European urology oncology最新文献

{"title":"A Phase 1b/2 Study of Talazoparib and Axitinib in Patients with Advanced Clear-cell Renal Cell Carcinoma.","authors":"Ritesh R Kotecha, Sahil D Doshi, Andrea Knezevic, Rachel Jacobi, Hyung Jun Woo, David H Aggen, Deaglan J McHugh, Neil J Shah, Maria I Carlo, Niamh M Keegan, Yogini Gayadin, Joshua Chaim, Mark T A Donoghue, Gopa Iyer, Chung-Han Lee, Darren R Feldman, Robert J Motzer, Martin H Voss","doi":"10.1016/j.euo.2025.03.010","DOIUrl":"https://doi.org/10.1016/j.euo.2025.03.010","url":null,"abstract":"<p><p>Inactivation of the VHL gene leads to HIF accumulation, angiogenesis, and genomic instability. In this phase 1b/2 study, we assessed the safety and antitumor activity of axitinib combined with talazoparib in treatment-refractory clear-cell renal cell carcinoma (ccRCC). Patients received escalating doses of talazoparib with a fixed standard dose of axitinib in a 3 + 3 design. This was followed by a dose expansion phase in a separate cohort. The primary endpoints were determination of the recommended phase 2 dose (RP2D) and the objective response rate. From 2020 to 2023, 23 patients with ccRCC were enrolled: 15 in the dose escalation cohort and eight in the dose expansion cohort. The RP2D was identified as talazoparib 1 mg daily with axitinib 5 mg twice daily. At the RP2D, 13/14 patients discontinued treatment because of disease progression. Median progression-free survival was 6.1 mo (95% confidence interval 3.5-8.4). Thirteen patients (56%) experienced at least one grade 3+ treatment-emergent adverse event (AE), while nine (39%) experienced at least one treatment-related grade ≥3 AE, of which diarrhea, nausea, and anemia were the most common. This is the first report on a VEGFR-targeted tyrosine kinase inhibitor combined with a PARP inhibitor for ccRCC. While our results demonstrate the safety of this strategy, the combination did not meet a predefined efficacy threshold for continued evaluation. This trial is registered on Clinicaltrials.gov as NCT04337970.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751760","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":"Predictive Factors for Oligometastatic Renal Cell Carcinoma Treated with Stereotactic Radiation: A Retrospective Study.","authors":"Allen Yen, Shanshan Tang, Alana Christie, Joseph Kwon, Mihailo Miljanic, Tidie Song, Aurelie Garant, Chul Ahn, Ang Gao, Robert Timmerman, James Brugarolas, Jing Wang, Raquibul Hannan","doi":"10.1016/j.euo.2025.03.009","DOIUrl":"https://doi.org/10.1016/j.euo.2025.03.009","url":null,"abstract":"<p><strong>Background and objective: </strong>Stereotactic ablative radiotherapy (SAbR) has shown promise in controlling oligometastatic renal cell carcinoma (omRCC). Careful patient selection is critical, and yet the selection criteria remain unknown for patients who will not be harmed by delayed systemic therapy using SAbR. Here, we analyzed long-term follow-up of omRCC patients treated with SAbR to derive the predictors of survival benefit.</p><p><strong>Methods: </strong>We retrospectively reviewed patients with up to five omRCC sites treated with sequential SAbR from November 2007 to July 2022. Overall survival (OS), progression-free survival (PFS), local control (LC), and toxicity were analyzed. The predictors of PFS were analyzed using a univariate analysis and a Cox proportional hazard (CPH) model-based machine learning approach.</p><p><strong>Key findings and limitations: </strong>We analyzed 153 patients who underwent SAbR to 337 metastases with a median follow-up of 27 mo. The median OS and PFS were 61.3 and 32 mo, respectively. The rate of grade ≥3 toxicity was 1.3%, and the 3-yr rate of LC was 98%. Patients with bone and brain metastases had lower PFS on the univariate analysis. When compared with historical controls, the delayed-onset PFS with first-line systemic therapy in this cohort was not compromised. The CPH model found bone, brain, and number of metastases at diagnosis to be the predictors of PFS, with a C-index of 0.66 and 1-yr area under the curve of 0.68.</p><p><strong>Conclusions and clinical implications: </strong>For selected patients, SAbR is effective in controlling omRCC for >2 yr and can delay systemic therapy without compromising patient outcome. Bone and brain metastases, as well as an increasing number of metastases are poor predictive factors for omRCC patients treated with sequential SAbR who may benefit from upfront systemic therapy. Prospective studies are required to verify these findings.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751763","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":"Hall of Fame","authors":"","doi":"10.1016/S2588-9311(25)00075-6","DOIUrl":"10.1016/S2588-9311(25)00075-6","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 2","pages":"Page xi"},"PeriodicalIF":8.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683049","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":"Treatment of Metastatic Renal Cell Carcinoma: Lack of Consensus Urges the Need for a Well-organized Multidisciplinary Team.","authors":"Stijn Muselaers, Daniel Heng, Chiara Ciccarese, Shankar Siva","doi":"10.1016/j.euo.2025.02.008","DOIUrl":"https://doi.org/10.1016/j.euo.2025.02.008","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639444","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":"Stereotactic Radiation for Primary Renal Cell Carcinoma: Is It Ready for Prime Time?","authors":"Raquibul Hannan, Veronica Mollica, Carlotta Palumbo, Selcuk Erdem","doi":"10.1016/j.euo.2025.02.014","DOIUrl":"https://doi.org/10.1016/j.euo.2025.02.014","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633764","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":"Active Surveillance of Grade Group 2 Prostate Cancer: Oncological Outcomes from a Contemporary European Cohort.","authors":"Michael Baboudjian, Riccardo Leni, Marco Oderda, Arthur Peyrottes, Claudia Kesch, Mulham Al-Nader, Alessandro Uleri, Charles Dariane, Helene Baud, Jonathan Olivier, Anna Redondo Rios, Francesco Sanguedolce, Vincent Benard, Olivier Windisch, Massimo Valerio, Giorgio Gandaglia, Guillaume Ploussard","doi":"10.1016/j.euo.2025.01.009","DOIUrl":"https://doi.org/10.1016/j.euo.2025.01.009","url":null,"abstract":"<p><strong>Background and objective: </strong>Uptake of active surveillance for patients with Gleason grade group (GG) 2 prostate cancer (PCa) remains low. Magnetic resonance imaging (MRI) before biopsy would allow better patient selection, but there are no published data on this strategy. Our aim was to report one of the first European AS series of patients with GG 2 PCa selected via MRI before image-guided biopsy.</p><p><strong>Methods: </strong>This multicenter study enrolled patients with GG 2 PCa managed with AS between 2016 and 2024 in ten reference centers in France, Spain, Italy, Switzerland, and Germany. Patients deemed unsuitable for curative treatment (ie, watchful waiting) were excluded. The primary endpoint was metastasis-free survival.</p><p><strong>Key findings and limitations: </strong>A total of 139 patients with GG 2 PCa were included. Baseline MRI revealed a lesion with a Prostate Imaging-Reporting and Data System score of 4-5 in 81 patients (59%). Median event-free follow-up was 38 mo (interquartile range 20-63). Two cases of metastasis were observed, and there were no deaths due to PCa. The estimated 3-yr metastasis-free survival rate was 98.1% (95% confidence interval 95.5-100%). Overall, 56 patients underwent definitive treatment and 26 were reclassified as having GG 3 PCa during follow-up. Among the 28 patients who underwent radical prostatectomy, final pathology revealed adverse features (GG 3 and/or pT3a) in 13 cases (46%), but very aggressive disease (GG ≥4 and/or ≥pT3b and/or pN1) was noted in only two cases (7%). There were no statistically significant differences in outcomes between groups that did and did not meet the European Association of Urology inclusion criteria for AS (all log-rank tests p > 0.05).</p><p><strong>Conclusions and clinical implications: </strong>In the era of prebiopsy MRI and image-guided biopsy, AS is a safe management option for selected patients with GG 2 PCa. Future studies should focus on redefining current inclusion criteria for AS in the targeted biopsy era, as many patients with GG 2 PCa are at low absolute risk of distant progression.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448353","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":"Are Patients with Prostate Imaging Reporting and Data System 5 Lesions Eligible for Active Surveillance? A Multicentric European Study.","authors":"Arthur Peyrottes, Michael Baboudjian, Romain Diamand, Quentin Ducrot, Cyril Vitard, Arthur Baudewyns, Olivier Windisch, Julien Anract, Charles Dariane, Thibault Tricard, Julien Sarkis, Yvanne Sadreux, Marco Oderda, Thibaut Long Depaquit, Alexandre De La Taille, Jonathan Olivier, Laurent Brureau, Olivier Rouviere, Sébastien Crouzet, Alain Ruffion, François Desgrandchamps, Matthieu Roumiguie, Morgan Rouprêt, Guillaume Ploussard, Gaelle Fiard","doi":"10.1016/j.euo.2025.01.008","DOIUrl":"https://doi.org/10.1016/j.euo.2025.01.008","url":null,"abstract":"<p><strong>Background and objective: </strong>Patients with Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions are at a high risk of clinically significant prostate cancer (PCa), extracapsular extension, and biochemical recurrence (BCR) after local treatment. Managing these patients with active surveillance (AS) can be particularly challenging when targeted biopsies indicate favorable-risk tumors. This study aims to evaluate the outcomes of patients with PI-RADS 5 lesions managed with AS.</p><p><strong>Methods: </strong>We analyzed data from 126 patients treated at 16 centers in France, Italy, Switzerland, and Belgium, whose initial magnetic resonance imaging revealed at least one PI-RADS 5 lesion and who subsequently underwent AS. The primary endpoint was BCR-free survival. The secondary endpoints included metastasis-free survival, time to biopsy grade reclassification, and time to AS discontinuation, along with their predictors.</p><p><strong>Key findings and limitations: </strong>After a median follow-up of 36 mo after confirmatory biopsies (95% confidence interval [CI] 23-55), BCR was observed in five patients, with the median time not reached. The 5-yr BCR-free survival rate was 88% (95% CI 79-99%). No metastatic progression was reported. Seventeen patients experienced biopsy grade reclassification (median time not reached), and 55 patients discontinued AS. The median time to AS discontinuation was 55 mo (95% CI 46 mo-not applicable). The 5-yr AS discontinuation-free survival rate was 41% (95% CI 30.8-54.6%). On a multivariate Cox regression analysis, baseline prostate-specific antigen density and the percentage of positive biopsy cores were associated with biopsy grade reclassification, AS discontinuation, and BCR.</p><p><strong>Conclusions and clinical implications: </strong>With strict monitoring, AS is a safe management option for patients with PI-RADS 5 lesions and favorable-risk PCa. Limitations are mainly inherent to the retrospective design of this study.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448481","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":"Comparative Performance of Machine Learning Models in Reducing Unnecessary Targeted Prostate Biopsies.","authors":"Fuyao Chen, Roxana Esmaili, Ghazal Khajir, Tal Zeevi, Moritz Gross, Michael Leapman, Preston Sprenkle, Amy C Justice, Sandeep Arora, Jeffrey C Weinreb, Michael Spektor, Steffan Huber, Peter A Humphrey, Angelique Levi, Lawrence H Staib, Rajesh Venkataraman, Darryl T Martin, John A Onofrey","doi":"10.1016/j.euo.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.euo.2025.01.005","url":null,"abstract":"<p><strong>Background and objective: </strong>Conventional core needle biopsy for prostate cancer diagnosis can lead to diagnostic uncertainty and complications, prompting exploration of alternative risk assessment approaches that use clinical and imaging features. Our aim was to evaluate the effectiveness of machine learning (ML) models in reducing unnecessary biopsies.</p><p><strong>Methods: </strong>We conducted a retrospective analysis of data for 1884 patients across two academic centers who underwent prostate magnetic resonance imaging and biopsy between 2016 and 2020 or 2004 and 2011. Twelve ML models were assessed for prediction of clinically significant prostate cancer (csPCa; Gleason grade group ≥2) using combinations of clinical features, including patient age, prostate-specific antigen level and density, Prostate Imaging-Reporting and Data System/Likert score, lesion volume, and gland volume. The models were trained and validated using a tenfold split for intrasite, intersite, and combined-site data sets. Model effectiveness was evaluated using the area under the receiver operating characteristic curve and decision curve analysis.</p><p><strong>Key findings and limitations: </strong>The best-performing ML model would reduce the number of biopsies by 13.07% at a false-negative rate of 1.91%. Performance was consistent across sites, although the study is limited by the small number of centers and the absence of specific clinical data.</p><p><strong>Conclusions and clinical implications: </strong>ML-enhanced clinical models provide an effective and generalizable approach for prediction of csPCa using standard clinical data. These models allow personalized risk assessment and follow-up, support clinical decision-making, and improve workflow efficiency.</p><p><strong>Patient summary: </strong>Models that are enhanced by machine learning can predict the severity of prostate cancer and help doctors in tailoring treatments for individual patients. This approach can simplify health care decisions and improve clinical efficiency.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382127","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":"Towards a Consensus on the Management of Metastatic Renal Cell Carcinoma: Insights from a European Delphi Study.","authors":"Laurence Albiges, Marine Gross-Goupil, Philippe Barthélémy, Aristotelis Bamias, Jens Bedke, Axel Bex, Mário Fontes-Sousa, Viktor Grünwald, Bohuslav Melichar, Lisa Pickering, Camillo Porta, Giuseppe Procopio, Sylvie Rottey, Manuela Schmidinger, Cristina Suárez, Guillermo Velasco, Bernard Escudier","doi":"10.1016/j.euo.2025.01.007","DOIUrl":"https://doi.org/10.1016/j.euo.2025.01.007","url":null,"abstract":"<p><strong>Background and objective: </strong>Management of metastatic renal cell carcinoma (mRCC) remains complex despite clinical guidelines. The aim of this Delphi study was to achieve consensus among RCC experts on the definition, diagnosis, and first-line treatments for mRCC.</p><p><strong>Methods: </strong>Between May 2023 and April 2024, 14 experts from ten European countries completed two Delphi rounds of a 51-item questionnaire covering four topics: (1) oligometastatic RCC; (2) first-line treatment for metastatic clear-cell RCC; (3) treatment duration for metastatic clear-cell RCC; and (4) treatment of non-clear-cell RCC. Agreement was scored as absent/poor (<50%), fair (50-74%), or consensus (≥75%).</p><p><strong>Key findings and limitations: </strong>Consensus was reached for 12 of 51 items (24%) in the first round and 25 of 49 items (51%) by the study end. Notably, 79% of experts defined oligometastatic RCC as five or fewer metastases and agreed that it typically does not require immediate systemic treatment. All experts (100%) emphasized the importance of clinical performance status in guiding treatment for metastatic clear-cell RCC, with 86% agreeing on additional factors such as International Society of Urological Pathology grade and sarcomatoid features. Nivolumab plus cabozantinib was favored for patients with brain or bone metastases (93% and 86% agreement, respectively), while there was fair agreement on pembrolizumab plus lenvatinib for patients with liver metastases. In addition, 71% supported stopping immune checkpoint inhibitors after 2 yr, while 86% agreed on the undefined duration of tyrosine kinase inhibitor therapy.</p><p><strong>Conclusions and clinical implications: </strong>This Delphi study offers insights into mRCC management, and highlights the importance of multidisciplinary discussions for this challenging disease.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382130","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":"Re: Bertrand F. Tombal, Francisco Gomez-Veiga, Alvaro Gomez-Ferrer, et al. A Phase 2 Randomized Open-label Study of Oral Darolutamide Monotherapy Versus Androgen Deprivation Therapy in Men with Hormone-sensitive Prostate Cancer (EORTC-GUCG 1532). Eur Urol Oncol 2024;7:1051-60.","authors":"Francesco Montorsi, Giorgio Gandaglia, Francesco Barletta, Alberto Briganti","doi":"10.1016/j.euo.2025.01.012","DOIUrl":"https://doi.org/10.1016/j.euo.2025.01.012","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374042","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}