Nature Reviews Urology最新文献

{"title":"Finding a brush when you expect a broom: a novel model of paediatric Wilms tumour evolution.","authors":"Andrew L Hong, Elizabeth A Mullen","doi":"10.1038/s41585-025-01082-y","DOIUrl":"10.1038/s41585-025-01082-y","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":" ","pages":""},"PeriodicalIF":14.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HER2 and urothelial carcinoma: current understanding and future directions","authors":"Daniele Raggi, Emanuele Crupi, Filippo Pederzoli, Alberto Martini, Alberto Briganti, Omar Alhalabi, Peter H. O’Donnell, Jeffrey Ross, Shilpa Gupta, Ashish M. Kamat, Bishoy M. Faltas, Peter C. Black, Phillip E. Spiess, Petros Grivas, Jianjun Gao, Andrea B. Apolo, Robert A. Huddart, Andrea Necchi, Matthew D. Galsky","doi":"10.1038/s41585-025-01075-x","DOIUrl":"10.1038/s41585-025-01075-x","url":null,"abstract":"Human epidermal growth factor receptor 2 (HER2) has emerged as a crucial biomarker across various cancers, shaping therapeutic strategies and prognostic evaluations. In urothelial carcinoma, HER2 positivity rates can reach up to 68% when HER2-low tumours (immunohistochemistry 1+) are included in the analysis. HER2 overexpression and ERBB2 genomic alterations have been linked to advanced disease stages and poor outcomes in urothelial carcinoma. Emerging evidence suggests that HER2-low tumours might be a distinct and actionable subgroup. Accurate and consistent assessment of HER2 status is increasingly vital to identify patients likely to benefit from HER2-targeted therapies, raising interest in refining thresholds for HER2 expression, aiming to predict treatment response. HER2 heterogeneity across stages and histological subtypes complicates its evaluation, with definitions of HER2 positivity differing between clinical trials and treatments. In urothelial carcinoma, HER2-targeted therapies, such as tyrosine kinase inhibitors, monoclonal antibodies and antibody–drug conjugate (ADCs) have been explored. Unlike tyrosine kinase inhibitors and monoclonal antibodies, which act through HER2-related pathways, ADCs use HER2 as a target but achieve efficacy through additional mechanisms, enabling their activity even at low HER2 expression levels. Trastuzumab deruxtecan, a novel anti-HER2 ADC, has received FDA tumour-agnostic approval for unresectable or metastatic HER2+ solid tumours, including urothelial carcinoma, after prior therapies. Interactions between HER2 protein and putative biomarkers such as EGFR, NECTIN4, PDL1 and FGFR3 genomic alterations might influence therapeutic outcomes, offering opportunities for improved patient selection and innovative combination strategies. In this Review the authors explore the emerging role of HER2 in urothelial carcinoma, highlighting its biological and clinical significance, the challenges of using HER2 as a biomarker, and the variability and complexity of HER2 assessment. Evidence supporting HER2-targeted therapies and future directions for research and clinical applications are also discussed.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 2","pages":"110-132"},"PeriodicalIF":14.6,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144851323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visual clues — dermatological manifestations of sexually transmitted infections in men","authors":"Marcelo Mass Lindenbaum, Daniela Calderón, Vivek Aslot, Bernardita Ljubetic, Daria Harlamova, Raevti Bole, Petar Bajic, Jorge Navarrete","doi":"10.1038/s41585-025-01071-1","DOIUrl":"10.1038/s41585-025-01071-1","url":null,"abstract":"Considering the increasing prevalence of sexually transmitted infections, accurate diagnosis and management based on the diverse dermatological presentations of sexually transmitted infections are crucial. A strong visual diagnostic skill set guides clinicians towards prompt recognition, directs appropriate diagnostic testing and enables timely initiation of treatment. This procedure in turn helps to interrupt infection transmission and mitigate long-term complications. Thus, incorporating visual learning and a dermatological perspective into urology training is essential, empowering urologists to make a difference in improving sexual health outcomes and supporting public health efforts. Sexually transmitted infections are associated with dermatological visual manifestations. This Review provides a comprehensive overview of cutaneous manifestations of sexually transmitted infections in men, with the aim of providing an up-to-date resource to help urologists and primary care physicians in the recognition and management of these visual cues.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 2","pages":"89-109"},"PeriodicalIF":14.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"State of the art — biomarkers in advanced prostate cancer","authors":"Vincenza Conteduca, Himisha Beltran","doi":"10.1038/s41585-025-01080-0","DOIUrl":"https://doi.org/10.1038/s41585-025-01080-0","url":null,"abstract":"Advances in molecular profiling technologies that capture both genotype and phenotype, coupled with an improved understanding of the biological mechanisms underlying prostate cancer progression, set new molecular biomarkers for advancement into the clinic to improve prognostication, therapy selection and disease monitoring for patients with prostate cancer.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"67 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The state of the art in artificial intelligence and digital pathology in prostate cancer","authors":"Heyuan Michael Ni, Ramez Kouzy, Ali Sabbagh, Michael K. Rooney, Jean Feng, Simon P. Castillo, Sherif M. Gadoue, Zakaria El Kouzi, Karen Hoffman, Yinyin Yuan, Anant Madabhushi, Osama Mohamad","doi":"10.1038/s41585-025-01070-2","DOIUrl":"10.1038/s41585-025-01070-2","url":null,"abstract":"Prostate cancer is among the most common cancers worldwide, with ~1.5 million new diagnoses globally every year. The sheer mass of data becoming available on prostate cancer, as well as other types of cancer, is increasing exponentially. The growth of digital pathology has particularly sparked interest in developing artificial intelligence (AI) approaches to data synthesis to predict cancer grade and outcomes in men with prostate cancer. Progress has been made in this field, particularly in applications for diagnosis, prognosis and inferring molecular alterations, but several challenges remain. Variability in tissue processing and scanning contribute to dataset heterogeneity. The absence of well-annotated, multi-institutional databases hinders AI model development and generalization of model performances across clinical settings. Regulatory frameworks for AI-driven diagnostics remain nascent. Moreover, bias in training datasets skewing against under-represented demographic groups poses a fundamental challenge to developing equitable models. By mapping contemporary evidence around each of these hurdles and identifying tangible interventions, we can advance AI-augmented digital pathology towards reliable and generalizable tools to improve prostate cancer care. This Review discusses different uses of digital pathology in prostate cancer, from data selection to model training and validation. Ethical and societal implications, as well as future directions in the field, are also discussed.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 1","pages":"13-28"},"PeriodicalIF":14.6,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAUTIon — not all UTIs are the same","authors":"Jonathan J. Molina, Ana L. Flores-Mireles","doi":"10.1038/s41585-025-01065-z","DOIUrl":"10.1038/s41585-025-01065-z","url":null,"abstract":"Urinary tract infections are one of the most common infections, accounting for ~400 million diagnoses per year worldwide. Uncomplicated urinary tract infections (uUTIs) occur in healthy individuals with no structural or functional abnormalities of the urinary system and primarily affect women. Catheter-associated urinary tract infections (CAUTIs) are a type of complicated UTI affecting patients who have a urinary catheter in place, often hospitalized patients or patients with conditions that prevent them from urinating naturally. Both infections share common symptoms, diagnostics and treatment options but also differ greatly in pathophysiology, aetiology, risk factors and comorbidities. These differences could explain why antibiotic treatments — which generally lead to positive outcomes in patients with uUTIs — often fail in patients with CAUTIs. Understanding these differences could guide evidence-based insights into why treatments for CAUTIs should be different from those for uUTIs, specifically, by modifying catheters, which initiate the damage-induced segue for UTIs. This Review provides a thorough comparison between uncomplicated urinary tract infections and catheter-associated urinary tract infections, highlighting that these infections are similar in terms of pathogens and sequelae, but many differences exist, for example, in pathophysiology and risk factors. The authors highlight how these differences should be considered to guide differential treatment.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"22 12","pages":"799-814"},"PeriodicalIF":14.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting the molecular landscape of fumarate hydratase-deficient RCC: towards precision oncology","authors":"Maria I. Carlo, A. Ari Hakimi","doi":"10.1038/s41585-025-01074-y","DOIUrl":"10.1038/s41585-025-01074-y","url":null,"abstract":"New research has provided a comprehensive molecular understanding of fumarate hydratase-deficient renal cell carcinoma, showing distinct molecular divergence from other renal tumour subtypes. These molecular findings have implications for precision oncology for patients with this rare disease.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 3","pages":"154-155"},"PeriodicalIF":14.6,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers for renal cell carcinoma — a pragmatic approach","authors":"Ziad Bakouny, A. Ari Hakimi, Ed Reznik, Robert J. Motzer","doi":"10.1038/s41585-025-01073-z","DOIUrl":"10.1038/s41585-025-01073-z","url":null,"abstract":"The management of metastatic renal cell carcinoma (RCC) has undergone a major transformation, with median survival increasing from <1 year to ~5 years. However, biomarker development in RCC has lagged, largely because the most effective therapies, such as immune checkpoint inhibitors and VEGFR tyrosine kinase inhibitors, act on the tumour microenvironment rather than directly on tumour cells. Although predictive biomarker development in RCC remains challenging, selected tools such as circulating biomarkers and tissue-based RNA signatures are shaping a personalized approach to care, with some emerging biomarkers showing clinical potential, and additional biomarkers poised to enter clinical practice.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 3","pages":"151-153"},"PeriodicalIF":14.6,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iatrogenic upper urinary tract injuries during ureteroscopy for urolithiasis: a comprehensive review on incidence, mechanisms and preventative strategies","authors":"Orla Cullivan, Eva Browne, Sorcha O’Meara, Andreas Skolarikos, Bhaskar Somani, Eoghan M. Cunnane, Michael T. Walsh, Fergal J. O’Brien, Niall F. Davis","doi":"10.1038/s41585-025-01067-x","DOIUrl":"10.1038/s41585-025-01067-x","url":null,"abstract":"The incidence of urolithiasis is increasing globally, with a prevalence of 13% in North America and 9% in Europe. Ureteroscopy is a minimally invasive approach for treating conditions affecting the upper urinary tract, including urolithiasis, for which its efficacy and safety is well recognized. There is a risk of complications associated with ureteroscopy, including iatrogenic mechanical ureteric injuries. These injuries are multifactorial in nature, with ureteroscopes and auxiliary endoscopic equipment having an important role, in addition to patient and stone factors. Excessive friction and insertion forces during ureteroscope and ureteric access sheath insertion, apparatus malfunction or thermal injuries during laser lithotripsy might cause injury to the upper urinary tract. Ureteric avulsion is a serious event, which necessitates further intervention such as ureteric reimplantation or nephrectomy. Ureteric mucosal injuries can be managed with a period of ureteric stenting, although stent-related symptoms can be challenging for patients. The ability of endoscopic equipment to injure the ureter is an area that requires further study to reduce incidence and minimize patient morbidity. In this article, we review the operative mechanisms that contribute to iatrogenic mechanical ureteric injuries and discuss preventative strategies. This Review outlines the operative mechanisms that contribute to iatrogenic mechanical ureteric injuries. The authors aim to increase awareness among urologists of the aetiology of these injuries, so that they can be avoided in practice, ultimately enhancing patient safety.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"22 12","pages":"815-825"},"PeriodicalIF":14.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms and implications of epithelial cell plasticity in the bladder","authors":"Kan Wu, Xu Liu, Jiapeng Zhang, Xianding Wang, Xiang Li, Chong Chen","doi":"10.1038/s41585-025-01066-y","DOIUrl":"10.1038/s41585-025-01066-y","url":null,"abstract":"Cellular plasticity, the ability of cells to reprogramme and alter their fate, has a pivotal role in maintaining homeostasis and facilitating tissue regeneration after injury. The bladder urothelium, a dynamic transitional epithelial layer, displays a highly plastic phenotype that enables its remarkable regenerative capacity in response to wounding. During both development and repair, urothelial cells exhibit considerable plasticity through processes such as dedifferentiation, transdifferentiation and epithelial-to-mesenchymal transition. Urothelial plasticity is not only crucial for healthy tissue repair but is also involved in pathological conditions, including cancer. In bladder tumorigenesis, urothelial cells exploit plasticity to acquire new phenotypic and functional characteristics, transitioning between distinct cellular states. This plasticity contributes to tumour heterogeneity, subtype switching, progression, metastasis and resistance to therapies. These dynamic cellular transitions are regulated by intrinsic and extrinsic factors, including transcriptional and epigenetic mechanisms, as well as microenvironmental influences. Targeting urothelial plasticity could offer novel therapeutic strategies for bladder-related diseases. In this Review the authors describe current knowledge on cellular plasticity in the bladder urothelium, emphasizing its role in bladder repair and tumorigenesis, and explore the molecular mechanisms of urothelial plasticity and discuss its potential as a novel therapeutic target for bladder-related diseases.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 2","pages":"70-88"},"PeriodicalIF":14.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}