European urology oncology最新文献

{"title":"Prognostic Implications of Very High Decipher Scores in Prostate Cancer: Towards a Refined Genomic Risk Classification.","authors":"Rohan Sharma, Marcio C Moschovas, Seetharam K R Bhatt, Shady Saikali, Yu Ozawa, Marco Sandri, Yavuz Onol, Ahmed Gamal, Travis Rogers, Vipul R Patel","doi":"10.1016/j.euo.2025.09.009","DOIUrl":"https://doi.org/10.1016/j.euo.2025.09.009","url":null,"abstract":"<p><strong>Background and objective: </strong>The 22-gene Decipher genomic classifier (DGC) is validated for risk stratification in prostate cancer. Our aim was to evaluate the association of a novel very high-risk (VHR) group (DGC score >0.85) with recurrence outcomes after radical prostatectomy (RP) and to assess the impact of integrating DGC scores with Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) scores and European Association of Urology (EAU) biochemical recurrence (BCR) risk groups on prognostication.</p><p><strong>Methods: </strong>We retrospectively analyzed data for 1673 patients who underwent RP (2015 and 2022). DGC scores were categorized as low risk (<0.45), intermediate (0.45-0.60), high (0.61-0.85), or VHR (>0.85). BCR was analyzed using the Kaplan-Meier method and log-rank tests. DGC scores were combined with CAPRA-S scores, and separately with EAU BCR risk groups to assess associations with BCR. Associations between DGC scores and adverse pathological features were also evaluated.</p><p><strong>Key findings and limitations: </strong>Among the 1673 men who underwent RP, the incidence of adverse pathological features (International Society of Urological Pathology grade group ≥4, pT3b/T4, or pN1) increased with increasing DGC score (p < 0.001). DGC VHR was an independent predictor of BCR (hazard ratio 1.70, 95% confidence interval 1.26-2.52; p = 0.008). DGC scores further refined risk stratification within the EAU BCR and CAPRA-S risk groups. Decision curve analysis showed that combining DGC scores with CAPRA-S scores or EAU risk groups yielded a greater net benefit in comparison to using each model alone across the risk threshold range from 0.18 to 0.50. The retrospective, single-institution nature of the study highlights the need for external validation.</p><p><strong>Conclusion and clinical implications: </strong>A DGC score >0.85 delineates a distinct subgroup with markedly adverse oncologic outcomes. Recognition of this VHR category refines postoperative assessment and supports personalized adjuvant or salvage therapy.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257867","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 Trajectories in Metastatic Hormone-sensitive Prostate Cancer: A PIONEER+ Big Data Analysis.","authors":"Rossella Nicoletti, Alex Qinyang Liu, Susan Evans-Axelsson, Asieh Golozar, Katharina Beyer, Bertrand De Meulder, Riccardo Campi, Mauro Gacci, Jeremy Yuen-Chun Teoh, Carl Steinbesser, Ayman Hijazy, Artem Harbachou, James T Brash, Peter-Paul M Willemse, Teemu Murtola, Monique J Roobol, Jesus Moreno Sierra, Anders Bjartell, Axel S Merseburger, Pawel Rajwa, Philip Cornford, Thomas Abbott, James Ndow, Juan Gomez Rivas, Eleanor Davies, Qi Feng, Robert Snijder","doi":"10.1016/j.euo.2025.08.007","DOIUrl":"https://doi.org/10.1016/j.euo.2025.08.007","url":null,"abstract":"<p><strong>Background and objective: </strong>The treatment landscape for metastatic hormone-sensitive prostate cancer (mHSPC) is evolving rapidly. Real-world data (RWD) are essential to understand actual treatment use and outcomes. This study aimed to describe treatment trajectories and clinical outcomes in a large, multicenter RWD cohort under the PIONEER project.</p><p><strong>Methods: </strong>Eight European and US databases (2016-2020), including electronic health records, insurance claims, primary care data, and cancer registries, were standardized to the Observational Medical Outcome Partnership Common Data Model. Patients diagnosed with mHSPC and those receiving treatment were identified. The compared and analyzed outcomes included treatment switch, symptomatic progression, adverse events, and death.</p><p><strong>Key findings and limitations: </strong>In total, 107 438 patients with mHSPC were identified, and 67 909 received treatment. Most of the patients received androgen deprivation therapy (ADT) monotherapy (69.4%), followed by ADT + an androgen receptor pathway inhibitor (ARPI; 15.2%), ADT + chemotherapy (14.0%), and triplet therapy (1.2%). The use of ARPIs increased over time. ADT + ARPI showed the highest persistence (53.8%) and a 5-yr switch-free survival rate of up to 72.3%. ADT monotherapy had 5-yr switch-free survival rates of 21.3-58.6% and adverse event-free survival rates of 64.7-81.2%. Addition of an ARPI improved switch-free survival (24.1-72.3%) but lowered adverse event-free survival (55.2-82.7%). Chemotherapy-based and triplet therapies showed variable results without consistent survival benefit. Limitations include residual confounding, inconsistent adverse event reporting, and possible data overlap.</p><p><strong>Conclusions and clinical implications: </strong>This is the largest RWD study of systemic mHSPC treatment. Despite evidence, ADT monotherapy remains the most used first-line therapy. Increased use ADT + ARPI is associated with better persistence and improved outcomes in the real-world setting, supporting its broader adoption in clinical practice.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250528","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":"Cabazitaxel Versus Abiraterone or Enzalutamide for Poor-prognosis Metastatic Castration-resistant Prostate Cancer After Docetaxel: A Phase 2 Trial with a Circulating Tumor DNA Analysis.","authors":"Karan Parekh, Kim van der Zande, Sarah W S Ng, Cameron Herberts, Edmond M Kwan, Gillian Vandekerkhove, Vincent van der Noort, Milou P H Busard, Aart Beeker, Pieter van den Berg, Jeantine M de Feijter, Vincent Dezentje, Paul Hamberg, Danny Houtsma, Suzan Ras, Metin Tascilar, Rebecca D Tutuhatunewa-Louhanepessy, Yi Jou Ruby Liao, Sofie H Tolmeijer, Gráinne Donnellan, Kim N Chi, Alexander W Wyatt, Wilbert Zwart, Andries M Bergman","doi":"10.1016/j.euo.2025.07.006","DOIUrl":"https://doi.org/10.1016/j.euo.2025.07.006","url":null,"abstract":"<p><strong>Background and objective: </strong>Whether cabazitaxel or an androgen receptor pathway inhibitor (ARPI) is the optimal treatment option for poor-prognosis metastatic castration-resistant prostate cancer (mCRPC), progressing on docetaxel, remains unclear. There are limited prospective data supporting a preference for one of these treatments and few candidate biomarkers to inform individual patient management. This study aims to compare the clinical efficacy of cabazitaxel versus ARPIs in patients with poor-prognosis mCRPC who have progressed on docetaxel, and to evaluate the prognostic and predictive utility of circulating tumor DNA (ctDNA) in this treatment-refractory population.</p><p><strong>Methods: </strong>A multicenter, open-label, phase 2b trial randomized poor-prognosis mCRPC patients to an ARPI (1000 mg abiraterone plus prednisone or 160 mg enzalutamide daily) or cabazitaxel (25 mg/m² every 3 wk plus prednisone daily). The primary endpoint was the clinical benefit rate (CBR) at 12 wk. The secondary endpoints included radiographic progression-free survival (rPFS), overall survival (OS), and PSA50 response. Genomic analyses on plasma utilized targeted cell-free DNA sequencing at baseline, 12 wk, and progression.</p><p><strong>Key findings and limitations: </strong>In total, 106 patients were randomized. The CBR at 12 wk was 62.3% (66/106), with no difference between treatments (p = 0.54). Between groups, rPFS and OS (median follow-up of 30.9 mo) were not different. PSA50 was higher in the ARPI arm (47.2%) than in the cabazitaxel arm (26.9%; p = 0.04). Prior ARPI exposure (in 37.7%) predicted inferior outcomes on ARPIs but not on cabazitaxel. Adverse events of grade ≥3 were more frequent with cabazitaxel (65.4% vs 30.2%). A high baseline ctDNA fraction correlated with reduced rPFS and OS; plasma AR copy number status was not associated with outcomes, but PTEN alterations were linked with shorter OS (hazard ratio: 1.9, multivariable p = 0.02).</p><p><strong>Conclusions and clinical implications: </strong>No significant differences in CBR or time-to-event endpoints were observed between cabazitaxel and ARPIs. However, prior ARPI exposure, a higher baseline ctDNA fraction, and PTEN alterations were strongly prognostic.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206111","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":"Apalutamide in Patients with High Burden of Metastatic Hormone-sensitive Prostate Cancer: A Subgroup Analysis of TITAN.","authors":"Alejo Rodriguez-Vida, Angel Borque, Fernando Lopez-Campos, Alvaro Juarez Soto, Beatriz Garcillan, Cristian Vidal, Joana Lencart, Amitabha Bhaumik, Suneel D Mundle, Suzy Van Sanden, Kim N Chi, Anders Bjartell, Neeraj Agarwal, Axel S Merseburger","doi":"10.1016/j.euo.2025.07.002","DOIUrl":"https://doi.org/10.1016/j.euo.2025.07.002","url":null,"abstract":"<p><strong>Background and objective: </strong>A post hoc analysis of TITAN evaluated the clinical benefit of apalutamide plus androgen-deprivation therapy (ADT) versus ADT alone in metastatic hormone-sensitive prostate cancer (mHSPC) with high disease burden.</p><p><strong>Methods: </strong>Patients were assessed in subgroups of those with four to fewer than ten, ten to <20, or ≥20 bone metastases; with lung but not liver metastases; and with no/mild or moderate/severe pain at baseline. Prostate-specific antigen (PSA) response, overall survival (OS), other endpoints, and safety were assessed using descriptive statistics, Kaplan-Meier method, and Cox proportional hazard model.</p><p><strong>Key findings and limitations: </strong>Higher proportions of patients receiving apalutamide than those receiving placebo achieved a deep PSA response of ≤0.2 ng/ml at 3, 6, and 12 mo of treatment initiation regardless of the disease burden. OS benefit favored apalutamide plus ADT versus ADT alone in all bone metastasis subgroups: four to fewer than ten (hazard ratio [HR]: 0.68 [95% confidence interval 0.44-1.03]; p = 0.07), ten to <20 (0.61 [0.37-1.00]; p = 0.048), or ≥20 (0.53 [0.39-0.72]; p < 0.001) bone metastases. Addition of apalutamide to ADT was beneficial across other endpoints and in patients with lung but no liver metastases and regardless of pain at baseline. No new safety signals were observed across subgroups.</p><p><strong>Conclusions and clinical implications: </strong>These findings provide strong evidence for early intensification with apalutamide plus ADT in patients with mHSPC regardless of the disease burden.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198963","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":"Prognostic Significance of the Cytoplasmic Expression of UDP-glucuronosyltransferase 2B17 in Localized Prostate Cancer: Insights from the Canadian Prostate Cancer Biomarker Network and PROCURE Multi-institutional Cohorts.","authors":"Ashwini Uchil, Louis Lacombe, Hélène Hovington, Hervé Brisson, David Simonyan, Patrick Caron, Véronique Ouellet, Mathieu Latour, Armen Aprikian, Alain Bergeron, Simone Chevalier, Ginette McKercher, Fadi Brimo, Ladan Fazli, Neil Fleshner, Martin Gleave, Pierre I Karakiewicz, Michel Carmel, Zineb Hamilou, Dominique Trudel, Theodorus van der Kwast, Anne-Marie Mes-Masson, Xuesen Dong, Fred Saad, Chantal Guillemette, Eric Lévesque","doi":"10.1016/j.euo.2025.07.014","DOIUrl":"https://doi.org/10.1016/j.euo.2025.07.014","url":null,"abstract":"<p><strong>Background and objective: </strong>Prostate cancer (PCa) is hormone dependent, with UDP-glucuronosyltransferase 2B17 (UGT2B17) playing a central role in androgen inactivation. This study aimed to evaluate whether UGT2B17 expression in prostatectomy specimens can serve as a prognostic marker for lethal PCa.</p><p><strong>Methods: </strong>A prespecified hypothesis posited that UGT2B17 expression (>25%) in primary tumors is associated with an aggressive disease phenotype, leading to metastasis, castration resistance (castration-resistant PCa [CRPC]), and mortality in men initially diagnosed with localized disease. Two high-density prostate tumor tissue microarray datasets were analyzed: the first from the Canadian Prostate Cancer Biomarker Network biobank (n = 1454) and the second from the PROCURE cohort (n = 1562). Kaplan-Meier and Cox proportional hazard ratio analyses were used to evaluate metastasis-free survival, CRPC, and PCa-specific mortality. Steroid levels were measured in plasma samples by mass spectrometry, and a linear regression model was used to evaluate variations in hormone levels based on tumoral UGT2B17 expression.</p><p><strong>Key findings and limitations: </strong>UGT2B17 was associated with prognostic factors and linked to elevated levels of androsterone glucuronide (60%), the major circulating androgen-inactive metabolite, which is inactivated by UGT2B17. Kaplan-Meier and multivariable Cox analyses revealed that higher tumoral UGT2B17 is associated with an increased risk of progression to metastatic/CRPC stages and with PCa-specific mortality.</p><p><strong>Conclusions and clinical implications: </strong>UGT2B17 expression influences hormone levels and identifies a subset of patients at an increased risk of progression to an incurable disease stage. Findings support the notion that enhanced UGT2B17, through increased androgen inactivation, creates a low-androgen tumor environment that drives tumor progression to a more aggressive phenotype.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148632","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":"MicroRNA as a Liquid Biomarker to Detect Malignancy in Small Testicular Masses.","authors":"Julian Chavarriaga, Carley Langleben, João Lobo, Lucia Nappi, George M Yousef, Gizem Ozcan, Nastaran Khazamipour, Nuno Tiago Tavares, Ioannis Prassas, Lampros Dimitrakopoulos, Xiaotian Yuan, Adam Bobrowski, Susan Prendeville, Lynn Anson-Cartwright, Carmen Jeronimo, Keith Jarvi, Martin O'Malley, Ricardo Leão, Katherine Lajkosz, Robert J Hamilton","doi":"10.1016/j.euo.2025.08.004","DOIUrl":"https://doi.org/10.1016/j.euo.2025.08.004","url":null,"abstract":"<p><strong>Background and objective: </strong>Approximately 1-4% of individuals undergoing scrotal ultrasound are found with incidental small (≤2 cm) testicular masses (STMs), with the vast majority being benign (∼13-21% malignant). This study explores the potential of microRNAs (miRNAs) as liquid biomarkers for predicting germ cell tumors (GCTs) in STMs.</p><p><strong>Methods: </strong>From 2009 to 2023, we identified patients with STMs who had banked serum/plasma prior to orchiectomy. Eligible samples were analyzed using different miRNA expression methods (reverse transcription quantitative polymerase chain reaction [RT-qPCR] and digital droplet polymerase chain reaction) and platforms across three research laboratory facilities (Portugal, Vancouver, and Toronto). The miRNA assays included 371a-3p, 372, 373, and 367. The primary objective was to evaluate the diagnostic accuracy of miR-371a-3p to predict the presence of testicular cancer using the area under the curve (AUC).</p><p><strong>Key findings and limitations: </strong>Our cohort included 61 patients: 37 patients with confirmed GCTs, 20 patients with benign histology, and four patients who had been on surveillance for >24 mo and were deemed to have benign STMs. Across all three laboratories, miR-371a-3p consistently outperformed all the miRNAs, with the other miRNAs proving uninformative. Extraction from plasma and an RT-qPCR analysis (Vancouver laboratory) proved best, with sensitivity of 87% and specificity of 91%, translating into an AUC of 0.93. The receiver operating characteristic scores for the other two laboratories were 0.77 and 0.73 for Portugal and Toronto, respectively. This single-center study is limited by a potential selection bias and fewer evaluable samples due to technical and logistical issues.</p><p><strong>Conclusions and clinical implications: </strong>This is the largest series of STMs with banked blood/serum to date. Among the miRNAs, miR-371a-3p was found to be sensitive and specific for detecting the presence of GCTs in STMs. Plasma with an RT-qPCR approach proved to be a superior method of analysis.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148542","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":"Stage Migration on Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Comparison to Conventional Imaging in Patients with High-risk Prostate Cancer Referred for Radiation Therapy: Results from the Phase 2/3 THUNDER Trial.","authors":"Fleur Kleiburg, Piet Dirix, Valérie Fonteyne, Samuel Bral, Bart De Troyer, Brieuc Sautois, Maréva Lamande, Nick Liefhooghe, Guillaume Grisay, Sabine Meersschout, Ad Vandermeulen, Nicolas Jullian, Lorenzo Staelens, Filip Poelaert, Michiel Strijbos, Jolien Verschueren, Karolien Goffin, Nadia Withofs, Piet Ost","doi":"10.1016/j.euo.2025.08.005","DOIUrl":"https://doi.org/10.1016/j.euo.2025.08.005","url":null,"abstract":"<p><strong>Background and objective: </strong>In high-risk prostate cancer, the proPSMA trial showed upstaging with prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) in 14% of patients. We hypothesised that the probability of stage migration in a patient population referred for curative-intent radiotherapy would be higher. Here we report stage migration results according to PSMA PET/CT in the first year of inclusion in the phase 2/3 THUNDER trial (NCT06282588).</p><p><strong>Methods: </strong>Patients with high-risk prostate cancer screened between December 2023 and December 2024 in the THUNDER trial with both conventional imaging (CT, bone scintigraphy) and PSMA PET/CT within 16 weeks before screening were included (n = 142). Stage migration according to the TNM classification versus the molecular imaging (miTNM) classification (PROMISE v2 criteria) was assessed using descriptive statistics.</p><p><strong>Key findings and limitations: </strong>PSMA PET/CT led to stage migration in 43 patients, of whom 42 (30%) were upstaged and one (1%) was downstaged. Upstaging to miN1-2 disease occurred in 32 patients (23%), and to miM1a-c disease in 19 patients (13%). The probability of upstaging increased with the number of high-risk features. In the subgroup meeting the STAMPEDE M0 high-risk criteria (n = 73), PSMA PET/CT upstaged 27 patients (37%), including upstaging to miM1a-c disease in 14 (19%). Limitations include the absence of central review of the imaging procedures.</p><p><strong>Conclusions and clinical implications: </strong>One-third of patients with high-risk prostate cancer referred for curative-intent radiotherapy were upstaged on PSMA PET/CT. This finding supports the use of PSMA PET/CT for staging, especially in patients with multiple high-risk features, and suggests a need for treatment adaptations accordingly, which will be further investigated in the THUNDER trial.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147964","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":"Fibroblast Growth Factor Receptor Alteration Testing for >3600 Patients with Locally Advanced/Metastatic Urothelial Cancer and Non-muscle-invasive Bladder Cancer: An Analysis of the Global ANNAR Biomarker Study.","authors":"Nobuaki Matsubara, Yohann Loriot, Severine Banek, Begoña Perez Valderrama, Jason Hwang, Kris Deprince, Spyros Triantos, Shibu Thomas, Jenna Cody Carcione, Sanket Patel, Arlene Siefker-Radtke","doi":"10.1016/j.euo.2025.07.009","DOIUrl":"https://doi.org/10.1016/j.euo.2025.07.009","url":null,"abstract":"<p><strong>Background and objective: </strong>Successful fibroblast growth factor receptor alterations (FGFRalt) testing is essential for identifying patients eligible for erdafitinib. This analysis of the global ANNAR biomarker study assessed the proportion of valid fibroblast growth factor receptor (FGFR) test results, reasons for test failure, and proportion of FGFRalt in locally advanced/metastatic urothelial cancer (mUC) and non-muscle-invasive bladder cancer (NMIBC).</p><p><strong>Methods: </strong>Archival tumor tissue was tested using the QIAGEN therascreen FGFR real-time polymerase chain reaction kit, an approved companion diagnostic for erdafitinib.</p><p><strong>Key findings and limitations: </strong>A total of 2706 mUC and 962 NMIBC samples were tested. The proportion of valid test results was significantly different between mUC and NMIBC (86% and 66%, respectively; p < 0.001), which declined with older archival sample age for both mUC (<1 yr 89% and ≥3 yr 77%; p < 0.001) and NMIBC (<1 yr 72% and ≥3 yr 43%; p < 0.001). For mUC, the proportion of valid test results was higher for the primary tumor than for metastatic samples (92% and 55%, respectively; p < 0.001) but similar between upper and lower tract disease (87% and 86%, respectively; p = 0.7). Common reasons for test failure were low tumor content and insufficient RNA. FGFRalt were found in 19% of mUC (83% mutations; 15% fusions) and 53% of NMIBC (92% mutations; 6.3% fusions) samples. Limitations include the lack of data on sample collection method.</p><p><strong>Conclusions and clinical implications: </strong>This is the first and largest report on factors affecting FGFR test results. To ensure valid FGFR test results, adequate tumor sample amount, RNA quality, short archival sample age, and primary tumor samples are important factors.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130419","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":"Genomic Predictors of Response to Metastasis-directed Therapy With or Without Androgen Deprivation Therapy.","authors":"Philip Sutera, Kim Van der Eecken, Yang Song, Amol C Shetty, Elai Davicioni, James A Proudfoot, Alexander Hakansson, Keara English, Jarey Wang, Ozan Cem Guler, Soha Bazyar, Sofie Verbeke, Jo Van Dorpe, Valérie Fonteyne, Bram De Laere, Lara Hathout, Ronald Ennis, Salma K Jabbour, Biren Saraiya, Ryan Stephenson, Tina Mayer, Mark Mishra, Zaker Rana, Jason Molitoris, Ana Kiess, Daniel Y Song, Theodore DeWeese, Kenneth J Pienta, Phuoc T Tran, Alejandro Berlin, Cem Onal, Piet Ost, Matthew P Deek","doi":"10.1016/j.euo.2025.07.007","DOIUrl":"10.1016/j.euo.2025.07.007","url":null,"abstract":"<p><p>Metastasis-directed therapy (MDT) is an emerging treatment option for metachronous oligometastatic castration-sensitive prostate cancer (omCSPC) and can delay time to progression and the need to initiate androgen deprivation therapy (ADT). However, optimal ways to synergize MDT and ADT are not known, and better personalization of MDT is needed. We examined the role of combined ADT and MDT and the ability of genomic alterations to provide prognostic and predictive information regarding response to MDT. We found that high-risk (HiRi) mutations in TP53, BRCA1/2, ATM, and Rb1 are poor prognostic markers in omCSPC. In addition, patients harboring HiRi mutations experienced greater benefit from addition of ADT to MDT, indicating that these alterations are predictive biomarkers for treatment intensification. Our results suggest that genetic biomarkers might aid in treatment personalization for patients with omCSPC.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112405","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 Impact of Elastic Magnetic Resonance Imaging-Transrectal Ultrasound Fusion Biopsy on Concordance of Detection of Clinically Significant Prostate Cancer by International Society of Urological Pathology Grade in Biopsy-naïve Men with Prostate-specific Antigen ≤20 ng/ml and cT1-2 Disease.","authors":"Bogdan Adrian Buhas, Adrien Gregoris, Mihaela Iancu, Alessandro Uleri, Rawad Abou-Zahr, Iulia Andras, Nicolae Crisan, Maximilian Buzoianu, Stefana Tartamus, Razvan-George Rahota, Alae Touzani, Claudia Kesch, Giorgio Calleris, Alberto Martini, Jean-Baptiste Beauval, Guillaume Ploussard","doi":"10.1016/j.euo.2025.09.001","DOIUrl":"https://doi.org/10.1016/j.euo.2025.09.001","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) fusion guided biopsy is the cornerstone of prostate cancer (PC) diagnosis. While prior studies have focused on detection rates, the impact of fusion registration methods-elastic registration techniques (ERT) versus rigid registration techniques (RRT)-on International Society of Urological Pathology (ISUP) grade concordance remains underexplored. Our objectives were to assess the effect of ERT versus RRT on the concordance between targeted biopsy (TBx) and overall biopsies (OBx) for detection of (1) clinically significant PC (csPC; defined as ISUP grade ≥2) and (2) high-grade PC (hgPC; defined as ISUP grade ≥3) in biopsy-naïve men with confirmed PC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Our multicenter retrospective study included 888 biopsy-naïve men with confirmed PC (prostate-specific antigen ≤20 ng/ml, cT1-2, Prostate Imaging-Reporting and Data System [PI-RADS] score 3-5) who underwent MRI-TRUS fusion guided biopsy using ERT (n = 479) or RRT (n = 409) at two high-volume institutions. After 1:1 propensity score matching (PSM) to control for confounding, a sample of 674 patients was included in the final analysis. The primary endpoint was the concordance of csPC detection between TBx and OBx. Secondary endpoints included concordance for hgPC detection (ISUP grade ≥3) between TBx and OBx, concordance for hgPC (ISUP grade ≥3) between systematic biopsy (SBx) and OBx, biopsy sampling metrics, and subgroup analyses for PI-RADS 3 lesions. Multivariable logistic binomial regression models adjusted for clinical and imaging covariates were tested.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key findings and limitations: &lt;/strong&gt;There was a significant difference in the frequency of csPC concordance between the ERT and RRT groups (60.2% vs 33.6%; p &lt; 0.0001). Moreover, the ERT approach was associated with significantly higher odds of being classified as concordant csPC in comparison to RRT (adjusted odds ratio [aOR] 4.82, 95% confidence interval 2.82-8.24). ERT was also significantly associated with higher odds of hgPC concordance after adjusting for PSA density, clinical TNM stage and PI-RADS score (aOR 2,51, 95% confidence interval 1.51-4.16; corrected p = 0.0014). ERT reduced overgrading of ISUP grade 1 lesions (12.5% vs 39.2%; p &lt; 0.001). Despite lower core volume and fewer positive cores, ERT achieved similar maximum cancer core length, suggesting superior spatial targeting. PI-RADS 3 subgroup analyses showed favorable trends for ERT, although the results were not statistically significant (p &gt;0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and clinical implications: &lt;/strong&gt;ERT was associated with better concordance for detection of both csPC and hgPC on TBx, supporting more accurate risk stratification while reducing detection of indolent cancer. While our findings indicate diagnostic advantages for ERT over RRT, prospective multicenter studies with centralized pathology review are warrant","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102833","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}