European urology oncology最新文献

{"title":"Re: Rohan Garje, Irbaz Bin Riaz, Syed Arsalan Ahmed Naqvi, et al. Systemic Therapy in Patients with Metastatic Castration-resistant Prostate Cancer: ASCO Guideline Update. J Clin Oncol 2025;43:2311-34.","authors":"Giandomenico Roviello","doi":"10.1016/j.euo.2025.07.010","DOIUrl":"https://doi.org/10.1016/j.euo.2025.07.010","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741691","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: Benedikt Hoeh, Felix Preisser, Fabio Zattoni, et al. Risk of Biochemical Recurrence and Metastasis in Prostate Cancer Patients Treated with Radical Prostatectomy After a 10-year Disease-free Interval. Eur Urol Oncol 2025;8:372-9.","authors":"Francesco Montorsi, Leonardo Quarta, Alberto Briganti, Giorgio Gandaglia","doi":"10.1016/j.euo.2025.06.013","DOIUrl":"https://doi.org/10.1016/j.euo.2025.06.013","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729059","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":"FGFR1/3 Signaling as an Achilles' Heel of Phenotypic Diversity in Urothelial Carcinoma.","authors":"Renate Pichler, Nils C H van Creij, Laura S Mertens, Francesco Del Giudice, Florestan Koll, Francesco Soria, José Daniel Subiela, Henning Plage, Piotr Tymoszuk, Roman Mayr, Gerald Klinglmair, Andreas Seeber, Martin Pichler, Michael Günther, Steffen Ormanns, Eva Compérat, Roger Li, Marco Moschini, Benjamin Pradére","doi":"10.1016/j.euo.2025.07.005","DOIUrl":"https://doi.org/10.1016/j.euo.2025.07.005","url":null,"abstract":"<p><p>FGFR inhibitors are a new therapeutic option for urothelial carcinoma (UC) with FGFR2/3 alterations. In this study, we analyzed genetic alterations, co-regulation, and differential expression for 45 genes encoding FGF, FGFR, or FGF-binding proteins (FGFBPs) in five published UC cohorts (n = 3939 MIBC) and 39 UC cell lines (DepMap portal). Network analyses identified FGFR1/3 genes as critical oncogenic hubs, co-regulated with their ligands and co-receptors, and abundantly expressed at protein level in the HPA immunohistochemistry data set. Machine learning with 38 FGFR-, FGF-, and FGFBP-coding transcripts reproduced consensus molecular subtypes with high accuracy of 0.72-0.84 (Cohen's κ 0.59-0.77). FGFR3 mutations in the transmembrane/hinge region, which were enriched in luminal papillary tumors, trigger ligand-independent signaling. Conversely, overexpression of FGFR1 and its ligands and accessory protein transcripts indicates ligand-dependent FGFR1 signaling in stroma-rich and basal/squamous subtypes. The sensitivity of most DepMap UC cell lines to pan-FGFR inhibitors in the GDSC and PRISM drug screens was independent of FGFR3 alterations. In vitro, erdafitinib reduced proliferation in FGFR wild-type UC cell lines in a similar manner to FGFR3-mutated cell lines. Our findings highlight FGFR1 and FGFR3 as pivotal signaling pathways with distinct, molecular subtype-specific activation mechanisms. The results suggest that FGFR inhibitors may have therapeutic applications beyond UC tumors with FGFR2/3 alterations.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144729058","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":"Fast Biparametric Versus Multiparametric Magnetic Resonance Imaging for Triage of Men with Elevated Prostate-specific Antigen: The PRO-TRIAGE Prospective Comparative Trial.","authors":"Hyungwoo Ahn, Mi Yeon Park, Jeong In Shin, Bumjin Lim, Yoon Soo Kyung, Bokyung Ahn, Yong Mee Cho, In Gab Jeong, Kye Jin Park","doi":"10.1016/j.euo.2025.07.001","DOIUrl":"https://doi.org/10.1016/j.euo.2025.07.001","url":null,"abstract":"<p><strong>Background and objective: </strong>The increasing demand for prostate magnetic resonance imaging (MRI) underscores the need for better accessibility. We conducted a prospective study to compare fast biparametric MRI (fast-bpMRI) with multiparametric MRI (mpMRI) in terms of the number of men requiring biopsy and the detection rate for clinically significant prostate cancer (csPC).</p><p><strong>Methods: </strong>From May 2021 to December 2023, fast-bpMRI and mpMRI scans for 364 men were randomly assigned at a 1:1 ratio to two different readers for evaluation using Prostate Imaging-Reporting and Data System (PI-RADS) version 2.1. A third researcher who was unaware of the MRI protocol used reviewed the readers' report to identify MRI-suspicious lesions (PI-RADS ≥3) and performed biopsy. The primary outcome was the proportion of men requiring biopsy. Secondary outcomes were the proportion of equivocal cases (PI-RADS 3), csPC detection rates (Gleason score ≥ 3 + 4), and diagnostic performance for csPC detection. The PRO-TRIAGE study was registered on cris.nih.go.kr as KCT0006181.</p><p><strong>Key findings and limitations: </strong>The number of men requiring biopsy for MRI-suspicious lesions (PI-RADS ≥3) was 195 (53.6%) according to fast-bpMRI and 185 (50.8%) according to mpMRI (p = 0.28). Equivocal cases (PI-RADS 3) were observed in 65 men (17.9%) according to fast-bpMRI and 58 (15.9%) according to mpMRI (p = 0.46). The csPC detection rate was 26.4% for both protocols. Using PI-RADS ≥3 as a cutoff, the sensitivity for csPC detection was 92.8% with fast-bpMRI and 90.7% with mpMRI (p = 0.41), while the specificity was 53.8% with fast-bpMRI and 56.7% with mpMRI (p = 0.52).</p><p><strong>Conclusions and clinical implications: </strong>Fast-bpMRI resulted in a slightly higher proportion of men requiring biopsy in comparison to mpMRI, with a comparable csPC detection rate.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717835","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":"Patient-reported Outcomes in KEYLYNK-010: Pembrolizumab Plus Olaparib Versus Abiraterone or Enzalutamide for Participants with Biomarker-unselected, Previously Treated Metastatic Castration-resistant Prostate Cancer.","authors":"Niven Mehra, Emmanuel S Antonarakis, Se Hoon Park, Jeffrey C Goh, Ray McDermott, Nuria Sala Gonzalez, Peter C Fong, Richard Greil, Maria De Santis, Patricio Eduardo Yanez, Yi-Hsiu Huang, Stephen D Begbie, Felipe Rey, Gero Kramer, Hiroyoshi Suzuki, Todd L Saretsky, Sameer R Ghate, Yi Cui, Christian Hosius, Evan Y Yu","doi":"10.1016/j.euo.2025.04.018","DOIUrl":"https://doi.org/10.1016/j.euo.2025.04.018","url":null,"abstract":"<p><strong>Background and objective: </strong>Pembrolizumab plus olaparib did not significantly improve radiographic progression-free survival or overall survival versus a next-generation hormonal agent (NHA) in participants with biomarker-unselected, pretreated metastatic castration-resistant prostate cancer (mCRPC) in the phase 3 KEYLYNK-010 trial. We present prespecified patient-reported outcomes (PROs) from KEYLYNK-010.</p><p><strong>Methods: </strong>Participants were randomly assigned 2:1 to receive pembrolizumab plus olaparib or an NHA (abiraterone acetate or enzalutamide). PROs were evaluated using the Brief Pain Inventory-Short Form (BPI-SF), Functional Assessment of Cancer Therapy-Prostate Cancer (FACT-P), and EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaires. The PRO endpoints included time to pain progression (TTPP) as per BPI-SF and the least squares mean (LSM) change from baseline to week 15 in FACT-P total, BPI-SF, and EQ-5D visual analog scale (VAS) scores.</p><p><strong>Key findings and limitations: </strong>The PRO analysis population included 774 participants (pembrolizumab plus olaparib, n = 520; NHA, n = 254). The median follow-up was 18.7 (range, 6.1-31.7) mo. No meaningful differences were observed in TTPP for pembrolizumab plus olaparib versus NHA (median: 13.5 vs 12.0 mo; hazard ratio 0.95; 95% confidence interval 0.72-1.26). From baseline to week 15, no meaningful LSM differences were observed between the treatment groups in FACT-P total, BPI-SF, and EQ-5D VAS scores. Limitations include no formal hypothesis testing.</p><p><strong>Conclusions and clinical implications: </strong>No meaningful differences were observed in health-related quality of life (HRQoL) or disease-related symptom scores for pembrolizumab plus olaparib versus NHA in participants with biomarker-unselected, pretreated mCRPC. These findings suggest that pembrolizumab plus olaparib did not negatively impact HRQoL in participants with pretreated mCRPC.</p><p><strong>Clinical trial registry: </strong>NCT03834519.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674263","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":"Radiotherapy- Versus Surgery-based Treatment Strategy in High-risk Prostate Cancer.","authors":"Soumyajit Roy, Yilun Sun, James A Eastham, Martin Gleave, Christopher J D Wallis, Himisha A Beltran, Amar U Kishan, Angela Y Jia, Nicholas G Zaorsky, Himanshu Nagar, Jorge A Garcia, Eric J Small, Paul Nguyen, Gerhardt Attard, Rana R McKay, Oliver Sartor, Alejandro Berlin, Seth A Rosenthal, Susan Halabi, Randy Vince, Lee Ponsky, Scott C Morgan, Raquibul Hannan, Adam Raben, Mack Roach, Jeff M Michalski, Michael J Morris, Howard M Sandler, Daniel E Spratt","doi":"10.1016/j.euo.2025.06.009","DOIUrl":"https://doi.org/10.1016/j.euo.2025.06.009","url":null,"abstract":"<p><strong>Background and objective: </strong>Optimal management for high-risk prostate cancer is unclear. Using individual patient data from two contemporaneous North American cooperative group phase 3 randomized controlled trials (RCTs), we compared the outcomes of high-risk prostate cancer patients treated with radiotherapy-based and radical prostatectomy (RP)-based treatment strategies.</p><p><strong>Methods: </strong>Data were collected from newly diagnosed high-risk prostate cancer patients enrolled in NRG/RTOG 0521 who received radiotherapy-based treatment (2005-2009), and those enrolled in CALGB 90203 who received surgery-based treatment (2006-2015). Patients received radiotherapy plus 24 mo of androgen deprivation therapy (ADT) ± six cycles of adjuvant docetaxel versus RP with personalized postoperative therapy ± neoadjuvant six cycles of docetaxel and 18-24 wk of ADT. The primary objective was to compare the cumulative incidence of distant metastasis considering death as a competing event using the inverse probability of treatment weighting (IPTW).</p><p><strong>Key findings and limitations: </strong>Overall, 1290 patients (radiotherapy n = 557, RP n = 733) were included with similar follow-up (median 6.4 [interquartile range {IQR}: 5.6-6.9] yr and 6.4 [IQR: 4.7-8.5] yr, respectively). Patients who received surgery had generally more favorable prognostic features and were younger relative to those who received radiotherapy. After IPTW, the cumulative incidence of distant metastasis was significantly lower in patients who underwent radiotherapy-based compared with RP-based treatment (8-yr distant metastasis: 15% [95% confidence interval {CI} 9.3-21] vs 22% [95% CI 18-26]; adjusted subdistribution hazard ratio [sHR] 0.58 [95% CI 0.42-0.81]; p = 0.001). We did not find any significant difference in the incidence of deaths after distant metastasis (adjusted sHR 0.98 [95% CI 0.61-1.58]) between the two groups.</p><p><strong>Conclusions and clinical implications: </strong>High-risk prostate cancer patients enrolled in RCTs had a significantly lower incidence of distant metastasis with a radiotherapy-based treatment strategy than with an RP-based treatment strategy, while the risk of deaths after distant metastasis was similar in the two groups.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667466","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":"Transcriptomic Analysis of Localized High-risk Prostate Cancer Improves Prognostication and Identifies Benefit from Adding Docetaxel to Definitive Radiotherapy with Androgen Suppression in the NRG Oncology/RTOG 0521 Phase 3 Trial.","authors":"Ryan M Phillips, James A Proudfoot, Elai Davicioni, Yang Liu, Daniel E Spratt, Jeff M Simko, Robert B Den, Alan Pollack, Seth A Rosenthal, A Oliver Sartor, Christopher J Sweeney, Gerhardt Attard, Leslie Longoria, Samir Patel, Michael W Straza, Jason A Efstathiou, Amit B Shah, Karen E Hoffman, Joseph P Rodgers, Howard M Sandler, Felix Y Feng, Phuoc T Tran","doi":"10.1016/j.euo.2025.04.009","DOIUrl":"10.1016/j.euo.2025.04.009","url":null,"abstract":"<p><strong>Background and objective: </strong>NRG/RTOG 0521 randomized men with high-risk localized prostate cancer (PC) to androgen suppression (AS) and definitive radiotherapy (RT) ± docetaxel-based chemotherapy (CT). The overall survival (OS) benefit with CT initially reported was lost on longer follow-up. The Decipher genomic classifier (GC) measures multiple transcripts relevant to docetaxel action. Basal/luminal differentiation portends differential response to AS and CT for high-risk localized and metastatic hormone-sensitive PC. We validated the Decipher GC in pretreatment biopsy samples for risk stratification and examined basal-luminal subtyping to predict docetaxel response.</p><p><strong>Methods: </strong>Decipher GC scores and basal-luminal cellular subtypes were generated for specimens from NRG/RTOG 0521. The primary objective was to validate the independent prognostic ability of GC for metastasis-free survival (MFS). Treatment effects in luminal proliferating (LP) and non-LP cell subtypes were examined in relation to MFS, OS, and distant metastasis (DM).</p><p><strong>Key findings and limitations: </strong>Samples were obtained from 283 patients and yielded 183 GC scores. Over median follow-up of 9.9 yr, 67 metastasis events were observed, including 34 DM events. Multivariable analysis revealed that GC was independently associated with DM (subdistribution hazard ratio 1.45) and MFS (hazard ratio 1.20). No biomarker-by-treatment interaction with GC and docetaxel was detected. The 10-yr restricted mean survival time difference in OS with CT was 13.7 mo for LP (p = 0.053) and 2.5 mo for non-LP (p = 0.63) tumors.</p><p><strong>Conclusions and clinical implications: </strong>The Decipher GC score was independently associated with DM and MFS, and LP tumors may benefit from addition of CT. Validation of these findings may allow more effective use of CT in men with localized PC. The original NRG/RTOG 0521 trial is registered on ClinicalTrials.gov as NCT00288080.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658834","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":"Years of Life Lost in Metastatic and Locally Advanced Prostate Cancer.","authors":"Fabian Falkenbach, Quynh Chi Le, Mattia Longoni, Andrea Marmiroli, Calogero Catanzaro, Michele Nicolazzini, Federico Polverino, Zhe Tian, Jordan A Goyal, Riccardo Schiavina, Carlotta Palumbo, Gennaro Musi, Felix K H Chun, Alberto Briganti, Fred Saad, Shahrokh F Shariat, Gunhild von Amsberg, Thomas Steuber, Markus Graefen, Pierre I Karakiewicz","doi":"10.1016/j.euo.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.euo.2025.04.008","url":null,"abstract":"<p><strong>Background and objective: </strong>Prostate cancer (PCa) is the second most common cancer-specific cause of death in the USA. However, the effects of metastatic or locally advanced PCa on individual years of life lost (YLL) have not been addressed.</p><p><strong>Methods: </strong>Within the Surveillance, Epidemiology, and End Results (SEER) database 2004-2021, metastatic (cM1) and locally advanced (cT3/4, cN1) PCa patients aged 45-75 yr were included. The Monte Carlo method was used to simulate and illustrate individual survival according to the Social Security Administration life tables. Subsequently, the average YLL until the age of 75 yr between patients and simulated controls were quantified using the Kaplan-Meier method.</p><p><strong>Key findings and limitations: </strong>Overall, 21 488 and 53 506 patients with metastatic and locally advanced PCa, respectively, were included. Metastatic and locally advanced PCa patients lost, respectively, 5.76 and 0.77 yr of life compared with controls (p < 0.001). YLL due to metastatic PCa were most pronounced in younger patients (age 45-60 yr: 12.15 YLL), those diagnosed in more historic years (2004-2009: 6.37 YLL), and Black (6.86 YLL) and unmarried (6.66 YLL) individuals. Similar observations were made in patients with locally advanced PCa, although absolute YLL values were substantially lower. Limitations include the life expectancy estimation method that did not take comorbidities into account.</p><p><strong>Conclusions and clinical implications: </strong>Metastatic and locally advanced PCa resulted in 5.76 and 0.77 YLL values, respectively, relative to controls. Young, Black, and unmarried individuals were affected most. Therefore, these groups represent targets of particular interest for the early detection, treatment intensification, and psychosocial interventions.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658835","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":"Assessing the Impact of Treatment Timing Protocols in Clinical Trials for Bacillus Calmette-Guérin-unresponsive Non-muscle-invasive Bladder Cancer.","authors":"Christopher Guske, Seyed Behzad Jazayeri, Christian Harrs, Nagashree Rao, Facundo Davaro, Hongzhi Xu, Logan Zemp, Alice Yu, Scott M Gilbert, Michael Poch, Philippe E Spiess, Wade Sexton, Joshua Linscott, Roger Li","doi":"10.1016/j.euo.2025.05.022","DOIUrl":"https://doi.org/10.1016/j.euo.2025.05.022","url":null,"abstract":"<p><p>Patients with bacillus Calmette-Guérin (BCG)-unresponsive (UR) non-muscle-invasive bladder cancer (NMIBC) who are ineligible for or decline radical cystectomy may pursue bladder-sparing therapy (BST). Currently, most BST trials in the BCG-UR setting mandate treatment initiation within 60-90 d of histopathologic confirmation. Given the lack of data on optimal treatment windows, we evaluated whether these time restrictions have oncologic merit. We retrospectively reviewed data for patients with BCG-UR NMIBC treated with BST at a tertiary referral center. Commonly used clinical trial cutoffs for time to treatment were assessed using Kaplan-Meier analysis. Multivariable Cox regression analysis was also performed, with time to treatment included as a continuous variable. Progression-free survival (PFS) was the primary endpoint, defined as progression to muscle-invasive disease or metastasis. Similar PFS was observed when using 30-d, 60-d, and 90-d cutoffs (all p > 0.05). These results were corroborated on multivariable analysis with adjustment for BST type. Secondary endpoints, including cystectomy-free survival and overall survival, were comparable across time-to-treatment intervals (all p > 0.05), with findings supported by multivariable analyses. These results indicate that inclusion criteria based on time to treatment can probably be expanded, which would allow more patients to participate in clinical trials by avoiding leadtime exclusion.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648965","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":"Randomized Phase 2 Trial of Presurgical Androgen Deprivation Therapy With or Without Axitinib in Prostate Cancer Presenting With Lymph Node Metastasis.","authors":"Amado J Zurita, Rebecca S Tidwell, Brian F Chapin, Deborah R Harris, Miao Zhang, Louis L Pisters, Ana Aparicio, John C Araujo, Sara Arce-Gallego, Keyi Zhu, Maria L Lozano, Lance Pagliaro, Joaquin Mateo, Christopher Logothetis, Patricia Troncoso, John W Davis","doi":"10.1016/j.euo.2025.04.015","DOIUrl":"https://doi.org/10.1016/j.euo.2025.04.015","url":null,"abstract":"<p><strong>Background and objective: </strong>Strategies that combine systemic and locoregional therapies are increasingly used in prostate cancer (PC) with lymph node metastasis (LNM) at presentation. We investigated whether the presurgical combination of androgen deprivation therapy (ADT) and the antiangiogenic agent axitinib would be more effective than ADT alone in achieving time off systemic therapy after surgery in these patients.</p><p><strong>Methods: </strong>Patients with newly diagnosed PC with either clinically detected LNM (cTxN1M0 or cTxNxM1a) or at very high risk for subclinical LNM were treated with ADT for 2 mo and then randomized 2:1 to addition of axitinib to ADT versus continuing ADT alone for an additional 4 mo before surgery and discontinuation of systemic therapy. The primary endpoint was the rate of freedom from treatment failure in the intention-to-treat population at 1 yr postoperatively (\"success\"). Failure was defined as prostate-specific antigen >1.0 ng/ml, objective progression, or initiation of additional treatment.</p><p><strong>Key findings and limitations: </strong>Of the 73 patients accrued, 49 received axitinib + ADT and 24 received ADT alone. Of the 49 patients who had surgery on protocol, success was achieved in 26, of whom 22 received axitinib + ADT and four received ADT alone. In the node-positive group of 55 patients, the success rate was 36.8% (95% credible interval [CrI] 22.5-52.5%) for axitinib + ADT and 19.0% (95% CrI 5.7-37.9%) for ADT alone; the probability of a higher success rate with axitinib + ADT was 0.935. The median time to progression was 9.8 mo (95% confidence interval [CI] 7.6-17.4) with axitinib + ADT versus 5.7 mo (95% CI 4.0-11.3) with ADT alone (p = 0.03). Pathologic responses, time to metastatic progression, and overall survival were similar between the arms. There were no grade 4-5 toxicities or unexpected perioperative complications.</p><p><strong>Conclusions and clinical implications: </strong>In patients with newly diagnosed PC with LNM, a presurgical strategy that combines axitinib + ADT was feasible and was more likely than ADT alone to achieve significant time off treatment. However, the overall efficacy was limited, suggesting that patient selection and more effective combinations are needed.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616853","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}