Pub Date : 2025-10-30DOI: 10.1038/s41585-025-01098-4
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
{"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":"https://doi.org/10.1038/s41585-025-01098-4","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"3 1","pages":""},"PeriodicalIF":15.3,"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}
Pub Date : 2025-10-13DOI: 10.1038/s41585-025-01095-7
Dmitry Ratner,Jason L Vassy
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.
{"title":"Clinical translation of polygenic scores for prostate cancer screening.","authors":"Dmitry Ratner,Jason L Vassy","doi":"10.1038/s41585-025-01095-7","DOIUrl":"https://doi.org/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.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"120 1","pages":""},"PeriodicalIF":15.3,"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}
Pub Date : 2025-10-13DOI: 10.1038/s41585-025-01099-3
Henry H Woo
{"title":"A urologist as a urological patient.","authors":"Henry H Woo","doi":"10.1038/s41585-025-01099-3","DOIUrl":"https://doi.org/10.1038/s41585-025-01099-3","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"19 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283444","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}
Immune-checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD1) and programmed cell death 1 ligand 1 (PDL1) have improved survival for patients with different types of solid tumour. However, clinical response in patients with muscle-invasive bladder cancer (MIBC) is limited, with only 20-30% demonstrating a sustained response. An improved understanding of ICI mechanisms and robust biomarkers will increase efficacy and enable patient stratification in MIBC. Hypoxia (low oxygen tension) and neutrophil infiltration are prevalent in MIBC and are associated with immunotherapy resistance. Hypoxia-associated extracellular matrix (ECM) remodelling can induce pro-tumour or anti-tumour neutrophil polarization through biomechanical and biochemical signalling. Hypoxia-associated ECM mechanisms alter neutrophil recruitment, polarization, activation and affect T cell-centric immunotherapies. However, the specific mechanisms by which hypoxia, ECM and neutrophils confer immunotherapy resistance in MIBC are not yet fully understood. ICI resistance could be overcome by targeting specific ECM remodelling-related and neutrophil-related pathways to elicit durable and efficacious responses in 70-80% of patients with MIBC who are currently non-responsive to ICIs.
{"title":"The hypoxic ECM and neutrophils in MIBC immunotherapy resistance.","authors":"Fraser Child,Sapna Lunj,Julie Gough,Martin J Humphries,Luisa Vanesa Biolatti,Peter J Hoskin,Ananya Choudhury,Conrado Guerrero Quiles","doi":"10.1038/s41585-025-01092-w","DOIUrl":"https://doi.org/10.1038/s41585-025-01092-w","url":null,"abstract":"Immune-checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD1) and programmed cell death 1 ligand 1 (PDL1) have improved survival for patients with different types of solid tumour. However, clinical response in patients with muscle-invasive bladder cancer (MIBC) is limited, with only 20-30% demonstrating a sustained response. An improved understanding of ICI mechanisms and robust biomarkers will increase efficacy and enable patient stratification in MIBC. Hypoxia (low oxygen tension) and neutrophil infiltration are prevalent in MIBC and are associated with immunotherapy resistance. Hypoxia-associated extracellular matrix (ECM) remodelling can induce pro-tumour or anti-tumour neutrophil polarization through biomechanical and biochemical signalling. Hypoxia-associated ECM mechanisms alter neutrophil recruitment, polarization, activation and affect T cell-centric immunotherapies. However, the specific mechanisms by which hypoxia, ECM and neutrophils confer immunotherapy resistance in MIBC are not yet fully understood. ICI resistance could be overcome by targeting specific ECM remodelling-related and neutrophil-related pathways to elicit durable and efficacious responses in 70-80% of patients with MIBC who are currently non-responsive to ICIs.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"7 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283443","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}
Pub Date : 2025-10-13DOI: 10.1038/s41585-025-01100-z
Melissa L Abel,Adam Sharp,Edwin M Posadas,Fatima Karzai,Frank I Lin,Peter L Choyke,Ravi A Madan
{"title":"Therapeutic targeting of prostate-specific membrane antigen could limit its potential as benchmark imaging.","authors":"Melissa L Abel,Adam Sharp,Edwin M Posadas,Fatima Karzai,Frank I Lin,Peter L Choyke,Ravi A Madan","doi":"10.1038/s41585-025-01100-z","DOIUrl":"https://doi.org/10.1038/s41585-025-01100-z","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"19 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145283694","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}
Pub Date : 2025-10-10DOI: 10.1038/s41585-025-01096-6
Magdalena Görtz, Carlos Brandl, Anna Nitschke, Anja Riediger, Daniel Stromer, Michael Byczkowski, Vincent Heuveline, Matthias Weidemüller
‘Digital twins’, also called ‘digital patient twins’ or ‘virtual human twins’ — digital patient-specific models derived from multimodal health data — are a strong focus in health care and are emerging as a promising tool for improving personalized care in uro-oncology. These models can integrate clinical, genomic, imaging and histopathological information to simulate organ behaviour and disease progress as well as predict responses to treatments. The concept of digital twins has shown potential in various fields, but its application in uro-oncology is still evolving, with few assessments of their feasibility and clinical utility. The advent of artificial intelligence adds a new dimension to their development, potentially enabling the synthesis of diverse, high-quality datasets to improve modelling accuracy and support real-time decision-making. However, substantial challenges exist, including data integration, patient privacy, computational demands and ethical frameworks. In addition, the interpretability of predictions remains essential for gaining clinical trust and guiding patient-centred decisions. The use of digital twins in uro-oncology has the potential to improve patient stratification and treatment planning; however, barriers must be overcome for their successful implementation in clinical routine. By integrating new technologies, fostering interdisciplinary collaboration and prioritizing transparency, digital twins could shape the future of precision uro-oncology. This Review focuses on the clinical effects and translational potential of digital twin applications in uro-oncology, highlights challenges and discusses future directions for implementing digital twins to achieve personalized uro-oncological diagnostics and treatment.
{"title":"Digital twins for personalized treatment in uro-oncology in the era of artificial intelligence","authors":"Magdalena Görtz, Carlos Brandl, Anna Nitschke, Anja Riediger, Daniel Stromer, Michael Byczkowski, Vincent Heuveline, Matthias Weidemüller","doi":"10.1038/s41585-025-01096-6","DOIUrl":"10.1038/s41585-025-01096-6","url":null,"abstract":"‘Digital twins’, also called ‘digital patient twins’ or ‘virtual human twins’ — digital patient-specific models derived from multimodal health data — are a strong focus in health care and are emerging as a promising tool for improving personalized care in uro-oncology. These models can integrate clinical, genomic, imaging and histopathological information to simulate organ behaviour and disease progress as well as predict responses to treatments. The concept of digital twins has shown potential in various fields, but its application in uro-oncology is still evolving, with few assessments of their feasibility and clinical utility. The advent of artificial intelligence adds a new dimension to their development, potentially enabling the synthesis of diverse, high-quality datasets to improve modelling accuracy and support real-time decision-making. However, substantial challenges exist, including data integration, patient privacy, computational demands and ethical frameworks. In addition, the interpretability of predictions remains essential for gaining clinical trust and guiding patient-centred decisions. The use of digital twins in uro-oncology has the potential to improve patient stratification and treatment planning; however, barriers must be overcome for their successful implementation in clinical routine. By integrating new technologies, fostering interdisciplinary collaboration and prioritizing transparency, digital twins could shape the future of precision uro-oncology. This Review focuses on the clinical effects and translational potential of digital twin applications in uro-oncology, highlights challenges and discusses future directions for implementing digital twins to achieve personalized uro-oncological diagnostics and treatment.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 1","pages":"29-39"},"PeriodicalIF":14.6,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145261507","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}
Pub Date : 2025-10-08DOI: 10.1038/s41585-025-01069-9
Karl H. Pang, Hussain M. Alnajjar, Alex Lal, Asif Muneer
Priapism is an abnormal prolonged penile erection that persists in the absence of any sexual stimulation. Priapism can be subcategorized into three types: ischaemic (low-flow or veno-occlusive), non-ischaemic (high-flow or arterial) and stuttering priapism. Ischaemic priapism is the most common subtype and is associated with multiple aetiologies, most commonly haemoglobinopathies and antipsychotic medications. The mechanisms underlying stuttering priapism are complex, and involve dysregulation of the nitric oxide signalling pathway, Rho–Rho kinase pathway, adenosine, opiorphins, oxidative stress and androgens. The investigation and management of priapism involve a stepwise approach. A clinical history, examination and a blood-gas analysis from the corpus cavernosum helps to distinguish between ischaemic and non-ischaemic subtypes. Colour Doppler ultrasonography and penile MRI can be used in more complex cases, or those with a delayed presentation. Treatment involves cavernosal blood aspiration followed by instillation of an α-adrenergic receptor agonist such as phenylephrine, proceeding to penile shunt surgery (within the first 24–48 h) if the priapism persists. Insertion of a penile prosthesis is indicated when a shunting procedure or penoscrotal decompression fails, or if a patient presents with a priapism persisting longer than 36–48 h depending on the guidelines used. For non-ischaemic priapism following failed conservative treatment, selective arterial embolization of the arteriocorporal fistula can be performed. The aetiology and pathophysiology of the different priapism subtypes help to determine the management of specific patients. Priapism — an abnormal prolonged penile erection that persists in the absence of any sexual stimulation — can be subcategorized into three types: ischaemic (low-flow or veno-occlusive), non-ischaemic (high-flow or arterial) and stuttering, also known as recurrent ischaemic, priapism. The mechanisms underlying stuttering priapism are complex and involve dysregulation of the nitric oxide signalling pathway, Rho–Rho kinase pathway, adenosine, opiorphins, oxidative stress and androgens, and treatment can target these pathways, or be surgical in approach. In this Review, the authors discuss the pathology of the different types of priapism and provide an update on the different therapeutic options available.
{"title":"An update on mechanisms and treatment options for priapism","authors":"Karl H. Pang, Hussain M. Alnajjar, Alex Lal, Asif Muneer","doi":"10.1038/s41585-025-01069-9","DOIUrl":"10.1038/s41585-025-01069-9","url":null,"abstract":"Priapism is an abnormal prolonged penile erection that persists in the absence of any sexual stimulation. Priapism can be subcategorized into three types: ischaemic (low-flow or veno-occlusive), non-ischaemic (high-flow or arterial) and stuttering priapism. Ischaemic priapism is the most common subtype and is associated with multiple aetiologies, most commonly haemoglobinopathies and antipsychotic medications. The mechanisms underlying stuttering priapism are complex, and involve dysregulation of the nitric oxide signalling pathway, Rho–Rho kinase pathway, adenosine, opiorphins, oxidative stress and androgens. The investigation and management of priapism involve a stepwise approach. A clinical history, examination and a blood-gas analysis from the corpus cavernosum helps to distinguish between ischaemic and non-ischaemic subtypes. Colour Doppler ultrasonography and penile MRI can be used in more complex cases, or those with a delayed presentation. Treatment involves cavernosal blood aspiration followed by instillation of an α-adrenergic receptor agonist such as phenylephrine, proceeding to penile shunt surgery (within the first 24–48 h) if the priapism persists. Insertion of a penile prosthesis is indicated when a shunting procedure or penoscrotal decompression fails, or if a patient presents with a priapism persisting longer than 36–48 h depending on the guidelines used. For non-ischaemic priapism following failed conservative treatment, selective arterial embolization of the arteriocorporal fistula can be performed. The aetiology and pathophysiology of the different priapism subtypes help to determine the management of specific patients. Priapism — an abnormal prolonged penile erection that persists in the absence of any sexual stimulation — can be subcategorized into three types: ischaemic (low-flow or veno-occlusive), non-ischaemic (high-flow or arterial) and stuttering, also known as recurrent ischaemic, priapism. The mechanisms underlying stuttering priapism are complex and involve dysregulation of the nitric oxide signalling pathway, Rho–Rho kinase pathway, adenosine, opiorphins, oxidative stress and androgens, and treatment can target these pathways, or be surgical in approach. In this Review, the authors discuss the pathology of the different types of priapism and provide an update on the different therapeutic options available.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"22 12","pages":"826-845"},"PeriodicalIF":14.6,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246499","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}
Pub Date : 2025-10-08DOI: 10.1038/s41585-025-01097-5
Mihir S. Shah, Matthew Buck
Large language models have been rapidly adopted in general and clinically; they could also be incorporated into medical education. Results of a recent study suggest that a combination of traditional learning methods and large language model use could improve learning outcomes for medical students.
{"title":"Man plus machine: large language models can augment medical student education","authors":"Mihir S. Shah, Matthew Buck","doi":"10.1038/s41585-025-01097-5","DOIUrl":"10.1038/s41585-025-01097-5","url":null,"abstract":"Large language models have been rapidly adopted in general and clinically; they could also be incorporated into medical education. Results of a recent study suggest that a combination of traditional learning methods and large language model use could improve learning outcomes for medical students.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"23 1","pages":"12-12"},"PeriodicalIF":14.6,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246500","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}
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