European urology oncology最新文献

{"title":"Assessing the Clinical Utility of Published Prostate Cancer Polygenic Risk Scores in a Large Biobank Data Set","authors":"Randy A. Vince Jr ,&nbsp;Helen Sun ,&nbsp;Udit Singhal ,&nbsp;Fredrick R. Schumacher ,&nbsp;Erika Trapl ,&nbsp;Johnie Rose ,&nbsp;Jennifer Cullen ,&nbsp;Nicholas Zaorsky ,&nbsp;Jonathan Shoag ,&nbsp;Holly Hartman ,&nbsp;Angela Y. Jia ,&nbsp;Daniel E. Spratt ,&nbsp;Lars G. Fritsche ,&nbsp;Todd M. Morgan","doi":"10.1016/j.euo.2024.04.017","DOIUrl":"10.1016/j.euo.2024.04.017","url":null,"abstract":"<div><h3>Background and objective</h3><div>Polygenic risk scores (PRSs) have been developed to identify men with the highest risk of prostate cancer. Our aim was to compare the performance of 16 PRSs in identifying men at risk of developing prostate cancer and then to evaluate the performance of the top-performing PRSs in differentiating individuals at risk of aggressive prostate cancer.</div></div><div><h3>Methods</h3><div>For this case-control study we downloaded 16 published PRSs from the Polygenic Score Catalog on May 28, 2021 and applied them to Michigan Genomics Initiative (MGI) patients. Cases were matched to the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry to obtain granular clinical and pathological data. MGI prospectively enrolls patients undergoing surgery at the University of Michigan, and MUSIC is a multi-institutional registry that prospectively tracks demographic, treatment, and clinical variables. The predictive performance of each PRS was evaluated using the area under the covariate-adjusted receiver operating characteristic curve (aAUC), and the association between PRS and disease aggressiveness according to prostate biopsy data was measured using logistic regression.</div></div><div><h3>Key findings and limitations</h3><div>We included 18 050 patients in the analysis, of whom 15 310 were control subjects and 2740 were prostate cancer cases. The median age was 66.1 yr (interquartile range 59.9–71.6) for cases and 56.6 yr (interquartile range 42.6–66.7) for control subjects. The PRS performance in predicting the risk of developing prostate cancer according to aAUC ranged from 0.51 (95% confidence interval 0.51–0.53) to 0.67 (95% confidence interval 0.66–0.68). By contrast, there was no association between PRS and disease aggressiveness.</div></div><div><h3>Conclusions and clinical implications</h3><div>Prostate cancer PRSs have modest real-world performance in identifying patients at higher risk of developing prostate cancer; however, they are limited in distinguishing patients with indolent versus aggressive disease.</div></div><div><h3>Patient summary</h3><div>Risk scores using data for multiple genes (called polygenic risk scores) can identify men at higher risk of developing prostate cancer. However, these scores need to be refined to be able to identify men with the highest risk for clinically significant prostate cancer.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 1","pages":"Pages 47-55"},"PeriodicalIF":8.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907915","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 Determinants Associated with Modes of Progression and Patterns of Failure in Metachronous Oligometastatic Castration-sensitive Prostate Cancer","authors":"Philip Sutera ,&nbsp;Yang Song ,&nbsp;Amol C. Shetty ,&nbsp;Keara English ,&nbsp;Kim Van der Eecken ,&nbsp;Ozan Cem Guler ,&nbsp;Jarey Wang ,&nbsp;Yufeng Cao ,&nbsp;Soha Bazyar ,&nbsp;Sofie Verbeke ,&nbsp;Jo Van Dorpe ,&nbsp;Valérie Fonteyne ,&nbsp;Bram De Laere ,&nbsp;Mark Mishra ,&nbsp;Zaker Rana ,&nbsp;Jason Molitoris ,&nbsp;Matthew Ferris ,&nbsp;Ana Kiess ,&nbsp;Daniel Y. Song ,&nbsp;Theodore DeWeese ,&nbsp;Matthew P. Deek","doi":"10.1016/j.euo.2024.05.011","DOIUrl":"10.1016/j.euo.2024.05.011","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background and objective&lt;/h3&gt;&lt;div&gt;Oligometastatic castration-sensitive prostate cancer (omCSPC) represents an early state in the progression of metastatic disease for which patients experience better outcomes in comparison to those with higher disease burden. Despite the generally more indolent nature, there is still much heterogeneity, with some patients experiencing a more aggressive clinical course unexplained by clinical features alone. Our aim was to investigate correlation of tumor genomics with the mode of progression (MOP) and pattern of failure (POF) following first treatment (metastasis-directed and/or systemic therapy) for omCSPC.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We performed an international multi-institutional retrospective study of men treated for metachronous omCSPC who underwent tumor next-generation sequencing with at least 1 yr of follow-up after their first treatment. Descriptive MOP and POF results are reported with respect to the presence of genomic alterations in pathways of interest. MOP was defined as class I, long-term control (LTC; no radiographic progression at last follow-up), class II, oligoprogression (1–3 lesions), or class III, polyprogression (≥4 lesions). POF included the location of lesions at first failure. Genomic pathways of interest included &lt;em&gt;TP53&lt;/em&gt;, &lt;em&gt;ATM, RB1, BRCA1/2, SPOP&lt;/em&gt;, and WNT (&lt;em&gt;APC, CTNNB1, RNF43)&lt;/em&gt;. Genomic associations with MOP/POF were compared using χ&lt;sup&gt;2&lt;/sup&gt; tests. Exploratory analyses revealed that the COSMIC mutational signature and differential gene expression were also correlated with MOP/POF. Overall survival (OS) was calculated via the Kaplan-Meier method from the time of first failure.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Key findings and clinical implications&lt;/h3&gt;&lt;div&gt;We included 267 patients in our analysis; the majority had either one (47%) or two (30%) metastatic lesions at oligometastasis. The 3-yr OS rate was significantly associated with MOP (71% for polyprogression vs 91% for oligoprogression; &lt;em&gt;p&lt;/em&gt; = 0.005). &lt;em&gt;TP53&lt;/em&gt; mutation was associated with a significantly lower LTC rate (27.6% vs 42.3%; &lt;em&gt;p&lt;/em&gt; = 0.04) and &lt;em&gt;RB1&lt;/em&gt; mutation was associated with a high rate of polyprogression (50% vs 19.9%; &lt;em&gt;p&lt;/em&gt; = 0.022). Regarding POF, bone failure was significantly more common with tumors harboring &lt;em&gt;TP53&lt;/em&gt; mutations (44.8% vs25.9%; &lt;em&gt;p&lt;/em&gt; = 0.005) and less common with &lt;em&gt;SPOP&lt;/em&gt; mutations (7.1% vs 31.4%; &lt;em&gt;p&lt;/em&gt; = 0.007). Visceral failure was more common with tumors harboring either WNT pathway mutations (17.2% vs 6.8%, &lt;em&gt;p&lt;/em&gt; = 0.05) or &lt;em&gt;SPOP&lt;/em&gt; mutations (17.9% vs 6.3%; &lt;em&gt;p&lt;/em&gt; = 0.04). Finally, visceral and bone failures were associated with distinct gene-expression profiles.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions and clinical implications&lt;/h3&gt;&lt;div&gt;Tumor genomics provides novel insight into MOP and POF following treatment for metachronous omCSPC. Patients with &lt;em&gt;TP53&lt;/em&gt; and &lt;em&gt;RB1&lt;/em&gt; mutations have a higher likelihood","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 1","pages":"Pages 111-118"},"PeriodicalIF":8.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small Testicular Masses: An Individualized Approach Is Warranted","authors":"Axel Heidenreich","doi":"10.1016/j.euo.2024.11.012","DOIUrl":"10.1016/j.euo.2024.11.012","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 1","pages":"Pages 5-6"},"PeriodicalIF":8.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767648","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":"Expert Consensus Recommendations on the Management of Treatment-emergent Adverse Events Among Men with Prostate Cancer Taking Poly-ADP Ribose Polymerase Inhibitor + Novel Hormonal Therapy Combination Therapy","authors":"Neal D. Shore ,&nbsp;Michael S. Broder ,&nbsp;Pedro C. Barata ,&nbsp;Tony Crispino ,&nbsp;André P. Fay ,&nbsp;Jennifer Lloyd ,&nbsp;Begoña Mellado ,&nbsp;Nobuaki Matsubara ,&nbsp;Nicklas Pfanzelter ,&nbsp;Katrin Schlack ,&nbsp;Paul Sieber ,&nbsp;Andrey Soares ,&nbsp;Hannah Dalglish ,&nbsp;Alexander Niyazov ,&nbsp;Saif Shaman ,&nbsp;Michael A. Zielinski ,&nbsp;Jane Chang ,&nbsp;Neeraj Agarwal","doi":"10.1016/j.euo.2024.05.009","DOIUrl":"10.1016/j.euo.2024.05.009","url":null,"abstract":"<div><h3>Background and objective</h3><div>Recent clinical trials have shown improvement in progression-free survival in men with metastatic prostate cancer (mPC) treated with combination poly-ADP ribose polymerase (PARP) inhibitors (PARPi) and novel hormonal therapy (NHT). Regulatory bodies in the USA, Canada, Europe, and Japan have recently approved this combination therapy for mPC. Common adverse events (AEs) include fatigue, nausea and vomiting, and anemia. Nuanced AE management guidance for these combinations is lacking. The panel objective was to develop expert consensus on AE management in patients with mPC treated with the combination PARPi + NHT.</div></div><div><h3>Methods</h3><div>The RAND/University of California Los Angeles modified Delphi Panel method was used. AEs were defined using the Common Terminology Criteria for Adverse Events. Twelve experts (seven medical oncologists, one advanced practice registered nurse, three urologists, and one patient advocate) reviewed the relevant literature; independently rated initial AE management options for the agent suspected of causing the AE for 419 patient scenarios on a 1–9 scale; discussed areas of agreement (AoAs) and disagreement (AoDs) at a March 2023 meeting; and repeated these ratings following the meeting. Second-round ratings formed the basis of guidelines.</div></div><div><h3>Key findings and limitations</h3><div>AoDs decreased from 41% to 21% between the first and second round ratings, with agreement on at least one management strategy for every AE. AoAs included the following: (1) continue therapy with symptomatic treatment for patients with mild AEs; (2) for moderate fatigue, recommend nonpharmacologic treatment, hold treatment temporarily, and restart at a reduced dose when symptoms resolve; (3) for severe nausea or any degree of vomiting where symptomatic treatment fails, hold treatment temporarily and restart at a reduced dose when symptoms resolve; and (4) for hemoglobin 7.1–8.0 g/dl and symptoms of anemia, hold treatment temporarily and restart at a reduced dose after red blood cell transfusion.</div></div><div><h3>Conclusions and clinical implications</h3><div>This expert guidance can support management of AEs in patients with mPC receiving combination PARPi + NHT therapy.</div></div><div><h3>Patient summary</h3><div>A panel of experts developed guidelines for adverse event (AE) management in patients with metastatic prostate cancer treated with a combination of poly-ADP ribose polymerase inhibitors and novel hormonal therapy. For mild AEs, continuation of cancer therapy along with symptomatic treatment is recommended. For moderate or severe AEs, cancer therapy should be stopped temporarily and restarted at the same or a reduced dose when AE resolves.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 1","pages":"Pages 94-104"},"PeriodicalIF":8.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liquid Biopsy in Progressing Prostate Cancer Patients Starting Docetaxel with or Without Enzalutamide: A Biomarker Study of the PRESIDE Phase 3b Trial","authors":"Maria Ruiz-Vico ,&nbsp;Daniel Wetterskog ,&nbsp;Francesco Orlando ,&nbsp;Suparna Thakali ,&nbsp;Anna Wingate ,&nbsp;Anuradha Jayaram ,&nbsp;Paolo Cremaschi ,&nbsp;Osvaldas Vainauskas ,&nbsp;Nicole Brighi ,&nbsp;Daniel Castellano-Gauna ,&nbsp;Lennart Åström ,&nbsp;Vsevolod B. Matveev ,&nbsp;Sergio Bracarda ,&nbsp;Adil Esen ,&nbsp;Susan Feyerabend ,&nbsp;Elżbieta Senkus ,&nbsp;Marta López-Brea Piqueras ,&nbsp;Santosh Gupta ,&nbsp;Rick Wenstrup ,&nbsp;Gunther Boysen ,&nbsp;Gerhardt Attard","doi":"10.1016/j.euo.2024.08.006","DOIUrl":"10.1016/j.euo.2024.08.006","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background and objective&lt;/h3&gt;&lt;div&gt;The PRESIDE (NCT02288247) randomized trial demonstrated prolonged progression-free survival (PFS) with continuing enzalutamide beyond progression in metastatic castration-resistant prostate cancer (mCRPC) patients starting docetaxel. This study aims to test the associations of PFS and circulating tumor DNA (ctDNA) prior to and after one cycle (cycle 2 day 1 [C2D1]) of docetaxel and with a liquid biopsy resistance biomarker (LBRB; plasma androgen receptor [&lt;em&gt;AR&lt;/em&gt;] gain and/or circulating tumor cells [CTCs] expressing AR splice variant 7 [CTC-AR-V7]) prior to continuation of enzalutamide/placebo.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Patients consenting to the biomarker substudy and donating blood before starting docetaxel with enzalutamide/placebo (&lt;em&gt;N&lt;/em&gt; = 157) were included. Sequential plasma DNA samples were characterized with a prostate-cancer bespoke next-generation-sequencing capture panel (PCF_SELECT), and CTCs were assessed for AR-V7 (Epic Sciences, San Diego, CA, USA). Cox models, Kaplan-Meier, and restricted mean survival time (RMST) at 18 mo were calculated.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Key findings and limitations&lt;/h3&gt;&lt;div&gt;There was a significant association of worse PFS with pre-docetaxel ctDNA detection (&lt;em&gt;N&lt;/em&gt; = 86 (55%), 8.1 vs 10.8 mo hazard ratio [HR] = 1.78, &lt;em&gt;p&lt;/em&gt; = 0.004) or persistence/rise of ctDNA at C2D1 (&lt;em&gt;N&lt;/em&gt; = 35/134, 5.5 vs 10.9 mo, HR = 1.95, 95% confidence interval [CI] = 1.15–3.30, &lt;em&gt;p&lt;/em&gt; = 0.019). LBRB-positive patients (&lt;em&gt;N&lt;/em&gt; = 62) had no benefit from continuing enzalutamide with docetaxel (HR = 0.78, 95% CI = 0.41–1.48, &lt;em&gt;p&lt;/em&gt; = 0.44; RMST: 7.9 vs 7.1 mo, &lt;em&gt;p&lt;/em&gt; = 0.50). Conversely, resistance biomarker–negative patients (&lt;em&gt;N&lt;/em&gt; = 87) had significantly prolonged PFS (HR = 0.49, 95% CI = 0.29–0.82, &lt;em&gt;p&lt;/em&gt; = 0.006; RMST: 11.5 vs 8.9 mo, &lt;em&gt;p&lt;/em&gt; = 0.005). Eight patients were unevaluable. An exploratory analysis identified increased copy-number gains (&lt;em&gt;CDK6&lt;/em&gt;/&lt;em&gt;CDK4&lt;/em&gt;) at progression on docetaxel. Limitations included relatively low detection of CTC-AR-V7. Validation of impact on overall survival is required.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions and clinical implications&lt;/h3&gt;&lt;div&gt;Liquid biopsy gives an early indication of docetaxel futility, could guide patient selection for continuing enzalutamide, and identifies cell cycle gene alterations as a potential cause of docetaxel resistance in mCRPC.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Patient summary&lt;/h3&gt;&lt;div&gt;In the PRESIDE biomarker study, we found that detecting circulating tumor DNA in plasma after starting treatment with docetaxel (chemotherapy) for metastatic prostate cancer resistant to androgen deprivation therapy can predict early how long patients will take to respond to treatment. Patients negative for a liquid biopsy resistance biomarker (based on the status of androgen receptor (&lt;em&gt;AR&lt;/em&gt;) gene and AR splice variant 7 in circulating tumor cells) benefit from continuing enzalutamide in ","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 1","pages":"Pages 135-144"},"PeriodicalIF":8.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frailty and Renal Cell Carcinoma: Integration of Comprehensive Geriatric Assessment into Shared Decision-making","authors":"Alessio Pecoraro ,&nbsp;Giuseppe Dario Testa ,&nbsp;Laura Marandino ,&nbsp;Laurence Albiges ,&nbsp;Axel Bex ,&nbsp;Umberto Capitanio ,&nbsp;Ilaria Cappiello ,&nbsp;Lorenzo Masieri ,&nbsp;Carme Mir ,&nbsp;Morgan Roupret ,&nbsp;Sergio Serni ,&nbsp;Andrea Ungar ,&nbsp;Giulia Rivasi ,&nbsp;Riccardo Campi","doi":"10.1016/j.euo.2024.09.001","DOIUrl":"10.1016/j.euo.2024.09.001","url":null,"abstract":"<div><h3>Context</h3><div>Frailty, a geriatric syndrome characterized by decreased resilience and physiological reserve, impacts the prognosis and management of older adults significantly, particularly in the context of surgical and oncological care.</div></div><div><h3>Objective</h3><div>To provide an overview of frailty assessment in the management of older patients with a renal mass/renal cell carcinoma (RCC), focusing on its implications for diagnostic workup, treatment decisions, and clinical outcomes.</div></div><div><h3>Evidence acquisition</h3><div>A narrative review of the literature was conducted, focusing on frailty definitions, assessment tools, and their application in geriatric oncology, applied to the field of RCC. Relevant studies addressing the prognostic value of frailty, its impact on treatment outcomes, and potential interventions were summarized.</div></div><div><h3>Evidence synthesis</h3><div>Frailty is a poor prognostic factor and can influence decision-making in the management of both localized and metastatic RCC. Screening tools such as the Geriatric Screening Tool 8 (G8) and the Mini-COG test can aid clinicians to select older patients (ie, aged ≥65 yr) for a further comprehensive geriatric assessment (CGA) performed by dedicated geriatricians. The CGA provides insights to risk stratify patients and guide subsequent treatment pathways. As such, the involvement of geriatricians in multidisciplinary tumor boards emerges as an essential priority to address the complex needs of frail patients and optimize clinical outcomes. Herein, we propose a dedicated care pathway as a first key step to implement frailty assessment in clinical practice and research for RCC.</div></div><div><h3>Conclusions</h3><div>Frailty has emerged as a crucial factor influencing the management and outcomes of older patients with RCC. Involvement of geriatricians in diagnostic and therapeutic pathways represents a pragmatic approach to screen and assess frailty, fostering individualized treatment decisions according to holistic patient risk stratification.</div></div><div><h3>Patient summary</h3><div>Frailty, a decline in resilience and physiological reserve, influences treatment decisions and outcomes in elderly patients with renal cell carcinoma, guiding personalized care. In this review, we focused on pragmatic strategies to screen patients with a renal mass suspected for renal cell carcinoma, who are older than 65 yr, for frailty and on personalized management algorithms integrating geriatric input beyond patient- and tumor-related factors.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 1","pages":"Pages 190-200"},"PeriodicalIF":8.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to Riccardo Leni, Andreas Roder, and Hein V. Stroomberg’s Letter to the Editor re: Julien Anract, Clément Klein, Ugo Pinar, Morgan Rouprêt, Nicolas Barry Delongchamps, Grégoire Robert. Incidental Prostate Cancer in Patients Undergoing Surgery for Benign Prostatic Hyperplasia: A Predictive Model. Eur Urol Oncol. 2025;8:145–51","authors":"Julien Anract ,&nbsp;Clément Klein ,&nbsp;Ugo Pinar ,&nbsp;Morgan Rouprêt ,&nbsp;Nicolas Barry Delongchamps ,&nbsp;Grégoire Robert","doi":"10.1016/j.euo.2024.12.001","DOIUrl":"10.1016/j.euo.2024.12.001","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 1","pages":"Pages 213-214"},"PeriodicalIF":8.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871899","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":"Short-term Darolutamide (ODM-201) Concomitant to Radiation Therapy for Patients with Unfavorable Intermediate-risk Prostate Cancer: The Darius (AFU-GETUG P15) Phase 2 Trial Protocol","authors":"Paul Sargos ,&nbsp;Carine Bellera ,&nbsp;Rita Bentahila ,&nbsp;Marie Guerni ,&nbsp;Nicolas Benziane-Ouaritini ,&nbsp;Diego Teyssonneau ,&nbsp;Nam-Son Vuong ,&nbsp;Guillaume Ploussard ,&nbsp;Morgan Roupret ,&nbsp;Guilhem Roubaud","doi":"10.1016/j.euo.2024.04.023","DOIUrl":"10.1016/j.euo.2024.04.023","url":null,"abstract":"<div><h3>Background</h3><div>Combination of androgen deprivation therapy (ADT) with external beam radiation therapy (EBRT) is a standard of care for patients with intermediate-risk prostate cancer (PCa). However, 6 months of ADT generates multiple side effects impacting quality of life (QoL). Darolutamide (an androgen receptor targeting agent [ARTA]) is associated with low blood-brain barrier penetrance and less drug-drug interaction.</div></div><div><h3>Objective</h3><div>To assess the efficacy of a combination of 6 months of darolutamide with EBRT to treat patients with unfavorable intermediate-risk PCa.</div></div><div><h3>Design, setting, and participants</h3><div>The DARIUS trial is a multicenter randomized non comparative phase 2 trial, randomizing the 6-months darolutamide + EBRT arm versus 6-months ADT + EBRT in patients with unfavorable intermediate-risk PCa.</div></div><div><h3>Outcome measurements and statistical analysis</h3><div>The primary endpoint is a biological response defined as prostate-specific antigen ≤0.1 ng/ml at month six of darolutamide or ADT. The key secondary endpoints are biochemical recurrence–free survival, disease-free survival, safety, and QoL. Ancillary studies using radiomics and genomic classifier are planned. Sixty-two patients will be included.</div></div><div><h3>Results and limitations</h3><div>In this population of patients requiring ADT combined with EBRT, the use of an ARTA alone, such as darolutamide, may demonstrate antitumoral efficacy while minimizing toxicity and maintaining QoL. Limitations are mainly inherent to the open-label design of this study.</div></div><div><h3>Conclusions</h3><div>Six months of darolutamide + EBRT compared with 6 months of ADT + EBRT may be efficient in terms of a biological response, avoiding toxicity and altered QoL attributable to ADT in patients with unfavorable intermediate-risk PCa.</div></div><div><h3>Patient summary</h3><div>The ongoing DARIUS clinical trial assesses short-term (6 months) darolutamide treatment in association with external beam radiation therapy in men with localized prostate cancer. The trial investigates whether single-agent darolutamide can improve the biological response while maintaining a favorable tolerability profile.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 1","pages":"Pages 73-79"},"PeriodicalIF":8.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957059","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":"Association Between Hypoglycemia Agents and Long-term Survival Outcomes for Patients with Non–muscle-invasive Bladder Cancer Treated with Intravesical Bacillus Calmette-Guérin Immunotherapy","authors":"Kang Liu ,&nbsp;Hongda Zhao ,&nbsp;Xuan Chen ,&nbsp;Hongwei Wu ,&nbsp;Chris Ho-Ming Wong ,&nbsp;Ivan Ching-Ho Ko ,&nbsp;Rossella Nicoletti ,&nbsp;Peter Ka-Fung Chiu ,&nbsp;Chi-Fai Ng ,&nbsp;Jeremy Yuen-Chun Teoh","doi":"10.1016/j.euo.2024.12.002","DOIUrl":"10.1016/j.euo.2024.12.002","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background and objective&lt;/h3&gt;&lt;div&gt;There is a lack of data on the impact of hypoglycemia agents, especially metformin, on prognosis for non–muscle-invasive bladder cancer (NMIBC). Our aim was to investigate the association between hypoglycemia agents, especially metformin, and long-term survival outcomes for patients with NMIBC treated with bacillus Calmette-Guérin.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;All patients with NMIBC treated with intravesical BCG therapy from 2001 to 2020 were identified in a territory-wide database in Hong Kong. Patients were stratified into two groups according to whether or not they were taking a hypoglycemia agent at BCG treatment initiation. We analyzed data for overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS) using the Kaplan-Meier method. Multivariable Cox regression analysis was used to adjust for potential confounding factors and estimate hazard ratio (HRs) and 95% confidence intervals (CIs). Subgroup analyses were conducted to assess the specific influence of metformin on survival outcomes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Key findings and limitations&lt;/h3&gt;&lt;div&gt;Of 2602 patients with NMIBC treated with intravesical BCG, 19.5% (&lt;em&gt;n&lt;/em&gt; = 507) were taking a hypoglycemia agent at BCG initiation (treatment group) and 80.5% (&lt;em&gt;n&lt;/em&gt; = 2095) were not (control group). At median follow-up of 11 yr, Kaplan-Meier analysis revealed a significant difference in OS between the groups (&lt;em&gt;p&lt;/em&gt; &lt; 0.01), but not in CSS (&lt;em&gt;p&lt;/em&gt; = 0.36), RFS (&lt;em&gt;p&lt;/em&gt; = 0.19), or PFS (&lt;em&gt;p&lt;/em&gt; = 0.05). Subgroup analysis comparing outcomes for patients taking metformin, patients taking a hypoglycemia agent other than metformin, and control subjects revealed significant differences in OS (&lt;em&gt;p&lt;/em&gt; &lt; 0.01) and RFS (&lt;em&gt;p&lt;/em&gt; = 0.02), but not in CSS (&lt;em&gt;p&lt;/em&gt; = 0.59) or PFS (&lt;em&gt;p&lt;/em&gt; = 0.08). Multivariable Cox regression analysis identified metformin-based treatment for hypoglycemia as an independent risk factor for RFS (HR 1.22, 95% CI 1.02–1.46), whereas hypoglycemia agents other than metformin were not significantly associated with RFS (HR 0.71, 95% CI 0.47–1.06).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions and clinical implications&lt;/h3&gt;&lt;div&gt;Metformin-based hypoglycemia treatment was an independent risk factor for RFS in BCG-treated NMIBC. Hypoglycemia treatment with an agent other than metformin was not related to long-term survival outcomes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Patient summary&lt;/h3&gt;&lt;div&gt;We investigated the relationship between treatment for high blood sugar and long-term survival for patients with intermediate-risk or high-risk non–muscle-invasive bladder cancer. The patients had received BCG (bacillus Calmette-Guérin) treatment in Hong Kong for their bladder cancer over the past two decades. Our results show that metformin, but not other drugs used to treat high blood sugar, was associated with poorer survival free from bladder cancer recurrence for these patien","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 1","pages":"Pages 164-170"},"PeriodicalIF":8.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846116","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":"Validation of Prognostic and Predictive Models for Therapeutic Response in Patients Treated with [177Lu]Lu-PSMA-617 Versus Cabazitaxel for Metastatic Castration-resistant Prostate Cancer (TheraP): A Post Hoc Analysis from a Randomised, Open-label, Phase 2 Trial","authors":"Andrei Gafita ,&nbsp;Andrew J. Martin ,&nbsp;Louise Emmett ,&nbsp;Matthias Eiber ,&nbsp;Amir Iravani ,&nbsp;Wolfgang P. Fendler ,&nbsp;James Buteau ,&nbsp;Shahneen Sandhu ,&nbsp;Arun A. Azad ,&nbsp;Ken Herrmann ,&nbsp;Martin R. Stockler ,&nbsp;Ian D. Davis ,&nbsp;Michael S. Hofman","doi":"10.1016/j.euo.2024.03.009","DOIUrl":"10.1016/j.euo.2024.03.009","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Prognostic models have been developed using data from a multicentre noncomparative study to forecast the likelihood of a 50% reduction in prostate-specific antigen (PSA50), longer prostate-specific antigen (PSA) progression-free survival (PFS), and longer overall survival (OS) in patients with metastatic castration-resistant prostate cancer receiving [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-PSMA radioligand therapy. The predictive utility of the models to identify patients likely to benefit most from [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-PSMA compared with standard chemotherapy has not been established.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To determine the predictive value of the models using data from the randomised, open-label, phase 2, TheraP trial (primary objective) and to evaluate the clinical net benefit of the PSA50 model (secondary objective).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Design, setting, and participants&lt;/h3&gt;&lt;div&gt;All 200 patients were randomised in the TheraP trial to receive [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-PSMA-617 (&lt;em&gt;n&lt;/em&gt; = 99) or cabazitaxel (&lt;em&gt;n&lt;/em&gt; = 101) between February 2018 and September 2019.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Outcome measurements and statistical analysis&lt;/h3&gt;&lt;div&gt;Predictive performance was investigated by testing whether the association between the modelled outcome classifications (favourable vs unfavourable outcome) was different for patients randomised to [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-PSMA versus cabazitaxel. The clinical benefit of the PSA50 model was evaluated using a decision curve analysis.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results and limitations&lt;/h3&gt;&lt;div&gt;The probability of PSA50 in patients classified as having a favourable outcome was greater in the [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-PSMA-617 group than in the cabazitaxel group (odds ratio 6.36 [95% confidence interval {CI} 1.69–30.80] vs 0.96 [95% CI 0.32–3.05]; &lt;em&gt;p&lt;/em&gt; = 0.038 for treatment-by-model interaction). The PSA50 rate in patients with a favourable outcome for [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-PSMA-617 versus cabazitaxel was 62/88 (70%) versus 31/85 (36%). The decision curve analysis indicated that the use of the PSA50 model had a clinical net benefit when the probability of a PSA response was ≥30%. The predictive performance of the models for PSA PFS and OS was not established (treatment-by-model interaction: &lt;em&gt;p&lt;/em&gt; = 0.36 and &lt;em&gt;p&lt;/em&gt; = 0.41, respectively).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;A previously developed outcome classification model for PSA50 was demonstrated to be both predictive and prognostic for the outcome after [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-PSMA-617 versus cabazitaxel, while the PSA PFS and OS models had purely prognostic value. The models may aid clinicians in defining strategies for patients with metastatic castration-resistant prostate cancer who failed first-line chemotherapy and are eligible for [&lt;sup&gt;177&lt;/sup&gt;Lu]Lu-PSMA-617 and cabazitaxel.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Patient summary&lt;/h3&gt;&lt;div&gt;In this report, we validated previously developed statistical models that can predict a response to Lu-PSMA ra","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 1","pages":"Pages 21-28"},"PeriodicalIF":8.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140735439","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}