipsen, Eisai, MSD, Merck KGa, AstraZeneca, AAA/Novartis, Amgen, Johnson & Johnson, Teilx Pharmaceuticals, Gilead Sciences, Roche; consultations: Bristol-Myers Squibb, Pfizer, Novartis, MSD, Ipsen, Johnson & Johnson, Eisai, Debiopharm, Gilead Sciences, Oncorena, Synthekine, Recordati Travel support: Pfizer, Johnson & Johnson, Merck KGa, Ipsen. NK: Personal fees, travel costs and speaker's honoraria from Astellas, Novartis, Ipsen, Photocure, MSD, Merck. Advisory role for Astellas, Eisai, Merck, MSD, Bicycle Therapeutics. Research funding from Bicycle Therapeutics. J.S. reports travel support by Janssen. M.H. reports travel expenses, honoraria for webinars and research support (consumables) from TME Pharma AG unrelated to this work. M.H. also reports honoraria and clinical advisory board membership from OncoMAGNETx Inc unrelated to this work. All other authors declare no competing interest. ### Funding Statement We would like to thank the NGS and Bioinformatics Core Facility of the Medical Faculty at the University of Bonn for providing support and instrumentation funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation). M.H. is a member of the CANTAR project, which receives funding from the Netzwerke 2021 program, an initiative of the Ministry of Culture and Science of the State of North Rhine-Westphalia. The sole responsibility for the content of this publication lies with the authors. A.E. and T.P. were funded by the Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy-EXC-2047/1-390685813 and EXC2151-390873048. M.H. was supported Deutsche Forschungsgemeinschaft under Germany's Excellence Strategy EXC2151-project ID 390873048. M.I.T and M.H. were supported by a joint grant by the Deutsche Forschungsgemeinschaft - project ID 497667643. M.I.T., A.E., M.H. are members of ImmunoSensation - the immune sensory system (EXC2151). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Patient samples (ccRCC ALI cohort): The Ethics Committee at the University Hospital Bonn, University of Bonn, Bonn Germany gave ethical approval for the work involving organoids as well as biomarker analyses using fresh-frozen or FFPE archived tissues (immunohistochemistry, transcriptome analyses, mutations) (EK417/17; EK 233/20; EK 285/21). Learning-based algorithm PropSegNet: The Ethics Committee at the University Hospital Bonn, University of Bonn, Bonn, Germany gave ethical approval to this work including AI-based methods to detect tumor growth pattern (Az. 2024-312-BO). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data availability: Raw 3'mRNA sequencing data will be available in Zenodo. Processed data from the JAVELIN Renal 101 study can be accessed from the publication by Motzer et al.20. Redistribution of the data from IMotion151 study is not possible17, but data access can be requested from the Genentech data access committee (DAC, EGAC00001001813) via the European Genome-Phenome Archive (EGA): https://www.ega-archive.org/dacs/EGAC00001001813. Other data produced in the present work are contained in the manuscript as supplementary tables. Code availability: Code for PropSegNet will be published on acceptance. The SPACEc code for the analyses of multiplex immunofluorescence imaging data is available on GitHub: https://github.com/yuqiyuqitan/SPACEc.34 Standard code for the analyses of multiplex immunofluorescence imaging data and survival analyses will be also available in GitHub.

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.

Clear-cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cell carcinoma, and its prognosis in a metastatic stage is poor. Although therapeutic options are continuously improving, better combination therapies and individualized approaches are still needed. Reticulocalbin-1 (RCN1), located in the endoplasmic reticulum (ER), is associated with aggressiveness and poor prognosis in many solid tumors, but its role in ccRCC has not been analyzed before. In this study, we performed in-silico transcriptomic data mining to analyze RCN1 expression at mRNA and protein levels using large publicly available databases and conducted the first large-scale cohort study on the impact of RCN1 in ccRCC, including data from 306 patients who underwent tumor resection at the Clinic of Urology, University Hospital Bonn. We examined the correlation of RCN1 expression with clinicopathological parameters and overall survival. Additionally, we analyzed the association of RCN1 expression with CD8 T-lymphocyte and macrophage infiltration. In vitro functional analysis was performed by silencing RCN1 using siRNA in Caki-1 and A498 cell lines to determine its role in tumor cell behavior. RCN1 is highly expressed in ccRCC at both the mRNA and protein levels in public databases, which was confirmed by our cohort data, where RCN1 was found to be highly and homogenously expressed in 63.7

AIMS:We aimed to analyze CD63, a cell surface protein that has been associated with tumor aggressiveness in several cancers, including breast, colorectal, and lung cancer, as well as melanoma, in prostate cancer. METHODS:CD63 expression was analyzed immunohistochemically in a cohort of primary prostate cancers from 281 patients. The results were correlated with clinico-pathologic parameters, including biochemical recurrence. In addition, CD63 expression in 251 of the 281 patients with prostate cancer was compared with CD63 expression in matched benign tissue samples (490 tissue samples). The analysis was performed automatically using the open-source software QuPath© and tested for statistical significance. For comparison with the diagnostic markers AMACR and GOLPH2, CD63 was analyzed in an additional cohort of 198 prostate cancers. RESULTS:CD63 expression was found in 100% of prostate cancer cases and benign tissue spots. Increased CD63 expression was significantly associated with higher tumor stage (pT), tumor grade (ISUP), as well as shorter progression-free survival (PFS). Compared with the CD63 intensity of benign tissue, expression in tumor tissue was higher in >80% of cases. In addition, combining the expression of CD63 and AMACR, positivity reached 97.2%, making CD63 a promising diagnostic biomarker in challenging cases. CONCLUSIONS:CD63 is commonly overexpressed in prostate cancer, and higher levels are associated with earlier biochemical tumor progression; hence, CD63 is a promising diagnostic and prognostic biomarker in primary prostate cancer.

PURPOSE:The association of metastatic timing (synchronous vs. metachronous) in metastatic renal cell carcinoma (mRCC) with survival outcomes in the immunooncology (IO) combination therapy era is not well understood to date. To assess progression-free survival (PFS) and overall survival (OS) based on the time to metastasis in mRCC patients treated with IO therapy combination therapies. MATERIAL AND METHODS:Data from a multi-center retrospective German patient cohort was used to compare synchronous metastasis (occurring within 3 months of the initial cancer diagnosis) with metachronous metastasis (4-24 months vs. ≥25 months). PFS and OS were analyzed using Kaplan-Meier curves. Cox multivariable regression analyses were adjusted for baseline characteristics. RESULTS:The cohort comprised 381 mRCC patients treated with 1st-line IO-combination therapies, categorized by time of metastatic onset: 167 (44%) in 0-3 months, 94 (25%) in 4 to 24 months, and 120 (31%) in ≥25 months. Differences in initial diagnosis age, ECOG performance status, local kidney treatment, and systemic treatment type were noted (all P < 0.05). Median PFS was 10.6 months for 0 to 3 months, 13.8 months for 4 to 24 months, and 16.8 months for ≥25 months (log-rank test: P = 0.028). Here, ≥25 months group showed significantly prolonged PFS in univariable (HR: 0.63; 95% CI:0.45-0.83) and multivariable Cox regression (HR: 0.64; 95% CI:0.41-0.99). Median OS was 28.0 months for 0 to 3 months, 39.7 months for 4 to 24 months, and 49.3 months for ≥25 months (P < 0.001). Multivariable Cox regression showed prolonged OS for both 4 to 24 months (HR: 0.45; 95% CI:0.26-0.76) and ≥25 months (HR: 0.56; 95% CI:0.33-0.95). CONCLUSIONS:Within this contemporary cohort of mRCC patients treated with IO-combination therapy, timing of metastatic disease and initiation of systemic treatment was associated with OS. PATIENT SUMMARY:This study examined the impact of when metastases occur on survival outcomes in kidney cancer patients treated with first-line immune-combination therapies. The findings show that a longer interval before the development of metastases is associated with better outcomes.

Supplementary Table 2. Baseline characteristics of the multicenter EV cohort.

Prostate cancer diagnosis primarily relies on histological confirmation via needle core biopsy, with systematic 12-core biopsies (SB) being commonly used. Multiparametric magnetic resonance imaging (mpMRI) and MRI-targeted biopsies have shown enhanced detection of clinically significant prostate cancer. This study compares two tumor grading methods—aggregate and individual grading—used in MRI-targeted biopsies to assess their correlation with the final ISUP Grade Group (GG) of the RPE. A cohort of 108 patients with ≥ 2 positive cores in at least one MRI-targeted biopsy, totaling 179 positive lesions, was analyzed. Systematic and MRI-targeted biopsies were correlated with RPE specimens. The mean highest ISUP GG for systematic biopsies was 2.77 (SD ± 1.29), compared to 2.62 (SD ± 1.13) for targeted biopsies using the aggregate method. Comparing the highest ISUP GG in systematic as well as targeted biopsies with the final ISUP GG of the RPE, exact correlation between GG was found in 70.1% (aggregate) and 66.4% (individual) for targeted biopsies and 58.1% for systematic biopsies. The results of the individual method showed slightly better correlation with the final ISUP GG from the RPE specimen in only 0.93%, while in 2.8% of cases, it resulted in inferior correlation compared to the aggregate method. Our findings suggest that the aggregate grading method of targeted biopsies is preferable due to its comparable predictive accuracy, lower workload, and alignment with existing clinical guidelines. This supports the ISUP’s recommendation to use the aggregate method for MRI-targeted biopsies in clinical practice. Further research is needed to standardize reporting protocols for MRI-targeted biopsies and refine their integration into prostate cancer risk stratification models.

575 Background: Clear cell renal cell carcinoma (ccRCC) is a highly vascularized tumor with histological heterogenous appearance. We explored whether vascular pattern (VP) are predictive to response of therapy. Methods: We defined three categories of VP in the publicly available TCGA cohort: high-branching (HB), low-branching (LB) and sinusoid. VP-based gene signatures were generated by integrating the transcriptomes of matched ccRCC samples. We developed a learning-based (AI) algorithm for the classification of VP based on CD31 immunohistochemistry and analyzed histology specimens from patients treated with tyrosine kinase inhibitors +/- immunotherapy (TKI) (University Clinic Dresden, retrospective cohort n=38, and NivoSwitch trial NCT: NCT03013946 , n=38 respectively) as well as the publicly available transcriptome datasets from two phase III clinical trials (JAVELIN Renal 101; IMmotion 151). Multiplex immunofluorescence (CODEX) was used for spatial mapping. Outcome measures employed KM-plots and log-rank analyses. Results: We identified a trajectory from a HB to LB vascular phenotype, paralleled by a decline in the expression of proximal tubule cell lineage traits. Applying the VP gene signatures to the transcriptome datasets from JR101 and IM151 we found that the progression-free survival (PFS) benefit from adding immunotherapy to anti-angiogenic therapy (IMmotion151: Bevacizumab; JAVELIN Renal 101: Axitinib) was limited to low-branching ccRCC (IM151: HR (95% CI): 0.64 (0.51-0.80), JR101: HR (95% CI): 0.45 (0.33-0.61, both p < 0.001), respectively) and linked to an immune cell infiltrated microenvironment. Patients with a HB ccRCC demonstrated prolonged PFS in the Dresden TKI cohort (p = 0.026) and in the NivoSwitch trial (p = 0.01). CODEX analysis using the SPACEc pipeline revealed profound differences in cellular neighborhoods, characterized by dense immune cell infiltration of ccRCC with LB compared to HB vascular patterns. Using 30 ccRCC patient-derived organoid in air-liquid interface (ALI) cultures, we confirmed the association between LB pattern and higher T cell infiltration, resulting in reduced viability of LB ccRCC organoids under immune-stimulating conditions. Conclusions: Vascular pattern can reliably predict therapy response in advanced ccRCC. Tumors with high branching phenotype respond better to anti-angiogenic TKI therapy. Low branching pattern was associated with improved response to immunotherapy.

Supplementary Table 1. Clinico-pathological characteristics of the UC progression PRIM-MET study cohort. BRA=brain metastasis; HEP=hepatic metastasis; LYM=non-locoregionary lymph node metastasis; OSS=bone metastasis; OTH= metastasis at other locations including soft tissue; PER=peritoneal metastasis; PUL=pulmonary metastasis.

PURPOSE:The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit is only achieved in a small, yet uncharacterized patient subset. NECTIN4 is located on chromosome 1q23.3, and 1q23.3 gains represent frequent copy number variations (CNVs) in urothelial cancer. Here, we aimed to evaluate NECTIN4 amplifications as a genomic biomarker to predict EV response in patients with mUC. MATERIALS AND METHODS:We established a NECTIN4-specific fluorescence in situ hybridization (FISH) assay to assess the predictive value of NECTIN4 CNVs in a multicenter EV-treated mUC patient cohort (mUC-EV, n = 108). CNVs were correlated with membranous NECTIN4 protein expression, EV treatment responses, and outcomes. We also assessed the prognostic value of NECTIN4 CNVs measured in metastatic biopsies of non-EV-treated mUC (mUC-non-EV, n = 103). Furthermore, we queried The Cancer Genome Atlas (TCGA) data sets (10,712 patients across 32 cancer types) for NECTIN4 CNVs. RESULTS:NECTIN4 amplifications are frequent genomic events in muscle-invasive bladder cancer (TCGA bladder cancer data set: approximately 17%) and mUC (approximately 26% in our mUC cohorts). In mUC-EV, NECTIN4 amplification represents a stable genomic alteration during metastatic progression and associates with enhanced membranous NECTIN4 protein expression. Ninety-six percent (27 of 28) of patients with NECTIN4 amplifications demonstrated objective responses to EV compared with 32% (24 of 74) in the nonamplified subgroup (P < .001). In multivariable Cox analysis adjusted for age, sex, and Bellmunt risk factors, NECTIN4 amplifications led to a 92% risk reduction for death (hazard ratio, 0.08 [95% CI, 0.02 to 0.34]; P < .001). In the mUC-non-EV, NECTIN4 amplifications were not associated with outcomes. TCGA Pan-Cancer analysis demonstrated that NECTIN4 amplifications occur frequently in other cancers, for example, in 5%-10% of breast and lung cancers. CONCLUSION:NECTIN4 amplifications are genomic predictors of EV responses and long-term survival in patients with mUC.

Objective Utilizing personalized risk assessment for clinically significant prostate cancer (csPCa) incorporating multiparametric magnetic resonance imaging (mpMRI) reduces biopsies and overdiagnosis. We validated both multi- and univariate risk models in biopsy-naïve men, with and without the inclusion of mpMRI data for csPCa detection. Methods N = 565 men underwent mpMRI-targeted prostate biopsy, and the diagnostic performance of risk calculators (RCs), mpMRI alone, and clinical measures were compared using receiver operating characteristic curve (ROC) analysis and decision curve analysis (DCA). Subgroups were stratified based on mpMRI findings and quality. Results csPCa was detected in 56.3%. PI-RADS score achieved the highest area under the curve (AUC) when comparing univariate risk models (AUC 0.82, p < 0.001). Multivariate RCs showed only marginal improvement in csPCa detection compared to PI-RADS score alone, with just one of four RCs showing significant superiority. In mpMRI-negative cases, the non-MRI-based RC performed best (AUC 0.80, p = 0.016), with the potential to spare biopsies for 23%. PSA-density and multivariate RCs demonstrated comparable performance for PI-RADS 3 constellation (AUC 0.65 vs. 0.60–0.65, p > 0.5; saved biopsies 16%). In men with suspicious mpMRI, both mpMRI-based RCs and the PI-RADS score predicted csPCa excellently (AUC 0.82–0.79 vs. 0.80, p > 0.05), highlighting superior performance compared to non-MRI-based models (all p < 0.002). Quality-assured imaging consistently improved csPCa risk stratification across all subgroups. Conclusion In tertiary centers serving a high-risk population, high-quality mpMRI provides a simple yet effective way to assess the risk of csPCa. Using multivariate RCs reduces multiple biopsies, especially in mpMRI-negative and PI-RADS 3 constellation.

Purpose Investigation of Microtubuli-associated Protein 2 (MAP2) expression and its clinical relevance in prostate cancer. Material and Methods MAP2 expression was immunohistochemically analysed on radical prostatectomy specimens using whole block sections ( n = 107) and tissue microarrays (TMA; n = 310). The staining intensity was evaluated for carcinoma, benign tissue and prostatic intraepithelial neoplasia. Expression data were correlated with clinicopathological parameters and biochemical recurrence-free survival. Additionally, MAP2 protein expression was quantitatively analysed in the serum of histologically confirmed prostate carcinoma patients and the control group using a commercial enzyme-linked immunosorbent assay. Results MAP2 staining was significantly stronger in neoplastic tissue than in non-neoplastic prostatic glands, both in whole block sections ( p < 0.01) and in TMA sections ( p < 0.05). TMA data revealed significantly stronger MAP2 staining in high-grade tumors. Survival analysis showed a significant correlation between strong MAP2 staining in carcinoma and shortened biochemical recurrence-free survival after prostatectomy ( p < 0.001). Multivariate Cox regression analysis confirmed MAP2 as an independent predictor for an unfavourable course. Mean MAP2 serum levels for non-PCA vs. PCA patients differed significantly (non-PCA = 164.7 pg/ml vs. PCA = 242.5 pg/ml, p < 0.001). Conclusion The present data support MAP2 as a novel biomarker in PCA specimens. MAP2 is correlated with tumor grade and MAP2 high-expressing PCA is associated with an increased risk of biochemical recurrence after radical prostatectomy. Future studies are necessary to evaluate MAP2 as a valuable immunohistochemical biomarker in preoperative PCA diagnostic procedures, in particular with regard to treatment modalities.

We report a case of a 24-year-old male with a history of kidney biopsy at young age due to chronic renal dysfunction and challenging hypertension, who presented with flank pain and hematuria. Initial imaging suggested renal pelvis enlargement, but MRI revealed a massive renal arteriovenous malformation (AVM). Angiographic embolization was abandoned due to extensive effluent flow, followed by successful surgical resection preserving healthy kidney tissue. This case underscores the importance of considering renal AVMs in the differential diagnosis of young patients with gross hematuria or refractory hypertension to prevent complications and improve patient outcomes.