Nature Reviews Urology最新文献

{"title":"Author Correction: Atypical intraductal proliferation in prostate biopsy — a diagnostic grey zone with clinical implications","authors":"Rui M. Bernardino, João Lobo, Jihad Kaouk, Theodorus van der Kwast, Susan Prendeville, Fabio Zattoni, Lorenzo Bianchi, Alberto Martini, Pawel Rajwa, Veeru Kasivisvanathan, Giancarlo Marra, Neil Fleshner, Young Academic Urologists Working Group Prostate Cancer Board","doi":"10.1038/s41585-025-01114-7","DOIUrl":"10.1038/s41585-025-01114-7","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 6","pages":"417-417"},"PeriodicalIF":14.6,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41585-025-01114-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145541426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sperm mitochondrial sheath formation — how and why?","authors":"Maddison L. Graffeo, Jessica E. M. Dunleavy, Brendan J. Houston, Moira K. O’Bryan","doi":"10.1038/s41585-025-01109-4","DOIUrl":"10.1038/s41585-025-01109-4","url":null,"abstract":"The sperm tail is a modified motile cilium analogous to those found in tissues including the lung and brain. They have been evolutionarily sculpted to optimize motility and, therefore, fertility, through the dynamic and challenging environment of the female reproductive tract. Sperm tails are composed of three structurally distinct regions: the midpiece, the principal piece and the end piece. The most proximal region — the midpiece — is surrounded by a mitochondrial sheath, which has been proposed to provide structural integrity and ATP as fuel for sperm tail movement. Despite the main phases of mitochondrial sheath assembly being described, the specific biological mechanisms that underpin its formation and maturation remain poorly defined and, in many cases, unknown. Moreover, emerging evidence has highlighted that the precise contribution of the mitochondrial sheath to energy production in sperm has been misunderstood. ATP generation via glycolysis and mitochondrial respiration, previously believed to be physically uncoupled, engage in crosstalk to maximize sperm function, competition and overall fertility. Understanding these processes could not only provide vital insights into the aetiology of male infertility and offer targets for contraceptive development but could also provide insights into mechanisms of relevance to other tissues in which mitochondrial dynamics is challenging to monitor. In this Review, the authors describe the mechanisms that mediate mitochondrial sheath formation and its maintenance and function within the mature sperm. They also provide the field with a strong and up-to-date background on current data and hypotheses.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 5","pages":"288-308"},"PeriodicalIF":14.6,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491463","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":"Emerging evidence for sequencing and combining PSMA-based therapies in prostate cancer","authors":"Sola Adeleke, Joao R. Galante, Yishen Wang, Gurdip Azad, Simon Wan, Athar Haroon, Diletta Bianchini, Jamshed Bomanji, Michael S. Hofman, Travis S. Young, Gary J. R. Cook","doi":"10.1038/s41585-025-01107-6","DOIUrl":"10.1038/s41585-025-01107-6","url":null,"abstract":"Prostate-specific membrane antigen (PSMA) is upregulated in prostate cancer cells relative to other cells. The increased expression and enzymatic activity of PSMA in high-stage disease confers a selective advantage on such cells, contributing to their increased proliferation, the tendency to metastasize and the development of a castration-resistant phenotype. The decades of radiobiochemical advances in the development of PSMA targeting radiolabelled ligands has led to the subsequent FDA approval of a number of radiotracers and radiotherapeutics for clinical use. Novel developments in therapeutic advances using PSMA-based combinatorial approaches include PSMA-targeted antibody–drug conjugates and PSMA-targeted radionuclide payloads. Combining and sequencing some of these strategies with standard therapy options such as surgery, radiotherapy and androgen receptor pathway inhibitors could improve patient outcomes. Immunotherapy and chimeric antigen receptor T cell therapy are relevant to PSMA-based therapies as PSMA can serve as a specific target antigen for these treatments, enabling precise tumour recognition and enhanced efficacy of prostate cancer therapies. In this Perspective, the authors evaluate the current status of prostate-specific membrane antigen (PSMA) ligand-enabled imaging, summarizing novel developments, therapeutic advances and combinatorial approaches. The potential future role of PSMA-based strategies in the future management of prostate cancer is also discussed.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 6","pages":"395-416"},"PeriodicalIF":14.6,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145477817","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":"20 years of taxane therapy in prostate cancer — the past, present and future","authors":"Marc Carceles-Cordon, Veronica Rodriguez-Bravo, Daniel P. Petrylak, Josep Domingo-Domenech","doi":"10.1038/s41585-025-01104-9","DOIUrl":"10.1038/s41585-025-01104-9","url":null,"abstract":"2024 marked the twentieth anniversary of FDA approval for taxane therapy, namely docetaxel, in the treatment of advanced prostate cancer. Approval of this treatment modality signified a breakthrough in the field, as it demonstrated for the first time that a non-antiandrogen targeting agent could significantly improve survival of patients with prostate cancer. New evidence has further solidified the role of taxanes, demonstrating that it improves survival when used in combination with androgen-targeting therapy in early-stage metastatic hormone-sensitive prostate cancer. Consequently, taxane therapy is currently considered a gold standard and mainstay in the treatment of prostate cancer. In this Review, we present an up-to-date analysis of the pivotal role of taxanes in the treatment of prostate cancer, discuss reasons why taxanes are effective and discuss how the mechanisms that confer resistance to taxanes in prostate cancer might be exploited to develop more effective therapeutic strategies. In this Review, the authors describe the pivotal role of taxanes in the treatment of prostate cancer and discuss how mechanisms that confer resistance to taxanes might be exploited to develop more effective therapeutic strategies","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 6","pages":"358-373"},"PeriodicalIF":14.6,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145484858","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":"Persistent Müllerian duct syndrome — a rare but important cause of male factor infertility","authors":"Michael George, Susan Wong, Raj Mathur, Nikolaos Tsampras, Alexander Lewis, Ian Pearce, Theodora Stasinou, Vaibhav Modgil","doi":"10.1038/s41585-025-01108-5","DOIUrl":"10.1038/s41585-025-01108-5","url":null,"abstract":"Persistent Müllerian duct syndrome (PMDS) is a rare difference of sex development, characterized by the presence of Müllerian duct derivatives in 46,XY individuals with male-typical development. PMDS typically presents during childhood with features of cryptorchidism, inguinal hernia or transverse testicular ectopia. Untreated PMDS is associated with risks of infertility and malignancy. Infertility is common, arising from cryptorchidism, anatomical malformations (such as epididymal aplasia) or extrinsic compression of the ejaculatory duct by Müllerian structures. At the time of diagnosis, just one in five men with PMDS are reported to have conceived naturally. Preservation of fertility potential requires prompt diagnosis and management via a holistic patient-centred approach that addresses the underlying cause. With cryptorchidism, which is a common manifestation of PMDS, early orchidopexy is the key initial intervention. The input of fertility specialists and assisted reproductive techniques can further support successful conception. Beyond its effects on fertility, PMDS carries a risk of malignant transformation in the testes and Müllerian structures, warranting complex management with inclusion of a multi-disciplinary team and consideration of orchidopexy, orchidectomy, excision of Müllerian remnants and onward surveillance. Thus, although rare, PMDS is an important cause of male factor infertility that might be encountered by urologists. Preservation of fertility potential requires a high index of clinical suspicion and timely intervention. Raising awareness of PMDS among clinicians is crucial to improve its detection, advance its clinical management and provide a basis for future research. Persistent Müllerian duct syndrome (PMDS) is a rare difference in sex development, characterized by the presence of Müllerian duct derivatives in 46,XY individuals with male-typical development. Untreated PMDS is associated with risks of infertility and malignancy. In this Review, the authors provide an comprehensive primer on the epidemiology, pathophysiology and management of the condition, considering the need for a high index of clinical suspicion and timely intervention, raised awareness of PMDS among clinicians and multidisciplinary care to optimize outcomes for patients.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 6","pages":"385-394"},"PeriodicalIF":14.6,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145461317","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":"Atypical intraductal proliferation in prostate biopsy — a diagnostic grey zone with clinical implications","authors":"Rui M. Bernardino, João Lobo, Jihad Kaouk, Theodorus van der Kwast, Susan Prendeville, Fabio Zattoni, Lorenzo Bianchi, Alberto Martini, Pawel Rajwa, Veeru Kasivisvanathan, Giancarlo Marra, Neil Fleshner, Young Academic Urologists Working Group Prostate Cancer Board","doi":"10.1038/s41585-025-01106-7","DOIUrl":"10.1038/s41585-025-01106-7","url":null,"abstract":"Atypical intraductal proliferation (AIP) is considered a borderline lesion, characterized by architectural complexity and cytological atypia greater than that seen in high-grade prostatic intraepithelial neoplasia, but insufficient to fulfil the diagnostic criteria for intraductal carcinoma (IDC). Consequently, AIP remains diagnostically challenging, and the clinical significance of this lesion is still uncertain. Emerging evidence suggests that AIP in prostate biopsy specimens is a strong predictor of unsampled IDC and other adverse pathological features, warranting reconsideration of the AIP role in prostate cancer risk stratification. Results from prospective and molecular studies indicate that AIP frequently coexists with intermediate-risk prostate cancer and shares molecular alterations with IDC, such as PTEN loss and ERG overexpression, reinforcing AIP potential as a marker of occult aggressive disease. Considering the growing emphasis on precision diagnostics and active surveillance in prostate cancer management, understanding the implications of AIP is particularly relevant. Atypical intraductal proliferation is a prostate biopsy finding with morphological features intermediate between high-grade prostatic intraepithelial neoplasia and intraductal carcinoma. This Review discusses histopathological features, molecular characteristics and clinical outcomes associated with AIP, and highlights the clinical implications of AIP, primarily due to the frequent association of AIP with clinically significant prostate cancer.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 6","pages":"374-384"},"PeriodicalIF":14.6,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462022","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":"Mitochondrial metabolic alterations fuel bladder cancer initiation","authors":"Maria Chiara Masone","doi":"10.1038/s41585-025-01110-x","DOIUrl":"10.1038/s41585-025-01110-x","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"22 12","pages":"794-794"},"PeriodicalIF":14.6,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440648","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":"Optimizing local control in the surgical management of bladder cancer","authors":"Martin Egger, Vincent D. D’Andrea, Clara Steiner, Nnamdi O. Onochie, Timothy N. Clinton, Chong-Xian Pan, Adam S. Kibel, Cheryl T. Lee, Kent W. Mouw, Matthew Mossanen","doi":"10.1038/s41585-025-01098-4","DOIUrl":"10.1038/s41585-025-01098-4","url":null,"abstract":"Bladder cancer is a highly prevalent disease in the Western World, and the treatment paradigm is actively evolving. For decades, the most commonly used standard of care for localized muscle-invasive disease has been neoadjuvant chemotherapy followed by open radical cystectomy with urinary diversion. Considering the high postoperative morbidity of this procedure, efforts have focused on improving patient outcomes. Over the past decade, substantial advances have been introduced in imaging, prehabilitation, perioperative care, robotic surgery and organ-sparing techniques. Bladder preservation after complete clinical response to neoadjuvant treatment or after trimodal treatment is increasingly being implemented. In addition, novel biomarkers are increasingly being used to monitor treatment response and select patients for adequate therapy. Last, innovative approaches, such as intraoperative imaging, sentinel lymph-node biopsy or the use of artificial intelligence, are currently under investigation. Radical cystectomy with urinary diversion is the standard of care for the treatment of localized muscle-invasive bladder cancer but is associated with severe morbidity. This Review highlights advancements in several aspects of bladder cancer care, including surgery techniques, prehabilitation measures, multimodal treatments and novel biomarkers, aimed at improving patient selection, optimizing local control and improving surgical outcomes.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 4","pages":"266-282"},"PeriodicalIF":14.6,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145396910","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":"Excluding PLND in favourable intermediate-risk prostate cancer: a PSMA-PET-directed perspective","authors":"David Song, Kamil Malshy, Edward M. Messing, Jean V. Joseph, Jathin Bandari","doi":"10.1038/s41585-025-01105-8","DOIUrl":"10.1038/s41585-025-01105-8","url":null,"abstract":"Deciding whether to perform pelvic lymph node dissection at the time of prostate cancer surgery could be assisted by using prostate-specific membrane antigen-PET imaging. In favourable intermediate-risk prostate cancer, this imaging technique could be used to identify patients who could forego pelvic lymph node dissection.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 8","pages":"492-493"},"PeriodicalIF":13.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357750","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":"Clinical translation of polygenic scores for prostate cancer screening","authors":"Dmitry Ratner, Jason L. Vassy","doi":"10.1038/s41585-025-01095-7","DOIUrl":"10.1038/s41585-025-01095-7","url":null,"abstract":"Interest in using polygenic scores (PGS) to improve the risk stratification for and early detection of prostate cancer is considerable. Despite the absence of clinical guidelines for the use of prostate cancer PGS in patient care, existing and emerging standards for the clinical translation and reporting of genetic testing generally and PGS specifically provide a relevant framework to help guide these efforts. This framework is intended to harmonize advances in the development of PGS clinical assays and standardization of PGS reporting in the context of prostate cancer PGS specifically. The analytical and clinical validity of prostate cancer PGS have been progressively refined, but evidence firmly establishing clinical utility beyond modelling studies is still lacking. Standardized approaches for designing, explaining and reporting prostate cancer PGS are key to accelerating clinical implementation in a manner that would increase access to the benefits of precision prostate cancer screening to patients across ancestry backgrounds. In this Review, the authors describe standards informing the development and use of polygenic scores and illustrate their application to advance the clinical translation of polygenic scores to precision prostate cancer screening.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 4","pages":"256-265"},"PeriodicalIF":14.6,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283445","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}