Clinical genitourinary cancer最新文献

{"title":"Review of Relapse Detection Methods in Stage 1 Testicular Germ Cell Tumors in Patients After Orchidectomy Managed With Active Surveillance: Is Physical Examination Required?","authors":"A.E. Smith ,&nbsp;R. Zielinski ,&nbsp;P. Grimison ,&nbsp;F. Honeyball","doi":"10.1016/j.clgc.2025.102365","DOIUrl":"10.1016/j.clgc.2025.102365","url":null,"abstract":"<div><h3>Background</h3><div>Active surveillance (AS) is the preferred management for most patients with stage 1 testicular germ cell tumors (GCT) after orchidectomy as it avoids chemotherapy in up to 85% of patients. International guidelines recommend a combination of imaging, serum tumor markers and physical examination. The aim of this review was to analyze the diagnostic yield of physical examination for detecting relapse in these patients.</div></div><div><h3>Methods</h3><div>Systematic review of the literature from 1976 to 2024 detailing method of relapse detection for patients with stage I GCT managed with AS. Studies commencing after 1990 were assigned to the ‘Modern Cohort’ and those prior to this date were assigned to the “Older Cohort.” Descriptive statistical analysis of discrete data was performed to determine recurrence and proportion of patients, where relevant. The chi squared test was used to determine statistical significance.</div></div><div><h3>Results</h3><div>Twenty articles were identified representing 2232 (20%) relapses amongst 11,414 patients managed with AS. Relapses were detected by imaging alone in 60%, tumor markers alone in 24%, imaging and markers in 15%, and physical examination in 1.5%. Comparing the Modern cohort (n = 4771) to the older cohort (n = 6643), there were fewer relapses detected by physical examination (0.3% vs. 2%, <em>P</em> = .01) and more relapses detected by imaging alone (71% vs. 55%, <em>P</em> &lt; .00001).</div></div><div><h3>Conclusions</h3><div>Almost all relapses are detected by routine imaging, serum tumor markers or a combination of these methods. Physical examination alone rarely identified relapses, particularly in the Modern cohort which we hypothesize was driven by improvement in imaging techniques. AS can be conducted safely without mandatory physical examination.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 4","pages":"Article 102365"},"PeriodicalIF":2.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084725","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":"Integrating Genomic Classifiers and Nonsuspicious Magnetic Resonance Imaging Findings in Predictive Modelling for Lymph Node Metastasis in Patients With Localized Prostate Cancer","authors":"Vinayak G. Wagaskar ,&nbsp;Ashutosh Maheshwari ,&nbsp;Osama Zaytoun ,&nbsp;Yashaswini Agarwal ,&nbsp;Kaushik P. Kolanukuduru ,&nbsp;Neeraja Tillu ,&nbsp;Manish K. Choudhary ,&nbsp;Ash K. Tewari","doi":"10.1016/j.clgc.2025.102364","DOIUrl":"10.1016/j.clgc.2025.102364","url":null,"abstract":"<div><h3>Objectives</h3><div>To develop and validate model predicting lymph node involvement(LNI) in men undergoing radical prostatectomy with/without suspicious magnetic resonance imaging(MRI) with/without genomic classifiers (GC).</div></div><div><h3>Methods</h3><div>Retrospective analysis of patients that underwent extended pelvic lymphadenectomy(ePLND) during robot-assisted radical prostatectomy(RARP). ePLND was defined as removal of obturator, internal and external iliac and distal part of common iliac lymph nodes. Based on preoperative work-up, imaging, and GC testing, we stratified patients into three cohorts. Cohort I with suspicious MRI (<em>n</em> = 2172), cohort II with nonsuspicious MRI (<em>n</em> = 1233) and cohort III with GC irrespective of MRI findings (<em>n</em> = 1003). Logistic regression analysis performed to create nomogram for predicting LNI. Receiver operative characteristics (ROC) and decision curve analysis (DCA) were performed to evaluate net benefit. Statistical analyses were performed using R 4.3.3. We also utilized artificial neural network (ANN) for calculating LNI risk by using binary classification model.</div></div><div><h3>Results</h3><div>Overall 138 (6.4%), 49 (3.9%) and 69 (6.8%) patients had LNI in cohort I,II and III respectively. Multivariable analysis showed prostate specific antigen (PSA), biopsy Gleason Grade Group (GGG), number of positive cores, MRI LNI were significant predictors of LNI in all cohorts; MRI lesion size, MRI T stage (cohort I), MRI prostate volume (cohort II) and biopsy GC (cohort III) were significant. ROC for predicting LNI were 0.92, 0.84 and 0.91 for cohort I,II and III respectively. Using the ANN, we calculated ROC curves were 0.90,0.82 and 0.91 for cohort I, II and III, respectively. DCA showed a clinical benefit for the model detection of LN metastases for each cohort.</div></div><div><h3>Conclusions</h3><div>We developed the nomogram that integrate clinical, radiological, histological and genomic parameters to predict lymph node metastases during prostatectomy. This will avoid unnecessary lymphadenectomy at cost of missing of few metastases.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 4","pages":"Article 102364"},"PeriodicalIF":2.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144105710","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":"The Sensitivity and Specificity of Total Prostate Specific Antigen in the Diagnosis of Prostate Cancer in a Resource-Limited African Setting: A 5-Year Review in a Kenyan Hospital","authors":"Chinonso P. Shu ,&nbsp;Tsamayem G.T. Sop ,&nbsp;Tanyi J. Tanyi ,&nbsp;Somo J. Lambi ,&nbsp;Ndonku A. Signang ,&nbsp;P. Irungu Juma","doi":"10.1016/j.clgc.2025.102363","DOIUrl":"10.1016/j.clgc.2025.102363","url":null,"abstract":"<div><h3>Introduction</h3><div>Prostate cancer (CaP) is the most common cancer in males. With rising life expectancy, CaP incidence is increasing. There is a drift from the use of total prostate specific antigen (tPSA) to other PSA parameters for screening. However, theseparameters are not readily available in resource-limited settings.</div></div><div><h3>Objective</h3><div>To evaluate the sensitivity and specificity of tPSA to make the diagnosis of CaP in an African population.</div></div><div><h3>Methodology</h3><div>This was a 5-year retrospective review at the AIC Kijabe hospital between January 2018 to December 2022. We included all records of patients treated for prostate disease who had a prostate biopsy and excluded records of patients who had been on a 5-alpha reductase inhibitor or alphablocker and those with urinary tract infection. We used tPSA cut-offs of 4, 10, 20 and 100 ng/ml to calculate sensitivity and specificity.</div></div><div><h3>Results</h3><div>We included 710 records, of which CaP was the histopathological diagnosis in 327 (46.1%). The mean tPSA was 69.70 ± 2.9 ng/mL. Serum tPSA sensitivity and NPV to diagnose CaP dropped from 99.4% and 96.6% respectively at tPSA ≥ 4 to 59.3% and 72.7% respectively at a tPSA ≥ 100. The specificity and PPV rose from 14.9% and 49.9% respectively at tPSA ≥ 4 to 92.4% and 87.0% at tPSA ≥ 100.</div></div><div><h3>Conclusion</h3><div>In resource-limited settings, tPSA is still a good screening tool for CaP, with cost-effective PSA cut-off ≥ 10 ng/mL for further investigations. PSA ≥ 100 ng/ml is almost always CaP until proven otherwise.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 4","pages":"Article 102363"},"PeriodicalIF":2.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143948106","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":"Phenotypic Diversity of Immunosuppressive B Cells Associated in Urothelial Carcinoma of the Bladder","authors":"Karuppasamy David Raja ,&nbsp;Aishwarya Singh ,&nbsp;Shamima Akhtar ,&nbsp;Prabhjot Singh ,&nbsp;Amlesh Seth ,&nbsp;Seema Kaushal ,&nbsp;Alpana Sharma","doi":"10.1016/j.clgc.2025.102351","DOIUrl":"10.1016/j.clgc.2025.102351","url":null,"abstract":"<div><h3>Background</h3><div>Urothelial carcinoma of the bladder presents a complex tumor microenvironment, with tumor-infiltrating B cells (TIL-Bs) playing a significant role in disease progression. Although their presence is acknowledged, the phenotypic diversity of regulatory TIL-Bs in bladder cancer remain underexplored.</div></div><div><h3>Materials and Methods</h3><div>In this study, we evaluated core B cell subsets and their immunosuppressive phenotypes in both peripheral blood (n=40) and bladder tumor tissues (n=40) to evaluate their relationship with disease severity.</div></div><div><h3>Results</h3><div>Our findings revealed that high-grade bladder tumors are enriched with B cells and their subsets, particularly transitional B cells and plasmacytes (plasmablasts and plasma cells). However, total memory B cells were reduced in the tumor microenvironment compared to non-tumor tissues. It was further revealed that the high-grade tumors demonstrated significant infiltration of regulatory B cells (Breg), with elevated levels of IL10+ and TGFβ+ Breg cells as well as IL-10+TGF-β+ dual-cytokine-secreting Breg cells, suggesting their role in fostering an immunosuppressive microenvironment. Memory B cells demonstrated the highest frequency of Breg phenotypes among the B cell subsets. Additionally, Tertiary Lymphoid Structure formation and frequency were associated with disease severity, the differentiated B cells and IL10+ Breg cell counts, emphasizing the importance of these structures in bladder cancer progression and the potential involvement in Breg cells formation.</div></div><div><h3>Conclusion</h3><div>This study demonstrates the enrichment of the bladder cancer tumor microenvironment with diverse B cell subsets, including functional Breg cells, which correlates with disease severity.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 4","pages":"Article 102351"},"PeriodicalIF":2.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144990","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":"Clinical Outcomes and Safety Profile of Neoadjuvant PD-1 Inhibitors Combined With VEGFR-TKI Versus VEGFR-TKI in Nonmetastatic Renal Cell Carcinoma","authors":"Cheoklong Ng ,&nbsp;Cheng Peng ,&nbsp;Shangqian Wang ,&nbsp;Lei Zheng ,&nbsp;Le Qu ,&nbsp;Pei Dong ,&nbsp;Changwei Ji ,&nbsp;Jun Xiao ,&nbsp;Minfeng Chen ,&nbsp;Zhankui Jia ,&nbsp;Tao Zhang ,&nbsp;Xiaoyi Hu ,&nbsp;Taile Jing ,&nbsp;Wei Xiong ,&nbsp;Jianping Wu ,&nbsp;Xiongjun Ye ,&nbsp;Fan Li ,&nbsp;Qing Yang ,&nbsp;Qi Tang ,&nbsp;Juping Zhao ,&nbsp;Jiwei Huang","doi":"10.1016/j.clgc.2025.102353","DOIUrl":"10.1016/j.clgc.2025.102353","url":null,"abstract":"<div><h3>Objective</h3><div>The effectiveness of combining immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) in neoadjuvant therapy for renal cell carcinoma (RCC) remains unclear. This study aim to compare the efficacy and safety of neoadjuvant ICI plus TKI combination therapy versus TKI monotherapy in locally RCC patients.</div></div><div><h3>Methods</h3><div>This study included 185 cases of locally RCC disease(TanyNanyM0) receiving neoadjuvant therapy from 29 centers across China from January 2019 to Feburary 2024. Primary endpoint was the objective response rate (ORR) in all patients and patients with tumor thrombus (TT). Secondary endpoints included recurrence-free survival (RFS), overall survival (OS), surgical outcomes, and safety. Statistical analysis was performed to compare the results between 2 groups.</div></div><div><h3>Results</h3><div>Combination therapy group had higher ORR compared to the TKI monotherapy group(30.9% vs. 16.3% in all patients, 34.5% vs. 15.6% in patients with TT) and pCR rate (14.8% vs. 0%). RFS rates were improved in patients with TT receiving combination therapy (<em>P</em> = .047). Furthermore, the combination therapy group had lower blood loss during surgery (200 mL vs. 300 mL, <em>P</em> = .004). The main limitation is the retrospective study design.</div></div><div><h3>Conclusions</h3><div>Neoadjuvant ICI plus TKI combination therapy showed promising efficacy and acceptable toxicity. These findings suggest that further investigation is warranted to explore the potential of this treatment approach.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 4","pages":"Article 102353"},"PeriodicalIF":2.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055463","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":"Very Early Relapse (< 1 year) in de novo Metastatic Seminoma is Associated With Reduced Overall Survival","authors":"Pia Paffenholz ,&nbsp;F. Seelemeyer ,&nbsp;Ruben Gößmann ,&nbsp;Melanie von Brandenstein ,&nbsp;David Pfister ,&nbsp;Axel Heidenreich","doi":"10.1016/j.clgc.2025.102347","DOIUrl":"10.1016/j.clgc.2025.102347","url":null,"abstract":"<div><h3>Introduction</h3><div>As the characteristics and outcome associated with relapse in seminomatous testicular germ cell tumors (STGCT) are still unclear, this study aims at evaluating the differences between very early relapse (VER) and later relapse (LR) in this cohort of patients.</div></div><div><h3>Material and methods</h3><div>This retrospective analysis included 459 patients with STGCT treated from 2000 to 2024, analysing patient characteristics with nonparametric statistics as well as follow-up using Kaplan Meier analyses. VER was defined as tumour recurrence &lt; 12 months after successful treatment.</div></div><div><h3>Results and limitations</h3><div>About 94 (20%) patients relapsed during a median follow-up of 19 months [IQR 2-68]. De novo metastatic patients with VER (<em>n</em> = 38, 40%) showed a significantly higher number of clinical stages 2C-3 disease (21% vs. 4%, <em>P</em> = .007), M-stage (<em>P</em> = .009) at diagnosis as well as a higher HCG level (<em>P</em> = .030) and LDH levels (<em>P</em> &lt; .001; &gt;2x ULN <em>P</em> = .039) at start of chemotherapy compared to patients with LR (<em>n</em> = 56; 60%). Initial treatment did not significantly differ between VER and LR (<em>P</em> = .199). VER after initial metastatic disease was associated with a significantly reduced overall survival compared to LR (<em>P</em> = .046), however not after de novo stage I. Our study is limited by its retrospective design.</div></div><div><h3>Conclusion</h3><div>Relapse in seminoma occurred in 20% of all patients. In the initial metastatic stage, VER was associated with a higher metastatic burden at diagnosis compared to LR, leading to a reduced overall survival in VER. Consequently, treating physicians should be aware of these patients portending a worse prognosis, potentially discussing an early intensification of systemic treatment.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 4","pages":"Article 102347"},"PeriodicalIF":2.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143922425","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":"Evaluation of the Performance of Systematic Sampling Combined With MRI-TRUS Fusion Biopsy and Concordance After Radical Prostatectomy","authors":"Héctor Ayerra Perez ,&nbsp;Javier Fermin Barba Abad ,&nbsp;Virginia Moreno Nieto ,&nbsp;Josep M. Campa Bortolo ,&nbsp;Egoitz Tolosa Eizaguirre","doi":"10.1016/j.clgc.2025.102361","DOIUrl":"10.1016/j.clgc.2025.102361","url":null,"abstract":"<div><h3>Background</h3><div>MRI-guided prostate biopsy allows the targeted sampling of suspicious lesions. However, limitations of MRI and MRI-TRUS fusion biopsy techniques may lead to an underdiagnosis, and thus, some patients may benefit from combining systematic sampling with targeted sampling during prostate biopsy. We aim to assess the diagnostic yield of systematic sampling on MRI-TRUS fusion biopsy pathological result and the histopathological concordance after radical prostatectomy.</div></div><div><h3>Methods</h3><div>We retrospectively compared the prostate cancer (PCa) and clinically significant prostate cancer (csPCa) detection rate (CDR) during the MRI-TRUS fusion biopsy in the targeted sampling with the combination of targeted and systematic samplings. A subgroups analysis was performed considering the PSA density, PIRADS score and the personal history of previous biopsies. We also evaluated the concordance after radical prostatectomy.</div></div><div><h3>Results</h3><div>188 patients submitted to targeted and systematic sampling during the MRI-TRUS fusion biopsy were included. Overall increases of 5.8% and 2.2% in terms of CDR of PCa and csPCa were observed by adding a systematic sampling over the targeted one. Patients with a PIRADS score 4 to 5, PSA density ≥ 0.15 ng/mL², or a history of biopsy showed a significant increase in CDR. Combining systematic sampling with targeted sampling improved the concordance in ISUP grade by 10% (43.6% vs 33.3%) and the kappa statistic by 0.08 (0.20 vs. 0.12).</div></div><div><h3>Conclusions</h3><div>In our experience, the combination of systematic sampling improves the cancer detection rate, especially in patients with highly suspicious radiological findings or a history of biopsy, and increases the concordance after radical prostatectomy.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 4","pages":"Article 102361"},"PeriodicalIF":2.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070382","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":"Histotripsy in the Management of RCC: A New Frontier in Focused Therapies","authors":"Etan Eigner ,&nbsp;Kamil Malshy ,&nbsp;Jathin Bandari ,&nbsp;Nicola Fazaa ,&nbsp;Ameer Nsair ,&nbsp;Laena Hines ,&nbsp;Melissa Atallah ,&nbsp;Jean V. Joseph ,&nbsp;Phillip M. Rappold","doi":"10.1016/j.clgc.2025.102360","DOIUrl":"10.1016/j.clgc.2025.102360","url":null,"abstract":"<div><div>Histotripsy is a noninvasive, ultrasound-based tissue focused technique that uses focused high-intensity sound waves to mechanically fractionate tissue without causing thermal damage. Initially explored in preclinical studies, histotripsy has shown promising results in various solid tumor models, demonstrating its potential as an effective treatment option for oncological conditions. The technique works by creating microbubbles within the targeted tissue, leading to mechanical disruption and cell death while minimizing harm to surrounding healthy structures. This makes histotripsy particularly advantageous for tumors located near critical anatomical structures or in patients for whom traditional surgical methods are not viable.</div><div>Early <em>in vitro</em> and <em>in vivo</em> studies have reported promising outcomes, including successful tumor reduction and improved survival in animal models. However, the translation of these findings into clinical practice is still in progress. Ongoing clinical trials aim to determine the safety, efficacy, and long-term outcomes of histotripsy in the treatment of primary solid renal tumors. These trials will help define optimal treatment protocols, identify ideal patient populations, and explore potential combinations with other therapies. As clinical evidence continues to emerge, histotripsy is expected to become a valuable noninvasive alternative for treating solid tumors, including RCC. It holds particular promise for patients with tumors in challenging locations or those who are poor candidates for conventional interventions.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 4","pages":"Article 102360"},"PeriodicalIF":2.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935364","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 Renal Function Eligibility Criteria on Clinical Trials and Real-World Survival Outcomes Among Patients With Metastatic Renal Cell Carcinoma","authors":"Xiaoliang Wang ,&nbsp;Jill Hasler ,&nbsp;Benjamin Miron ,&nbsp;Mengru Wang ,&nbsp;Anosheh Afghahi ,&nbsp;Trevor J. Royce ,&nbsp;Daniel M. Geynisman","doi":"10.1016/j.clgc.2025.102362","DOIUrl":"10.1016/j.clgc.2025.102362","url":null,"abstract":"<div><h3>Background</h3><div>Registration trials of first-line (1L) therapies in metastatic renal cell carcinoma (mRCC) employed strict renal function criteria, which may not reflect real-world patients. We evaluated the impact of trial-based renal function eligibility criteria on real-world outcomes.</div></div><div><h3>Methods</h3><div>Using a nationwide, deidentified electronic health record-derived database, we included patients diagnosed with mRCC between January 2011 and April 2023 who received 1L systemic therapy. Renal function criteria were based on trial protocols and included serum creatinine (≤1.5 vs &gt;1.5 x upper limit of normal), estimated glomerular filtration rate (≥30 vs &lt;30 mL/min/1.73 m²), and calculated creatinine clearance (≥40 vs &lt;40 mL/min). Outcomes were real-world progression-free survival (rwPFS) and overall survival (rwOS) from 1L. Statistical analyses included inverse probability of treatment weighted Kaplan-Meier methods and Cox proportional hazard models with multiple imputation.</div></div><div><h3>Results</h3><div>Among 6896 patients, 4647 (67.4%) met all renal function criteria (<em>Included</em>), 586 (8.5%) met at least one (<em>Relaxed</em>), 174 (2.5%) met none (<em>Excluded</em>), and 1489 (21.6%) had unknown renal function (<em>Unknown</em>). In adjusted analyses, patients in the Relaxed and Excluded groups combined had a lower median rwPFS (hazard ratio [HR], 1.12; 95% CI, 1.00-1.25) and rwOS (HR, 1.23, 95% CI, 1.08-1.39) than those in the Included group.</div></div><div><h3>Conclusion</h3><div>Patients who met all renal function criteria had better survival outcomes than those who did not, suggesting that clinical trial results for mRCC may not be fully generalizable to real-world patients.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 4","pages":"Article 102362"},"PeriodicalIF":2.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112943","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":"Targeting KIT With Antibody-Drug Conjugates in Chromophobe Renal Cell Carcinoma","authors":"Michel Alchoueiry ,&nbsp;Hadi Mansour ,&nbsp;Damir Khabibullin ,&nbsp;Tiegang Han ,&nbsp;Saireudee Chaturantabut ,&nbsp;Wafaa Bzeih ,&nbsp;Yan Tang ,&nbsp;Jessica F. Williams ,&nbsp;Michelle S. Hirsch ,&nbsp;Carmen Priolo ,&nbsp;William R. Sellers ,&nbsp;Elizabeth P. Henske","doi":"10.1016/j.clgc.2025.102359","DOIUrl":"10.1016/j.clgc.2025.102359","url":null,"abstract":"<div><h3>Introduction</h3><div>Chromophobe renal cell carcinoma (ChRCC) is the third most common type of RCC. There are no proven therapies for patients with metastatic ChRCC, with a median survival of 27 months. KIT (CD117) is a membrane-associated tyrosine kinase receptor. Antibody-drug conjugates (ADC) targeting KIT were previously found to be safe and effective in preclinical models of KIT-positive cancers but have not been tested in ChRCC.</div></div><div><h3>Results</h3><div>In The Cancer Genome Atlas, KIT mRNA expression is higher in ChRCC than any other tumor type with the mean expression 12 times higher than matched normal kidney. Of the 15 metastatic ChRCC specimens stained for KIT at our institution, 87% were positive. In single-cell RNA sequencing data, KIT and SCF, the KIT ligand, are co-expressed in ChRCC tumor cells.</div><div>We found that KIT mRNA expression is significantly higher in ChRCC-derived cells compared to clear cell renal cell carcinoma (ccRCC)-derived cells and normal kidney cells. Western blot analysis confirmed KIT expression in 5 ChRCC cell lines. Despite high KIT expression, knockdown of KIT or treatment with KIT targeting tyrosine kinase inhibitors did not decrease ChRCC cell proliferation.</div><div>LOP628, a KIT ADC, decreased the viability of the ChRCC-derived cells by ∼60% with no effect on ccRCC cells.</div></div><div><h3>Conclusion</h3><div>Together, these data demonstrate that KIT is a viable therapeutic target for antibody-drug conjugates in ChRCC, providing a foundation for further investigation into KIT-targeted therapies.</div></div>","PeriodicalId":10380,"journal":{"name":"Clinical genitourinary cancer","volume":"23 4","pages":"Article 102359"},"PeriodicalIF":2.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144105637","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}