Nature Reviews Urology最新文献

{"title":"Rare prostate cancer histologies: detection, characteristics and treatment.","authors":"Bárbara Vieira Lima Aguiar Melão, Denis Leonardo Jardim, Roger Li, Katrina Collins, Neeraj Agarwal, Petros Grivas, Alberto Briganti, Andrea Necchi, Liang Cheng, Philippe E Spiess","doi":"10.1038/s41585-026-01194-z","DOIUrl":"https://doi.org/10.1038/s41585-026-01194-z","url":null,"abstract":"<p><p>Relatively rare histologies of prostate cancer collectively account for <5% of all prostate cancers and comprise mucinous adenocarcinoma, intraductal carcinoma, ductal adenocarcinoma, neuroendocrine prostate cancer (including treatment-emergent small-cell neuroendocrine carcinoma), sarcomatoid carcinoma and basal cell carcinoma. These histologies have distinct morphological, molecular and clinical features from each other and the most common histological type, acinar adenocarcinoma. The perceived rarity of these histologies often reflects sampling limitations rather than biological prevalence, as many treatment-emergent phenotypes are seldom encountered in routine practice owing to the infrequent use of metastatic biopsies. These histologies demonstrate aggressive behaviour, atypical metastatic patterns and reduced responsiveness to conventional therapies. Despite their clinical importance, these entities remain under-represented in standard guidelines and clinical trials. Histological types and subtypes, such as ductal, mucinous, intraductal, neuroendocrine and sarcomatoid carcinomas, pose diagnostic and therapeutic challenges, and conventional screening with PSA exhibits limitations, so they are often diagnosed at advanced stages. Multiparametric MRI, immunohistochemistry and genomic profiling are crucial tools for accurate recognition and risk stratification. Histological type-specific genomic alterations, including DNA repair deficiencies, RB1 and TP53 loss, and mismatch repair mutations, provide potential therapeutic opportunities, but treatment recommendations are still largely extrapolated from acinar adenocarcinoma. Limited retrospective data suggest worse outcomes for patients with a rare histology than those with typical acinar adenocarcinoma, highlighting the urgent need for prospective registries and dedicated clinical trials. Rare histologies of prostate cancer are an under-recognized source of morbidity and mortality. Improved diagnostic precision, incorporation of molecular profiling and collaborative data collection efforts are essential to develop evidence-based strategies.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224709","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":"Combination therapy for BCG-unresponsive non-muscle-invasive bladder cancer: biological rationale and ongoing clinical strategies.","authors":"Siamak Daneshmand, Stephen A Boorjian, Joshua J Meeks, Yair Lotan, Wassim Kassouf, Girish S Kulkarni, Paolo Gontero, Peter Albers, Jørn S Jakobsen, Kristian Juul","doi":"10.1038/s41585-026-01193-0","DOIUrl":"https://doi.org/10.1038/s41585-026-01193-0","url":null,"abstract":"<p><p>Radical cystectomy is the current first-line treatment for patients with BCG-unresponsive non-muscle-invasive bladder cancer; however, this surgical procedure is associated with considerable morbidity and mortality. Bladder-preserving treatments, including single agents - such as nadofaragene firadenovec, a nonreplicating adenoviral-vector-based gene therapy; pembrolizumab, an immune checkpoint inhibitor immunotherapy; and single-agent intravesical chemotherapy using valrubicin or controlled-release gemcitabine - and combination therapies, including nogapendekin alfa inbakicept-pmln (an IL-15 receptor agonist immunotherapy) plus BCG - and multiagent intravesical chemotherapy (for example, gemcitabine plus docetaxel) are also recommended by current guidelines. Single-agent therapies can lead to development of acquired immune resistance; thus, combination therapies are a key area of interest for improving patient outcomes. Options for this approach include combinations of intravesical chemotherapy, BCG, immunotherapy, gene therapy and radiotherapy. These bladder-preserving combination therapies have the potential to change the treatment paradigm for patients with BCG-unresponsive non-muscle-invasive bladder cancer by improving clinical efficacy and avoiding the need for cystectomy. Future studies must evaluate the benefits and risks associated with combination treatment, considering patient convenience, toxicity, efficacy, the risk of progression and treatment cost.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195760","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":"Return-to-play with a solitary kidney after renal tumour.","authors":"Filippo Spreafico, William Zardo","doi":"10.1038/s41585-026-01203-1","DOIUrl":"https://doi.org/10.1038/s41585-026-01203-1","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183585","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":"Bacterial strategies for surviving antibiotics during urinary tract infection: could uropathogenic Escherichia coli be persisters?","authors":"Ariana Costas, Bill Söderström, Molly A Ingersoll","doi":"10.1038/s41585-026-01191-2","DOIUrl":"https://doi.org/10.1038/s41585-026-01191-2","url":null,"abstract":"<p><p>Treating bacterial infections, such as urinary tract infection (UTI), with antibiotics does not always resolve the infection and often results in subsequent re-infection. Treatment failure can be driven by bacterial mechanisms of resistance, tolerance or persistence, collectively known as the antibiotic non-response. Antibiotic resistance is well characterized across various bacterial species and implicated in poor clinical outcomes in various infection settings. In the instance of resistance, bacteria harbour genetic determinants to evade antibiotics and continue to grow during treatment. Notably, bacteria can escape antibiotic killing in the absence of resistance genes. In response to the environment, an entire bacterial population can slow its growth rate, becoming tolerant to bactericidal antibiotic exposure. Alternatively, a subpopulation of bacteria, known as persister cells, survive whereas the remainder of the population is eliminated by bactericidal antibiotics. Both mechanisms enable bacteria to survive treatment, with the capacity to regrow following cessation of antibiotic treatment. However, our understanding of tolerance and persistence in the context of UTI is limited. Thus, two bacterial phenotypes that might contribute to poor outcomes are overlooked both in the clinic and in research, which could add to the challenges of treatment failure and recurrent UTI.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183443","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":"Moving towards standardized outcomes in penile cancer and inguinal lymph node dissections.","authors":"Pablo E Puente, Luis G Medina, Giovanni E Cacciamani, Philippe E Spiess, Rene Sotelo","doi":"10.1038/s41585-026-01192-1","DOIUrl":"https://doi.org/10.1038/s41585-026-01192-1","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183508","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":"Update on testosterone deficiency and therapeutic options for testosterone replacement therapy.","authors":"Thomas Thompson, Mohamed Mubarak, T Hugh Jones, Ian Pearce, Vaibhav Modgil","doi":"10.1038/s41585-026-01190-3","DOIUrl":"https://doi.org/10.1038/s41585-026-01190-3","url":null,"abstract":"<p><p>Testosterone deficiency, or male hypogonadism, is a clinical syndrome characterized by the presence of clinical features with persistently low serum testosterone levels. Testosterone deficiency is an important health concern owing to its wide-ranging effects on sexual function, metabolic health, bone integrity, mood and overall quality of life. Testosterone deficiency can be classified as primary (testicular), secondary (hypothalamic-pituitary) or functional hypogonadism - the latter is commonly associated with ageing, obesity and chronic systemic disease. Diagnosis requires both clinical symptoms and biochemical confirmation of low testosterone levels, typically assessed using morning serum testosterone measurements. In instances of borderline values or discordance between symptoms and total testosterone levels, free testosterone and sex hormone-binding globulin measurements can provide additional diagnostic clarity. Evidence demonstrates that testosterone replacement therapy can provide clinically meaningful benefits in appropriately selected men with confirmed testosterone deficiency. Improvements have been reported in sexual function, mood, anaemia, body composition, bone mineral density and metabolic parameters, and contemporary data do not support an increased risk of prostate cancer or major adverse cardiovascular events when therapy is appropriately monitored. Multiple therapeutic formulations are available, including transdermal, oral, intramuscular, subdermal and intranasal preparations, each with distinct pharmacokinetic profiles and practical considerations. Individualized treatment selection, careful patient counselling and ongoing monitoring are essential to optimize clinical outcomes and minimize potential risks in men undergoing testosterone therapy.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166962","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":"Cribriform and intraductal carcinoma in prostate cancer - implications for risk stratification and therapeutic decision-making.","authors":"Rui M Bernardino, João Lobo, Zeyad Schwen, Theodorus van der Kwast, Adam B Weiner, Robert E Reiter, Jane K Nguyen, Estevão Lima, Robert Stein, Nicolas Soputro, Rashed Ghandour, Alp Tuna Beksac, Karim Daher, Ricardo Leão, Mark L Gonzalgo, Roderick van den Bergh, Juan Garisto, Giancarlo Marra, Jennifer Le Guévelou Kammerer, Sara M Falzarano, Cristina Magi-Galuzzi, Cosimo De Nunzio, Susan Prendeville, Neil Fleshner, Jihad Kaouk, Riccardo Autorino","doi":"10.1038/s41585-026-01189-w","DOIUrl":"https://doi.org/10.1038/s41585-026-01189-w","url":null,"abstract":"<p><p>Intraductal carcinoma of the prostate (IDC) and invasive cribriform carcinoma (invasive Crib) are closely related high-risk morphologies that frequently coexist and are associated with adverse pathology, early metastasis and disease-specific mortality across the prostate cancer continuum. These morphologies are common in intermediate- and high-risk disease, but remain under-recognized and inconsistently reported, contributing to undergrading and potentially inappropriate selection of patients for de-escalation strategies such as active surveillance or focal therapy. Biopsy detects these patterns in only about half of affected men, and magnetic resonance imaging (MRI)-targeted sampling does not reliably close this gap. These tumours are enriched for loss of the tumour-suppressor gene PTEN, DNA-damage-repair alterations and genomic instability, and are associated with immunologically 'cold', fibroblast-rich tumour niches. These findings provide a rationale for evaluating biomarker-directed strategies, including inhibition of the PARP and AKT pathways and therapies targeting B7-H3 (also known as CD276). However, definitive evidence that either IDC or invasive Crib predicts benefit from any of these treatments has not been established. A deeper understanding of the biological and clinical behaviour of these tumours, together with rigorous, standardized reporting, is essential for accurate risk stratification, rational use of active surveillance and focal approaches, selection of patients for intensified local and systemic treatment, and the design of biomarker-driven trials for this aggressive disease subset.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149072","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":"ctDNA in muscle-invasive bladder cancer — clinically actionable, not yet standardized","authors":"Daniele Raggi,Emanuele Crupi,Lars Dyrskjøt","doi":"10.1038/s41585-026-01197-w","DOIUrl":"https://doi.org/10.1038/s41585-026-01197-w","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"6 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088835","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":"Preclinical animal models of lower urinary tract dysfunction associated with metabolic syndrome","authors":"Claudia Covarrubias,Stephanie Sirmakesyan,Aalya Hamouda,Sami Lasri,Abdulla AlAmeeri,Diery-Leando Saint-Vil,Philippe G. Cammisotto,Lysanne Campeau","doi":"10.1038/s41585-026-01188-x","DOIUrl":"https://doi.org/10.1038/s41585-026-01188-x","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"11 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088836","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":"Spermatology makes a strong return in sunny Birmingham","authors":"Louise Lloyd","doi":"10.1038/s41585-026-01201-3","DOIUrl":"https://doi.org/10.1038/s41585-026-01201-3","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"171 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088842","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}