Urologic Oncology-seminars and Original Investigations最新文献

{"title":"Emerging roles of vaspin and myonectin as novel biomarkers in prostate cancer diagnosis and staging vaspin and myonectin as novel biomarkers for prostate cancer","authors":"Saime Ozbek Sebin M.D., Ph.D. ,&nbsp;Yılmaz Aksoy M.D. ,&nbsp;Ahmet Emre Cinislioglu M.D. ,&nbsp;Ahmet Utku Kukus M.D. ,&nbsp;Basak Gulakar M.Sc. ,&nbsp;Ahmet Selim Aksoy M.D. ,&nbsp;Esra Laloglu M.D. ,&nbsp;Mustafa Yagmur M.D.","doi":"10.1016/j.urolonc.2025.10.024","DOIUrl":"10.1016/j.urolonc.2025.10.024","url":null,"abstract":"<div><h3>Aim</h3><div>The second most frequent kind of cancer in males is prostate cancer (CaP), with high mortality and morbidity rates due to false negatives and positives in biochemical tests used in early diagnosis. This study investigated whether serum vaspin and myonectin levels can serve as potential biomarkers for CaP diagnosis and staging.</div></div><div><h3>Method</h3><div>A total of 213 men, 50 healthy controls, 72 BPH patients, and 91 CaP patients, who applied to the Urology clinic and volunteered to participate in the study, were included. Of the 91 CaP patients, 51 had local, 20 locally advanced, and 20 metastatic CaP.</div></div><div><h3>Results</h3><div>Serum vaspin and myonectin values were higher in CaP than in BPH and control groups. Compared to patients with local and locally advanced CaP, those with metastatic CaP had considerably greater vaspin levels. For distinguishing CaP from controls, vaspin demonstrated an AUC of 0.772 (sensitivity 68%, specificity 78%). Importantly, for discriminating metastatic CaP from nonmetastatic disease, vaspin achieved an AUC of 0.90 (sensitivity 85%, specificity 82%).</div></div><div><h3>Conclusion</h3><div>The findings of this study demonstrate that serum vaspin exhibited superior diagnostic performance compared to prostate-specific antigen (PSA) in distinguishing CaP cases from controls (AUC = 0.772). Moreover, vaspin concentrations increased progressively with advancing disease stages, achieving an AUC of 0.90 for discriminating metastatic disease, highlighting its potential utility not only in diagnosis but also in non-invasive staging. The diagnostic performance of myonectin appeared favorable compared to PSA; however, as it showed no association with disease staging, this finding should be interpreted with caution.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"44 2","pages":"Pages 125.e11-125.e22"},"PeriodicalIF":2.3,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145550996","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":"Partial vs. radical nephrectomy in pT3a renal cancer: Cancer-specific mortality according to fat invasion pattern","authors":"Michele Nicolazzini M.D. ,&nbsp;Calogero Catanzaro M.D. ,&nbsp;Federico Polverino M.D. ,&nbsp;Jordan A. Goyal ,&nbsp;Riccardo Schiavina M.D. ,&nbsp;Nicola Longo M.D., Ph.D. ,&nbsp;Fred Saad M.D. ,&nbsp;Shahrokh F. Shariat M.D. ,&nbsp;Carlotta Palumbo M.D. ,&nbsp;Alessandro Volpe M.D. ,&nbsp;Pierre I. Karakiewicz M.D., Ph.D.","doi":"10.1016/j.urolonc.2025.10.017","DOIUrl":"10.1016/j.urolonc.2025.10.017","url":null,"abstract":"<div><h3>Introduction</h3><div>Within the SEER database (2010–2021), we tested for differences in cancer-specific mortality (CSM) between partial (PN) vs. radical (RN) nephrectomy in patients with pT3a renal cell carcinoma with either perinephric fat invasion (PFI) or sinus fat invasion (SFI).</div></div><div><h3>Patients and Methods</h3><div>Separate propensity score matching (PSM), multivariable competing risk regression (mCRR) analyses and cumulative incidence plots addressed CSM in patients with PFI and subsequently in patients with SFI, according to PN vs. RN. Subgroup analyses focused on patients with additional adverse pathological features: tumor size &gt;4 cm, high nuclear grade or sarcomatoid dedifferentiation.</div></div><div><h3>Results</h3><div>Of 9,664 pT3aN0M0 RCC patients with fat invasion, 4379 (45.3%) had exclusive PFI vs. 4398 (45.5%) had exclusive SFI. In PFI patients, 1,321 (30.2%) patients underwent PN vs. 3,058 (69.8%) RN. After 1:1 PSM, 5-years CSM rates were 8.2 vs. 9.3% in PN vs. RN patients. In mCRR, PN vs. RN did not affect CSM (HR 0.99, <em>P</em> = 0.9), even in patients with additional adverse pathological features. In SFI patients, 395 (9.0%) patients underwent PN vs. 4003 (91.0%) RN. After 1:3 PSM, 5-years CSM rates were 7.5 vs. 10.3% in PN vs. RN patients. In mCRR, PN vs. RN did not affect CSM (HR 0.74, <em>P</em> = 0.2), even in patients with additional adverse pathological features.</div></div><div><h3>Conclusion</h3><div>PN does not predispose patients to a survival disadvantage in presence of either PFI or SFI, even in those with additional adverse pathological features defined as tumor size &gt;4 cm, high nuclear grade or sarcomatoid dedifferentiation.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"44 2","pages":"Pages 122.e1-122.e10"},"PeriodicalIF":2.3,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145550968","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":"Utilization of radical nephrectomy for patients with clinical stage T1 renal masses: Evaluation of opportunities for quality improvement","authors":"Alice Semerjian M.D. ,&nbsp;Emily Fisher M.D. ,&nbsp;Amit Patel M.D. ,&nbsp;Anna Johnson M.S. ,&nbsp;Monica Van Til M.S. ,&nbsp;Sabrina L. Noyes B.S. ,&nbsp;Brian Seifman M.D. ,&nbsp;William K. Johnston M.D. ,&nbsp;Jason Hafron M.D. ,&nbsp;Thomas Maatman M.D. ,&nbsp;Craig G. Rogers M.D. ,&nbsp;Brian R. Lane M.D., Ph.D.","doi":"10.1016/j.urolonc.2025.10.019","DOIUrl":"10.1016/j.urolonc.2025.10.019","url":null,"abstract":"<div><h3>Purpose</h3><div>To determine opportunities for quality improvement (QI) in patient selection for radical nephrectomy (RN) for cT1 renal masses (cT1RM).</div></div><div><h3>Materials and Methods</h3><div>The MUSIC (Michigan Urological Surgery Improvement Collaborative) registry was queried for RN performed for any localized RM ≤4 cm (cT1aRM) or low/intermediate/unrecorded complexity RM 4 to 7 cm (cT1bRM). Eight experienced kidney surgeons reviewed characteristics (age, GFR, medical comorbidities, RENAL score, tumor size, and more) of de-identified cases. Each reviewer provided a score regarding opportunity for QI (none = 0, minor = 1, moderate = 2, major = 3) that were averaged.</div></div><div><h3>Results</h3><div>171 cases met inclusion criteria, including 77 cT1aRM and 94 cT1bRM. Urologists agreed on a score of no (0) or minor (0.1–1) QI opportunities in 40% (<em>n</em> = 68) and 41% (<em>n</em> = 70) of cases, respectively. These patients had (1) ≥1 of the following features: on dialysis; elderly, comorbid, or anticoagulated with normal GFR; (2) cT1bRM and RENAL ≥8; (3) not amenable to partial nephrectomy (PN) or biopsy based on location or cystic nature; or (4) attempted PN. Thirty-three cases had moderate (14%) or major (4%) QI opportunities including 30% of cT1aRM and 11% of reviewed cT1bRM. Case characteristics included: smaller and/or lower complexity tumors, younger age, baseline CKD, and/or would have benefitted from active surveillance and/or pretreatment biopsy.</div></div><div><h3>Conclusions</h3><div>Surgeon-reviewers identified moderate/major opportunities for QI in 33 patients that underwent RN who may have been spared from kidney loss. Kidney loss can be prevented by considering active surveillance, confirmatory imaging, renal mass biopsy, and/or kidney-sparing interventions in patients with T1aRM, low/intermediate complexity T1bRM, young patients, and patients with CKD.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"44 2","pages":"Pages 122.e19-122.e28"},"PeriodicalIF":2.3,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145535035","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":"Urine metabolic analysis as a noninvasive method to diagnose prostate cancer","authors":"Jorge Panach-Navarrete M.D., Ph.D. ,&nbsp;Vannina González-Marrachelli M.D., Ph.D. ,&nbsp;José Manuel Morales-Tatay M.D., Ph.D. ,&nbsp;Francisco García-Morata M.D. ,&nbsp;María Ángeles Sales-Maicas M.D. ,&nbsp;Daniel Monleón-Salvado Ph.D. ,&nbsp;José María Martínez-Jabaloyas M.D., Ph.D.","doi":"10.1016/j.urolonc.2025.10.015","DOIUrl":"10.1016/j.urolonc.2025.10.015","url":null,"abstract":"<div><h3>Objectives</h3><div>This study used urine NMR spectroscopy to define a potential metabolic profile indicating presence of prostate cancer, which could be a useful noninvasive method for diagnosis of this neoplasia.</div></div><div><h3>Methods</h3><div>Urine samples were obtained from patients undergoing transrectal prostate biopsy after prostate massage. Patients were classified as diseased if cancerous tissue was obtained from biopsy histology, and all spectra were acquired using a Bruker Avance III DRX 600 spectrometer. Univariate and multivariate analyses were performed with metabolites and clinical variables with the objective of predicting tumor presence.</div></div><div><h3>Results</h3><div>A total of 201 patients were included in the study, with a mean age of 67.20 ± 7.90 years. Prostate cancer was diagnosed in 107 (53.2%) cases, with a negative result for malignancy in the other 94 (46.8%).Metabolic analysis revealed metabolic pathways such as glycolysis, Krebs cycle, and the metabolism of different amino acids as involved in the presence of prostate cancer. The 28 metabolites detected in urine, together with prostate volume and ultrasound suspicion for tumor, formed a predictive model of prostate cancer in tissue, with an area under the curve (AUC) of 0.89, a sensitivity of 89%, a positive predictive value (PPV) of 82% and a negative predictive value (NPV) of 83%.</div></div><div><h3>Conclusions</h3><div>Metabolomics can be used to build a useful predictive model for diagnosing prostate cancer from the metabolic profile in urine, using a total of 28 metabolites. Combining metabolites, particularly molecules of glycerophospholipid metabolism, glycolysis, and amino acid metabolism, with clinical variables provides an effective strategy.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"44 2","pages":"Pages 125.e1-125.e10"},"PeriodicalIF":2.3,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524340","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":"Outcomes of enfortumab vedotin plus pembrolizumab in patients with advanced urothelial cancer and severe renal dysfunction","authors":"Henry K. Litt M.D.,&nbsp;Ronac Mamtani M.D., M.S.C.E.,&nbsp;Ryan D. Chow M.D., Ph.D.","doi":"10.1016/j.urolonc.2025.10.016","DOIUrl":"10.1016/j.urolonc.2025.10.016","url":null,"abstract":"<div><h3>Background and Objective</h3><div>Enfortumab vedotin plus pembrolizumab (EV+P) is now the standard first-line (1L) therapy for advanced urothelial cancer (aUC), based on improved survival in the EV-302 trial. However, the trial excluded patients with creatinine clearance (CrCl) &lt;30 ml/min, leaving an evidence gap for patients with severely impaired renal function. To address this, we evaluated outcomes of EV+P in patients with aUC and CrCl &lt;30 ml/min using real-world data.</div></div><div><h3>Methods</h3><div>We conducted a real-world retrospective cohort study using a database derived from electronic health records from approximately 280 U.S. oncology practices. Adults with aUC initiating 1L EV+P between April 2023 and December 2024 were included. Outcomes included overall survival (OS), progression-free survival (PFS), and EV interruption-free survival (IFS), stratified by baseline CrCl (≥30 vs. &lt;30 ml/min). We constructed multivariable Cox models adjusted for demographics, clinical factors, and potential confounders.</div></div><div><h3>Results</h3><div>Among 462 eligible patients who initiated 1L EV+P between April 2023 and December 2024, 65 (14.1%) had CrCl &lt;30 ml/min. In multivariable Cox models, severely impaired renal function was not associated with worse overall survival (OS) (adjusted HR [aHR] = 0.95, 95% CI [0.61–1.49]; <em>P</em> = 0.84), progression-free survival (PFS) (aHR = 0.70 [0.47–1.06]; <em>P</em> = 0.092), or EV interruption-free survival (IFS) (aHR = 0.82 [0.48–1.38]; <em>P</em> = 0.45).</div></div><div><h3>Conclusions</h3><div>These real-world findings indicate that patients with CrCl &lt;30 ml/min experienced outcomes comparable to those with higher renal function, providing important evidence in a population that is often excluded from clinical trials.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"44 2","pages":"Pages 118.e1-118.e5"},"PeriodicalIF":2.3,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524387","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":"Zip code, race, and ethnicity: The impact of socioeconomic hardship on cancer presentation and survival among patients with testicular germ cell tumors","authors":"Serkan Karakus M.D.,&nbsp;Jackson Forrest Harmon B.S.,&nbsp;Anand Ganesh Iyer B.S.,&nbsp;Daniel Carlisle M.D.,&nbsp;Eric Umbreit M.D.,&nbsp;Deepak K Pruthi M.D, FRCSC, MSCI-TS","doi":"10.1016/j.urolonc.2025.10.011","DOIUrl":"10.1016/j.urolonc.2025.10.011","url":null,"abstract":"<div><h3>Introduction and objectives</h3><div>Testicular germ cell tumors (GCTs) are highly curable when diagnosed at early stages. Despite effective treatments, disparities in socioeconomic status (SES) play a significant role in cancer outcomes. We aim to explore the impact of the hardship index (HI), a composite metric encompassing factors such as poverty levels, per capita income, unemployment rates, educational attainment, housing density, and the dependency ratio (the proportion of young and elderly individuals), on patient presentation and survival rates.</div></div><div><h3>Methods</h3><div>We conducted a county-wide audit of all GCT cases diagnosed in Bexar, Texas, from 2012 to 2023. For cancer stage analysis, logistic regression was utilized using HI, insurance status, and distance to hospital. Cox proportional hazards (COX) models and Kaplan–Meier (KM) analyses were employed to estimate the impact of the HI on progression-free survival (PFS) and overall survival (OS). Lower HI scores indicate greater socioeconomic hardship.</div></div><div><h3>Results</h3><div>Of the 645 subjects, 297 GCT met the inclusion criteria. Neither age nor race/ethnicity (non-Hispanic White/Black, Hispanic, Other) was associated with late-stage diagnosis (Stages II–III). Greater hardship was significantly associated with late-stage diagnosis (OR: 1.02 per unit decrease, 95% CI: [1.01, 1.03], <em>P</em> = 0.002). Patients without insurance (OR: 2.30, <em>P</em> &lt; 0.001) and those with greater distance to hospital (OR: 1.07 per mile, <em>P</em> = 0.001) were also more likely to present with late-stage disease. Uninsured patients had significantly longer treatment delays (median: 83 vs. 40 days, <em>P</em> = 0.034). Furthermore, Cox analysis revealed that patients with greater hardship (scores ≤30) had a higher risk of progression (HR: 4.10, <em>P</em> = 0.0019). KM analysis demonstrated poorer PFS for the greater hardship group overall (<em>P</em> = 0.006) and for NSGCT patients (<em>P</em> = 0.0063), with no significant difference for seminoma patients (<em>P</em> = 0.43).</div></div><div><h3>Conclusions</h3><div>When GCTs are assessed comprehensively by evaluating socioeconomic hardship, those with greater hardship were more likely to present with late-stage diagnosis and have poorer PFS. Uninsured patients and those living farther from care are at higher risk for advanced-stage presentation. By comprehensively addressing economic, educational, and geographic barriers, early diagnosis and avoidance of toxic curative therapy may be achievable for this highly treatable disease, even in advanced stages. Interventions targeting these barriers could ultimately improve survival outcomes.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"44 2","pages":"Pages 126.e1-126.e9"},"PeriodicalIF":2.3,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145514337","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":"Featured SUO fellow: Rajnjade Chung, MD","authors":"Rajnjade Chung","doi":"10.1016/j.urolonc.2025.10.026","DOIUrl":"10.1016/j.urolonc.2025.10.026","url":null,"abstract":"","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"44 1","pages":"Page 1"},"PeriodicalIF":2.3,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145514234","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":"Protocol-driven same day discharge for robotic radical prostatectomy","authors":"Emily H. Roebuck M.D. ,&nbsp;Lila G. McGrath B.S. ,&nbsp;Myra Robinson M.S.P.H. ,&nbsp;Katherine Whitton N.P. ,&nbsp;Justin T. Matulay M.D. ,&nbsp;Peter E. Clark M.D. ,&nbsp;Stephen B. Riggs M.D., M.B.A.","doi":"10.1016/j.urolonc.2025.10.013","DOIUrl":"10.1016/j.urolonc.2025.10.013","url":null,"abstract":"<div><h3>Purpose</h3><div>Average length of stay following robot-assisted laparoscopic prostatectomy (RALP) ranges from 24 to 48 hours. This study evaluates the implementation, safety, and efficacy of a standardized same-day discharge (SDD) protocol for RALP patients compared to inpatient stay.</div></div><div><h3>Materials and Methods</h3><div>We conducted a retrospective cohort study of 220 patients who underwent RALP at a single academic center from January 2022 to September 2023. We implemented a standardized SDD protocol on August 1, 2022, expanding eligibility criteria and formalizing perioperative management. Patients were categorized into same-day discharge (SDD) or inpatient (IP-RALP) groups for analysis. Categorical endpoints were compared between cohorts with Fisher’s exact tests while continuous outcomes were compared with Wilcoxon rank sum tests.</div></div><div><h3>Results</h3><div>220 males underwent RALP, with 132 (88.6%) of 149 SDD-initiated patients successfully discharged on the same day. Outcomes including ED visits, 30-day readmission rates, were similar between groups, with no significant differences observed in 24-hour readmissions (SDD 0.8%, IP-RALP 0%, <em>P</em> &gt; 0.99). While 30-day readmissions were slightly higher in SDD (9.1% vs. 4.6%), this was not statistically significant (<em>P</em> = 0.29). Complication rates and number of follow-up calls were similar across cohorts. Formal SDD protocol implementation improved POD1 contact rates (48% vs. 73.8%, <em>P</em> = 0.01) and consistency in discharge medication management.</div></div><div><h3>Conclusions</h3><div>Our findings suggest SDD after prostatectomy is safe, with no observed increased risk of ED visits, readmissions, or complications compared to IP-RALP. Formal SDD protocol implementation improved consistency in discharge processes. Future studies are needed to further elucidate preoperative risk stratification for appropriate tailoring of protocol driven care.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"44 2","pages":"Pages 124.e17-124.e24"},"PeriodicalIF":2.3,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145507247","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":"Cover 2 - Masthead","authors":"","doi":"10.1016/S1078-1439(25)00433-8","DOIUrl":"10.1016/S1078-1439(25)00433-8","url":null,"abstract":"","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 12","pages":"Page IFC"},"PeriodicalIF":2.3,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145486048","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":"Multigenerational VHL family characterized by pathogenic germline ELOC variant: Response to belzutifan","authors":"Cathy D. Vocke Ph.D. ,&nbsp;Christopher J. Ricketts Ph.D. ,&nbsp;Lidenys O’Brien B.S.N., R.N. ,&nbsp;Alexandra P. Lebensohn M.S., C.G.C. ,&nbsp;Nityam Rathi M.D. ,&nbsp;Deborah Nielsen B.S.N., R.N. ,&nbsp;Rabindra Gautam D.H.S. ,&nbsp;Svetlana D. Pack Ph.D. ,&nbsp;Mark Raffeld M.D. ,&nbsp;Emily Y. Chew M.D. ,&nbsp;Prashant Chittiboina M.D., M.P.H. ,&nbsp;Ashkan A. Malayeri M.D. ,&nbsp;Mary R. Welch M.D. ,&nbsp;Maria J. Merino M.D. ,&nbsp;Ramaprasad Srinivasan M.D., Ph.D. ,&nbsp;Mark W. Ball M.D. ,&nbsp;W. Marston Linehan M.D.","doi":"10.1016/j.urolonc.2025.10.009","DOIUrl":"10.1016/j.urolonc.2025.10.009","url":null,"abstract":"<div><h3>Objective</h3><div>We describe a large family of patients with canonical Von Hippel-Lindau (VHL) manifestations, including central nervous system and retinal hemangioblastomas, clear cell renal cell carcinoma (ccRCC), pancreatic neuroendocrine tumors, and pheochromocytomas, all who lacked any detectable alteration within the VHL gene. Analysis of a ccRCC demonstrated a novel p.E92G variant in the Elongin C gene, <em>ELOC</em>, a known ccRCC tumor suppressor gene. We aim to confirm that the <em>ELOC</em> variant is responsible for the VHL manifestations in this family.</div></div><div><h3>Methods</h3><div>Germline testing and tumor analysis were performed to assess the molecular alterations in the lesions in this family. Abdominal imaging was used to determine the sizes of VHL-related lesions.</div></div><div><h3>Results</h3><div>We demonstrated this <em>ELOC</em> p.E92G variant was a germline alteration and was present in each affected individual that received genetic testing, demonstrating co-segregation of variant and disease. Analysis of tumors excised from 2 patients demonstrated loss of heterozygosity for the <em>ELOC</em> variant and single copy chromosomal loss of chromosome 8 that encodes the <em>ELOC</em> gene, consistent with inactivation of a tumor suppressor gene. Two patients who received Belzutifan showed a decrease in size of their kidney, pancreatic, and spinal lesions and 1 showed improvement of retinal manifestations.</div></div><div><h3>Conclusion</h3><div>These findings indicate that the p.E92G <em>ELOC</em> variant is responsible for the VHL manifestations in this family, and that these tumors are being driven by loss of the VCB-Cul2 E3-ubiquitin ligase complex activity</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"44 2","pages":"Pages 120.e21-120.e27"},"PeriodicalIF":2.3,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145507234","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}