European urology oncology最新文献

{"title":"Assessment of the Prognostic and Predictive Values of the Deficient Mismatch Repair Phenotype in Patients Treated with Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma","authors":"Pierre-Etienne Gabriel ,&nbsp;Eva Compérat ,&nbsp;Géraldine Cancel-Tassin ,&nbsp;Justine Varinot ,&nbsp;Mathieu Roumiguié ,&nbsp;Pierre-Marie Patard ,&nbsp;Gwendoline Daniel ,&nbsp;Christian Pfister ,&nbsp;Clara Delcourt ,&nbsp;Françoise Gobet ,&nbsp;Stéphane Larré ,&nbsp;Priscilla Léon ,&nbsp;Anne Durlach ,&nbsp;Pierre Bigot ,&nbsp;Julie Carrouget ,&nbsp;Caroline Eymerit ,&nbsp;Thomas Bessède ,&nbsp;Cédric Lebacle ,&nbsp;Sophie Ferlicot ,&nbsp;Alain Ruffion ,&nbsp;Thomas Seisen","doi":"10.1016/j.euo.2025.03.014","DOIUrl":"10.1016/j.euo.2025.03.014","url":null,"abstract":"<div><h3>Background and objective</h3><div>Given the conflicting evidence currently available in the literature, our aim was to assess the prognostic and predictive values of the deficient mismatch repair (dMMR) phenotype in a large cohort of upper tract urothelial carcinoma (UTUC) patients.</div></div><div><h3>Methods</h3><div>Based on our national network, we performed a retrospective multicenter study including 281 UTUC patients treated with radical nephroureterectomy between 2000 and 2015 at ten French hospitals. The dMMR phenotype as well as PD-L1 and PD-1 expression were determined using immunohistochemistry analyses based on 2-mm-core tissue microarrays. Multivariable Cox regression models were fitted to assess the impact of the dMMR phenotype on recurrence-free (RFS), cancer-specific (CSS), and overall (OS) survival using interaction terms to test the heterogeneity of the treatment effect of adjuvant chemotherapy (AC). Multivariable logistic regression models were also fitted to assess the impact of the dMMR phenotype on PD-L1 and PD-1 expression.</div></div><div><h3>Key findings and limitations</h3><div>Overall, 76 (27.0%) patients had a dMMR phenotype, which was an independent predictor of prolonged RFS (hazard ratio [HR] = 0.41; 95% confidence interval [CI] = [0.21–0.83]; <em>p</em> = 0.01), CSS (HR = 0.38; 95% CI = [0.18–0.83]; <em>p</em> = 0.02), and OS (HR = 0.44; 95% CI = [0.22–0.89]; <em>p</em> = 0.02), with a significant interaction with the use of AC in multivariable Cox regression models (all <em>p</em>_interaction &lt; 0.05). Subgroup analyses showed that the use of AC was significantly associated with prolonged RFS (HR = 0.14; 95% CI = [0.06–0.30]; <em>p</em> &lt; 0.001), CSS (HR = 0.10; 95% CI = [0.03–0.29]; <em>p</em> &lt; 0.001), and OS (HR = 0.23; 95% CI = [0.10–0.54]; <em>p</em> = 0.001) in non-dMMR patients only, without any significant benefit in dMMR patients (all <em>p</em> &gt; 0.05). In multivariable logistic regression analyses, the dMMR phenotype was significantly associated with inverse PD-L1 (OR = 0.20; 95% CI = [0.10–0.80]; <em>p</em> = 0.001) and PD-1 (OR = 0.36; 95% CI = [0.16–0.79]; <em>p</em> = 0.01) expression.</div></div><div><h3>Conclusions and clinical implications</h3><div>We observed that the dMMR phenotype was associated with favorable pathological characteristics and prognosis in UTUC patients, despite conferring decreased sensitivity to AC and lower PD-L1 or PD-1 expression.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 4","pages":"Pages 921-931"},"PeriodicalIF":9.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978931","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":"Associations Between Prostate Cancer and Dementia: A Nationwide Study in Sweden","authors":"Casey Crump ,&nbsp;Pär Stattin ,&nbsp;James D. Brooks ,&nbsp;Jan Sundquist ,&nbsp;Jingkai Wei ,&nbsp;Weiva Sieh ,&nbsp;Kristina Sundquist","doi":"10.1016/j.euo.2025.04.001","DOIUrl":"10.1016/j.euo.2025.04.001","url":null,"abstract":"<div><h3>Background and objective</h3><div>Prostate cancer (PC) and dementia may commonly co-occur; yet, prior evidence for bidirectional associations is inconsistent. This study aims to determine the associations between PC and dementia in large population-based studies, which may further inform clinical care.</div></div><div><h3>Methods</h3><div>To assess the dementia risk in men with PC, a national cohort study was conducted in 178 746 men diagnosed with PC in 1998–2017 and 1 787 460 age-matched control men in Sweden without prior dementia. Cox regression was used to estimate hazard ratios (HRs) for Alzheimer’s disease (AD) and vascular dementia (VaD) through 2018. Subanalyses explored differences by PC treatment during 2005–2017. To assess the PC risk in men with dementia, case-control analyses were performed in 180 189 men with PC and 1 801 890 age-matched control men. Logistic regression was used to estimate odds ratios (ORs) for PC associated with prior AD or VaD. All analyses were adjusted for sociodemographic factors and health care utilization.</div></div><div><h3>Results and limitations</h3><div>Among men with high-risk PC, those treated with androgen deprivation therapy (ADT) only had a higher risk of AD (HR, 1.37; 95% confidence interval [CI], 1.19–1.58) and VaD (1.51; 1.29–1.78), but not those who received other treatments. Men with low- or intermediate-risk PC had little or no increased risk of AD (HR, 1.10; 95% CI, 1.03–1.18) or VaD (0.90; 0.83–0.98). Men with AD or VaD had lower odds of high-risk PC (OR, 0.39; 95% CI, 0.35–0.45, and 0.36; 0.30–0.42, respectively) and low- or intermediate-risk PC (0.30; 0.25–0.36, and 0.30; 0.24–0.38, respectively). This study was limited to Sweden and will need replication when feasible.</div></div><div><h3>Conclusions</h3><div>In a large national study, men with high-risk PC treated with ADT had higher risks of AD and VaD. Such men should be monitored for timely detection and treatment of dementia. In contrast, men with AD or VaD had a lower subsequent risk of PC, possibly reflecting reduced screening in these subgroups.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 4","pages":"Pages 857-865"},"PeriodicalIF":9.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999897","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":"Early Results from the CONFIRM Trial: Utility of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Active Surveillance for Prostate Cancer","authors":"Jianliang Liu ,&nbsp;Laurence Harewood ,&nbsp;Dominic Bagguley ,&nbsp;Philip Dundee ,&nbsp;George Mirmilstein ,&nbsp;Declan G. Murphy ,&nbsp;Yee Chan ,&nbsp;Daniel Moon ,&nbsp;Paul Kearns ,&nbsp;Prassannah Satasivam ,&nbsp;Marlon Perera ,&nbsp;Dixon T.S. Woon ,&nbsp;Fairleigh Reeves ,&nbsp;Dinesh K. Agarwal ,&nbsp;Justin Peters ,&nbsp;Darren Katz ,&nbsp;Mariolyn Raj ,&nbsp;Renu Eapen ,&nbsp;Shomik Sengupta ,&nbsp;Niall Corcoran ,&nbsp;Nathan Lawrentschuk","doi":"10.1016/j.euo.2025.02.010","DOIUrl":"10.1016/j.euo.2025.02.010","url":null,"abstract":"<div><h3>Background and objective</h3><div>There is growing evidence on the utility of prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) for detection of clinically significant prostate cancer (csPC), but there are limited data on its use in active surveillance (AS). The CONFIRM trial aims to determine the utility of PSMA PET/CT in detecting csPC before confirmatory biopsy during AS.</div></div><div><h3>Methods</h3><div>This is an initial analysis of a prospective, nonrandomised, crossover clinical trial (ANZCTR ID ACTRN12621001648819) that included men on AS for newly diagnosed low-grade prostate cancer (PC) with “high-risk” features. High risk was defined as grade group (GG) 1 disease with elevated prostate-specific antigen (PSA; &gt;10 ng/ml, or PSA density &gt;0.15 ng/ml/ml), high-volume GG 1, GG 1 with Prostate Imaging-Reporting and Data System 4 or 5 lesion on magnetic resonance imaging (MRI), or low-volume GG 2 PC. Patients underwent multiparametric MRI and [¹⁸F]-labelled radioligand PSMA PET/CT 3–6 mo after diagnosis, and confirmatory biopsy 6–9 mo after diagnosis.</div></div><div><h3>Key findings and limitations</h3><div>Between November 2021 and September 2023, 60 patients (median age 62.5 yr) were enrolled. PSMA-avid lesions were identified in 44 patients (73.3%), of whom 27 (61.4%) harboured csPC (GG ≥2). Of the PSMA-avid lesions, 20 (45.5%) were MRI-occult. At a subsequent multidisciplinary meeting, active treatment was recommended for 24 patients (40%), with PSMA PET/CT findings influencing 12 (20%) of the decisions. PSMA PET/CT provided reassurance regarding the decision to continue AS by excluding PSMA-avid lesions in 14 cases (38.9%) and multifocal disease in four (11.1%). Our findings are limited by the small sample size and short follow-up.</div></div><div><h3>Conclusions and clinical implications</h3><div>PSMA PET/CT appears to hold promise for improving risk stratification during AS by identifying csPC and MRI-occult lesions.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 4","pages":"Pages 1118-1125"},"PeriodicalIF":9.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999813","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":"Outcomes for [177Lu]Lu-PSMA-617 with and Without Concurrent Use of Androgen Receptor Pathway Inhibitors in Patients with Metastatic Castration-resistant Prostate Cancer","authors":"Miguel Muniz ,&nbsp;Oliver Sartor ,&nbsp;Jacob J. Orme ,&nbsp;Regina M. Koch ,&nbsp;Zachary Scharf ,&nbsp;Elisabeth I. Heath ,&nbsp;Jabra G. Zarka ,&nbsp;Adam M. Kase ,&nbsp;Irbaz B. Riaz ,&nbsp;Jack R. Andrews ,&nbsp;Matthew P. Thorpe ,&nbsp;A. Tuba Kendi ,&nbsp;Gokce Belge Bilgin ,&nbsp;Geoffrey B. Johnson ,&nbsp;Eugene D. Kwon ,&nbsp;Daniel S. Childs","doi":"10.1016/j.euo.2025.06.004","DOIUrl":"10.1016/j.euo.2025.06.004","url":null,"abstract":"<div><h3>Background and objective</h3><div>Large clinical trials, including VISION, have established the safety of combining [¹⁷⁷Lu]Lu-PSMA-617 with an androgen receptor pathway inhibitor (ARPI). Most patients receiving [¹⁷⁷Lu]Lu-PSMA-617 in the real-world setting have already progressed on an ARPI. This study aimed to assess the efficacy of [¹⁷⁷Lu]Lu-PSMA-617 in patients with and without the concurrent use of an ARPI.</div></div><div><h3>Methods</h3><div>We analyzed data from the Mayo Clinic Rochester radiopharmaceutical database, focusing on patients with metastatic castration-resistant prostate cancer (mCRPC) who had progressed after prior exposure to an ARPI and started treatment with [¹⁷⁷Lu]Lu-PSMA-617 between March 2022 and March 2023. Patients receiving concurrent ARPIs (abiraterone, enzalutamide, apalutamide, or darolutamide) were identified. Baseline characteristics were compared using Mann-Whitney <em>U</em> test and chi-square test. Outcomes of interest included prostate-specific antigen (PSA) 50 response, median number of cycles, and overall survival (OS) from the start of [¹⁷⁷Lu]Lu-PSMA-617, analyzed using Kaplan-Meier estimates and multivariate Cox regression.</div></div><div><h3>Key findings and limitations</h3><div>Among 256 patients, 106 (41.4%) received an ARPI with [¹⁷⁷Lu]Lu-PSMA-617. Those receiving an ARPI had lower baseline PSA levels (3.4 vs 29.7 ng/ml, <em>p</em> &lt; 0.001) and lower rates of bone (77.4% vs 87.4%, <em>p</em> = 0.035) and visceral (18.9% vs 34%, <em>p</em> = 0.008) metastases. While patients on ARPIs were more likely to complete all six cycles of [¹⁷⁷Lu]Lu-PSMA-617 (63.2% vs 48.7%, <em>p</em> &lt; 0.001), PSA50 response rates were similar (49.1% vs 47.3%, <em>p</em> = 0.786). Median OS was longer with concurrent ARPI use (not reached vs 15.3 mo, <em>p</em> &lt; 0.001), but this difference was not significant on a multivariate analysis (hazard ratio = 1.03 [95% confidence interval: 0.68–1.55], <em>p</em> = 0.891) after accounting for baseline differences in other prognostic variables. Limitations include its single-center, retrospective design and a lack of standardized radiographic response assessment.</div></div><div><h3>Conclusions and clinical implications</h3><div>Among men with mCRPC previously exposed to an ARPI, continuation of the ARPI with [¹⁷⁷Lu]Lu-PSMA-617 did not improve PSA50 response rates or OS after adjusting for cohort imbalances in known prognostic factors. Further post hoc analyses using large clinical trial data are needed.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 4","pages":"Pages 1087-1093"},"PeriodicalIF":9.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768543","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":"A Systematic Review of the Diagnostic Accuracy of Deep Learning Models for the Automatic Detection, Localization, and Characterization of Clinically Significant Prostate Cancer on Magnetic Resonance Imaging","authors":"Sébastien Molière ,&nbsp;Dimitri Hamzaoui ,&nbsp;Guillaume Ploussard ,&nbsp;Romain Mathieu ,&nbsp;Gaelle Fiard ,&nbsp;Michael Baboudjian ,&nbsp;Benjamin Granger ,&nbsp;Morgan Roupret ,&nbsp;Hervé Delingette ,&nbsp;Raphaele Renard-Penna","doi":"10.1016/j.euo.2024.11.001","DOIUrl":"10.1016/j.euo.2024.11.001","url":null,"abstract":"<div><h3>Background and objective</h3><div>Magnetic resonance imaging (MRI) plays a critical role in prostate cancer diagnosis, but is limited by variability in interpretation and diagnostic accuracy. This systematic review evaluates the current state of deep learning (DL) models in enhancing the automatic detection, localization, and characterization of clinically significant prostate cancer (csPCa) on MRI.</div></div><div><h3>Methods</h3><div>A systematic search was conducted across Medline/PubMed, Embase, Web of Science, and ScienceDirect for studies published between January 2020 and September 2023. Studies were included if these presented and validated fully automated DL models for csPCa detection on MRI, with pathology confirmation. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool and the Checklist for Artificial Intelligence in Medical Imaging.</div></div><div><h3>Key findings and limitations</h3><div>Twenty-five studies met the inclusion criteria, showing promising results in detecting and characterizing csPCa. However, significant heterogeneity in study designs, validation strategies, and datasets complicates direct comparisons. Only one-third of studies performed external validation, highlighting a critical gap in generalizability. The reliance on internal validation limits a broader application of these findings, and the lack of standardized methodologies hinders the integration of DL models into clinical practice.</div></div><div><h3>Conclusions and clinical implications</h3><div>DL models demonstrate significant potential in improving prostate cancer diagnostics on MRI. However, challenges in validation, generalizability, and clinical implementation must be addressed. Future research should focus on standardizing methodologies, ensuring external validation and conducting prospective clinical trials to facilitate the adoption of artificial intelligence (AI) in routine clinical settings. These findings support the cautious integration of AI into clinical practice, with further studies needed to confirm their efficacy in diverse clinical environments.</div></div><div><h3>Patient summary</h3><div>In this study, we reviewed how artificial intelligence (AI) models can help doctors better detect and understand aggressive prostate cancer using magnetic resonance imaging scans. We found that while these AI tools show promise, these tools need more testing and validation in different hospitals before these can be used widely in patient care.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 4","pages":"Pages 1182-1202"},"PeriodicalIF":9.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638451","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":"Final Results of the ANDROCAN Study: Histopathological Characteristics and Biochemical Recurrence at 5 Years of Localized Prostate Cancer According to Preoperative Gonadal Status","authors":"Yann Neuzillet ,&nbsp;Jean-Pierre Raynaud ,&nbsp;Jean-François Dreyfus ,&nbsp;Camélia Radulescu ,&nbsp;Mathieu Rouanne ,&nbsp;Marc Schneider ,&nbsp;Sylvie Krish ,&nbsp;Morgan Rouprêt ,&nbsp;Sarah J. Drouin ,&nbsp;Eva Comperat ,&nbsp;Marc Galiano ,&nbsp;Xavier Cathelineau ,&nbsp;Pierre Validire ,&nbsp;Vincent Molinié ,&nbsp;Jean Fiet ,&nbsp;Franck Giton ,&nbsp;Thierry Lebret ,&nbsp;Henry Botto","doi":"10.1016/j.euo.2024.08.003","DOIUrl":"10.1016/j.euo.2024.08.003","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background and objective&lt;/h3&gt;&lt;div&gt;Failure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high; therefore, it is essential to improve the selection and identification of at-risk patients to reduce mortality. The aim of the ANDROCAN study was to evaluate the biochemical recurrence (BCR) in patients with localized PCa treated by total prostatectomy at 5 yr after surgery, according to their presurgery gonadal status.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A prospective cohort study was conducted including 1318 patients undergoing total prostatectomy for localized PCa with a 5-yr postoperative follow-up. Clinical and hormonal data (assays of total testosterone [TT], bioavailable testosterone [BT], dihydrotestosterone, estrone, and estradiol were performed by gas chromatography/mass spectrometry) as well as metabolic syndrome parameters were collected at baseline before surgery. Pathological data (predominant Gleason grade 4 and stage) were collected and cross-referenced centrally. Factors associated with BCR were assessed by a multivariate analysis, and BCR-free survival was assessed by a Kaplan-Meier analysis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Key findings and limitations&lt;/h3&gt;&lt;div&gt;Among the 1318 patients, 237 had BCR of PCa. Considering demographic characteristics, populations with and without BCR were similar. However, patients with BCR had cancers with a higher Gleason score (&lt;em&gt;p&lt;/em&gt; = 0.0001) and higher prostate-specific antigen (PSA) values (&lt;em&gt;p&lt;/em&gt; = 0.0005) at baseline. Gleason score, pT &gt;3a, and PSA level at baseline were positively correlated with BCR (&lt;em&gt;p&lt;/em&gt; &lt; 0.0001, &lt;em&gt;p&lt;/em&gt; &lt; 0.0001, and &lt;em&gt;p&lt;/em&gt; = 0.0048, respectively), while BT and TT levels were not associated with BCR. This study includes patients with varying clinical characteristics, such as cancer history and metabolic syndrome, introducing variability that makes it challenging to isolate the specific effects of gonadal status on BCR. Another limitation is the lack of evaluation of long-term BCR beyond 5 yr, potentially overlooking recurrences that occur between 5 and 15 yr after surgery. This could lead to an underestimation of the actual long-term recurrence rates.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions and clinical implications&lt;/h3&gt;&lt;div&gt;Overall, PSA levels, high Gleason score, and pT &gt;3a are associated with a greater likelihood of disease recurrence following initial treatment and could serve as important prognostic indicators for predicting the risk of BCR. In this prospective study&lt;strong&gt;,&lt;/strong&gt;&lt;span&gt; biochemical hypogonadism was not associated with a higher occurrence of BCR within 5 yr of prostatectomy. The biological gonadal status of preoperative patients could potentially be useful for therapeutic decisions but does not provide an indication for the oncological follow-up.&lt;/span&gt;&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Patient summary&lt;/h3&gt;&lt;div&gt;Five-year follow up of patients after surgery showed that there is no association between hypogon","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 4","pages":"Pages 1111-1117"},"PeriodicalIF":9.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105927","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":"Niraparib and Abiraterone Acetate plus Prednisone in Metastatic Castration-resistant Prostate Cancer: Final Overall Survival Analysis for the Phase 3 MAGNITUDE Trial","authors":"Kim N. Chi ,&nbsp;Elena Castro ,&nbsp;Gert Attard ,&nbsp;Matthew R. Smith ,&nbsp;Shahneen Sandhu ,&nbsp;Eleni Efstathiou ,&nbsp;Guilhem Roubaud ,&nbsp;Eric J. Small ,&nbsp;Andrea Pereira de Santana Gomes ,&nbsp;Dana E. Rathkopf ,&nbsp;Marniza Saad ,&nbsp;Howard Gurney ,&nbsp;Wonho Jung ,&nbsp;Won Kim ,&nbsp;Shiva Dibaj ,&nbsp;Daphne Wu ,&nbsp;Jenny Zhang ,&nbsp;Angela Lopez-Gitlitz ,&nbsp;Peter Francis ,&nbsp;David Olmos","doi":"10.1016/j.euo.2025.04.012","DOIUrl":"10.1016/j.euo.2025.04.012","url":null,"abstract":"<div><h3>Background and objective</h3><div>The phase 3 MAGNITUDE trial previously met its primary endpoint of an improvement in radiographic progression-free survival with niraparib + abiraterone acetate and prednisone (AAP) versus placebo + AAP in patients with metastatic castration-resistant prostate cancer (mCRPC) and alterations in genes involved in DNA homologous recombination repair (HRR⁺), particularly in <em>BRCA1/2</em>.</div></div><div><h3>Methods</h3><div>Patients were prospectively screened for HRR alterations and randomized 1:1 to niraparib + AAP (<em>n</em> = 212) or placebo + AAP (<em>n</em> = 211). We report results from the prespecified, event-driven, final analysis of secondary efficacy endpoints.</div></div><div><h3>Key findings and limitations</h3><div>Final analysis at median follow-up of 37.3 mo revealed no difference in overall survival (OS) between niraparib + AAP and placebo + AAP in the HRR⁺ population (hazard ratio [HR] 0.931, 95% confidence interval [CI] 0.720–1.203; <em>p</em> = 0.585) or the subgroup with <em>BRCA1/2</em> alterations (HR 0.788, 95% CI 0.554–1.120; nominal <em>p</em> = 0.183). Prespecified multivariate analyses adjusted for baseline prognostic factors showed a trend toward longer OS with niraparib + AAP over placebo + AAP in the HRR⁺ population (HR 0.785, 95% CI 0.606–1.016; nominal <em>p</em> = 0.066) and the <em>BRCA1/2</em> subgroup (HR 0.663, 95% CI 0.464–0.947; nominal <em>p</em> = 0.024). Niraparib + AAP led to a statistically significant, clinically meaningful improvement in time to symptomatic progression in both the HRR⁺ population (HR 0.547, 95% CI 0.396–0.754; <em>p</em> = 0.006) and the <em>BRCA1/2</em> subgroup (HR 0.562, 95% CI 0.371–0.849; nominal <em>p</em> = 0.006), and a clinically meaningful improvement in time to cytotoxic chemotherapy in the HRR⁺ population (HR 0.688, 95% CI 0.499–0.950; <em>p</em> = 0.022) and the <em>BRCA1/2</em> subgroup (HR 0.598, 95% CI 0.387–0.924; nominal <em>p</em> = 0.019) in comparison to placebo + AAP. The niraparib + AAP safety profile remains unchanged at longer follow-up; adverse events were primarily hematologic and manageable.</div></div><div><h3>Conclusions and clinical implications</h3><div>The MAGNITUDE final analysis showed that patients with HRR⁺ mCRPC, including those with the approved indication of <em>BRCA-</em>altered mCRPC, generally continue to benefit from first-line treatment with niraparib + AAP in comparison to placebo + AAP.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 4","pages":"Pages 986-998"},"PeriodicalIF":9.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001606","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":"Corrigendum to “Development and independent validation of a prognostic gene expression signature based on RB1, PTEN, and TP53 in metastatic hormone-sensitive prostate cancer patients” [Eur. Urol. Oncol. 7 (2024) 954–964]","authors":"Natalia Jiménez ,&nbsp;Marta Garcia de Herreros ,&nbsp;Òscar Reig ,&nbsp;Mercedes Marín-Aguilera ,&nbsp;Caterina Aversa ,&nbsp;Laura Ferrer-Mileo ,&nbsp;Samuel García-Esteve ,&nbsp;Leonardo Rodríguez-Carunchio ,&nbsp;Isabel Trias ,&nbsp;Albert Font ,&nbsp;Alejo Rodriguez-Vida ,&nbsp;Miguel Ángel Climent ,&nbsp;Sara Cros ,&nbsp;Isabel Chirivella ,&nbsp;Montserrat Domènech ,&nbsp;Mariona Figols ,&nbsp;Joan Carles ,&nbsp;Cristina Suárez ,&nbsp;Daniel Herrero Rivera ,&nbsp;Enrique González-Billalabeitia ,&nbsp;Begoña Mellado","doi":"10.1016/j.euo.2025.05.011","DOIUrl":"10.1016/j.euo.2025.05.011","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 4","pages":"Page 1219"},"PeriodicalIF":9.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157603","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 ,&nbsp;Seyed Behzad Jazayeri ,&nbsp;Christian Harrs ,&nbsp;Nagashree Rao ,&nbsp;Facundo Davaro ,&nbsp;Hongzhi Xu ,&nbsp;Logan Zemp ,&nbsp;Alice Yu ,&nbsp;Scott M. Gilbert ,&nbsp;Michael Poch ,&nbsp;Philippe E. Spiess ,&nbsp;Wade Sexton ,&nbsp;Joshua Linscott ,&nbsp;Roger Li","doi":"10.1016/j.euo.2025.05.022","DOIUrl":"10.1016/j.euo.2025.05.022","url":null,"abstract":"<div><div>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 <em>p</em> &gt; 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 <em>p</em> &gt; 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.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 4","pages":"Pages 888-892"},"PeriodicalIF":9.3,"publicationDate":"2025-08-01","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":"A Phase 1b/2 Study of Talazoparib and Axitinib in Patients with Advanced Clear-cell Renal Cell Carcinoma","authors":"Ritesh R. Kotecha ,&nbsp;Sahil D. Doshi ,&nbsp;Andrea Knezevic ,&nbsp;Rachel Jacobi ,&nbsp;Hyung Jun Woo ,&nbsp;David H. Aggen ,&nbsp;Deaglan J. McHugh ,&nbsp;Neil J. Shah ,&nbsp;Maria I. Carlo ,&nbsp;Niamh M. Keegan ,&nbsp;Yogini Gayadin ,&nbsp;Joshua Chaim ,&nbsp;Mark T.A. Donoghue ,&nbsp;Gopa Iyer ,&nbsp;Chung-Han Lee ,&nbsp;Darren R. Feldman ,&nbsp;Robert J. Motzer ,&nbsp;Martin H. Voss","doi":"10.1016/j.euo.2025.03.010","DOIUrl":"10.1016/j.euo.2025.03.010","url":null,"abstract":"<div><div>Inactivation of the <em>VHL</em><span> gene leads to HIF accumulation, angiogenesis, and genomic instability. In this phase 1b/2 study, we assessed the safety and antitumor activity of axitinib<span><span> 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 </span>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.</span></span></div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 4","pages":"Pages 866-870"},"PeriodicalIF":9.3,"publicationDate":"2025-08-01","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}