Urologic Oncology-seminars and Original Investigations最新文献

{"title":"OUTCOMES AND HEALTHCARE RESOURCE UTILIZATION OF PATIENTS RECEIVING DEFINITIVE VERSUS NON-DEFINITIVE TREATMENT FOR MUSCLE-INVASIVE BLADDER CANCER: A REAL-WORLD ANALYSIS WITHIN THE VETERANS AFFAIRS SYSTEM","authors":"Renning Zheng, Sanjay Das, Jaruda Ithisuphalap, Bolan Linghu, Kirk A Keegan, Raymond Harvey, Eleanor O. Caplan, Sydney McIntire, Joshua Parrish, Claire Trustram Eve, Amanda M De Hoedt, Stephen J. Freedland, Hussein Sweiti, Joel Greshock, Stephen B. Williams, Anirban P. Mitra","doi":"10.1016/j.urolonc.2024.12.036","DOIUrl":"10.1016/j.urolonc.2024.12.036","url":null,"abstract":"<div><h3>Introduction</h3><div>Approximately 25% of bladder cancer patients (pts) are diagnosed with muscle-invasive disease (MIBC). Current definitive treatments (DT) for MIBC with curative intent include radical cystectomy (RC) and chemoradiation (CR). Despite established survival benefits and strong recommendations for DT in guidelines, approximately 50% of MIBC pts only receive non-definitive treatments (NDT). The natural histories and outcomes of MIBC pts receiving NDT are insufficiently described. We analyzed real-world data to better characterize MIBC pts undergoing NDT by evaluating their demographic and clinical characteristics, survival, treatment patterns, health care resource utilization (HCRU) and associated costs, and compare them to pts receiving DT within the context of an equal-access health care system, the US Department of Veterans Affairs (VA).</div></div><div><h3>Methods</h3><div>Pts diagnosed with MIBC within VA system from 2010-2019 were identified by a natural language processing model and supplementary chart review, then categorized into one of two DT groups (RC or CR) or the NDT group. Baseline characteristics were summarized and compared by omnibus tests. Overall survival (OS) was visualized by the unadjusted Kaplan-Meier plot and compared by the log-rank test. Multivariable Cox proportional hazard models with time-dependent covariates tested the impact of treatment groups on OS and bladder cancer-specific mortality (BCSM), adjusting for baseline characteristics. Competing risk models accounted for death from other causes when analyzing BCSM. All-cause HCRU and associated costs were summarized on a per-pt per-year (PPPY) basis, and differences across treatment groups were assessed by omnibus tests.</div></div><div><h3>Results</h3><div>We identified 1,524 pts with MIBC: 650 received NDT, 740 received RC, and 134 received CR. NDT pts were older at MIBC diagnosis (median: 77[NDT], 68[RC], 73[CR] years; p<0.001) and had higher Charlson Comorbidity Index scores (mean: 1.9[NDT], 1.3[RC], 1.7[CR]; p<0.001). No difference was found for socioeconomic status among treatments. An OS advantage was observed for pts receiving DT vs NDT in both the unadjusted Kaplan-Meier plot (log-rank p<0.001) and the Cox model (adjusted hazard ratios (HR): 0.49[RC], 0.65[CR]; both, p<0.001) (Figure 1). Additionally, pts receiving DT had lower BCSM compared to those receiving NDT (adjusted HR: 0.45[RC], 0.57[CR]; both, p<0.001). In all-cause HCRU and costs, inpatient costs were highest for RC, outpatient costs were highest for CR, and the number of emergency room (ER) visits was highest for NDT (Table 1; all, p<0.001).</div></div><div><h3>Conclusions</h3><div>This real-world analysis in a large equal-access health care setting suggests that pts with MIBC receiving NDT were older, had more comorbidities, similar socioeconomic status, and worse survival compared to pts receiving DT. Although NDT was associated with lower inpatient an","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Page 14"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509712","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":"IMPLEMENTATION OF A PATIENT-CENTERED MOBILE APPLICATION TO REDUCE COMPLICATION BURDEN AFTER CYSTECTOMY: A PILOT STUDY","authors":"Kristin Weiss, Kathryn Marchetti, Abbigail Allen, Angela Smith, Jeffrey Montgomery, Kyle Richards, Bruce Jacobs, Tudor Borza","doi":"10.1016/j.urolonc.2024.12.031","DOIUrl":"10.1016/j.urolonc.2024.12.031","url":null,"abstract":"<div><h3>Introduction</h3><div>Radical cystectomy (RC) remains the mainstay of treatment for muscle invasive bladder cancer. RC carries high rates of morbidity and mortality, with readmission rates exceeding 25% within the first 90 days. Three quarters of these readmissions occur in the first 30 days following discharge, many of which are result from modifiable causes, such as dehydration and infection. These complications translate to worse patient outcomes, increased financial burden on patients and increased health care resource utilization. One method to identify and manage postoperative complications following discharge after RC is through enhanced post-operative patient monitoring and improved education. Mobile health presents an innovative and contemporary approach to tracking symptoms immediately following discharge. Our objective was to create and assess feasibility of an electronic medical record (EMR)-integrated platform to track post-operative symptoms for patients who underwent radical cystectomy.</div></div><div><h3>Methods</h3><div>A convenience sample of 15 patients who underwent robotic radical cystectomy by a single surgeon between August 2022-March 2024 at an academic medical center consented to participate. A cystectomy specific Care Companion (CC), an Epic© application that allows for push notifications and two-way communication between patients and providers, was created and integrated into the EMR. Following hospital discharge, patients received push notifications assessing post-operative symptoms, pain, nutritional intake, hydration, and activity. Abnormal responses prompted educational materials or generated clinical messages to the medical team, depending on severity. The frequency of push notifications decreased over time, but occurred at least daily until day 35. Concerning symptoms from the CC were automatically uploaded into the EMR, alerting all providers on the care team and promoting early follow-up.</div></div><div><h3>Results</h3><div>Patients were discharged from the hospital between 3-8 days postoperatively, with a median discharge day of POD4. Three patients experienced complications postoperatively, two of which required readmission. Readmission was due to bacteremia (n=1) and concurrent acute myeloid leukemia relapse (n=1).</div><div>11 of the 15 patients (73%) answered notifications at least once after discharge. Engagement with notifications was highest during the first 2 weeks after discharge, with 49% of patients responding to at least one notification daily, compared to 36% in weeks 3-5 (Figure 1). Two patients reported new symptoms through the triage questions, including new incision drainage and fever, both of which triggered provider alerts and follow-up. Of the two patients that were readmitted, one of the two patients used the care companion application regularly, responding 60% of days prior to readmission. Responses had high variability both between patients and within a single patient (Figure 2","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Page 12"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509718","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 PROGNOSTIC SIGNIFICANCE OF CIRCULATING TUMOR DNA IN PATIENTS WITH POSITIVE LYMPH NODE DISEASE AFTER ROBOTIC-ASSISTED RADICAL CYSTECTOMY","authors":"Reuben Ben-David,&nbsp;Sarah Lidagoster,&nbsp;Jack Geduldig,&nbsp;Kaushik P. Kolanukuduru,&nbsp;Yuval Elkun,&nbsp;Neeraja Tillu,&nbsp;Shivaram Cumarasamy,&nbsp;Jordan M Rich,&nbsp;Mohammed Almoflihi,&nbsp;Kyrollis Attalla,&nbsp;Reza Mehrazin,&nbsp;Peter Wiklund,&nbsp;John P. Sfakianos","doi":"10.1016/j.urolonc.2024.12.039","DOIUrl":"10.1016/j.urolonc.2024.12.039","url":null,"abstract":"<div><h3>Introduction</h3><div>Neoadjuvant therapy followed by radical cystectomy with lymphadenectomy remains the gold standard of treatment in patients with muscle-invasive bladder cancer. Pathologically positive lymph node (pN+) disease is known to convey a poor prognosis. Tumor-informed circulating tumor DNA (ctDNA) has emerged as a possible novel prognostic biomarker in the field. We seek to assess recurrence-free survival (RFS) for patients undergoing robotic-assisted radical cystectomy (RARC) with extended pelvic lymphadenectomy (ePLND) and to assess whether ctDNA status can be a prognostic marker for RFS outcomes in patients with pN+ disease.</div></div><div><h3>Methods</h3><div>Patients who underwent RARC + ePLND during 2015-2023 were included. A sub-group analysis (n=108) of patients who had prospectively collected serial-longitudinal tumor-informed ctDNA analyses during 2021-2023 was performed. Survival analysis and Cox-regression model were conducted.</div></div><div><h3>Results</h3><div>Included were 458 patients with a median age of 69 (IQR 63-76), and a median follow-up time of 20 months (IQR 10-37). RFS for pN0 (n=353) and pN+ (n=105) at 12, 24 and 36 months were 87% vs. 55%, 80% vs. 40%, and 75% vs. 36%, respectively (log-rank, p&lt;0.0001). Patients with pN+ disease had similar RFS to patients with pN0 disease if they had undetectable precystectomy ctDNA status (Figure 1A), undetectable postcystectomy ctDNA status (Figure 1B), or among patients that converted from precystectomy detectable to undetectable status at the postcystectomy period (Figure 1C). On Cox-regression multivariate sub-group analysis detectable precystectomy ctDNA status (HR=4.45 [1.55-12.7], p=0.005), and having both ≥pT3 with pN+ disease was predictive of disease recurrence (Table 1A). In the postcystectomy period detectable ctDNA status in the minimal residual disease window (HR=2.89 [1.12-7.4], p=0.028 was predictive of disease relapse (Table 1B).</div></div><div><h3>Conclusions</h3><div>Patients with pN+ after RARC + ePLND fared worse than patients with pN0 disease. Undetectable ctDNA status was informative of RFS regardless of nodal status at both the precystectomy and the minimal residual disease window. Patients with undetectable ctDNA status and pN+ disease may benefit from treatment de-escalation.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Pages 15-16"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509719","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 ASSOCIATION BETWEEN RACE/ETHNICITY AND TRUST IN SOURCES OF CANCER INFORMATION IN PATIENTS WITH UROLOGIC CANCERS","authors":"Apoorv Dhir,&nbsp;Avinash Maganty,&nbsp;Kristian Donald Stensland,&nbsp;Lindsey Allison Herrel,&nbsp;RIshi Robert Sekar","doi":"10.1016/j.urolonc.2024.12.027","DOIUrl":"10.1016/j.urolonc.2024.12.027","url":null,"abstract":"<div><h3>Introduction</h3><div>Where patients seek and obtain information regarding their cancer likely influences cancer care and treatment. Strategies to improve health communication and interventions rely on understanding variation in trust in sources of health information across populations. In this study, we evaluated the association between race/ethnicity and trust in different sources of cancer information.</div></div><div><h3>Methods</h3><div>We performed a cross-sectional analysis of the Health Information National Trends Survey – Surveillance, Epidemiology, and End Result (HINTS-SEER), a representative survey with respondents sampled from 3 SEER registries. We identified respondents with urologic cancers weighted to represent approximately 100,000 patients. Our primary outcome of interest was trust (A lot, Some, A little, None) in each of five sources of cancer information (doctor, family/friends, government health agencies, charitable organizations, and religious organizations). Survey weighted ordinal logistic regression was performed to test the association between race/ethnicity and trust in the five sources of cancer information</div></div><div><h3>Results</h3><div>We identified 348 survey respondents with urologic cancers including prostate (n=282), kidney (n=41), and bladder (n=25). Most respondents indicated \"A lot\" for trust in doctors (82.7%), \"Some\" for trust in government (50.7%) and charitable organizations (41.6%), \"A little\" for trust in family (42.1%), and \"None\" for trust in religious organizations (49.4%). On survey weighted analysis, the represented cohort consisted of 78.0% non-Hispanic White, 10.2% Hispanic, 6.3% Asian, 4.6% non-Hispanic Black, and 0.9% Other. On ordinal regression analysis, those who identified as Non-Hispanic Other were significantly less likely to trust doctors. Those who identified as Asian were more likely to trust friends and family and less likely to trust government agencies (Table 1).</div></div><div><h3>Conclusions</h3><div>Trust in sources of cancer information varies by race/ethnicity. A better understanding of this dynamic may guide strategies to optimize health communications and interventions and improve dissemination of critical cancer treatment and policy information for certain populations.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Page 10"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509785","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":"EVALUATING ARTIFICIAL INTELLIGENCE DATA EXTRACTION FROM PROSTATE MRI REPORTS: A COMPARATIVE STUDY WITH TRADITIONAL METHODS","authors":"Eugene Lee,&nbsp;Ruben Blachman-Braun,&nbsp;Charles Hesswani,&nbsp;William Azar,&nbsp;Braden Millan,&nbsp;Mitchell Hwang,&nbsp;Dylan Junkin,&nbsp;Christopher Koller,&nbsp;Sahil Parikh,&nbsp;Kyle Schuppe,&nbsp;Daniel Nethala,&nbsp;Neil Mendhiratta,&nbsp;Alexander Kenigsberg,&nbsp;Baris Turkbey,&nbsp;Maria Merino,&nbsp;George Zaki,&nbsp;Janelle Cortner,&nbsp;Sandeep Gurram,&nbsp;Peter Pinto","doi":"10.1016/j.urolonc.2024.12.095","DOIUrl":"10.1016/j.urolonc.2024.12.095","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Integrating large language models (LLMs) into healthcare is set to transform medical research. Most clinical research relies on data manually extracted by data managers, a laborious and time-consuming process. To streamline such tasks, the National Institutes of Health Integrated Data Analysis Platform (NIDAP) Text Extraction Program (NTEP) was developed. This artificial intelligence data aggregation platform, powered by LLMs, can output a collection of data within seconds after a prompt engineering process by the clinician. In this study, we aim to compare the accuracy of data extracted by NTEP with data that was manually extracted by NIH data managers in patients with prostate cancer enrolled in our institution's prospective trial.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We conducted a comparative analysis between datasets extracted by data managers and NTEP. Both were tasked to extract data for four MRI-related variables for patients enrolled in the prostate cancer natural history trial (NCT02594202): prostate volume, PSA density, number of lesions, and PI-RADS score. Custom-built LLM prompts were built by urologists using GPT-4 prompts aimed to extract the data directly from electronic medical record (EMR) documents. Both datasets were then subject to minor processing and formatting to allow for comparison between extraction methods. Prostate volumes were rounded to the appropriated absolute value, PSA density was rounded to three decimals places, and only the highest PI-RADS lesion reported by data managers was evaluated. Statistical analysis was performed with SPSS 29.0 to evaluate the correlation between pair observations in continuous variables via a Spearman's rho, and to quantify the level of agreement between categorical variables, a Cohen's kappa was performed.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 1728 MRIs from 1289 patients were evaluated. In comparing the datasets extracted by NIDAP and the data managers, we found that agreement between values occurred 1598 times (92.5%) for prostate volume, 1705 times (98.7%) for PSA density, 1221 times (70.7%) for number of lesions, and 1577 times (91.3%) for PI-RADS score. In reports that had pair observations, both NIDAP and data managers results appeared highly concordant, however, the results between both groups differed from 0.5% to 6.8%. There were also cases where the datasets were missing data entirely; notably, for the number of lesions on MRI, the data managers did not report data in 488 (28.2%) instances. (Table 1)&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;NTEP is a useful tool to facilitate data extraction from EMRs. Although there is a high concordance when data was reported by both NIDAP and data managers, NIDAP was able to extract more information, leading to fewer missing variables. Future research should involve larger cohorts to validate the platform's scalability and efficiency compared to traditional manual extraction methods, and data qua","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Page 38"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509801","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":"MEVROMETOSTAT (PF-06821497) IN COMBINATION WITH ENZALUTAMIDE IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER PREVIOUSLY TREATED WITH ABIRATERONE ACETATE: THE PHASE 3, RANDOMIZED MEVPRO-1 STUDY","authors":"Neeraj Agarwal,&nbsp;Michael T. Schweizer,&nbsp;Elena Castro,&nbsp;Arun A. Azad,&nbsp;Daniel J. George,&nbsp;Jayeta Chakrabarti,&nbsp;Sujata Narayanan,&nbsp;Yiyun Tang,&nbsp;Karim Fizazi","doi":"10.1016/j.urolonc.2024.12.008","DOIUrl":"10.1016/j.urolonc.2024.12.008","url":null,"abstract":"<div><h3>Introduction</h3><div>Resistance to androgen receptor (AR) pathway inhibitors (ARPI; e.g., abiraterone, enzalutamide) in metastatic castration-resistant prostate cancer (mCRPC) may be driven by preservation of AR signaling through various mechanisms. Enhancer of zeste homolog 2 (EZH2) is implicated in the pathogenesis of prostate cancer and ARPI resistance. Combining ARPI with therapies that modulate alternative signaling pathways, including epigenetic modifiers such as EZH2, could be a promising treatment approach to overcome resistance. Mevrometostat (PF-06821497) is a potent and selective small molecule EZH2 inhibitor. Results from the dose-escalation period of a phase 1 study (NCT03460977) showed promising activity for mevrometostat combined with enzalutamide, with a manageable adverse-event profile in abiraterone-exposed patients with mCRPC (Schweizer MT, et al. <em>J Clin Oncol</em>. 2024;42(16_suppl):5061). The current trial aims to evaluate radiographic progression-free survival (rPFS), overall survival (OS), and safety of mevrometostat plus enzalutamide compared with standard of care in patients with mCRPC previously treated with abiraterone.</div></div><div><h3>Methods</h3><div>MEVPRO-1 (registry#) is a global, open-label, phase 3 trial in patients with mCRPC aged ≥18 years with progression on/after ≥12 weeks abiraterone, castration testosterone levels ≤50 ng/dL, ECOG performance status 0–2, and life expectancy ≥6 months. Approximately 600 patients will be randomized 1:1 to receive mevrometostat (875mg BD with food) with enzalutamide (160mg QD), or physician's choice of enzalutamide (160mg QD) or docetaxel (75mg/m² intravenously every 21d). Randomization will be stratified by previous docetaxel in metastatic castration-sensitive setting, physician's choice of comparator (enzalutamide/docetaxel), and presence of hepatic metastases.</div><div>The primary endpoint is BICR-assessed rPFS per RECIST 1.1 (soft tissue) and PCWG3 (bone) assessed by blinded central radiology review. Key secondary endpoint is OS. Secondary endpoints include anti-tumor activity, safety, pharmacokinetics, ctDNA, and patient-reported outcomes. Stratified log-rank <em>P</em>-values, HRs, and 95% CIs will be estimated using a stratified Cox proportional hazard model, and Kaplan–Meier analysis will summarize time-to-event endpoints.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Pages 2-3"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509842","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":"DRIVER MUTATIONS ASSOCIATED WITH SIGNATURES OF PLATINUM SENSITIVITY IN GERM CELL TUMORS","authors":"Yun Cheng Sawa,&nbsp;Liewei Jia,&nbsp;Harris Krause,&nbsp;Margaret Frances Meagher,&nbsp;Frederick Millard,&nbsp;Andrew Elliott,&nbsp;John Lafin,&nbsp;Christina Jaimeson,&nbsp;Emmanuel Antonarakis,&nbsp;Anishka D'Souza,&nbsp;Krinio Giannikou,&nbsp;James Amatruda,&nbsp;Siamak Daneshmand,&nbsp;Rana McKay,&nbsp;Matthew Oberley,&nbsp;Chadi Nabhan,&nbsp;Aditya Bagrodia","doi":"10.1016/j.urolonc.2024.12.088","DOIUrl":"10.1016/j.urolonc.2024.12.088","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;A subset of patients with germ cell tumors (GCTs) develop platinum resistance disease resulting in inferior survival outomes. The mechanisms driving resistance are complex and not yet fully understood. We sought to evaluate the genomic and transcriptomic landscapes in primary and metastatic GCTs to uncover genetic factors that drive cisplatin resistance in GCTs.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;GCTs (N = 138) were analyzed by next-generation sequencing of DNA (592-gene or whole exome) and RNA (whole transcriptome). Prevalence was calculated for pathogenic mutations and high copy number amplifications (CNA ³ 6 copies). Primary (N = 65, primary), lymph node metastasis (N=14, lymph), and non-lymph metastatic lesions (N = 59, metastasis) were defined based on the tissue site relative to known primary site. An independent genitourinary pathologist reviewed H&amp;E-stained slides and designated tumors as chemo-naïve (PreC, N = 66) or post-chemotherapy (PostC, N = 17) based on absence or presence of morphologic evidence of treatment related changes. Platinum Resistant Alterations (PRAs, defined from prior literature) included &lt;em&gt;KRAS, TP53&lt;/em&gt;, and &lt;em&gt;KIT&lt;/em&gt; mutations, and &lt;em&gt;MDM2&lt;/em&gt; amplification. A transcriptomic signature associated with platinum sensitivity (Platinum sensitivity score: PSS, high score suggests increased platinum sensitivity) was applied. Mann-Whitney U and tests were applied as appropriate, with P-values adjusted for multiple comparisons.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Sixty-five primary tumors were sequenced, including 7 intracranial primary tumors, 5 mediastinal primary tumors, 16 ovarian primary tumors, and 37 testicular primary tumors. Seventy-three samples were obtained from metastatic sites (including lymph nodes) based on clinician annotation. This included two from bone, 11 from the brain, six from the liver, five from the lung, 14 from lymph nodes, four from the mediastinum, 12 from the peritoneum, one from the spermatic cord, and 18 from non-bone/liver/brain visceral sites (ie. kidney, small intestine, connective tissue, etc). Compared to non-lymph node and lymph node metastases, patients with biopsy from primary tumors had a significantly lower median age at the time of biopsy (24 vs 34 and 41 years, respectively, &lt;em&gt;p&lt;/em&gt; &lt; 0.001), were more frequently female (29.2% vs 13.6% and 7.1%, respectively, &lt;em&gt;p&lt;/em&gt; &lt; 0.42), and were more frequently chemo-naïve (92.1% vs 73.5% and 54.5%, respectively, &lt;em&gt;p&lt;/em&gt; &lt; 0.01) (Table 1). The genomic variation landscape of GCTs was sparse, and predominantly made up of recurrent genetic variants previously associated with driver mutation or chemotherapy resistance (&lt;em&gt;KIT&lt;/em&gt;-Mt, &lt;em&gt;KRAS&lt;/em&gt;-Mt, &lt;em&gt;TP53&lt;/em&gt;-Mt&lt;em&gt;, PTEN&lt;/em&gt;-Mt, &lt;em&gt;KRAS&lt;/em&gt;-Amp and &lt;em&gt;MDM2&lt;/em&gt;-Amp). As a result, our investigation focused on these genes (Fig 2). &lt;em&gt;KIT&lt;/em&gt; mutations were observed in 14.5% of primary versus 1.8% of met and 0% of lymph","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Page 35"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509929","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":"CIRCULATING LEPTIN AND IMMUNE-RELATED TRANSCRIPTOMIC SIGNATURES IN TUMOR AND PERINEPHRIC OF CLEAR CELL RENAL CELL CARCINOMA PATIENTS","authors":"Lina Posada Calderon,&nbsp;Linnea Olson,&nbsp;Fengshen Kuo,&nbsp;Hui Jiang,&nbsp;Mark Dawidek,&nbsp;Daniel Barbakoff,&nbsp;Marc Ganz,&nbsp;Jonathan Coleman,&nbsp;Paul Russo,&nbsp;Helena Furberg,&nbsp;A. Ari Hakimi","doi":"10.1016/j.urolonc.2024.12.059","DOIUrl":"10.1016/j.urolonc.2024.12.059","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Although obesity has been associated with improved outcomes in localized and metastatic clear cell renal cell carcinoma (ccRCC), the exact underlying mechanisms remain unknown. Obese individuals have higher circulating leptin, a metabolically and immunologically active adipokine. Leptin has been shown to promote inflammation, angiogenesis and modulate tumor growth and invasiveness in breast and colorectal cancers. Although previous attempts to understand the relationship between leptin and cancer have been made, only a few studies have focused on perinephric fat (PNF), where leptin exerts most of its effect. Furthermore, obese patients with ccRCC have been shown to have increased peritumoral adipose tissue inflammation. In this study, we examined how circulating leptin levels, and a transcriptomic signature of leptin activation, relate to both tumor and PNF immune-related transcriptomic patterns in a cohort of localized ccRCC patients.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;We conducted a retrospective cohort study of 92 treatment-naïve ccRCC patients undergoing nephrectomy at Memorial Sloan Kettering Cancer Center. Available data included circulating leptin from fasting blood samples, clinical characteristics from medical records, and, in a subset of patients, RNA sequencing data from tumor and PNF specimens. We performed differentially expressed genes (DEG) analysis according to circulating leptin levels and followed by Gene Set Enrichment Analysis (GSEA) with GO Biological Process gene set collection to describe pathways that were enriched by the changes of blood leptin level. Additionally, we used the Molecular Signatures Database (MSigDB) to identify a leptin downstream signature, which we validated in our cohort. This signature was then correlated to immune cell scores in the tumor and PNF. We performed the analysis both in the cohort as a whole and stratified by sex.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;From the 92 patients, 51 and 54 had available tumor and PNF RNA sequencing data, respectively. In total, 64 (70%) were male and most tumors were low grade and stage. Leptin distribution was significantly different in males (median 7 ng/ml, IQR 4-14) than females (median 22 ng/ml, IQR 9-52). Higher BMI was associated with higher leptin levels, with a correlation coefficient of 0.63 (p&lt;0.001) in males and 0.77 (p&lt;0.001) in females. Tumor GSEA results showed upregulation of pathways related to adaptive immunity in patients with higher leptin levels across sexes. Strikingly, in the PNF there were differences in opposite directions in female and male specimens, with females showing up-regulated genes significantly enriched in adaptive and humoral immune response gene sets. Similarly, the leptin downstream activation signature in the PNF showed a significant correlation with myeloid associated signatures in both sexes, while humoral responses were only associated to leptin in females.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclus","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Pages 23-24"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509956","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":"POINT OF CARE URINALYSIS IN PATIENTS WITH RENAL CELL CARCINOMA HAS PROGNOSTIC VALUE","authors":"Gregory Palmateer BA,&nbsp;Edouard H. Nicaise MD,&nbsp;Taylor Goodstein MD,&nbsp;Benjamin N. Schmeusser MD, MS,&nbsp;Krishna Parikh BS,&nbsp;Dattatraya Patil MBBS,&nbsp;Jason E. Abel MD,&nbsp;Daniel D. Shapiro MD,&nbsp;Adeboy Osunkoya MD,&nbsp;Shreyas Joshi MD,&nbsp;Vikram Narayan MD,&nbsp;Kenneth Ogan MD,&nbsp;Viraj Master MD, PhD","doi":"10.1016/j.urolonc.2024.12.063","DOIUrl":"10.1016/j.urolonc.2024.12.063","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Multiple prognostic models have been developed to help stratify patients with renal cell carcinoma (RCC) for the purposes of patient counseling and treatment selection. Utilization of histological features in these models, however, limits their application to the postoperative setting. A point of care (POC) urinalysis (UA) is a ubiquitous test in the field of urology and a standard part of the diagnostic workup for a renal mass in both the American Urological Association (AUA) and the European Association of Urology (EAU) guidelines. We sought to characterize the prevalence of abnormalities on preoperative UA among patients undergoing extirpative surgery for RCC, and whether presence of these factors impacts overall (OS) and cancer-specific survival (CSS).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Emory's prospectively maintained nephrectomy database was retrospectively reviewed for any stage, major histology (clear cell, chromophobe, papillary) RCC patients who underwent partial or radical nephrectomy from 2001-2022. Patient and pathologic characteristics were recorded for patients who had a UA within 90 days before surgery. Abnormal UA laboratory values were defined as specific gravity outside 1.005–1.030, ≥ +1 blood, and any protein, leukocyte esterase, glucose, or nitrites. Patients were categorized based on preoperative UA results: no abnormalities, 1 abnormality, and &gt;1 abnormality. Primary outcomes of interest were OS and CSS. Kaplan-Meier curves and multivariable COX Hazards models were utilized to evaluate OS and CSS. Each UA component was assessed in individual multivariable models to determine specific associations with survival.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;A total of 1607 patients were evaluated: 644 (40.1%) had a normal UA, 508 (31.6%) had 1 abnormal UA component, and 455 (28.3%) had &gt; 1 abnormal UA component. Univariable Kaplan Meier curves for ten-year OS and CSS based on the number of abnormalities on POC UA is shown in Figure 1. The presence of &gt; 1 abnormal preoperative UA component was associated with worse OS (HR 1.67, p &lt; 0.001) and CSS (HR 1.85, p &lt; 0.001; Table 1). Blood (HR 1.34, p &lt; 0.001), protein (HR 1.61, p &lt; 0.001), and nitrites (HR 2.17, p = 0.002) were all independently associated with worse OS. Blood (HR 1.48, p = 0.002), protein (HR 1.49, p = 0.002), nitrites (HR 2.43, p = 0.012), and leukocyte esterase (HR 1.46, p = 0.009) were all independently associated with worse CSS.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt; &lt;!--&gt;A POC UA is easily accessible in the preoperative settings and adds little to no cost, with abnormalities associated with a higher risk of all-cause and cancer-specific mortality for patients with RCC undergoing nephrectomy. Specifically, abnormalities in blood, protein, nitrites, and leukocyte esterase were found to be independently associated with worse survival. Future research should examine whether resolution of UA abnormalities is associat","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Page 25"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509960","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 FOLLOWING NEOADJUVANT CISPLATIN-BASED CHEMOTHERAPY AND CYSTECTOMY FOR MUSCLE INVASIVE UROTHELIAL CARCINOMA WITH CONCOMITANT CARCINOMA IN SITU","authors":"Ryan Davis,&nbsp;Leilei Xia,&nbsp;Gus Miranda,&nbsp;Jie Cai,&nbsp;Siamak Daneshmand","doi":"10.1016/j.urolonc.2024.12.047","DOIUrl":"10.1016/j.urolonc.2024.12.047","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Neoadjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy (RC) is a standard treatment for eligible patients with muscle invasive bladder cancer (MIBC). Studies on the effects of concomitant carcinoma in situ (CIS) at transurethral resection of bladder tumor (TURBT) before NAC are sparse and often limited by including non-cisplatin-based NAC, small samples, or multi-institutional data. Understanding the effect of concomitant CIS on final pathologic staging and survival outcomes is important. Thus, we aimed to compare complete response rates between patients with and without concomitant CIS with MIBC at TURBT using single-institution data from patients undergoing only cisplatin-based NAC prior to RC. We secondarily aimed to compare rates of other pathologic and oncologic outcomes as well.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;This was a single institution retrospective cohort study using data from our prospectively maintained IRB approved database of patients who undergo RC. Patients with clinical stage T2-4aN0M0 MIBC with or without concomitant CIS at most recent TURBT (performed within and outside of our institution) who received at least three cycles of cisplatin-based NAC followed by RC between 2002-2024 were identified. The primary outcome of interest was rate of pathologic complete response (pCR) in patients with concomitant CIS at TURBT compared to those without. Secondary outcomes included comparison of residual CIS (pTis), nodal metastasis, lack of response to NAC (stable or upstage), overall survival, and recurrence free survival.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;346 patients (predominantly male (n=280, 80.9%), average age 66.3 (SD=9.2)) who had a median of 25.3 (IQR: 182-1629) months of follow-up were included. Among these patients, 78 (22.5%) had concomitant carcinoma in situ (CIS), while 268 (77.5%) did not. A higher percentage of patients without concomitant CIS received gemcitabine-cisplatin compared to those with concomitant CIS (75.7% vs. 64.1%, &lt;em&gt;p&lt;/em&gt;=0.041). Patients with concomitant CIS had longer follow-up than patients without concomitant CIS (37.7 months vs. 18.4 months, &lt;em&gt;p&lt;/em&gt;=0.03). The cohorts did not significantly differ in any other baseline characteristics. On multivariable analyses, concomitant CIS was not associated with pCR (OR=0.57, 95% CI=[0.30-1.07], &lt;em&gt;p&lt;/em&gt;=0.089), pTisN0M0 (OR=1.68, 95% CI=[0.77-3.60], &lt;em&gt;p&lt;/em&gt;=0.185), nodal metastasis (OR=0.86, 95% CI=[0.36-1.92], &lt;em&gt;p&lt;/em&gt;=0.719), or lack of response to chemotherapy (OR=1.24, 95% CI=[0.65-2.46], &lt;em&gt;p&lt;/em&gt;=0.522). Concomitant CIS was also not significantly associated with overall survival (HR 0.58, 95% CI [0.32-1.05], &lt;em&gt;p&lt;/em&gt;=0.07) or recurrence free survival (HR 0.67, [0.38-1.18], &lt;em&gt;p&lt;/em&gt;=0.163).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;The presence of CIS in the setting of MIBC has no impact on complete response to NAC, pathologic outcomes, overall survival, or recurrence free surviva","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Pages 18-19"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510150","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}