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Clinical Evaluation of a Novel Deintensified Surveillance Protocol for Low-risk Non-muscle-invasive Bladder Cancer: A Prospective Study in 250 Patients. 低风险非肌肉侵袭性膀胱癌新型去强化监测方案的临床评价:250例患者的前瞻性研究
IF 9.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-12-17 DOI: 10.1016/j.euo.2025.11.004
Chandrarajan Premal Shah, Jennifer Gray, Tanya Lord-McKenzie, Paramananthan Mariappan

Background and objective: Recent Edinburgh-based research demonstrated high negative predictive value (NPV) for urinary dipstick testing for haematuria (UDH) in low-risk bladder cancer surveillance. This enabled a new protocol where flexible cystoscopy in surveillance years 2 and 4 is performed only if UDH is positive. Adopted across Scotland and included as aspirational in European Association of Urology guidelines, this protocol has yet to be validated in real-world settings. This study aims to evaluate the clinical outcomes of low-risk bladder cancer with the implementation of the new surveillance protocol.

Methods: The protocol began in December 2018. All patients with low-risk bladder cancer on initial transurethral resection of bladder tumour were included from January 2019 to February 2025. General practitioners conducted UDH in surveillance years 2 and 4; cystoscopy followed if positive. Patient and clinical data were prospectively recorded using a standardised institutional pro forma. This study performed the first clinical evaluation of the deintensified low-risk protocol. The study evaluated the recurrence and progression rates, NPV of UDH throughout surveillance, and number of check cystoscopies performed. The statistical analysis used Stata-BE version 19.0 for Mac.

Key findings and limitations: A total of 250 patients were observed with a recurrence rate of 14.4% and a progression rate of 1.6%, similar to preprotocol outcomes. The NPV of UDH remained above 94% throughout surveillance. Flexible cystoscopy use declined by 18.2%, saving at least £51 000. Limitations included a lack of randomisation, modest cohort sizes at 4 and 5 yr of surveillance, and absence of patient-reported outcomes.

Conclusions and clinical implications: The deintensified protocol appears safe, maintaining clinical outcomes whilst reducing procedural use and costs in low-risk bladder cancer.

背景和目的:最近爱丁堡的研究表明,血尿(UDH)尿试纸检测在低危膀胱癌监测中的阴性预测值(NPV)很高。这促成了一种新的方案,即只有在UDH阳性的情况下,才在监测第2年和第4年进行柔性膀胱镜检查。在整个苏格兰被采用,并被纳入欧洲泌尿学协会指南,但该方案尚未在现实环境中得到验证。本研究旨在评估新监测方案实施后低危膀胱癌的临床结果。方法:该方案于2018年12月开始实施。纳入2019年1月至2025年2月首次经尿道膀胱肿瘤切除术的所有低风险膀胱癌患者。全科医生在监测第2年和第4年开展了UDH;膀胱镜检查呈阳性。采用标准化的机构形式前瞻性地记录患者和临床数据。该研究首次对去强化低风险方案进行了临床评估。该研究评估了复发率和进展率,监测期间UDH的NPV,以及检查膀胱镜的次数。统计分析使用mac版Stata-BE 19.0。主要发现和局限性:共观察到250例患者,复发率为14.4%,进展率为1.6%,与方案前结果相似。在整个监测过程中,UDH的净现值保持在94%以上。柔性膀胱镜检查的使用下降了18.2%,节省了至少5.1万英镑。局限性包括缺乏随机化,4年和5年监测时的队列规模适中,以及缺乏患者报告的结果。结论和临床意义:去强化方案是安全的,在维持临床结果的同时减少了低危膀胱癌的手术使用和成本。
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引用次数: 0
Prostate-specific Antigen Nadir and Time to Nadir Predict Recurrence in Postprostatectomy Patients Treated with Salvage Radiotherapy Without Androgen Deprivation Therapy. 前列腺特异性抗原最低点及到达最低点的时间预测前列腺切除术后补救性放疗不加雄激素剥夺治疗的患者复发。
IF 9.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-12-15 DOI: 10.1016/j.euo.2025.12.001
Federico Mastroleo, Riccardo Villa, Mattia Zaffaroni, Maria Giulia Vincini, Ciro Franzese, Luca Nicosia, Fabio Matrone, Alessandra Donofrio, Alessandro Magli, Luca Triggiani, Salvina Barra, Giorgia Timon, Matteo Augugliaro, Vincenzo Burgio, Giulio Francolini, Maja Hasterok, Marcin Miszczyk, Nicola Simoni, Corrado Spatola, Filippo Alongi, Stefano Arcangeli, Marta Scorsetti, Giulia Marvaso, Barbara Alicja Jereczek-Fossa

Background and objective: Salvage radiotherapy (SRT) is often curative in men with biochemical recurrence (BCR) after radical prostatectomy (RP); however, a subset experiences progression. While the depth of prostate-specific antigen (PSA) nadir after SRT is a known prognostic factor, its combined role with time to nadir (TTN) in the salvage setting, in absence of androgen deprivation therapy (ADT), has not been evaluated systematically and the present study aims to evaluate it.

Methods: We retrospectively included RP patients treated with SRT across 15 European centers. No prior or concomitant ADT was allowed. Patients were stratified into four groups by PSA nadir (<0.1 vs ≥0.1 ng/ml) and TTN (<6 vs ≥6 mo). The primary endpoint was distant metastasis-free survival (DMFS). The secondary endpoint was BCR-free survival (BRFS).

Key findings and limitations: A total of 1189 patients were included in the study, with a median clinical follow-up of 4.4 (interquartile range, 2.7-6.4) yr, and 5-yr BRFS and DMFS probabilities of 62% (95% confidence interval [CI], 59-65%) and 89% (95% CI, 87-91%), respectively. Patients with favorable kinetics (nadir <0.1 ng/ml, TTN ≥6 mo; 56.3% of cohort) achieved a 5-yr DMFS rate of 96% (95% CI, 94-98%), while high-risk patients (nadir ≥0.1 ng/ml, TTN <6 mo; 14.7%) had poor outcomes (5-yr DMFS rate 63%; 95% CI, 55-72%). A multivariable analysis confirmed a nadir of ≥0.1 ng/ml (hazard ratio [HR] 10.1; 95% CI, 8.0-12.7 for BRFS, and HR 7.1; 95% CI, 4.5-11.2 for DMFS) and TTN <6 mo (HR 3.0; 95% CI, 2.3-3.8, and HR 1.8; 95% CI, 1.1-2.7, respectively) as independent adverse factors.

Conclusions and clinical implications: Our study showed that the combination of PSA nadir depth and TTN after SRT allows an improvement in prognostic stratification of SRT patients with BCR after RP. These findings might improve patient-tailored decisions between surveillance, active treatment, and treatment escalation.

背景与目的:补救性放疗(SRT)是根治性前列腺切除术(RP)后男性生化复发(BCR)的常用治疗方法;然而,一个子集经历了进步。虽然SRT后前列腺特异性抗原(PSA)最低点的深度是一个已知的预后因素,但在没有雄激素剥夺治疗(ADT)的情况下,其与到达最低点时间(TTN)的联合作用尚未得到系统评估,本研究旨在对其进行评估。方法:我们回顾性地纳入了15个欧洲中心接受SRT治疗的RP患者。不允许事先或同时使用ADT。根据PSA最低点将患者分为四组(主要发现和局限性:共有1189例患者纳入研究,中位临床随访时间为4.4年(四分位数间距为2.7-6.4)年,5年BRFS和DMFS概率分别为62%(95%置信区间[CI], 59-65%)和89% (95% CI, 87-91%)。结论和临床意义:我们的研究表明,SRT后PSA最低点深度和TTN的结合可以改善SRT患者RP后BCR的预后分层。这些发现可能会改善患者在监测、积极治疗和治疗升级之间的个性化决策。
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引用次数: 0
Re: M. Roupret, A. Bertaut, G. Pignot, et al. ALBAN (GETUG-AFU 37): A Phase 3, Randomized, Open-label, International Trial of Intravenous Atezolizumab and Intravesical Bacillus Calmette-Guérin (BCG) Versus BCG Alone in BCG-naive High-risk, Non-muscle-invasive bladder cancer (NMIBC). Ann Oncol. In press. https://doi.org/10.1016/j.annonc.2025.09.017. Re: M. Roupret, A. Bertaut, G. Pignot等。ALBAN (GETUG-AFU 37):一项静脉注射Atezolizumab和膀胱内卡介苗(BCG)与单独卡介苗治疗原发性高危非肌肉侵袭性膀胱癌(NMIBC)的3期、随机、开放标签的国际试验。安杂志。在出版社。https://doi.org/10.1016/j.annonc.2025.09.017。
IF 9.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-12-15 DOI: 10.1016/j.euo.2025.12.003
David D'Andrea, Shahrokh F Shariat
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引用次数: 0
Benchmarking Large Language Models Against Multidisciplinary Tumor Boards in Urological Oncology: Results from the Blinded, Prospective CONCORDIA Study. 针对泌尿肿瘤多学科肿瘤委员会的基准大语言模型:来自盲法、前瞻性CONCORDIA研究的结果。
IF 9.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-12-10 DOI: 10.1016/j.euo.2025.11.016
Emily Rinderknecht, Maximilian Haas, Marco J Schnabel, Anton P Kravchuk, Christof Schäfer, Stephan Siepmann, Roman Mayr, Dominik von Winning, Jochen Grassinger, Christopher Goßler, Fabian Pohl, Peter J Siska, Florian Zeman, Johannes Breyer, Anna Schmelzer, Christian Gilfrich, Sabine D Brookman-May, Maximilian Burger, Matthias May

Background and objective: Multidisciplinary tumor boards (MTBs) are the gold standard for oncological treatment planning, but their implementation is resource intensive. Large language models (LLMs) such as ChatGPT-4 and Claude 3.5 Sonnet have emerged as scalable tools for clinical decision support. As their comparative performance in urological oncology remains largely untested in prospective trials, this study aimed to prospectively evaluate them against real MTBs.

Methods: In this prospective, multicenter, noninferiority study (DRKS00034797), we evaluated whether therapeutic recommendations by ChatGPT-4 and Claude 3.5 Sonnet were noninferior to those of MTBs across 110 representative case scenarios involving locally advanced or metastatic genitourinary cancer. Standardized prompts elicited recommendations from both LLMs, which were rated independently by two blinded uro-oncologists using the validated modified System Causability Scale (mSCS). The predefined noninferiority margin was 0.15 mSCS points.

Key findings and limitations: The mean mSCS score of the MTBs was 0.849 (standard deviation [SD] = 0.157), setting the noninferiority margin at 0.699. Claude 3.5 Sonnet scored 0.731 (SD = 0.178; 95% confidence interval [CI]: 0.697-0.765), narrowly missing noninferiority. ChatGPT-4 scored 0.660 (SD = 0.193; 95% CI: 0.623-0.696), clearly below the margin. A subgroup analysis revealed better LLM performance in locally advanced versus metastatic cases (p < 0.05). Limitations include the use of synthetic cases and inherent LLM output variability.

Conclusions and clinical implications: Neither LLM matched the MTB standards. These findings highlight the current limitations of public LLMs, or of their use in our study, in supporting complex oncological decisions. This underscores the need for further validation and contextual refinement before integration into multidisciplinary care.

背景和目的:多学科肿瘤委员会(MTBs)是肿瘤治疗计划的金标准,但其实施是资源密集型的。大型语言模型(llm),如ChatGPT-4和Claude 3.5 Sonnet,已经成为临床决策支持的可扩展工具。由于它们在泌尿肿瘤学中的比较表现在很大程度上尚未在前瞻性试验中进行测试,因此本研究旨在对它们与真正的MTBs进行前瞻性评估。方法:在这项前瞻性、多中心、非劣效性研究(DRKS00034797)中,我们评估了ChatGPT-4和Claude 3.5 Sonnet推荐的治疗方案在110例涉及局部晚期或转移性泌尿生殖系统癌的代表性病例中是否优于MTBs。标准化提示从两位法学硕士那里获得建议,由两位盲法泌尿肿瘤学家使用经过验证的修改系统因果关系量表(mSCS)独立评估。预定的非劣效性裕度为0.15 mSCS点。主要发现和局限性:MTBs的平均mSCS评分为0.849(标准差[SD] = 0.157),非劣效裕度为0.699。Claude 3.5 Sonnet得分为0.731 (SD = 0.178; 95%可信区间[CI]: 0.697-0.765),差一点错过非劣效性。ChatGPT-4评分为0.660 (SD = 0.193; 95% CI: 0.623-0.696),明显低于临界值。一项亚组分析显示,LLM在局部晚期与转移性病例中的表现更好(p结论和临床意义:LLM均不符合MTB标准。这些发现突出了目前公共法学硕士在支持复杂肿瘤学决策方面的局限性,或者他们在我们的研究中使用的局限性。这强调了在整合到多学科治疗之前需要进一步验证和上下文优化。
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引用次数: 0
Prostate-specific Membrane Antigen Positron Emission Tomography Versus Conventional Imaging for Preoperative Staging High-risk Prostate Cancer Patients Undergoing Surgery for cN0M0 Disease: An European Association of Urology-Young Academic Urologists Prostate Cancer Working Group Multi-institutional Study. 前列腺特异性膜抗原正电子发射断层扫描与常规成像在术前分期高危前列腺癌患者接受cN0M0疾病手术:欧洲泌尿外科协会-年轻学术泌尿科医师前列腺癌工作组多机构研究。
IF 9.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-12-05 DOI: 10.1016/j.euo.2025.11.011
Lorenzo Bianchi, Matteo Droghetti, Calogero Catanzaro, Massimo Valerio, Quentin Novello, Andrea Mari, Riccardo Campi, Rossella Nicoletti, Isabel Heidegger, Giulia Giannini, Fabio Zattoni, Giuseppe Reitano, Matteo Bauckneht, Francesco Lanfranchi, Pawel Rajwa, Giancarlo Marra, Timo Soeterik, Roderick Van den Bergh, Wolfgang P Fendler, Christopher Darr, Juan Gomez Rivas, Claudia Kesch, Chiara Mignogna, Giorgio Gandaglia, Francesco Ceci, Andrea Farolfi, Paolo Gontero, Stefano Fanti, Lorenzo Masieri, Sergio Serni, Andrea Minervini, Alberto Briganti, Francesco Montorsi, Riccardo Schiavina

Background and objective: Current guidelines strongly recommend prostate-specific membrane antigen positron emission tomography (PSMA-PET) for staging high-risk prostate cancer (PCa) patients. This study aims to evaluate the impact of staging procedure (PSMA-PET vs conventional imaging) on short-term oncologic outcomes in a cohort of N0M0 high-risk PCa patients who underwent radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND).

Methods: We retrospectively included 1475 high-risk PCa patients who underwent RP and ePLND in 14 referral centers between 2014 and 2024. Each patient underwent either PSMA-PET (miN0M0) or conventional imaging (cN0M0). After a landmark analysis and 1:1 propensity score matching for age at diagnosis, year of surgery, initial serum prostate-specific antigen (PSA), cT stage, and International Society of Urological Pathology grade group at biopsy, the Kaplan-Meier methodology was used to assess biochemical recurrence (BCR)-free survival (BCR-FS) and multivariable Cox regression models to identify the predictors of BCR (time in months between the date of RP and the date of BCR).

Key findings and limitations: After propensity score matching, 463 (48.2%) versus 463 (90.1%) patients underwent PSMA-PET versus conventional imaging. PSA persistence was observed in 15 (3.2%) versus 64 (14%) miN0M0 patients at PSMA-PET versus cN0M0 patients at conventional imaging (p < 0.001). The BCR-FS rates at 36 mo were 90.9% and 82.2% in the PSMA-PET and conventional imaging cohorts, respectively. At multivariate Cox regression analyses, PSMA-PET (hazard ratio: 0.48; 95% confidence interval: 0.29-0.77) was an independent predictor of lower BCR rates (p = 0.003). In the PSMA-PET cohort, BCR-FS rates were similar between patients with one high-risk feature and those with two or more high-risk features, while in the conventional imaging cohort, two or more high-risk features were associated with significantly worse BCR-FS rates than one high-risk feature. Limitations include the retrospective design of the study.

Conclusions and clinical implications: Time to biochemical recurrence was longer in the miN0M0 cohort than in the cN0M0 cohort. Superior PSMA-PET staging accuracy seems to improve short-term oncologic outcomes of high-risk PCa patients following surgery.

背景和目的:目前的指南强烈推荐前列腺特异性膜抗原正电子发射断层扫描(PSMA-PET)用于高危前列腺癌(PCa)患者的分期。本研究旨在评估分期程序(PSMA-PET与常规成像)对接受根治性前列腺切除术(RP)和扩展盆腔淋巴结清扫(ePLND)的N0M0高危PCa患者的短期肿瘤预后的影响。方法:我们回顾性纳入1475例2014年至2024年间在14个转诊中心接受RP和ePLND的高危PCa患者。每位患者接受PSMA-PET (miN0M0)或常规影像学(cN0M0)检查。在对诊断年龄、手术年份、初始血清前列腺特异性抗原(PSA)、cT分期和国际泌尿外科病理学会活检分级组进行里程碑式分析和1:1倾向评分匹配后,使用Kaplan-Meier方法评估生化复发(BCR)无生存(BCR- fs)和多变量Cox回归模型来确定BCR的预测因子(RP日期和BCR日期之间的月间时间)。主要发现和局限性:倾向评分匹配后,463例(48.2%)和463例(90.1%)患者分别接受了PSMA-PET和常规影像学检查。在PSMA-PET检查中,miN0M0患者的PSA持续性为15例(3.2%),而在常规影像学检查中为64例(14%),而在cN0M0患者中为64例(p)。结论和临床意义:miN0M0患者比cN0M0患者的生化复发时间更长。优越的PSMA-PET分期准确性似乎可以改善手术后高风险PCa患者的短期肿瘤预后。
{"title":"Prostate-specific Membrane Antigen Positron Emission Tomography Versus Conventional Imaging for Preoperative Staging High-risk Prostate Cancer Patients Undergoing Surgery for cN0M0 Disease: An European Association of Urology-Young Academic Urologists Prostate Cancer Working Group Multi-institutional Study.","authors":"Lorenzo Bianchi, Matteo Droghetti, Calogero Catanzaro, Massimo Valerio, Quentin Novello, Andrea Mari, Riccardo Campi, Rossella Nicoletti, Isabel Heidegger, Giulia Giannini, Fabio Zattoni, Giuseppe Reitano, Matteo Bauckneht, Francesco Lanfranchi, Pawel Rajwa, Giancarlo Marra, Timo Soeterik, Roderick Van den Bergh, Wolfgang P Fendler, Christopher Darr, Juan Gomez Rivas, Claudia Kesch, Chiara Mignogna, Giorgio Gandaglia, Francesco Ceci, Andrea Farolfi, Paolo Gontero, Stefano Fanti, Lorenzo Masieri, Sergio Serni, Andrea Minervini, Alberto Briganti, Francesco Montorsi, Riccardo Schiavina","doi":"10.1016/j.euo.2025.11.011","DOIUrl":"https://doi.org/10.1016/j.euo.2025.11.011","url":null,"abstract":"<p><strong>Background and objective: </strong>Current guidelines strongly recommend prostate-specific membrane antigen positron emission tomography (PSMA-PET) for staging high-risk prostate cancer (PCa) patients. This study aims to evaluate the impact of staging procedure (PSMA-PET vs conventional imaging) on short-term oncologic outcomes in a cohort of N0M0 high-risk PCa patients who underwent radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND).</p><p><strong>Methods: </strong>We retrospectively included 1475 high-risk PCa patients who underwent RP and ePLND in 14 referral centers between 2014 and 2024. Each patient underwent either PSMA-PET (miN0M0) or conventional imaging (cN0M0). After a landmark analysis and 1:1 propensity score matching for age at diagnosis, year of surgery, initial serum prostate-specific antigen (PSA), cT stage, and International Society of Urological Pathology grade group at biopsy, the Kaplan-Meier methodology was used to assess biochemical recurrence (BCR)-free survival (BCR-FS) and multivariable Cox regression models to identify the predictors of BCR (time in months between the date of RP and the date of BCR).</p><p><strong>Key findings and limitations: </strong>After propensity score matching, 463 (48.2%) versus 463 (90.1%) patients underwent PSMA-PET versus conventional imaging. PSA persistence was observed in 15 (3.2%) versus 64 (14%) miN0M0 patients at PSMA-PET versus cN0M0 patients at conventional imaging (p < 0.001). The BCR-FS rates at 36 mo were 90.9% and 82.2% in the PSMA-PET and conventional imaging cohorts, respectively. At multivariate Cox regression analyses, PSMA-PET (hazard ratio: 0.48; 95% confidence interval: 0.29-0.77) was an independent predictor of lower BCR rates (p = 0.003). In the PSMA-PET cohort, BCR-FS rates were similar between patients with one high-risk feature and those with two or more high-risk features, while in the conventional imaging cohort, two or more high-risk features were associated with significantly worse BCR-FS rates than one high-risk feature. Limitations include the retrospective design of the study.</p><p><strong>Conclusions and clinical implications: </strong>Time to biochemical recurrence was longer in the miN0M0 cohort than in the cN0M0 cohort. Superior PSMA-PET staging accuracy seems to improve short-term oncologic outcomes of high-risk PCa patients following surgery.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145695973","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}
引用次数: 0
Germline DNA Repair and Immune-metabolic Alterations Suggest a Potentially Distinct Form of Early-onset Prostate Cancer in Men of African Descent. 生殖系DNA修复和免疫代谢改变提示非洲裔男性早发性前列腺癌的潜在不同形式。
IF 9.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-12-04 DOI: 10.1016/j.euo.2025.11.015
Jean-Samuel Loger, Emeline Colomba, Alexis Vallard, Mylène Annonay, Sarah Malsa, Taina Labeau, Sylviane Ulric-Gervaise, Sabrina Pennont, Ainara Martin-Martinez, Mickaelle Rose, Odile Béra, Sylvie Merle, Celine Minchaca, Johan Rose-Dite-Modestine, Régine Marlin

Background and objective: Early-onset prostate cancer (PCa) is more frequent in men of African descent; yet, the biological mechanisms underlying susceptibility remain unclear. While most germline studies have focused on DNA repair genes (DRGs), alternative pathways may also contribute to tumor initiation, which we aim to assess in this study.

Methods: We analyzed 71 Afro-Caribbean men diagnosed with early-onset PCa (≤51 yr old for sporadic cases and ≤56 yr old for familial cases). Germline testing combined targeted sequencing of 175 genes-including major DRGs-with whole-exome sequencing in patients without DRG alterations. Variants were filtered for rarity (minor allele frequency <0.01 in African populations) and their clinical classification as pathogenic or likely pathogenic (P/LP; ClinVar and ACMG/AMP guidelines). Genes were grouped by biological function.

Key findings and limitations: Rare P/LP germline variants were identified in 37 patients (52.1%). Among these patients, ten carried a DRG variant (including one also harboring HOXB13 X285K), 26 carried at least one variant in immune-metabolic pathways (one also with HOXB13 X285K), and one carried only HOXB13 X285K. Recurrent truncating variants were found in FLG, PGAM2, and TYRP1. Although no statistically significant association was observed between molecular subgroups and clinical aggressiveness, DRG variants tended to occur in more high-risk tumors, whereas immune-metabolic alterations were more frequent in patients with low- or intermediate-risk disease.

Conclusions and clinical implications: This study reveals a broader germline landscape in early-onset PCa among men of African descent. Inherited immune-metabolic dysfunction may contribute to tumorigenesis through microenvironmental dysregulation, highlighting novel pathways for investigation in larger and ancestrally diverse cohorts.

背景和目的:早发性前列腺癌(PCa)在非洲裔男性中更为常见;然而,潜在易感性的生物学机制仍不清楚。虽然大多数生殖系研究都集中在DNA修复基因(DRGs)上,但其他途径也可能有助于肿瘤的发生,我们在本研究中旨在评估这一点。方法:我们分析了71名被诊断为早发性PCa的非洲裔加勒比男性(散发性病例≤51岁,家族性病例≤56岁)。生殖系检测将175个基因(包括主要DRG)的靶向测序与无DRG改变患者的全外显子组测序相结合。关键发现和局限性:在37例(52.1%)患者中鉴定出罕见的P/LP种系变异。在这些患者中,10例携带DRG变体(包括1例也携带HOXB13 X285K), 26例携带至少一种免疫代谢途径的变体(1例也携带HOXB13 X285K), 1例仅携带HOXB13 X285K。在FLG、PGAM2和TYRP1中发现了反复的截断变异体。虽然分子亚群与临床侵袭性之间没有统计学意义上的关联,但DRG变异往往发生在高风险的肿瘤中,而免疫代谢改变在低或中危疾病患者中更常见。结论和临床意义:本研究揭示了非洲裔男性早发性前列腺癌的更广泛的生殖系景观。遗传免疫代谢功能障碍可能通过微环境失调促进肿瘤的发生,这为在更大的、祖先多样化的队列中进行研究提供了新的途径。
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引用次数: 0
Assessment of Pathologic Response in Kidney Cancer: Back to the Microscope for Now. 肾癌病理反应的评估:暂时回到显微镜下。
IF 9.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-12-03 DOI: 10.1016/j.euo.2025.11.013
Axel Bex, Grant D Stewart
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引用次数: 0
Penile Cancer Survivorship: Research Gaps in Psychosocial Health and Sexual Quality of Life. 阴茎癌幸存者:社会心理健康和性生活质量的研究差距。
IF 9.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-12-03 DOI: 10.1016/j.euo.2025.11.008
Cameron J Britton, Omar Almidani, Avi S Baskin, Chad Ritch, Omer Raheem, Curtis A Pettaway, Kelvin A Moses

We discuss the limited evidence in the literature on the psychosocial health and sexual quality of life of survivors of penile cancer and suggest some future directions for research in this setting.

我们讨论了文献中关于阴茎癌幸存者的社会心理健康和性生活质量的有限证据,并提出了一些未来研究的方向。
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引用次数: 0
Reply to Constance Huck, Paul Sargos, and Alberto Bossi's Letter to the Editor re: Markus Graefen, Fabian Falkenbach, Tobias Maurer, et al. Best Systemic Therapy With or Without Radical Prostatectomy in the Management of Men With Oligometastatic Prostate Cancer: The RAMPP Randomised Controlled Trial. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2025.09.4144. 回复Constance Huck, Paul Sargos和Alberto Bossi给编辑的信:Markus Graefen, Fabian Falkenbach, Tobias Maurer等。有或没有根治性前列腺切除术的男性少转移性前列腺癌的最佳全身治疗:RAMPP随机对照试验。Urol欧元。在出版社。https://doi.org/10.1016/j.eururo.2025.09.4144。
IF 9.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-12-03 DOI: 10.1016/j.euo.2025.11.012
Fabian Falkenbach, Markus Graefen, Burkhard Beyer
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引用次数: 0
Real-World Outcomes and Molecular Profiling for Patients with Metastatic Castration-resistant Prostate Cancer with Lung Metastases: A Long-term Multicenter Experience 转移性去势抵抗性前列腺癌伴肺转移患者的真实世界预后和分子分析:一项长期的多中心研究。
IF 9.3 1区 医学 Q1 ONCOLOGY Pub Date : 2025-12-01 DOI: 10.1016/j.euo.2025.05.002
Giuseppina Bruno , Maria Iole Natalicchio , Marianna Garofoli , Cristian Lolli , Aldo Rosano , Piergiorgio Di Tullio , Guido Giordano , Alice Mancino , Mariachiara Masucci , Vincenzo Emanuele Chiuri , Lucia Fratino , Elisa Zanardi , Giuseppe Schepisi , Luca Galli , Francesco Massari , Matteo Santoni , Nicole Brighi , Elisabetta Cornacchia , Pasquale Rescigno , Giuseppe Fornarini , Vincenza Conteduca

Background and objective

The prognostic impact of lung metastases (LuMs) in metastatic castration-resistant prostate cancer (mCRPC) remains poorly defined. Our aim was to evaluate the clinical and molecular characteristics of patients with mCRPC with LuMs and their outcomes.

Methods

This retrospective multicenter study included 930 patients with mCRPC across 13 centers in Italy. The primary endpoint was the impact of LuMs on overall survival (OS), progression-free survival (PFS), and prostate-specific antigen (PSA) response. As a secondary endpoint, next-generation sequencing for a subgroup with LuMs was used to identify molecular characteristics that might be useful in guiding personalized therapy.

Key findings and limitations

Among mCRPC patients treated with an androgen receptor signaling inhibitor, we observed no significant differences in median OS or PFS and PSA response between the LuMs group and the group with bone ± lymph node metastases. Multivariable analyses revealed that only Eastern Cooperative Oncology Group performance status, PSA level, prior docetaxel treatment, and number of metastatic lesions were significant independent factors for both OS and PFS. Comparison of the groups with LuMs only versus liver metastases revealed a significant association between LuMs and a longer OS (15 vs 10 mo; p = 0.002) and PFS (9 vs 5 mo; p = 0.002). The proportion of patients with a ≥50% PSA decline was higher in the LuMs group (odds ratio 3.57, 95% confidence interval 1.37–9.45; p = 0.004). Molecular profile results showed that TP53 mutations accounted for a lower proportion of the pathogenic variants in LuMs than in liver metastases (15% vs 89%). Limitations include the retrospective design and clinical heterogeneity of the population, in addition to unavailability of metastatic biopsies for more in-depth analyses.

Conclusions and clinical implications

Our findings suggest that patients with LuMs in mCRPC exhibit clinical and molecular features more similar to those with bone ± lymph nodal metastases than to patients with liver metastases. Further prospective studies are warranted.
背景和目的:肺转移(LuMs)对转移性去势抵抗性前列腺癌(mCRPC)的预后影响仍不明确。我们的目的是评估mCRPC合并LuMs患者的临床和分子特征及其预后。方法:这项回顾性多中心研究包括意大利13个中心的930例mCRPC患者。主要终点是LuMs对总生存期(OS)、无进展生存期(PFS)和前列腺特异性抗原(PSA)反应的影响。作为次要终点,对LuMs亚组的下一代测序用于鉴定可能有助于指导个性化治疗的分子特征。主要发现和局限性:在接受雄激素受体信号抑制剂治疗的mCRPC患者中,我们观察到LuMs组与骨±淋巴结转移组之间的中位OS或PFS和PSA反应无显著差异。多变量分析显示,只有Eastern Cooperative Oncology Group的表现状态、PSA水平、既往多西他赛治疗和转移灶数量是影响OS和PFS的重要独立因素。仅肝转移组与肝转移组的比较显示,肝转移组与更长的生存期(15个月vs 10个月;p = 0.002)和PFS (9 vs 5个月;p = 0.002)。LuMs组PSA下降≥50%的患者比例更高(优势比3.57,95%可信区间1.37-9.45;p = 0.004)。分子谱结果显示,lum中TP53突变占致病性变异的比例低于肝转移(15% vs 89%)。局限性包括回顾性设计和人群的临床异质性,以及无法获得转移性活检以进行更深入的分析。结论和临床意义:我们的研究结果表明,mCRPC中lum患者的临床和分子特征更类似于骨±淋巴结转移患者,而不是肝转移患者。进一步的前瞻性研究是必要的。
{"title":"Real-World Outcomes and Molecular Profiling for Patients with Metastatic Castration-resistant Prostate Cancer with Lung Metastases: A Long-term Multicenter Experience","authors":"Giuseppina Bruno ,&nbsp;Maria Iole Natalicchio ,&nbsp;Marianna Garofoli ,&nbsp;Cristian Lolli ,&nbsp;Aldo Rosano ,&nbsp;Piergiorgio Di Tullio ,&nbsp;Guido Giordano ,&nbsp;Alice Mancino ,&nbsp;Mariachiara Masucci ,&nbsp;Vincenzo Emanuele Chiuri ,&nbsp;Lucia Fratino ,&nbsp;Elisa Zanardi ,&nbsp;Giuseppe Schepisi ,&nbsp;Luca Galli ,&nbsp;Francesco Massari ,&nbsp;Matteo Santoni ,&nbsp;Nicole Brighi ,&nbsp;Elisabetta Cornacchia ,&nbsp;Pasquale Rescigno ,&nbsp;Giuseppe Fornarini ,&nbsp;Vincenza Conteduca","doi":"10.1016/j.euo.2025.05.002","DOIUrl":"10.1016/j.euo.2025.05.002","url":null,"abstract":"<div><h3>Background and objective</h3><div>The prognostic impact of lung metastases (LuMs) in metastatic castration-resistant prostate cancer (mCRPC) remains poorly defined. Our aim was to evaluate the clinical and molecular characteristics of patients with mCRPC with LuMs and their outcomes.</div></div><div><h3>Methods</h3><div>This retrospective multicenter study included 930 patients with mCRPC across 13 centers in Italy. The primary endpoint was the impact of LuMs on overall survival (OS), progression-free survival (PFS), and prostate-specific antigen (PSA) response. As a secondary endpoint, next-generation sequencing for a subgroup with LuMs was used to identify molecular characteristics that might be useful in guiding personalized therapy.</div></div><div><h3>Key findings and limitations</h3><div>Among mCRPC patients treated with an androgen receptor signaling inhibitor, we observed no significant differences in median OS or PFS and PSA response between the LuMs group and the group with bone ± lymph node metastases. Multivariable analyses revealed that only Eastern Cooperative Oncology Group performance status, PSA level, prior docetaxel treatment, and number of metastatic lesions were significant independent factors for both OS and PFS. Comparison of the groups with LuMs only versus liver metastases revealed a significant association between LuMs and a longer OS (15 vs 10 mo; <em>p</em> = 0.002) and PFS (9 vs 5 mo; <em>p</em> = 0.002). The proportion of patients with a ≥50% PSA decline was higher in the LuMs group (odds ratio 3.57, 95% confidence interval 1.37–9.45; <em>p</em> = 0.004). Molecular profile results showed that <em>TP53</em> mutations accounted for a lower proportion of the pathogenic variants in LuMs than in liver metastases (15% vs 89%). Limitations include the retrospective design and clinical heterogeneity of the population, in addition to unavailability of metastatic biopsies for more in-depth analyses.</div></div><div><h3>Conclusions and clinical implications</h3><div>Our findings suggest that patients with LuMs in mCRPC exhibit clinical and molecular features more similar to those with bone ± lymph nodal metastases than to patients with liver metastases. Further prospective studies are warranted.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 6","pages":"Pages 1513-1523"},"PeriodicalIF":9.3,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215319","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}
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European urology oncology
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