Clinical genitourinary cancer最新文献

{"title":"Nationwide Real-World Outcomes of Trial Eligible and Trial Ineligible Patients With Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab","authors":"Mette Syberg Jespersen ,&nbsp;Jesper Andreas Evers Palshof ,&nbsp;Niels Fristrup ,&nbsp;Niels Viggo Jensen ,&nbsp;Jon Røikjær Henriksen ,&nbsp;Ane Bundsbæk Bøndergaard Iversen ,&nbsp;Sarah Grønbech Steen ,&nbsp;Morten Andersen ,&nbsp;Kasper Madsen ,&nbsp;Inge Marie Svane ,&nbsp;Anne Kirstine Møller Darras","doi":"10.1016/j.clgc.2025.102450","DOIUrl":"10.1016/j.clgc.2025.102450","url":null,"abstract":"<div><h3>Introduction</h3><div>Clinical trials have demonstrated efficacy and safety of immune checkpoint inhibitor-based combination therapy in metastatic renal cell carcinoma (mRCC). However, patients who do not meet trial eligibility criteria constitute a large proportion of the real-world population, and their outcomes remain poorly described.</div></div><div><h3>Patients and Methods</h3><div>This nationwide, retrospective cohort study included all Danish patients with mRCC who initiated nivolumab plus ipilimumab (NIVO/IPI) by May 5, 2022. Clinical data were obtained from electronic patient records. Outcomes included median progression-free survival (mPFS), median overall survival (mOS), and objective response rate (ORR), assessed by treating physicians. Patients were classified as trial-eligible or ineligible according to CheckMate 214 (CM214) key criteria. Survival was estimated using Kaplan–Meier methods, and subgroups were explored.</div></div><div><h3>Results</h3><div>A total of 464 patients were included, with a median follow-up of 33 months. In the total cohort, mPFS was 9 months, mOS 41 months, and ORR 43%, including 13% complete responses. Among 282 trial-eligible patients, outcomes were comparable to CM214 with mPFS 12 months and mOS 49 month, while 182 ineligible patients had inferior outcomes, with mPFS 6 months and mOS 26 months (both <em>P</em> &lt; .001). The presence of brain metastases did not adversely affect OS, while patients with autoimmune disease demonstrated unexpectedly favorable outcomes. Severe treatment-related toxicity (≥ grade 3) occurred in 44% in the total cohort, comparable to CM214.</div></div><div><h3>Conclusion</h3><div>This is the first nationwide real-world study evaluating NIVO/IPI outcomes in unselected mRCC. Trial-eligible patients achieved survival outcomes comparable to clinical trial results. Although ineligible patients derived less benefit, they still experienced meaningful clinical outcomes. These findings provide benchmark data for treatment of real-world mRCC populations in routine clinical practice.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102450"},"PeriodicalIF":2.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenic Germline Variant Prevalence and Genetic Testing Outcomes in Patients With Urothelial Carcinoma","authors":"Eugene Oh ,&nbsp;Ye Chua ,&nbsp;Piroz Bahar ,&nbsp;Marie-Louise Accardo ,&nbsp;Xiaochen Li ,&nbsp;Erika Koeppe ,&nbsp;Steven Monda ,&nbsp;Phillip L. Palmbos ,&nbsp;Irene Tsung ,&nbsp;Zachery R. Reichert ,&nbsp;Ulka N Vaishampayan ,&nbsp;Udit Singhal ,&nbsp;Tobias Else ,&nbsp;Charles B. Nguyen","doi":"10.1016/j.clgc.2025.102451","DOIUrl":"10.1016/j.clgc.2025.102451","url":null,"abstract":"<div><h3>Introduction</h3><div>Urothelial carcinoma (UC) is rarely attributed to hereditary causes, but recent studies suggest inherited factors may play a larger role. Current guidelines recommend genetic evaluation in patients with UC diagnosed at &lt; 50 years old or features associated with Lynch syndrome. However, the full pathogenic germline variant landscape and optimal genetic evaluation criteria in UC remain poorly understood.</div></div><div><h3>Patients and Methods</h3><div>A retrospective analysis of all patients with UC referred for genetic evaluation between 2002 and 2024 was performed. Genetic testing outcomes, variant prevalence and characterization, and associated clinicopathologic features were recorded. Fisher’s Exact test was used to compare factors between patients with pathogenic or likely pathogenic (P/LP) variant versus those with negative testing.</div></div><div><h3>Results</h3><div>Overall, 128 patients underwent genetic evaluation. Median age at diagnosis was 59 (IQR: 48-68). Most (58.6%) had non-muscle invasive disease at initial diagnosis; 8.6% had metastatic disease. Pure urothelial histology was most frequent (71%). Upper tract disease was present at 14.8%. Among the cohort, 34 (26.6%) had a confirmed P/LP variant. The most common P/LP variants were Lynch syndrome-associated genes (9.4%) and DNA damage repair genes (9.4%). Having a history of ≥ 2 additional cancers was associated with a positive genetic test (<em>P</em> = .010). Otherwise, there were no statistically significant differences in testing outcomes based on age at diagnosis, primary tumor location, or initial stage at diagnosis.</div></div><div><h3>Conclusion</h3><div>Among patients with UC referred for genetic evaluation, 26.6% had a confirmed P/LP variant, although this cohort was a selected population. Age and traditional clinicopathologic features were not associated with testing results, though history of ≥ 2 additional cancers was associated. These findings may suggest a broader use of genetic evaluation in UC.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102451"},"PeriodicalIF":2.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral Toxicities of PSMA-Targeted Therapies: Mitigation Strategies and Translational Opportunities","authors":"Chitra Priya Emperumal ,&nbsp;Nagarajan Kannan ,&nbsp;Daniel S. Childs ,&nbsp;Bridget P. Keenan","doi":"10.1016/j.clgc.2025.102452","DOIUrl":"10.1016/j.clgc.2025.102452","url":null,"abstract":"<div><div>Prostate-specific membrane antigen (PSMA) has gained prominence as a key target in the treatment of metastatic castration-resistant prostate cancer (mCRPC) therapy. Integrating radionuclide therapies such as Lutetium-177 [¹⁷⁷Lu]-PSMA-617 has significantly advanced treatment outcomes while posing unique challenges related to off-tumor toxicities in other tissues that express PSMA, particularly in salivary glands. Furthermore, there are novel cancer therapeutics in development including PSMA-targeted immunotherapies and antibody drug conjugates which hold promise for the treatment of prostate cancer and may contribute to the burden of oral toxicity. The oral toxicity of PSMA-targeted radioligand therapy arises from PSMA-mediated salivary gland uptake and radionuclide retention, differing fundamentally from the nonspecific tissue damage mechanisms of traditional external beam radiotherapy. In parallel, targeted therapies, including small molecules and monoclonal antibodies, exert direct effects by binding to PSMA and delivering anti-tumor metabolites and/or amplifying the immune response. The resultant off-tumor on-target tissue damage can lead to distinct oral complications such as xerostomia, dysgeusia and mucositis. Although PSMA–targeted therapies are primarily used for the management of prostate cancer, they are also being explored in treatment of salivary gland malignancies including adenoid cystic carcinoma. This review explores the mechanisms and clinical manifestations of PSMA-related oral toxicities in the context of prostate cancer, diagnosis, possible mitigation strategies, the need for preclinical models to study regulation of PSMA expression leading to oral toxicities, current challenges and future directions.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102452"},"PeriodicalIF":2.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Experience With Lenvatinib Plus Everolimus (LEN+EVE) in Patients With Pretreated Advanced Renal Cell Carcinoma (RELEVANCE): A Retrospective, Multicenter Case Series","authors":"Hendrik Eggers ,&nbsp;Ramona Stelmacher ,&nbsp;Martin Bögemann ,&nbsp;Arne Strauß ,&nbsp;Christian Thomas ,&nbsp;Johannes Landmesser ,&nbsp;Stefanie Zschäbitz ,&nbsp;Philipp Ivanyi","doi":"10.1016/j.clgc.2025.102449","DOIUrl":"10.1016/j.clgc.2025.102449","url":null,"abstract":"<div><h3>Introduction</h3><div>Metastatic renal cell carcinoma (mRCC) has a poor prognosis despite recent changes in systemic treatment options. Lenvatinib plus everolimus (LEN+EVE), a combination of 2 targeted therapies, is approved after failure of one prior tyrosine kinase inhibitor (TKI) therapy. Our objective was to evaluate the effectiveness and safety of LEN+EVE therapy in patients with mRCC in a real-world setting.</div></div><div><h3>Patients and Methods</h3><div>This retrospective case series included patients with mRCC treatment with LEN+EVE between August 2016 and December 2021 at 6 academic centers in Germany. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety; all evaluated by local investigator. Subgroup analyses by risk scores, previous therapies, and initial dosing were performed.</div></div><div><h3>Results</h3><div>Eighty-one patients were assessed: median age was 61 years (range 42-80), 81.5% were men, and 80.2% of patients had an ECOG score of 0 or 1. Synchronous metastases were found in 39.5% of patients at initial diagnosis. The International Metastatic RCC Database Consortium (IMDC) risk status was favorable in 16.0%, intermediate in 48.1%, and poor in 16.0% of patients. The median number of treatment lines prior to LEN+EVE was 3 (range 0-7). Median treatment duration with LEN+EVE was 6.1 months (range 0.2-29.2). The ORR was 28.4%, DCR was 61.7%, median OS was 11.3 months (95% CI, 8.7-13.9), and median PFS was 6.5 months (95% CI, 5.4-7.6). Median PFS, OS and ORR were similar across patients with 0-2 versus ≥ 3 previous therapeutic lines and for patients with or without previous immunotherapy. The safety profile was manageable, with 6.2% of patients discontinuing treatment due to treatment-related adverse events.</div></div><div><h3>Conclusions</h3><div>LEN+EVE combination therapy demonstrated high effectiveness in heavily pre-treated, real-world cohort of patients with mRCC and challenging disease characteristics—regardless of treatment line, IMDC risk group, initial dosing, or previous treatment with immunotherapy.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102449"},"PeriodicalIF":2.7,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Clinicopathologic Features and Imaging Findings of TFE3-Rearranged Renal Cell Carcinoma","authors":"Jianqiang Liu ,&nbsp;Jinyan Wei ,&nbsp;Yuting Zhang ,&nbsp;Sitong Han ,&nbsp;Qi Zhang ,&nbsp;Enbo Hu ,&nbsp;Xuejian Sun ,&nbsp;Gang Wang ,&nbsp;Jianhong Zhao","doi":"10.1016/j.clgc.2025.102446","DOIUrl":"10.1016/j.clgc.2025.102446","url":null,"abstract":"<div><h3>Objective</h3><div>To examine the imaging features and clinicopathologic features of TFE3-rearranged renal cell carcinoma and highlight key imaging findings for clinical decision-making.</div></div><div><h3>Methods</h3><div>The imaging and clinicopathological data of 49 pathologically confirmed cases of TFE3-rearranged renal cell carcinoma from multiple institutions between January 2018 and December 2024 were retrospectively analyzed.</div></div><div><h3>Results</h3><div>Of the 49 patients, 17 were male and 32 were female; aged 44 ± 15 years (range: 10-82 years) , 22 were asymptomatic and 27 were symptomatic. Tumor size averaged 7.0 (range: 2.0-14.9) cm. Imaging showed 28 round-like and 21 lobulated lesions; 18 had distinct margins, while 31 had indistinct margins. A pseudocapsule was present in 36 cases, 24 of which were incomplete. Additionally, 42 tumors showed uneven density with necrosis or cystic degeneration; there were 25 cases of hemorrhage, 27 cases of irregular calcification, Peritumoral vessels were noted in 23 cases. Imaging modalities included CT (44 cases: 41 with both plain and enhanced scans, 3 with plain only), MRI (13 cases with plain and enhanced scans), and ultrasonography (15 cases, including 5 with contrast enhancement). Treatment included partial nephrectomy (21 cases), total nephrectomy (22 cases) , and biopsy (6 cases).With a median follow-up of 30 months (range: 1-72 months) until December 2024, 6 patients experienced tumor recurrence, 14 developed metastasis, and 7 died, while 5 patients were lost to follow-up.</div></div><div><h3>Conclusion</h3><div>TFE3-rearranged renal cell carcinoma is a rare renal tumor with distinct imaging and clinical features that can inform preoperative diagnosis, treatment, and prognosis.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102446"},"PeriodicalIF":2.7,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage Cell and Diagnostic Biomarkers in BLCA: Integrating Machine Learning With Single-Cell Analysis","authors":"Guangliang Che,&nbsp;Xuejun Zhao,&nbsp;Rongtuan Luo,&nbsp;Quanfeng Yu,&nbsp;Xiaofeng Guo,&nbsp;Ke Gao,&nbsp;Kangyu Chen,&nbsp;Erfeng Zhang","doi":"10.1016/j.clgc.2025.102447","DOIUrl":"10.1016/j.clgc.2025.102447","url":null,"abstract":"<div><h3>Introduction</h3><div>Bladder cancer (BLCA) has a poor prognosis and continues to pose a significant challenge for clinicians. Prior studies have demonstrated a close relationship of BLCA with macrophages. However, the key subpopulations and molecular functions of macrophages in BLCA have not been uncovered. It becomes possible to use single-cell sequencing technology to explore macrophage heterogeneity and identify new biomarkers.</div></div><div><h3>Patients and Methods</h3><div>Single-cell analysis, pseudo-time analysis, and cell-to-cell communication analysis were performed using single-cell sequencing data of PBMC, BLCA, and urothelial-derived cells (UDCs) obtained from the Gene Expression Omnibus (GEO). Scale-free network analysis was performed using hdWGCNA to select feature genes. LASSO regression and random forest analysis were performed based on TCGA_BLCA data. A prognostic model was established, which was then validated using the Gene Expression Omnibus (GEO) dataset. In addition, immune infiltration analysis was performed between high-risk and low-risk groups using the CIBERSORT, ESTIMATE algorithms, and the TIDE database.</div></div><div><h3>Results</h3><div>Nine macrophage subtypes were identified through single-cell analysis. 571 macrophage-associated genes were identified via hdWGCNA. Seven key genes, including MYO5A, KCNK6, DNAJB4, DEDD2, NFKBID, PSMB10, and ITPRID2, were selected by integrating LASSO regression and RF analysis. A prognostic model was constructed based on these genes. The high-risk cohort displayed markedly poorer overall survival (OS). The model’s prediction accuracy was verified in an independent group. Immune analysis revealed enhanced immune evasion in the high-risk cohort, potentially facilitating tumor progression and increasing the metastatic capacity of BLCA cells.</div></div><div><h3>Conclusions</h3><div>The prognostic model built on 7 macrophage-linked genes exhibited robust prediction performance in BLCA. The M2 macrophage phenotype was notably enriched in the high-risk cohort and appeared to cause elevated tumor invasiveness. Immune infiltration analysis suggested that the high-risk population showed a weaker response to immune checkpoint inhibitor (ICI) treatment. Among all identified genes, DEDD2 may serve as a promising prognostic biomarker for BLCA.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102447"},"PeriodicalIF":2.7,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subcentimeter Pulmonary Nodules in Patients With Clinical Stage I Non-Seminoma: Impact on Risk and Patterns of Disease Relapse","authors":"Adri M. Durant ,&nbsp;Kshitij Pandit ,&nbsp;Nadia Islam ,&nbsp;Mimi Nguyen ,&nbsp;Margaret Meagher ,&nbsp;Mai Dabbas ,&nbsp;Lanyu Mi ,&nbsp;Timothy D. Lyon ,&nbsp;Fred Millard ,&nbsp;Stephen A. Boorjian ,&nbsp;Bradley Leibovich ,&nbsp;Mark D. Tyson ,&nbsp;Aditya Bagrodia","doi":"10.1016/j.clgc.2025.102448","DOIUrl":"10.1016/j.clgc.2025.102448","url":null,"abstract":"<div><h3>Introduction</h3><div>Indeterminate subcentimeter pulmonary nodules identified during the initial staging of patients with clinical stage I non-seminoma germ cell tumor (NSGCT) remain of uncertain clinical significance and yet can increase patient anxiety and cloud management decisions. We seek to evaluate the incidence and risk of disease recurrence in stage I NSGCT patients with subcentimeter pulmonary nodules.</div></div><div><h3>Methods</h3><div>Patients with clinical stage I NSGCT receiving an orchiectomy from 2003 to 2024 with at least 3-months of follow-up were identified (<em>n</em> = 215). Patient demographics, pathologic characteristics, administration of adjuvant therapy, and disease relapse data were collected. Initial staging imaging reports were reviewed identifying patients with SPN (&lt; 1cm). The relationship between SPN and disease recurrence was investigated.</div></div><div><h3>Results</h3><div>We identified 215 patients with stage I NSGCT, of whom 71 (33.0%) had SPN on initial staging imaging. A total of 52 patients (24.2%) received adjuvant treatment (primary RPLND 31 patients, primary chemotherapy 21 patients), with no significant difference in therapy between patients with and without SPN (<em>P</em> = .09). At a median follow-up of 22-months, disease recurrence occurred in 51 (23.7%) patients. The presence of SPN was not associated with increased risk of disease recurrence on univariate analysis (<em>P</em> = .12) and was associated with a decreased risk of recurrence on multivariable analysis (OR (95% CI): 0.38 (0.17, 0.83); <em>P</em> = .02). Of 6 patients who progressed to metastatic lung disease, only 1 patient had SPN at the time of presentation.</div></div><div><h3>Conclusion</h3><div>Our study suggests that SPN in stage I NSGCT are not associated with an increased risk of disease relapse. These findings may be used in patient counseling and to avoid overtreatment in management decisions.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102448"},"PeriodicalIF":2.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145358547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathological and Clinical Implications of Tumor Microenvironment Evaluated With Multiplex Immunohistochemistry in Testicular Embryonal Carcinoma","authors":"Valentina Tateo ,&nbsp;Costantino Ricci ,&nbsp;Sofia Melotti ,&nbsp;Elisa Tassinari ,&nbsp;Matteo Rosellini ,&nbsp;Andrea Marchetti ,&nbsp;Linda Danielli ,&nbsp;Antonio Maestri ,&nbsp;Andrea Necchi ,&nbsp;Veronica Mollica ,&nbsp;Michelangelo Fiorentino ,&nbsp;Francesco Massari","doi":"10.1016/j.clgc.2025.102444","DOIUrl":"10.1016/j.clgc.2025.102444","url":null,"abstract":"<div><h3>Introduction</h3><div>Testicular germ cell tumors (TGCTs) are the most common cancer in young men. Their development is closely linked to embryogenesis, yet much about their pathogenesis remains unknown. TGCTs exhibit exceptional sensitivity to cisplatin-based chemotherapy, achieving high cure rates even in metastatic disease. Further research is needed to deepen our understanding of TGCTs and refine risk stratification. In this pilot study, we focused on embryonal carcinoma (EC), a subtype with increased risk of relapse and considered a key step in TGCT reprogramming.</div></div><div><h3>Patients and Methods</h3><div>We analyzed the tumor microenvironment (TME) in 49 EC samples using bright-field multiplex immunohistochemistry (BF-mIHC), which enables the simultaneous evaluation of multiple biomarkers, making it particularly useful for TME characterization. We evaluated B-cells (CD20), T-cells (CD3), and tumor-associated macrophages (TAMs, CD68) and established cutoffs that correlated with reprogramming phase, clinical stage, and relapse.</div></div><div><h3>Results</h3><div>High TAM levels (CD68 + &gt; 83/mm²) were strongly associated with phase I of reprogramming (pure EC or EC mixed only with seminoma), while low TAM characterized phase II (<em>P</em> <em>&lt;</em> <em>.</em>001), suggesting a role in stemness maintenance through epigenetic regulation. High CD68 (&gt; 46/mm²) and CD3 (&gt; 125.5/mm²) correlated with metastatic disease (<em>P</em> <em>&lt;</em> <em>.</em>001 and <em>P</em> <em>=</em> <em>.</em>026, respectively), whereas high CD20 (&gt; 38.5/mm²) and CD3 (&gt; 83/mm²) were linked to lower relapse risk (<em>P</em> <em>=</em> <em>.</em>014 and <em>P</em> <em>=</em> <em>.</em>017, respectively). Important limits are small sample size and few relapse events.</div></div><div><h3>Conclusions</h3><div>These findings highlight the relevance of TME in TGCT biology and prognosis. The observed associations suggest TME may influence tumor plasticity, metastatization and relapse risk, warranting validation in larger studies.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102444"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Systematic Review and Meta-Analysis of the Effectiveness and Safety of Immune Checkpoint Inhibitors in Patients With BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer","authors":"Asmaa Soliman ,&nbsp;Mohamed R. Murad ,&nbsp;George Jabrieh ,&nbsp;Esraa M. AlEdani ,&nbsp;Abdelrahman Saeed ,&nbsp;Zineddine Belabaci ,&nbsp;Thoria I. Essa Ghanm ,&nbsp;Israa Ahmed Qutob","doi":"10.1016/j.clgc.2025.102445","DOIUrl":"10.1016/j.clgc.2025.102445","url":null,"abstract":"<div><div>The primary cancer of the urinary system is bladder cancer, which includes 2 subtypes: muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Intravesical Bacillus Calmette-Guérin (BCG) therapy remains the gold standard for treating individuals with high-risk NMIBC. However, disease development and recurrence pose serious clinical problems. This study aims to evaluate the safety and efficacy of immune checkpoint inhibitors (ICIs) as innovative therapeutic approaches for patients with BCG-unresponsive NMIBC. We conducted this study according to the PRISMA guidelines. We systematically reviewed clinical trials that evaluated ICIs as a treatment for BCG-unresponsive NMIBC and reported predefined efficacy and safety outcomes. We synthesized data using R software and evaluated the risk of bias using the ROBINS-I tool. Nine studies (488 patients) were included in the review, of which 6 were pooled in the meta-analysis. Following ICI therapy, the complete response (CR) rates were 36% at 3 months, 25% at 6 months, and 18% at twelve months. Across all studies, 14% of patients had a radical cystectomy (RC), with the lowest rates occurring in patients receiving atezolizumab. Treatment-related adverse events (TrAEs) were common, occurring in 15% of patients at grades 3 to 5 and 67% of patients at grades 1 to 2. Adverse events related to the immune system (IrAEs) were noted in 6% of individuals with grades (3-5) and 22% of patients with (grades 1-2). Serious adverse events occurred in 15% of patients overall; the atezolizumab group had a greater incidence (21%) than the pembrolizumab group (11%). Immune checkpoint inhibitors have shown encouraging effectiveness and safety in treating BCG-unresponsive NMIBC. However, the observed variability in therapeutic response and adverse events highlights the necessity for large-scale RCTs to clarify long-term efficacy and inform patient selection for ICI-based therapies.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102445"},"PeriodicalIF":2.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145373468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Systemic Therapy for Renal Cell Carcinoma With a Tumor Thrombus: Results From the Intercontinental Collaboration on Renal Cell Carcinoma Database","authors":"Maxwell Sandberg ,&nbsp;Gregory Russell ,&nbsp;Dana Feldman ,&nbsp;Mitchell Hayes ,&nbsp;Reuben Ben David ,&nbsp;Justin Miller ,&nbsp;Kartik Patel ,&nbsp;Brejjette Aljabi ,&nbsp;Seok-Soon Byun ,&nbsp;Oscar Rodriguez Faba ,&nbsp;Donato Cannoletta ,&nbsp;Tatiana Letowski ,&nbsp;Gustavo Villoldo ,&nbsp;Patricio Garcia Marchinena ,&nbsp;Thiago Mourao ,&nbsp;Gaetano Ciancio ,&nbsp;Charles C. Peyton ,&nbsp;Rafael Zanotti ,&nbsp;Steven Chang ,&nbsp;Philippe E. Spiess ,&nbsp;Alejandro Rodriguez","doi":"10.1016/j.clgc.2025.102442","DOIUrl":"10.1016/j.clgc.2025.102442","url":null,"abstract":"<div><h3>Purpose</h3><div>The primary objective of this study was to assess the utility of using systemic therapy for patients with renal cell carcinoma with tumor thrombus (RCC-TT) in the setting of both metastatic (mRCC-TT) and non-mRCC-TT disease.</div></div><div><h3>Methods</h3><div>This was a multi-institutional retrospective analysis from 1999-present, and every patient underwent radical nephrectomy with tumor thrombectomy (RN-TT) plus/minus systemic therapy. Systemic therapy was defined as chemotherapy, immunotherapy, targeted therapy, or any combination administered ≤12 months from RN-TT. Overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS) were studied. We examined the effect of preoperative systemic therapy before RN-TT for non-mRCC-TT, preoperative systemic therapy before RN-TT for mRCC-TT, and postoperative systemic therapy after RN-TT.</div></div><div><h3>Results</h3><div>A total of 206 patients were nonmetastatic before RN-TT, and 146 (70.9%) did not receive systemic therapy and 60 (29.1%) did. There was no difference in OS and CSS (<em>p</em> &gt; .05), but MFS was significantly better in the no systemic therapy group (Median not reached; 80 months 50.6% of the cohort did not experience metastatic event vs. 13 months; <em>p</em> &lt; .0001). 117 patients had mRCC-TT before RN-TT, and of these, 84 (71.2%) received preoperative systemic therapy and 33 (28.2%) did not receive systemic therapy before surgery. Median OS was 24 months in the systemic therapy group and 5.7 months in the non-systemic therapy group (<em>p</em> = .0007). Median CSS was 27.6 months in the systemic therapy grouping and 6 months in the non-systemic therapy grouping (<em>p</em> = .0007). 315 patients were in the last analysis, and of these, 119 (37.8%) received systemic therapy after RN-TT and 196 (62.2%) did not. OS, CSS, and MFS did not differ (<em>p</em> &gt; .05).</div></div><div><h3>Conclusion</h3><div>There appears to be an OS and CSS benefit to preoperative systemic therapy for mRCC-TT. Further analysis is required to elucidate the best therapy regimens and ideal timing.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 6","pages":"Article 102442"},"PeriodicalIF":2.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145350479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}