European urology oncology最新文献

{"title":"Variation in Prostate Magnetic Resonance Imaging Performance: Data from the Prostate Biopsy Collaborative Group.","authors":"Sunny B Nalavenkata, Emily Vertosick, Alberto Briganti, Hashim Ahmed, David Eldred-Evans, Steven Gordon, Holly Raghallaigh, Christian Gratzke, Michael O'Callaghan, Michael Liss, Peter Chiu, Michael Müntener, John Yaxley, Cedric Poyet, Matthias Jahnen, Ants Toi, Sangeet Ghai, Daniel Margolis, Donna Ankerst, Behfar Ehdaie, Manish I Patel, Andrew J Vickers","doi":"10.1016/j.euo.2025.02.007","DOIUrl":"https://doi.org/10.1016/j.euo.2025.02.007","url":null,"abstract":"<p><strong>Background and objective: </strong>The quality and reporting of prostate magnetic resonance imaging (MRI) are operator dependent, leading to variations in estimates such as positive predictive value across sites. This impacts patient counseling, risk modeling, and risk calculators. This study assessed variation in Prostate Imaging Reporting and Data System (PI-RADS) score classification and subsequent probability of grade group (GG) ≥2 + prostate cancer.</p><p><strong>Methods: </strong>Data from the Prostate Biopsy Collaborative Group, including multiple sites in North America, Europe, and Asia Pacific, were analyzed. Patients underwent multiparametric MRI (mpMRI) of the prostate followed by prostate biopsy during the years 2010-2023. Only those with MRI-targeted biopsy and PI-RADS score ≥3 were included. The risk of being assigned PI-RADS 4 or 5 and risk of GG ≥2 disease for these scores were estimated using logistic regression.</p><p><strong>Key findings and limitations: </strong>The cohort included 7325 biopsies from 7320 unique patients from 13 sites. A two-fold variation in the probability of PI-RADS 4 or 5 assignment across sites persisted even after adjustment for patient risk (heterogeneity p < 0.001 for both). There were significant differences in the absolute risk of GG ≥2 disease for PI-RADS 4 and 5 (heterogeneity p < 0.001 for both), varying between 23% and 68% and between 49% and 87%, respectively. The use of prostate biopsy as a reference standard has limitations but reflects typical usage of mpMRI in clinical practice.</p><p><strong>Conclusions and clinical implications: </strong>The probability of being assigned PI-RADS 4 or 5 and subsequent detection of GG ≥2 disease varies widely between institutions. This impacts counseling, risk stratification, and clinical practice, necessitating better standardization in the performance and interpretation of mpMRI.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976835","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":"Avelumab First-line Maintenance for Advanced Urothelial Carcinoma: Long-term Analyses of Patient-reported Outcomes and Quality-adjusted Time Without Symptoms or Toxicity from the JAVELIN Bladder 100 Trial.","authors":"Petros Grivas, Jeanny B Aragon-Ching, Joaquim Bellmunt, Yohann Loriot, Miguel A Climent Duran, Srikala S Sridhar, Po-Jung Su, Se Hoon Park, Evgeny Kopyltsov, Yoshiaki Yamamoto, Natalia Jacob, Jason Hoffman, Karin Tyroller, Juliane Manitz, Mairead Kearney, Michael Schlichting, Thomas Powles","doi":"10.1016/j.euo.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.euo.2025.04.004","url":null,"abstract":"<p><strong>Background and objective: </strong>In JAVELIN Bladder 100, avelumab first-line maintenance plus best supportive care (BSC) significantly prolonged overall survival versus BSC alone, with no detrimental impact on quality of life (QOL), in patients with advanced urothelial carcinoma without progression following first-line platinum-based chemotherapy. We report long-term analyses of patient-reported outcomes (PROs) in patients treated with avelumab (any duration or ≥12 mo) and a post hoc analysis comparing quality-adjusted time without symptoms or toxicity (Q-TWiST) between arms.</p><p><strong>Methods: </strong>PROs were assessed using National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Bladder Symptom Index-18 (FBlSI-18) and EuroQol 5-level EQ-5D (EQ-5D-5L). Q-TWiST was calculated as the utility-weighted sum of mean time in three health states: time with all-cause grade 3/4 toxicity prior to progression, time without grade 3/4 toxicity or symptoms of progression, and time after progression.</p><p><strong>Key findings and limitations: </strong>In the overall avelumab plus BSC arm (n = 350) and the subgroup treated for ≥12 mo (n = 118), completion rates for PRO assessments during treatment were >80%. FBlSI-18 total and EQ-5D-5L index scores remained stable throughout 24 mo of treatment, with no clinically important changes from baseline. The mean Q-TWiST was 18.46 mo with avelumab plus BSC versus 15.13 mo with BSC alone (22% relative improvement). Limitations include open-label trial design and small patient numbers at later cycles.</p><p><strong>Conclusions and clinical implications: </strong>Patients receiving avelumab had preserved health-related QOL and control of cancer-related symptoms with manageable toxicity, further supporting avelumab first-line maintenance as the recommended treatment for advanced urothelial carcinoma not progressed after platinum-based chemotherapy.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005479","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":"Prediction of Prostate Cancer Biochemical Recurrence After Radical Prostatectomy by Collagen Models Using Multiomic Profiles.","authors":"Maria Frantzi, Piotr Tymoszuk, Stefan Salcher, Enrique Gomez-Gomez, Ana C Morillo, Felix Melchior, Ana Blanca, Harald Mischak, Antonia Vlahou, Andreas Pircher, Isabel Heidegger","doi":"10.1016/j.euo.2025.03.016","DOIUrl":"https://doi.org/10.1016/j.euo.2025.03.016","url":null,"abstract":"<p><strong>Background and objective: </strong>The interplay between prostate cancer and the tumor microenvironment is well documented and of primary importance in disease evolution. Herein, we investigated the prognostic value of tissue and urinary collagen-related molecular signatures in predicting biochemical recurrence (BCR) after radical prostatectomy (RP).</p><p><strong>Methods: </strong>A comprehensive analysis of 55 collagen-related features was conducted using transcriptomic datasets (n = 1393), with further validation at the proteomic level (n = 69). Additionally, a distinct cohort (n = 73) underwent a urine-based peptidomic analysis, culminating in the validation of a urine-derived prognostic model. Independent prognostic significance was assessed using Cox proportional hazards modeling, while the model's predictive performance was benchmarked against established clinical metrics.</p><p><strong>Key findings and limitations: </strong>An expression analysis of 55 collagen-related transcripts identified 11 transcripts significantly associated with BCR (C-index: 0.55-0.72, p < 0.002). Multivariable models incorporating these transcripts enhanced prognostic accuracy, surpassing clinical variables (C-index: 0.66-0.89, p < 0.002). Proteomic validation confirmed five key collagen proteins, while a urine-based collagen model (C-index: 0.73, 95% confidence interval: 0.62-0.85) demonstrated a strong prognostic potential, although limited by small patient numbers. Additionally, tissue collagen-based models predicted overall survival with a significant prognostic value (C-index: 0.59-0.70, p < 0.01).</p><p><strong>Conclusions and clinical implications: </strong>Collagen-based molecular signatures in both tissue and urine emerge as robust prognostic biomarkers for predicting BCR following RP.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964194","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 of Deep and Durable Prostate-specific Antigen Responses with Outcomes in Metastatic Hormone-sensitive Prostate Cancer: Insights from ARASENS and ARANOTE Trials.","authors":"Christopher J D Wallis, Sara Ekberg, Alicia K Morgans, Martin Boegemann, Noman Paracha, Elaine Gallagher, Michael J Crowther, Neal Shore","doi":"10.1016/j.euo.2025.03.001","DOIUrl":"https://doi.org/10.1016/j.euo.2025.03.001","url":null,"abstract":"<p><strong>Background and objective: </strong>Prostate-specific antigen (PSA) is a critical biomarker in metastatic hormone-sensitive prostate cancer (mHSPC), offering insights into disease progression and treatment efficacy. An early PSA response to intensified therapy has significant prognostic implications; however, traditional methods often categorize PSA levels and focus on fixed time points, neglecting its dynamic nature. Joint models integrate longitudinal PSA trajectories and survival outcomes to provide a more comprehensive analysis. This study aims to evaluate the association between longitudinal PSA trajectories and overall survival (OS) in patients with mHSPC.</p><p><strong>Methods: </strong>We analyzed data from two phase 3 trials: ARASENS (n = 1305; androgen deprivation therapy [ADT] + docetaxel ± darolutamide) and ARANOTE (n = 669; ADT ± darolutamide). PSA trajectories were modeled using linear mixed models with restricted cubic splines, while OS was assessed using a Weibull model. Longitudinal PSA changes and OS were linked through joint modeling.</p><p><strong>Key findings and limitations: </strong>In ARASENS, each doubling of the PSA decline rate was associated with a reduction in mortality rate of 29% (hazard ratio [HR] 0.71, 95% confidence interval [CI]: 0.69, 0.74); in ARANOTE, the reduction was 25% (HR 0.75, 95% CI: 0.72, 0.78). Higher baseline PSA levels and sharper postnadir increases were linked to worse outcomes. Darolutamide-treated patients showed favorable PSA trajectories, marked by steeper declines, prolonged nadirs, and slower increases, translating into improved OS. Limitations include interim OS data in ARANOTE and influence of prior treatments on baseline PSA.</p><p><strong>Conclusions and clinical implications: </strong>Joint modeling demonstrates a strong association between PSA dynamics and OS, underscoring darolutamide's potential to positively influence PSA trajectories and improve survival in mHSPC.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989830","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":"Adjuvant Docetaxel Versus Surveillance in Intermediate- or High-risk Prostate Cancer After Radical Curative Radiotherapy: Final Survival Results from the SPCG-13 Trial.","authors":"Pirkko-Liisa Kellokumpu-Lehtinen, Ann-Sofie Fransson, Timo Marttila, Ilari Lehtinen, Teppo Huttunen, Camilla Thellenberg-Karlsson","doi":"10.1016/j.euo.2025.04.013","DOIUrl":"https://doi.org/10.1016/j.euo.2025.04.013","url":null,"abstract":"<p><p>The SPCG-13 trial investigated whether six cycles of adjuvant docetaxel (aDoc) improves survival in patients with intermediate- or high-risk prostate cancer after radical curative radiotherapy and androgen deprivation therapy. There was no difference in biochemical recurrence-free survival (primary endpoint) at 5-yr between the surveillance (SV) and aDoc arms. Here we report 10-yr survival data (planned secondary endpoint). Updated overall survival (OS) and metastasis-free survival data were available for 233 patients. There were no demographic differences between the original randomized cohort and the 10-yr survival population. Thus, this 10-yr sample is deemed representative of the original patient population. Median OS was 14.5 yr in the SV and was not reached in the aDoc arm. No significant difference in Kaplan-Meier survival emerged between the arms over time (log-rank test p = 0.154). Estimates of the 10-yr OS rate favored aDoc (77.4% vs 66.8%). Cox regression analysis revealed a trend towards worse OS for patients with a high Gleason score (GS; hazard ratio [HR] 1.925, 95% confidence interval [CI] 1.213-3.053; p = 0.005). A Cox model adjusted for GS risk revealed an OS HR of 0.776 (95% CI 0.508-1.187; p = 0.242) for aDoc versus SV. In conclusion, aDoc was associated with a slight, but not statistically significant, improvement in 10-yr OS, especially in the high-GS group. PATIENT SUMMARY: Our 10-year survival analysis for the SPCG-13 trial showed that six cycles of chemotherapy with docetaxel after radiotherapy and androgen deprivation therapy for intermediate- or high-risk localized prostate cancer did not significantly increase survival. Survival was worse for cancers with a high Gleason score, so docetaxel could be considered after a careful discussion of the benefits and harms of chemotherapy. Further trials are needed to investigate options for this group of patients.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient- and Procedure-specific Risk Factors for Urinary Incontinence After Robot-assisted Radical Prostatectomy: A Nationwide, Population-based Study.","authors":"Katarina Koss Modig, Rebecka Arnsrud Godtman, Stefan Carlsson, Pär Stattin, Johan Styrke, Marianne Månsson, Johan Stranne","doi":"10.1016/j.euo.2025.03.015","DOIUrl":"https://doi.org/10.1016/j.euo.2025.03.015","url":null,"abstract":"<p><strong>Background and objective: </strong>Postprostatectomy urinary incontinence (PPI) is a common complication following robot-assisted laparoscopic radical prostatectomy (RALP), with incidence rates of 4-31%. This study examines associations between patient- and surgery-specific risk factors and PPI.</p><p><strong>Methods: </strong>We analysed data from 13 754 men who underwent RALP between 2017 and 2021, registered in the National Prostate Cancer Register of Sweden. Electronic patient-reported outcome measure (ePROM) questions were completed by 37% at 3 mo and 47% after 12 mo, including questions on pad use. PPI was defined as the use of more than one pad (primary) and any pad use (secondary). Poisson regression assessed the associations between PPI and factors such as age, comorbidity, prostate volume, nerve-sparing procedures, and surgical details.</p><p><strong>Key findings and limitations: </strong>At 12 mo, 17% (1086/6413) reported the use of more than one pad and 49% (3113/6413) reported any pad use. Significant risk factors for incontinence in a multivariable analysis (more than one pad) included age ≥75 versus <65 yr (p < 0.001; relative risk [RR] 2.03; 95% confidence interval [CI] 1.67-2.48), urethral division with margin from the apex versus maximal urethra length (p < 0.001; RR 1.95; 95% CI 1.57-2.43), non-nerve-sparing procedures (p < 0.001; RR 1.70; 95% CI 1.432.03), and prostate volume ≥90 versus <30 ml (p = 0.018; RR 1.47; 95% CI 1.07-2.01). Limitations included missing data on surgical variables and a relatively low ePROM response rate.</p><p><strong>Conclusions and clinical implications: </strong>Older age, large prostate size, and non-nerve-sparing surgery increase the risk of PPI, underscoring the importance of shared decision-making in treatment planning. However, these factors explain only a part of PPI.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960725","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":"Immunohistochemical Prostate-specific Membrane Antigen (PSMA) Expression Patterns of Primary Prostate Cancer Tissue as a Determining Factor for Prostate Cancer Staging with PSMA Positron Emission Tomography/Computed Tomography.","authors":"Francesca Ambrosini, Nataniele Piol, Matteo Bauckneht, Giovanni Drocchi, Benedetta Col, Marco Martiriggiano, Enrico Vecchio, Calogero Paola, Bruno Spina, Luca Sofia, Greta Celesti, Veronica Giasotto, Giuseppe Fornarini, Salvina Barra, Marco Borghesi, Gianmario Sambuceti, Nazareno Suardi, Guglielmo Mantica, Carlo Terrone","doi":"10.1016/j.euo.2025.02.012","DOIUrl":"https://doi.org/10.1016/j.euo.2025.02.012","url":null,"abstract":"<p><strong>Background and objective: </strong>In recent studies, prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has shown accuracy in staging patients diagnosed with prostate cancer. Here, we aim to evaluate the correlation between PSMA immunohistochemical characteristics of prostate cancer (PCa)-positive biopsy cores and whole-mount specimens, and test the predictive role of PSMA expression in biopsy samples for staging PSMA PET/CT.</p><p><strong>Methods: </strong>A total of 104 patients with high- or intermediate-risk PCa who underwent [68Ga]Ga-PSMA-11 PET/CT before radical prostatectomy were prospectively selected between June 2021 and July 2023. The analysis of immunohistochemical PSMA expression was performed using the Immunoreactive Score (IRS). The correlation between biopsy and final specimen was evaluated using Gwet's agreement coefficient for ordinal variables (AC1). Regression models tested the immunohistochemical PSMA expression in biopsy/vesicoprostatic block and the PSMA PET/CT maximum standardized uptake value (SUVmax).</p><p><strong>Key findings and limitations: </strong>A statistically significant strong correlation was found between PSMA expression in biopsy and vesicoprostatic block (AC1 = 0.8 [confidence interval {CI} 0.7-0.9], p < 0.01). According to the multivariable linear regression models, the IRSs of both the PCa-positive biopsy cores and the index lesion were statistically significant predictors of SUVmax (β = 3.3, CI 1.5-7.5, p < 0.01 and β = 4.9, CI 1.8-13, p < 0.01, respectively). Limitations include manual interpretation of immunohistochemistry, potential model overfitting, and a short follow-up.</p><p><strong>Conclusions and clinical implications: </strong>The immunohistochemical analysis of PSMA expression in PCa-positive biopsy cores showed a high correlation with the whole-mount specimen. The degree of PSMA expression is an independent predictor of SUVmax. The assessment of immunohistochemical PSMA expression in a preoperative setting may have implications for determining a more accurate, patient-specific diagnostic pathway.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971613","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":"Assessment of the Prognostic and Predictive Values of the Deficient Mismatch Repair Phenotype in Patients Treated with Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.","authors":"Pierre-Etienne Gabriel, Eva Compérat, Géraldine Cancel-Tassin, Justine Varinot, Mathieu Roumiguié, Pierre-Marie Patard, Gwendoline Daniel, Christian Pfister, Clara Delcourt, Françoise Gobet, Stéphane Larré, Priscilla Léon, Anne Durlach, Pierre Bigot, Julie Carrouget, Caroline Eymerit, Thomas Bessède, Cédric Lebacle, Sophie Ferlicot, Alain Ruffion, Emilien Seizilles de Mazancourt, Myriam Decaussin-Petrucci, Sébastien Crouzet, Xavier Matillon, Florence Mège-Lechevallier, Grégoire Robert, Nam-Son Vuong, Magali Philip, Hervé Lang, Pascal Mouracade, Véronique Lindner, Olivier Cussenot, Morgan Rouprêt, Thomas Seisen","doi":"10.1016/j.euo.2025.03.014","DOIUrl":"https://doi.org/10.1016/j.euo.2025.03.014","url":null,"abstract":"<p><strong>Background and objective: </strong>Given the conflicting evidence currently available in the literature, our aim was to assess the prognostic and predictive values of the deficient mismatch repair (dMMR) phenotype in a large cohort of upper tract urothelial carcinoma (UTUC) patients.</p><p><strong>Methods: </strong>Based on our national network, we performed a retrospective multicenter study including 281 UTUC patients treated with radical nephroureterectomy between 2000 and 2015 at ten French hospitals. The dMMR phenotype as well as PD-L1 and PD-1 expression were determined using immunohistochemistry analyses based on 2-mm-core tissue microarrays. Multivariable Cox regression models were fitted to assess the impact of the dMMR phenotype on recurrence-free (RFS), cancer-specific (CSS), and overall (OS) survival using interaction terms to test the heterogeneity of the treatment effect of adjuvant chemotherapy (AC). Multivariable logistic regression models were also fitted to assess the impact of the dMMR phenotype on PD-L1 and PD-1 expression.</p><p><strong>Key findings and limitations: </strong>Overall, 76 (27.0%) patients had a dMMR phenotype, which was an independent predictor of prolonged RFS (hazard ratio [HR] = 0.41; 95% confidence interval [CI] = [0.21-0.83]; p = 0.01), CSS (HR = 0.38; 95% CI = [0.18-0.83]; p = 0.02), and OS (HR = 0.44; 95% CI = [0.22-0.89]; p = 0.02), with a significant interaction with the use of AC in multivariable Cox regression models (all p_interaction < 0.05). Subgroup analyses showed that the use of AC was significantly associated with prolonged RFS (HR = 0.14; 95% CI = [0.06-0.30]; p < 0.001), CSS (HR = 0.10; 95% CI = [0.03-0.29]; p < 0.001), and OS (HR = 0.23; 95% CI = [0.10-0.54]; p = 0.001) in non-dMMR patients only, without any significant benefit in dMMR patients (all p > 0.05). In multivariable logistic regression analyses, the dMMR phenotype was significantly associated with inverse PD-L1 (OR = 0.20; 95% CI = [0.10-0.80]; p = 0.001) and PD-1 (OR = 0.36; 95% CI = [0.16-0.79]; p = 0.01) expression.</p><p><strong>Conclusions and clinical implications: </strong>We observed that the dMMR phenotype was associated with favorable pathological characteristics and prognosis in UTUC patients, despite conferring decreased sensitivity to AC and lower PD-L1 or PD-1 expression.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cabozantinib plus Pembrolizumab as First-line Therapy for Cisplatin-ineligible Advanced Urothelial Carcinoma: The PemCab Trial.","authors":"Rohit K Jain, Umang Swami, Mehmet A Bilen, Georges Gebrael, Kenneth M Boucher, Emma Braun, Jacqueline T Brown, Jad Chahoud, Sumati Gupta, Neeraj Agarwal, Guru Sonpavde, Benjamin L Maughan","doi":"10.1016/j.euo.2025.04.005","DOIUrl":"https://doi.org/10.1016/j.euo.2025.04.005","url":null,"abstract":"<p><strong>Background and objective: </strong>Pembrolizumab monotherapy is approved for patients with platinum-ineligible metastatic urothelial carcinoma (mUC). Cabozantinib is a multireceptor tyrosine kinase inhibitor with activity against MET and VEGFR2 and is approved as monotherapy or in combination with a PD-1 inhibitor for other malignancies. The objective was to determine the safety and efficacy of pembrolizumab + cabozantinib as first-line treatment for patients with mUC.</p><p><strong>Methods: </strong>In this open-label, single-arm, multicenter, phase 2 study, patients received pembrolizumab 200 mg every 3 wk + cabozantinib 40 mg daily. Key inclusion criteria were locally advanced UC or mUC, Eastern Cooperative Oncology Group performance status 0-2, ineligible for or refused cisplatin, and no prior PD-1/L1 inhibitor. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS) and overall survival (OS). According to the statistical plan, in a cohort of 35 evaluable participants, the lower bound of the 95% confidence interval (CI) would extend no more than 26% from the ORR observed, and in a scenario with ≥17 objective responses, the CI would exclude 32%.</p><p><strong>Key findings and limitations: </strong>Responses were observed in 16 of 35 evaluable patients, with an ORR of 46% (95% CI 31-62%). Median PFS and OS were 8 mo (95% CI 5-13) and 17 mo (95% CI 13-not reached), respectively. The most common treatment-emergent adverse events (any grade) were diarrhea (58%), fatigue (56%), pruritus (39%), nausea (36%), palmar-plantar erythrodysesthesia (36%), and a decrease in appetite (33%).</p><p><strong>Conclusions and clinical implications: </strong>This phase 2 trial of pembrolizumab + cabozantinib demonstrated a manageable toxicity profile and promising efficacy as a first-line therapy combination for cisplatin-ineligible patients with mUC.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980411","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":"Total and Regional Changes in Body Composition in Metastatic Hormone-sensitive Prostate Cancer Patients Randomized to Receive Androgen Deprivation + Enzalutamide ± Zoledronic Acid. The BONENZA Study","authors":"Martina Buffoni ,&nbsp;Alberto Dalla Volta ,&nbsp;Francesca Valcamonico ,&nbsp;Marco Bergamini ,&nbsp;Irene Caramella ,&nbsp;Donatella D’Apollo ,&nbsp;Andrea Zivi ,&nbsp;Giuseppe Procopio ,&nbsp;Piera Sepe ,&nbsp;Gianluca Del Conte ,&nbsp;Nunzia Di Meo ,&nbsp;Silvia Foti ,&nbsp;Stefania Zamboni ,&nbsp;Caterina Messina ,&nbsp;Eleonora Lucchini ,&nbsp;Roberto Maroldi ,&nbsp;Marta Laganà ,&nbsp;Marco Ravanelli ,&nbsp;Manuel Zamparini ,&nbsp;Francesca Zacchi ,&nbsp;Alfredo Berruti","doi":"10.1016/j.euo.2025.02.006","DOIUrl":"10.1016/j.euo.2025.02.006","url":null,"abstract":"<div><h3>Background and objective</h3><div>The reduction of lean body mass (LBM) and the increase of fat body mass (FBM) caused by androgen deprivation therapy (ADT) administered to prostate cancer patients are well known to lead to an increased risk of sarcopenia. The effects of the addition of androgen receptor pathway inhibitors (ARPIs) to ADT on body composition have not been studied thoroughly.</div></div><div><h3>Methods</h3><div>BONENZA (NCT03336983) is a prospective phase 2 trial in which metastatic hormone-sensitive prostate cancer patients were randomized to receive ADT plus enzalutamide with (EZ arm) or without (E arm) the addition of zoledronic acid. Total and regional body composition parameters were evaluated by dual-energy x-ray absorptiometry (DXA) scans at baseline and after 18 mo of therapy.</div></div><div><h3>Key findings and limitations</h3><div>Eighty-nine patients (46 from the EZ arm and 43 from the E arm) had paired DXA evaluation at both time points. After 18 mo of therapy, FBM increased by +22.8% (<em>p</em> &lt; 0.001), LBM reduced by –6.7% (<em>p</em> &lt; 0.001), and appendicular lean mass index (ALMI) decreased by –9.2% (<em>p</em> &lt; 0.001). The increase in FBM varied considerably according to body districts: from +36.1% in the right arms (<em>p</em> &lt; 0.001) to +3.7% in the head (<em>p</em> &lt; 0.01). Similarly, the decrease in LBM ranged from –9.4% (<em>p</em> &lt; 0.001) in the right arm to –6.4% (<em>p</em> &lt; 0.001) in the trunk. None of the patients met the criteria for sarcopenic obesity; however, after 18 mo of treatment, 11.76% of patients had FBM &gt;40.8%, 3.5% of patients had an ALMI of &lt;5.5, and the ALMI/FBM ratio decreased by –23.9% (<em>p</em> &lt; 0.001). Age and baseline LBM influenced these body composition changes significantly, with younger patients (&lt;70 yr) and those with higher baseline LBM experiencing more marked changes.</div></div><div><h3>Conclusions and clinical implications</h3><div>Body composition undergoes a significant change with the addition of ARPIs to ADT, with an increase in FBM and a reduction in LBM, which are twice as high as those expected with ADT alone. DXA has been proved to be a reliable tool for monitoring body composition, and an assessment of district variations can aid in implementing individual-supervised physical exercise to prevent the risk of sarcopenic obesity.</div></div>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":"8 3","pages":"Pages 782-791"},"PeriodicalIF":8.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975714","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}