European urology oncology最新文献

{"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, Alberto Dalla Volta, Francesca Valcamonico, Marco Bergamini, Irene Caramella, Donatella D'Apollo, Andrea Zivi, Giuseppe Procopio, Piera Sepe, Gianluca Del Conte, Nunzia Di Meo, Silvia Foti, Stefania Zamboni, Caterina Messina, Eleonora Lucchini, Roberto Maroldi, Marta Laganà, Marco Ravanelli, Manuel Zamparini, Francesca Zacchi, Nazareno Suardi, Davide Farina, Alfredo Berruti","doi":"10.1016/j.euo.2025.02.006","DOIUrl":"https://doi.org/10.1016/j.euo.2025.02.006","url":null,"abstract":"<p><strong>Background and objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Key findings and limitations: </strong>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% (p < 0.001), LBM reduced by -6.7% (p < 0.001), and appendicular lean mass index (ALMI) decreased by -9.2% (p < 0.001). The increase in FBM varied considerably according to body districts: from +36.1% in the right arms (p < 0.001) to +3.7% in the head (p < 0.01). Similarly, the decrease in LBM ranged from -9.4% (p < 0.001) in the right arm to -6.4% (p < 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 >40.8%, 3.5% of patients had an ALMI of <5.5, and the ALMI/FBM ratio decreased by -23.9% (p < 0.001). Age and baseline LBM influenced these body composition changes significantly, with younger patients (<70 yr) and those with higher baseline LBM experiencing more marked changes.</p><p><strong>Conclusions and clinical implications: </strong>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.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"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}

{"title":"Direct Treatment of All Visible Tumour in Synchronous Oligometastatic Prostate Cancer: Total Eradication of Tumour or the Full Monty Treatment.","authors":"Alexander Giesen, Niels De Preter, Tamás Fazekas, Gert De Meerleer, Giorgio Gandaglia, Giancarlo Marra, Shahrokh F Shariat, Steven Joniau, Pawel Rajwa","doi":"10.1016/j.euo.2025.04.011","DOIUrl":"https://doi.org/10.1016/j.euo.2025.04.011","url":null,"abstract":"<p><p>Recent advances in the management of synchronous oligometastatic prostate cancer (PC) highlight the potential of combining local and systemic therapies. However, there is growing interest in metastasis-directed therapy (MDT) in this setting. When all modalities are combined, this is referred as \"total eradication of tumour\" (TET) or \"full monty treatment\" (FMT). Retrospective studies have revealed promising outcomes with approaches such as cytoreductive radical prostatectomy or radiotherapy alongside MDT and combination systemic therapy. Multiple studies have demonstrated a significant proportion of cases with undetectable prostate-specific antigen and noncastrate testosterone, while one comparative trial (± MDT) revealed some evidence of an overall survival benefit. Results from the prospective trials indicate the feasibility and effectiveness of this intensive treatment strategy, with biochemical remission and disease-free states achieved in a significant proportion of cases. Overall, limitations persist, including a reliance on conventional imaging in all studies and the absence of long-term prospective data. Ongoing trials will provide definitive insights into the treatment efficacy and safety of TET/FMT. PATIENT SUMMARY: For patients with a new diagnosis of prostate cancer with only few metastases, cancer control results after treatment with local therapy, hormonal agents, and treatment targeted to all metastatic sites are promising. Further clinical trials of this approach with the inclusion of new scan techniques are eagerly awaited.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959877","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":"Novel Molecular Biomarkers to Guide Treatment Decision-making in Metastatic Urothelial Cancer-A Patient Cohort Analysis.","authors":"Debbie G J Robbrecht, Youssra Salhi, John W M Martens, Maureen J B Aarts, Paul Hamberg, Michiel S van der Heijden, Jens Voortman, Niven Mehra, Hans M Westgeest, Ronald de Wit, Reno Debets, Joost L Boormans, J Alberto Nakauma-González","doi":"10.1016/j.euo.2025.04.007","DOIUrl":"https://doi.org/10.1016/j.euo.2025.04.007","url":null,"abstract":"<p><p>The current options and recent developments in the field of systemic therapy for advanced urothelial cancer (UC) patients urge the need for selection criteria to identify the most optimal therapeutic option for individual patients. The molecular makeup of tumors, including molecular subtype, tumor microenvironment composition, and gene mutations, fusions, and amplifications, has previously been correlated with a response to immune checkpoint inhibitors, erdafitinib, or enfortumab vedotin (EV) monotherapy, and may withhold potential candidate biomarkers. In this study, we aimed to stratify metastatic UC (mUC) patients based on molecular biomarkers that might be associated with a response to EV, a fibroblast growth factor receptor inhibitor, or anti-PD-(L)1, by using whole-genome DNA-sequencing and paired RNA-sequencing data of fresh-frozen metastatic tumor biopsies of 155 mUC patients. We observed that NECTIN4 amplification, FGFR2/3 mutations, and the RNA expression-based T-cell-to-stroma enrichment (TSE) score were mutually exclusive, and may therefore reflect biologically distinct tumors and sensitivity to treatments. This finding was validated in two independent bladder cohorts: the IMvigor210 study and The Cancer Genome Atlas. Stratification of patients into subgroups based on these molecular features is possible. Our data challenge the concept of a one-treatment-fits-all paradigm and support the rationale for prospective clinical trials with biomarker-guided treatment selection of mUC patients.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960572","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":"Every Other Day or Once a Week: Long-term Oncological Outcomes in the Phase 2 PATRIOT Trial of Prostate Stereotactic Ablative Body Radiotherapy.","authors":"Wee Loon Ong, Harvey Quon, Aldrich Ong, Patrick Cheung, William Chu, Hans Chung, Danny Vesprini, Amit Chowdhury, Dilip Panjwani, Yasir Alayed, Geordi Pang, Renee Korol, Melanie Davidson, Ananth Ravi, Boyd McCurdy, Liying Zhang, Meghan Kulasingham-Poon, Alexandre Mamedov, Andrea Deabreu, Andrew Loblaw","doi":"10.1016/j.euo.2025.03.011","DOIUrl":"https://doi.org/10.1016/j.euo.2025.03.011","url":null,"abstract":"<p><strong>Background and objective: </strong>The PATRIOT multicentre phase 2 trial showed that prolongation of overall treatment time (OTT) for prostate stereotactic ablative body radiotherapy (SABR) was associated with better acute bowel and urinary quality of life. However, the impact on long-term cancer outcomes is unclear.</p><p><strong>Methods: </strong>Men with favourable-risk localised prostate cancer in the PATRIOT trial were randomised to five-fraction prostate SABR every other day (EOD; n = 77) or once weekly (QW; n = 75).The cancer outcomes evaluated in this post hoc analyses were biochemical failure (BF), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS).</p><p><strong>Key findings and limitations: </strong>Median follow-up was 91 mo. The 8-yr cumulative incidence rates for BF were 5.5% in the EOD arm versus 9.6% the QW arm (p = 0.2). The 8-yr probability rates were 100% versus 95.9% for MFS (p = 0.08), 100% versus 97.2% for PCSS (p = 0.2), and 96.0% versus 85.4% for OS (p = 0.3) for the EOD versus QW arms, respectively. The study is limited by the small sample size (powered to detect significant differences in acute bowel quality of life).</p><p><strong>Conclusions: </strong>This study suggests no significant differences in long-term cancer outcomes between EOD and QW schedules for five-fraction prostate SABR. This trial is registered on ClinicalTrials.gov as NCT01423474.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005649","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":"Oncological Outcomes in Patients with Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography-detected Oligometastatic Prostate Cancer Treated with Metastasis-directed Radiotherapy as the Single Treatment Modality.","authors":"Katelijne C C de Bie, Lotte G Zuur, Dennie Meijer, Philip Meijnen, Karel A Hinnen, Daniela E Oprea-Lager, Pim J van Leeuwen, Andre N Vis","doi":"10.1016/j.euo.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.euo.2025.04.002","url":null,"abstract":"<p><strong>Background and objective: </strong>In patients with biochemical recurrence (BCR), prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) can detect oligometastatic prostate cancer (PCa). However, the optimal treatment approach for oligometastatic disease remains unclear. This study aims to assess the oncological outcomes of metachronous oligometastatic PCa patients treated with metastasis-directed radiotherapy (MDRT).</p><p><strong>Methods: </strong>We retrospectively evaluated patients with hormone-sensitive, metachronous oligometastatic PCa who underwent MDRT for BCR (from July 2012 to September 2022). Patients had one to four lymph nodes and/or bone metastases on PSMA PET/CT and were irradiated with 5 × 7 or 3 × 10 Gy. The biochemical response to MDRT was assessed as undetectable prostate-specific antigen (PSA) at follow-up, PSA response (PSA ≤ pretreatment level), or biochemical progression (PSA > pretreatment level). Biochemical progression-free survival (bPFS) and local remission of disease (absence of disease at the MDRT site on follow-up PSMA PET/CT or undetectable PSA) were evaluated.</p><p><strong>Key findings and limitations: </strong>Eighty patients underwent MDRT for 105 PSMA PET/CT-confirmed lesions. The median time from curative treatment to MDRT was 55 mo (interquartile range [IQR] 31-103). At a median follow-up of 32 mo after MDRT (IQR 21-64), 10% of the patients were PSA free, 10% had a PSA response, and 80% experienced biochemical progression. The bPFS rates at 1 and 2 yr were 54% and 38%, respectively. A total of 87% of patients had local control of disease after MDRT, whereas 72% had new metastatic lesions on repeated PSMA PET/CT. Limitations include the retrospective design and a small cohort.</p><p><strong>Conclusions and clinical implications: </strong>MDRT for oligometastatic disease shows high local efficacy. However, disease progression is observed in a substantial proportion of patients.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062584","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":"Impact of Immune Checkpoint Inhibitors as Neoadjuvant Therapy for Muscle-invasive Bladder Cancer: A Systematic Review, Meta-analysis, and Network Meta-analysis.","authors":"Akihiro Matsukawa, Angelo Cormio, Marcin Miszczyk, Mehdi Kardoust Parizi, Tamás Fazekas, Ichiro Tsuboi, Stefano Mancon, Robert J Schulz, Giulio Litterio, Ekaterina Laukhtina, Paweł Rajwa, Thomas Seisen, Keiichiro Mori, Francesca Sanguedolce, Andrea Benedetto Galosi, Jun Miki, Takahiro Kimura, Shahrokh F Shariat, Takafumi Yanagisawa","doi":"10.1016/j.euo.2025.02.009","DOIUrl":"https://doi.org/10.1016/j.euo.2025.02.009","url":null,"abstract":"<p><strong>Background and objective: </strong>The availability of immune checkpoint inhibitors (ICIs) has expanded perioperative treatment options for urothelial carcinoma. Our aim was to evaluate the effect of neoadjuvant ICI-based regimens on oncological outcomes for patients with muscle-invasive bladder cancer (MIBC).</p><p><strong>Methods: </strong>We systematically searched MEDLINE, Embase, Web of Science, and ClinicalTrials.gov in September 2024 for studies on neoadjuvant therapies for MIBC. A proportion meta-analysis and network meta-analysis (NMA) using random-effect models were conducted to evaluate pooled pathological complete response (pCR) rates and to compare overall survival (OS) and adverse events. The review is registered on PROSPERO (CRD42024587964).</p><p><strong>Key findings and limitations: </strong>We included 12 randomized controlled trials (RCTs; 5004 patients) and 35 non-RCTs (2964 patients). ICI-chemotherapy combination therapy was associated with a significantly higher pCR rate versus chemotherapy alone (40.6% vs 17.9%; p < 0.01). In the two phase 3 RCTs included (1556 patients) there was no significant difference in OS between dose-dense methotrexate + vinblastine + Adriamycin + cisplatin (ddMVAC) and durvalumab + gemcitabine + cisplatin (GC; hazard ratio 1.06, 95% confidence interval [CI] 0.72-1.55; p = 0.8). ddMVAC significantly increased the risk of grade ≥3 anemia (risk ratio [RR] 2.81, 95% CI 1.62-4.88) and asthenia (RR 3.46, 95% CI 1.68-7.14) in comparison to GC, while durvalumab + GC did not. Limitations include data heterogeneity across studies and the limited number of studies included in the NMA.</p><p><strong>Conclusions and clinical implications: </strong>ICI addition to chemotherapy in the neoadjuvant MIBC setting significantly increased pCR rates in comparison to chemotherapy alone. However, there was no difference in OS between durvalumab + GC and ddMVAC. Further studies are needed to clarify the OS benefit of ICI-based combination therapy in comparison to the current standard chemotherapy regimen.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963822","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":"Presence of an Artificial Intelligence-powered Predictive Biomarker Is Associated with a Poor Response to Intravesical Bacillus Calmette-Guerin but Not to Intravesical Sequential Gemcitabine/Docetaxel in Patients with High-grade Non-muscle-invasive Bladder Cancer.","authors":"Vignesh T Packiam, Ian M McElree, Saum Ghodoussipour, Vivek Nimgaonkar, Viswesh Krishna, Joon Kyung Kim, Derek B Allison, Jordan R Richards, K D Anand Rajan, Stephanie J Chen, Yair Lotan, Stephen B Williams, Haochen Zhang, Drew Watson, Damir Vrabac, Waleed M Abuzeid, Anirudh Joshi, Ashish M Kamat, Michael A O'Donnell, Patrick J Hensley","doi":"10.1016/j.euo.2025.04.006","DOIUrl":"https://doi.org/10.1016/j.euo.2025.04.006","url":null,"abstract":"<p><p>Intravesical bacillus Calmette-Guerin (BCG) is considered first-line adjuvant therapy for high-risk or high-grade non-muscle-invasive bladder cancer (NMIBC). Recently, sequential intravesical gemcitabine and docetaxel (Gem/Doce) has emerged as a promising alternative to intravesical BCG. Biomarkers to select the optimal treatment regimen could facilitate clinical decision-making. The Computational Histologic Artificial Intelligence (CHAI) platform was previously used to develop an artificial intelligence-augmented histologic assay (CHAI biomarker) that identified patients with NMIBC at an increased risk of recurrence and progression events following BCG treatment. In this study, we assessed use of the CHAI biomarker among patients with treatment-naive high-grade NMIBC who received intravesical BCG or Gem/Doce. Among patients with the presence of the CHAI biomarker, those treated with BCG had a 24-mo high-grade recurrence-free survival (HG-RFS) rate of 56% (95% confidence interval [CI] 43-73%) and those treated with Gem/Doce had an HG-RFS rate of 90% (95% CI 79-100%; hazard ratio [HR] 5.4, 95% CI 1.6-18.3, p = 0.007). Among patients with an absence of the CHAI biomarker, those treated with BCG or Gem/Doce had no significant difference in HG-RFS (HR 1.3, 95% CI 0.6-2.6, p = 0.5). The interaction term between the CHAI biomarker and the treatment type was significant (p = 0.029), indicating an association between the biomarker and the clinical outcome that is dependent on the treatment received. This study suggests that the CHAI biomarker predicts which specific high-grade NMIBC patients are less likely to benefit from BCG and may benefit from alternative treatments including, potentially, Gem/Doce.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005098","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}