European urologyPub Date : 2025-05-16DOI: 10.1016/j.eururo.2025.05.009
Jan Adamowicz, Krzysztof Koper, Tomasz Drewa
{"title":"Re: Preventative Function-sparing Radical Prostatectomy: Experience in a Tertiary Referral Centre","authors":"Jan Adamowicz, Krzysztof Koper, Tomasz Drewa","doi":"10.1016/j.eururo.2025.05.009","DOIUrl":"https://doi.org/10.1016/j.eururo.2025.05.009","url":null,"abstract":"No Abstract","PeriodicalId":12223,"journal":{"name":"European urology","volume":"24 1","pages":""},"PeriodicalIF":23.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067299","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}
European urologyPub Date : 2025-05-16DOI: 10.1016/j.eururo.2025.05.003
W. Marston Linehan, Christopher J. Ricketts, Daniel R. Crooks, Laura S. Schmidt
{"title":"The Critical Role of FLCN, TFE3, and TFEB in Bioenergetic and Nutrient Sensing, Renal Cancer Tumorigenesis and Metabolic Health","authors":"W. Marston Linehan, Christopher J. Ricketts, Daniel R. Crooks, Laura S. Schmidt","doi":"10.1016/j.eururo.2025.05.003","DOIUrl":"https://doi.org/10.1016/j.eururo.2025.05.003","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>FLCN function</h2>FLCN is an ancient cellular bioenergetic and nutrient sensor that controls activation of the TFE3 and TFEB transcription factors and regulates lysosomal and mitochondrial biogenesis and function. FLCN, and its binding partner FNIP1, act as a GTP-activating protein (GAP) for the small GTPase Ras-related GTP-binding protein C (RagC). FLCN and FNIP activate a noncanonical mTORC1 signaling pathway that leads to phosphorylation of members of the microphthalmia/transcription factor E (MiT/TFE) family</section></section><section><section><h2><em>FLCN</em> mutation in BHD RCC</h2>BHD-associated hybrid RCC, chromophobe RCC, and oncocytoma tumors are characterized by biallelic inactivation of <em>FLCN</em> due to a combination of the germline pathogenic variation and somatic loss of function of the remaining allele via “second hit” mutation or deletion events. FLCN loss in BHD renal tumors leads to dephosphorylation and nuclear translocation of TFE3 [7] and TFEB, resulting in increased lysosomal and mitochondrial biogenesis (Fig. 1D). This is reflected in immunohistochemical</section></section><section><section><h2>Dysregulation of MiT/TFE transcription factors in renal cancer</h2>Activation of TFE3 and/or TFEB is recognized as an important driver event in many different types of renal cancer, including sporadic RCC's resulting from somatic TFE3/TFEB translocation or amplification of TFEB, as well as hereditary RCCs caused by germline variants in <em>MITF</em>, <em>TSC1</em>, <em>TSC2</em>, and <em>PRDM10</em>. These tumor types demonstrate overlapping histologies with BHD-associated RCCs, with TFE3/TFEB translocation RCC and PRDM10-associated RCC strongly reflecting the rarer but more aggressive</section></section><section><section><h2>Clinical management and therapy</h2>Identification of the <em>FLCN</em> gene, which was made possible by studying patients affected by BHD, has enabled clinicians to improve clinical management and surgical care for these patients. It also provides a foundation for the development of therapeutic or preventive approaches for BHD using small molecules that target TFE3/TFEB stability, agents targeting PGC1α transcriptional activity, antibody-drug conjugates and CAR-T cell therapies targeting cell-surface GPNMB expression.</section></section><section><section><h2>Implications of the physiologic role of FLCN on metabolic health</h2>As a sensor of bioenergetic and nutrient stress, FLCN is thought to potentially have significant importance in human health. FLCN is likely to play a critical role in the body’s response to exercise and restriction of caloric intake on long-term health. Gosis et al [8] showed that a decrease in FLCN in the liver could reverse nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in animals fed a diet high in fructose, cholesterol, and trans fats. Zhang et al [9] demonstrated that</section></section>","PeriodicalId":12223,"journal":{"name":"European urology","volume":"30 1","pages":""},"PeriodicalIF":23.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067384","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}
European urologyPub Date : 2025-05-16DOI: 10.1016/j.eururo.2025.04.009
Catherine Graham, Laurence Albiges, Marc-Oliver Grimm, Thomas Powles
{"title":"Belzutifan in Europe: A New Targeted Therapy for Clear Cell Renal Cancer","authors":"Catherine Graham, Laurence Albiges, Marc-Oliver Grimm, Thomas Powles","doi":"10.1016/j.eururo.2025.04.009","DOIUrl":"https://doi.org/10.1016/j.eururo.2025.04.009","url":null,"abstract":"No Abstract","PeriodicalId":12223,"journal":{"name":"European urology","volume":"54 1","pages":""},"PeriodicalIF":23.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067289","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}
European urologyPub Date : 2025-05-16DOI: 10.1016/j.eururo.2025.05.001
Ella Schofield, James W.F. Catto, Jon Griffin
{"title":"Subtypes and Sequencing in Bladder Cancer: Powering Personalised Treatment or Extraneous Information?","authors":"Ella Schofield, James W.F. Catto, Jon Griffin","doi":"10.1016/j.eururo.2025.05.001","DOIUrl":"https://doi.org/10.1016/j.eururo.2025.05.001","url":null,"abstract":"No Abstract","PeriodicalId":12223,"journal":{"name":"European urology","volume":"30 1","pages":""},"PeriodicalIF":23.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067287","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}
European urologyPub Date : 2025-05-16DOI: 10.1016/j.eururo.2025.05.010
David Hennes, Abdullah Al-Khanaty, David C. Chen, Eoin Dineen, Christa Babst, Nathan Lawrentschuk, Marlon L. Perera, Declan G. Murphy
{"title":"Re: Local Anaesthetic Transperineal Biopsy Versus Transrectal Prostate Biopsy in Prostate Cancer Detection (TRANSLATE): A Multicentre, Randomised, Controlled Trial","authors":"David Hennes, Abdullah Al-Khanaty, David C. Chen, Eoin Dineen, Christa Babst, Nathan Lawrentschuk, Marlon L. Perera, Declan G. Murphy","doi":"10.1016/j.eururo.2025.05.010","DOIUrl":"https://doi.org/10.1016/j.eururo.2025.05.010","url":null,"abstract":"No Abstract","PeriodicalId":12223,"journal":{"name":"European urology","volume":"18 1","pages":""},"PeriodicalIF":23.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067300","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}
European urologyPub Date : 2025-05-14DOI: 10.1016/j.eururo.2025.05.005
José Daniel Subiela, Pietro Scilipoti, Roberto Contieri, Nijati Lobo, Renate Pichler, Ashish M. Kamat
{"title":"Management Dilemma for Very High-risk Non–muscle-invasive Bladder Cancer: Real-World Data Challenge the Guideline Recommendation for Upfront Radical Cystectomy","authors":"José Daniel Subiela, Pietro Scilipoti, Roberto Contieri, Nijati Lobo, Renate Pichler, Ashish M. Kamat","doi":"10.1016/j.eururo.2025.05.005","DOIUrl":"https://doi.org/10.1016/j.eururo.2025.05.005","url":null,"abstract":"No Abstract","PeriodicalId":12223,"journal":{"name":"European urology","volume":"41 3 1","pages":""},"PeriodicalIF":23.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979667","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}
European urologyPub Date : 2025-05-10DOI: 10.1016/j.eururo.2025.04.023
Palle Osther
{"title":"Re: Development of Prediction Models for Severe Pain and Urinary Symptoms After Ureteroscopy with Ureteral Stent Placement: Results from the STENTS Study and Initial Validation of Pain Interference","authors":"Palle Osther","doi":"10.1016/j.eururo.2025.04.023","DOIUrl":"https://doi.org/10.1016/j.eururo.2025.04.023","url":null,"abstract":"No Abstract","PeriodicalId":12223,"journal":{"name":"European urology","volume":"1 1","pages":""},"PeriodicalIF":23.4,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931066","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}
European urologyPub Date : 2025-05-10DOI: 10.1016/j.eururo.2025.04.025
Douglas G. Ward, Richard T. Bryan
{"title":"Should We Incorporate Urinary Tumour DNA Status in Treatment Decisions for Patients with Non–muscle-invasive Bladder Cancer?","authors":"Douglas G. Ward, Richard T. Bryan","doi":"10.1016/j.eururo.2025.04.025","DOIUrl":"https://doi.org/10.1016/j.eururo.2025.04.025","url":null,"abstract":"No Abstract","PeriodicalId":12223,"journal":{"name":"European urology","volume":"126 1","pages":""},"PeriodicalIF":23.4,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932650","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}