Pub Date : 2025-12-17DOI: 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.
{"title":"Clinical Evaluation of a Novel Deintensified Surveillance Protocol for Low-risk Non-muscle-invasive Bladder Cancer: A Prospective Study in 250 Patients.","authors":"Chandrarajan Premal Shah, Jennifer Gray, Tanya Lord-McKenzie, Paramananthan Mariappan","doi":"10.1016/j.euo.2025.11.004","DOIUrl":"https://doi.org/10.1016/j.euo.2025.11.004","url":null,"abstract":"<p><strong>Background and objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Key findings and limitations: </strong>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.</p><p><strong>Conclusions and clinical implications: </strong>The deintensified protocol appears safe, maintaining clinical outcomes whilst reducing procedural use and costs in low-risk bladder cancer.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145780616","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}
Pub Date : 2025-12-15DOI: 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.
{"title":"Prostate-specific Antigen Nadir and Time to Nadir Predict Recurrence in Postprostatectomy Patients Treated with Salvage Radiotherapy Without Androgen Deprivation Therapy.","authors":"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","doi":"10.1016/j.euo.2025.12.001","DOIUrl":"https://doi.org/10.1016/j.euo.2025.12.001","url":null,"abstract":"<p><strong>Background and objective: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Key findings and limitations: </strong>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.</p><p><strong>Conclusions and clinical implications: </strong>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.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767669","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}
Pub Date : 2025-12-15DOI: 10.1016/j.euo.2025.12.003
David D'Andrea, Shahrokh F Shariat
{"title":"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.","authors":"David D'Andrea, Shahrokh F Shariat","doi":"10.1016/j.euo.2025.12.003","DOIUrl":"https://doi.org/10.1016/j.euo.2025.12.003","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145767681","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}
Pub Date : 2025-12-10DOI: 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.
{"title":"Benchmarking Large Language Models Against Multidisciplinary Tumor Boards in Urological Oncology: Results from the Blinded, Prospective CONCORDIA Study.","authors":"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","doi":"10.1016/j.euo.2025.11.016","DOIUrl":"https://doi.org/10.1016/j.euo.2025.11.016","url":null,"abstract":"<p><strong>Background and objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Key findings and limitations: </strong>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.</p><p><strong>Conclusions and clinical implications: </strong>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.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741765","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}
Pub Date : 2025-12-05DOI: 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.
{"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}
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.
{"title":"Germline DNA Repair and Immune-metabolic Alterations Suggest a Potentially Distinct Form of Early-onset Prostate Cancer in Men of African Descent.","authors":"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","doi":"10.1016/j.euo.2025.11.015","DOIUrl":"https://doi.org/10.1016/j.euo.2025.11.015","url":null,"abstract":"<p><strong>Background and objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Key findings and limitations: </strong>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.</p><p><strong>Conclusions and clinical implications: </strong>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.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687134","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}
Pub Date : 2025-12-03DOI: 10.1016/j.euo.2025.11.013
Axel Bex, Grant D Stewart
{"title":"Assessment of Pathologic Response in Kidney Cancer: Back to the Microscope for Now.","authors":"Axel Bex, Grant D Stewart","doi":"10.1016/j.euo.2025.11.013","DOIUrl":"https://doi.org/10.1016/j.euo.2025.11.013","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676946","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}
Pub Date : 2025-12-03DOI: 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。
{"title":"Penile Cancer Survivorship: Research Gaps in Psychosocial Health and Sexual Quality of Life.","authors":"Cameron J Britton, Omar Almidani, Avi S Baskin, Chad Ritch, Omer Raheem, Curtis A Pettaway, Kelvin A Moses","doi":"10.1016/j.euo.2025.11.008","DOIUrl":"https://doi.org/10.1016/j.euo.2025.11.008","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676895","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}
Pub Date : 2025-12-03DOI: 10.1016/j.euo.2025.11.012
Fabian Falkenbach, Markus Graefen, Burkhard Beyer
{"title":"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.","authors":"Fabian Falkenbach, Markus Graefen, Burkhard Beyer","doi":"10.1016/j.euo.2025.11.012","DOIUrl":"https://doi.org/10.1016/j.euo.2025.11.012","url":null,"abstract":"","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":9.3,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676936","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}
Pub Date : 2025-12-01DOI: 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 , 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","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}