Urologic Oncology-seminars and Original Investigations最新文献

{"title":"LEVEL OF NODAL METASTASIS IN PATIENTS UNDERGOING RADICAL CYSTECTOMY AND LYMPHADENECTOMY: IS THERE A ROLE OF EXTENDED LYMPHADENECTOMY IN THE POST-S1011 ERA?","authors":"Leilei Xia,&nbsp;Anosh Dadabhoy,&nbsp;Luis Santos Molina,&nbsp;Erika Wood,&nbsp;Yeonsoo Lee,&nbsp;Gus Miranda,&nbsp;Jie Cai,&nbsp;Hooman Djaladat,&nbsp;Anne Schuckman,&nbsp;Siamak Daneshmand","doi":"10.1016/j.urolonc.2024.12.048","DOIUrl":"10.1016/j.urolonc.2024.12.048","url":null,"abstract":"<div><h3>Introduction</h3><div>S1011 trial showed no benefits of extended lymphadenectomy (ELND) compared to standard LND (SLND) in patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC). Debate still exists regarding the role of ELND in selected patients. We aim to investigate the impact of level of nodal metastasis (N+) on outcomes and rate of skip nodal metastases.</div></div><div><h3>Methods</h3><div>Using our IRB approved perspective institutional database, we identified patients with cT2-4aN0M0 urothelial cancer who underwent RC and super-extended LND +/- neoadjuvant chemotherapy (NAC) between 2002 and 2023. Level of LNs were divided into 3 levels (Figure 1): level 1 – external/internal iliac, and obturator LNs (SLND); level 2 - common iliac, pre-sciatic, and pre-sacral LNs (ELND); level 3 - paraaortic and paracaval LNs (ELND) The cohort was stratified into three groups based on the highest level of N+. Skip N+ was defined as having level 2 or 3 N+ without having lower-level positive nodes.</div></div><div><h3>Results</h3><div>A total of 738 patients were included and N+ was seen in 159 (21.5%) patients. Among patients with N+, 100 (62.9%) had highest/only N+ at level 1, 22 (13.8%) had highest N+ at level 2, and 37 (23.3%) had highest N+ at level 3 (Figure 2). Only 7 (4.4%) patients had skip N+ including 3 (1.9%) skip level 2 and 4 (2.5%) skip level 3. Two-year (2-y) recurrence free survival (RFS) for node negative, level 1, level 2, and level 3 N+ was 81%, 52%, 36%, and 23%, respectively and 2-y overall survival (OS) were 82%, 60%, 49%, and 27%, respectively. For patients with level 1 N+ who did not receive peri-operative chemotherapy (n=38), 2-y RFS was 45% and 2-y OS was 43%. However, for patients with higher level (2-3) N+ who did not receive peri-operative chemotherapy (n=16), 14 (88%) died within 2 years and 10 (63%) died within 1 year.</div></div><div><h3>Conclusions</h3><div>The therapeutic benefit of ELND is very small for patients with higher level of N+ due to the poor prognosis without chemotherapy. The incidence of skip N+ is low and diagnostic benefit of ELND may also be limited. The role of ELND in the post-S1011 era may be very limited and further prospective studies are needed to identify if any MIBC patients benefit from ELND.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Page 19"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510151","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 TELEMEDICINE IN CANCER PATIENTS: CONTEMPORARY ANALYSIS OF THE NATIONAL HEALTH INTERVIEW SURVEY DURING AND POST COVID-19 ERA","authors":"Madhumita Parmar,&nbsp;Khalid Y. Alkhatib,&nbsp;Sydney Chambule,&nbsp;Yash Shah,&nbsp;Avanti Rangnekar,&nbsp;Roby Daniel,&nbsp;Morgan Leff,&nbsp;Katharine F. Michel,&nbsp;Thomas J. Guzzo,&nbsp;Phillip M. Pierorazio","doi":"10.1016/j.urolonc.2024.12.033","DOIUrl":"10.1016/j.urolonc.2024.12.033","url":null,"abstract":"<div><h3>Introduction</h3><div>During and after COVID-19 pandemic, the demand for telemedicine has skyrocketed. Evidence suggests that high-quality Uro-oncological care can be delivered by means of telemedicine, with some caveats. Against this backdrop, we sought to analyze the use of telemedicine among cancers, hypothesizing that its use may be higher for certain oncological conditions relative to others.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional study on cancer patients using data starting from July 2020 using in the National Health Interview Survey (NHIS). We utilized an affirmative answer to <em>“Have you EVER been told by a doctor or other health professional that you had Cancer or a malignancy of any kind?”</em> to identify patients with cancer history. We used the question <em>“In the past 12 months, have you had an appointment with a doctor, nurse, or other health professional by video or by phone?”</em> to identify telemedicine recipients. Survey-weighted multivariable Poisson regression analysis adjusted for potential confounders was conducted to estimate risk ratios (RR) for receipt of telemedicine, and a two-way interaction between currently receiving treatment and cancer type was assessed for any effect modification.</div></div><div><h3>Results</h3><div>We identified 7,784 individuals with a cancer history, representing a weighted population of 40 million. The prevalence of telemedicine utilization was 47.8%. Relative to breast cancer, we found that PCa was a significant predictor of receipt of telemedicine (RR: 1.39, 95% CI: [1.06-1.81], P= 0.02), (see Table). A significant interaction was found between those currently receiving treatment for cancer and cancer type P_int&lt;0.01; marginal probability analysis showed patients currently receiving PCa treatment were more likely to receive telemedicine, with an adjusted risk difference of 0.18, (95% CI[0.01-0.35], P=0.04).</div></div><div><h3>Conclusions</h3><div>Our study suggests that telemedicine appointments were widely used among cancer survivors after July 2020, with PCa survivors more likely to use telemedicine compared to other malignancies. Such findings may point to wider adoption of telemedicine among urologists, as suggested by other studies, or that PCa care lends itself better to telemedicine, compared to other malignancies. Future studies should focus on understanding the dynamics of such patient- and provider-level factors.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Page 13"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509713","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":"ROBOTIC PARTIAL CYSTECTOMY FOLLOWING NEOADJUVANT CHEMOTHERAPY FOR MUSCLE INVASIVE BLADDER CANCER: A SINGLE CENTER EXPERIENCE WITH A MULTIMODAL BLADDER-PRESERVING REGIMEN","authors":"Samuel Gold,&nbsp;Sidney Roberts,&nbsp;Vitaly Margulis","doi":"10.1016/j.urolonc.2024.12.037","DOIUrl":"10.1016/j.urolonc.2024.12.037","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Utilizing advances in multimodal treatment paradigms and minimally invasive surgical techniques, we investigated the role of robotic-assisted partial cystectomy (RAPC) as an alternative to radical cystectomy in a select cohort of patients with muscle-invasive bladder cancer (MIBC). Along with standard-of-care neoadjuvant platinum-based chemotherapy, we sought to assess whether RAPC provides similar oncologic efficacy as radical cystectomy with reduced rates of associated morbidity.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A retrospective review was conducted of all patients with MIBC of primarily urothelial origin who underwent platinum-based neoadjuvant chemotherapy (NAC) and RAPC at our institution between 2018-2023. Patients with MIBC and unifocal tumors at the anterior, anterolateral bladder, or bladder dome were considered for RAPC. Biopsy and restaging was performed with transurethral resection of bladder tumor (TURBT). Immediately prior to RAPC, intravesical chemotherapy was administered. A robotic transperitoneal approach was used with concurrent cystoscopy to guide bladder resection. Bilateral pelvic lymph node dissection was performed. Pathology data was collected after each surgical episode. Primary endpoint was 30-day complications. Secondary endpoints included intravesical recurrences, disease progression to metastasis, systemic chemotherapy/immunotherapy, and/or death.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Seventeen patients met inclusion criteria. Median operative time was 289 minutes (IQR 229-312) and EBL was 100 mL (IQR 75-150). No patients experienced intraoperative complications, 11/17 (65%) were discharged on postoperative day 1. There was one 30-day complication: pelvic abscess requiring percutaneous drain placement and IV antibiotics.&lt;/div&gt;&lt;div&gt;Eight patients were ypT0 (47%) after RAPC. Of the seven patients who had no malignancy on post-NAC TURBT, 6/7 (86%) were ypT0 and one was ypTIS. Seven patients (41%) had MIBC on final pathology. No patients had positive margins.&lt;/div&gt;&lt;div&gt;Median follow-up was 6.8 months (IQR 3.7-20.3) with 7 patients having follow-up &gt;12 months. Three (19%) had intravesical recurrences: CIS (x2) and MIBC with CIS (x1). Time to recurrence ranged 7.2-12.5 months. No patients required salvage cystectomy. One patient developed metastatic progression; he was ypT0 after RAPC. Two patients died; neither had evidence of disease at times of death.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;While the gold standard treatment for MIBC remains platinum-based chemotherapy followed by radical cystectomy, there is significant morbidity associated with this surgical intervention. In a selected patient population, RAPC may serve as a less toxic surgical alternative. In this study population, RAPC is shown to be a safe procedure with minimal long-term morbidity. In the short term, response to NAC predicted pathologic complete response after RAPC. Durability of response is an ongoing focus of t","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Pages 14-15"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509716","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":"UNDETECTABLE PRECYSTECTOMY TUMOR-INFORMED CTDNA AND CONVERSION DYNAMICS AFTER RADICAL CYSTECTOMY PREDICTS IMPROVED ONCOLOGICAL OUTCOMES","authors":"Reuben Ben-David,&nbsp;Sarah Lidagoster,&nbsp;Jack Gedulding,&nbsp;Kaushik P. Kolanukuduru,&nbsp;Yuval Elkun,&nbsp;Neeraja Tillu,&nbsp;Asher Mandel,&nbsp;Mohammed Almoflihi,&nbsp;Basil Kaufmann,&nbsp;Kyrollis Attalla,&nbsp;Reza Mehrazin,&nbsp;Peter Wiklund,&nbsp;John P. Sfakianos","doi":"10.1016/j.urolonc.2024.12.038","DOIUrl":"10.1016/j.urolonc.2024.12.038","url":null,"abstract":"<div><h3>Introduction</h3><div>umor-informed circulating tumor DNA (ctDNA) has emerged as a novel prognostic biomarker in bladder cancer. We seek to assess recurrence-free survival (RFS) outcomes in patients with undetectable precystectomy ctDNA and to evaluate if patients who converted from detectable to undetectable ctDNA status post radical cystectomy have similar RFS outcomes as those with persistently undetectable ctDNA status.</div></div><div><h3>Methods</h3><div>Patients who underwent radical cystectomy had prospectively and longitudinally collected tumor-informed ctDNA analyses during 2021-2023. The ctDNA status was informed from the pre-cystectomy specimen. The minimal residual disease (MRD) window was defined as the initial 90 days after radical cystectomy. RFS was evaluated using the Kaplan-Meier method.</div></div><div><h3>Results</h3><div>The cohort included 135 patients with 647 ctDNA analyses. The median age was 71 years (IQR 63-77). During a median follow-up time of 11 months (IQR 7-18), 41 patients (30%) had a recurrence. Precystectomy undetectable ctDNA status was found in 54 patients (40%). The RFS rates at 6, 12, and 21 months were 98%, 93%, and 82%, respectively. Seventy-seven patients had undetectable ctDNA status at the MRD window available for conversion dynamics analysis (Table 1); 43 had persistently undetectable ctDNA status (both at precystectomy and MRD window) and 31 converted from precystectomy detectable to MRD undetectable status (conversion group). The persistently undetectable group had significantly better RFS than the conversion group (log-rank, p=0.0002), with 12- month RFS rates of 97% vs. 51%, and 18-month RFS rates of 88% vs. 51%, respectively (Figure 1).</div></div><div><h3>Conclusions</h3><div>Patients with undetectable precystectomy ctDNA status have a favorable prognosis and may be candidates for treatment de-escalation. Those with persistently undetectable ctDNA had superior RFS compared to the conversion group. Precystectomy ctDNA status should be incorporated in trials examining the use of ctDNA in clinical decision-making.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Page 15"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509717","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":"PROPENSITY SCORE-MATCHED ANALYSIS OF NEOADJUVANT VS. ADJUVANT THERAPY IN RENAL CELL CARCINOMA","authors":"Cesare Saitta,&nbsp;Mimi V. Nguyen,&nbsp;Giacomo Musso,&nbsp;Kevin Hakimi,&nbsp;Dattatraya Patil,&nbsp;Hajime Tanaka,&nbsp;Luke Wang,&nbsp;Margaret F. Meagher,&nbsp;Dhruv Puri,&nbsp;Kit Yuen,&nbsp;Masaki Kobayashi,&nbsp;Shohei Fukuda,&nbsp;Giuseppe Garofano,&nbsp;Giovanni Lughezzani,&nbsp;Nicolò M. Buffi,&nbsp;Viraj Master,&nbsp;Ithaar H. Derweesh","doi":"10.1016/j.urolonc.2024.12.051","DOIUrl":"10.1016/j.urolonc.2024.12.051","url":null,"abstract":"<div><h3>Introduction</h3><div>To compare outcomes in high-risk localized RCC (HRL-RCC) patients treated with adjuvant (AT) and neoadjuvant therapy (NT) utilizing a propensity score matched model (PSM)</div></div><div><h3>Methods</h3><div>We conducted a multicenter analysis for patients who underwent AT or NT. AT was defined as systemic therapy given postoperatively in absence of metastases; NT was presurgical therapy in setting of localized disease. AT and NT utilized included target molecular therapy (TMT) or immunotherapy (IO). PSM model was conducted using a nearest neighbor matching algorithm in a 1:2 ratio. Primary outcome was all-cause mortality (ACM); secondary outcomes were cancer-specific mortality (CSM) and recurrence. Cox regression multivariable analysis (MVA) was fitted to elucidate predictors of outcomes.</div></div><div><h3>Results</h3><div>After PSM 311 patients were analyzed [adjuvant n=221, 127 TMT vs. 94 IO; neoadjuvant n=90, 61 TMT vs. 29 IO]; median follow-up 44 (IQR 20-74) months. MVA revealed AT as associated with increased ACM (HR=1.97, p=0.007), CSM (HR=2.37, p=0.007) and recurrence (HR 1.64, p=0.02). Sub-analysis of AT cohort revealed IO to be associated with decreased ACM (HR 0.59, p=0.015). In the neoadjuvant cohort TMT and IO were associated with decreased ACM (HR 0.49; p=0.016; HR 0.32, p=0.016, respectively) and CSM risk (HR 0.47, p=0.036; HR 0.18, p=0.017).</div></div><div><h3>Conclusions</h3><div>Our findings suggest a potential advantage of NT for HRL-RCC. Adjuvant immunotherapy was associated with decreased risk of ACM, while in the neoadjuvant TMT and IO therapy had similar outcomes. Our findings call for consideration of a clinical trial to compare outcomes of AT vs. NT.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Page 20"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143510047","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":"COMPLICATIOMS OF ROBOTIC PELVIC LYMPH NODE DISSECTION FOR PROSTATE CANCER: AN ANALYSIS OF THE NATIONAL SURGICAL QUALITY IMPROVEMENT PROGRAM TARGETED RADICAL PROSTATECTOMY DATABASE","authors":"Vatsala Mundra,&nbsp;Susan Xu,&nbsp;Renil Titus,&nbsp;Eusebio Luna,&nbsp;Carlos Riveros,&nbsp;Sanjana Ranganathan,&nbsp;Brian Miles,&nbsp;Dharam Kaushik,&nbsp;CJ Wallis,&nbsp;Raj Satkunasivam","doi":"10.1016/j.urolonc.2024.12.011","DOIUrl":"10.1016/j.urolonc.2024.12.011","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Prostate cancer is the second most common cancer in men worldwide and accounts for&lt;/div&gt;&lt;div&gt;3.8% of all cancer deaths in men. Treatment of localized prostate cancer includes radical prostatectomy (RP) with or without pelvic lymph node dissection (PLND). Multiple guidelines recommend PLND for staging purposes and there may also be a therapeutic benefit. However, PLND is not without complications and nomograms predicting risk of LN metastasis may be employed to optimize selection. There remains, however, a paucity of real-world data assessing the morbidity of contemporary robot assisted PLND. We therefore sought to use the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) targeted prostatectomy database to quantify the rates of real-world 30-day post-operative outcomes of patients undergoing PLND at the time of RP for prostate cancer, quantify the incremental morbidity by comparing to those who underwent RP without PLND.&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 using the ACS-NSQIP database of adult patients undergoing radical prostatectomy from 2019-2022. The primary outcome was a composite of any of the following 30-day major postoperative outcomes: mortality, reoperation, cardiac event, and neurologic event. Secondary outcomes were composed of individual complications of the composite primary outcome as well as infectious and venous thromboembolic complications, unplanned intubation and ventilation, transfusion, readmission, and prolonged length of stay (LOS). We also assessed the rates of procedure specific outcomes such as rectal injury, ureteral obstruction, and lymphocele. PLND and non-PLND groups were balanced using propensity score matching (PSM) with a 1:1 ratio with a caliper of 0.01 using demographic characteristics (age, race, BMI, modified frailty index etc.), prior medical history (prior pelvic radiotherapy or operations), and cancer staging (pathologic T stage). Likelihood of complications was assessed by conditional logistic regression.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;There were 13,413 patients identified between 2019 and 2022 who underwent prostatectomy: 11,341 (85%) had PLND while 2,072 (15%) did not. After PSM, our cohort included 2,071 matched pairs of patients with and without PLND. In PLND cohort, the detectable prevalence of PLND related complications included lymphocele or lymphatic leak (1.8%), urinary leak or fistula (1.4%), ureter obstruction (0.29%) and rectal injury (.38%). In the non-PLND cohort, the prevalence of complications was: lymphocele or lymphatic leak (0.43%), urinary leak or fistula (1.3%), ureter obstruction (0.20%), and rectal injury (0.30%). There were no significant differences between the two groups in primary outcome (OR 0.84; 95% CI 0.48, 1.48). Receipt of PLND was associated with higher rates of deep vein thrombosis (DVT, OR 2.51; 95% CI 1.10, 5.74) as well as lymphocele or other lymphatic ","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Pages 3-4"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509845","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 NONCANONICAL WNT PATHWAY (FYN/STAT3) ACTIVATED BY YY1 PROMOTES THE NEUROENDOCRINE DIFFERENTIATION OF PROSTATE CANCER CELLS.","authors":"Ruij Liu","doi":"10.1016/j.urolonc.2024.12.004","DOIUrl":"10.1016/j.urolonc.2024.12.004","url":null,"abstract":"<div><h3>Introduction</h3><div>A growing number of studies have shown that Yin Yang 1 (YY1) promotes the development of multiple tumors. Here we aimed to uncover the underlying mechanisms by which YY1 mediates neuroendocrine differentiation of prostate cancer (NEPC) cells undergoing cellular plasticity.</div></div><div><h3>Methods</h3><div>Bioinformatics analysis was performed to determine the expression of YY1 in different types of prostate cancer. Aberrant YY1 expression was validated in PCa tissues and cell lines via qRT-PCR. In vitro and in vivo functional experiments were performed to evaluate the role of YY1 in PCa malignancy. RNA sequencing, luciferase reporter assay and ChIP-PCR were used to identify the key downstream genes regulated by YY1. Ubiquitination modification and interaction between proteins were detected via Co-IP and western blotting.</div></div><div><h3>Results</h3><div>Using the TCGA and GEO databases, we bioinformatically analyzed the expression of YY1 in prostate cancer (PCa). Aberrant YY1 expression was validated in different PCa tissues and cell lines via RT qPCR, western blotting, and IHC. In vivo and in vitro functional assays verified the oncogenicity of YY1 in PCa. Bioinformatics analysis revealed aberrant YY1 expression in primary PCa, which was further validated in CRPC and NEPC tissues. Proliferation and metastasis of PCa cells were demonstrated in vitro and in vivo by functional assays. Further functional assays showed that ectopic expression of YY1 promoted cellular plasticity in PCa cells through epithelial-mesenchymal transition (EMT) induction and NE differentiation. Mechanically, androgen deprivation therapy (ADT) induces a decrease in ubiquitination of YY1 protein, enhances its stability, and thus enhances the transcriptional activity of FZD8. Castration enhances the binding of FZD8 to Wnt9A and mediates cellular plasticity by activating the noncanonical Wnt (FZD8/FYN/STAT3) pathway.</div></div><div><h3>Conclusions</h3><div>We identified YY1 as a novel dysregulated transcription factor that plays an important role in NEPC progression in this study. We hypothesize that an in-depth investigation of the underlying mechanisms of YY1-mediated disease may lead to improved NEPC therapies.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Page 1"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509346","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":"ARE WOMEN UNDERREPRESENTED IN UROLOGIC ONCOLOGY CLINICAL TRIALS?","authors":"Madison Krischak,&nbsp;Alice Semerjian,&nbsp;Gretchen Piatt,&nbsp;Zach Landis-Lewis,&nbsp;Geoffrey Barnes,&nbsp;Patrick Lewicki,&nbsp;Todd Morgan,&nbsp;Megan Caram,&nbsp;Lindsey Herrel,&nbsp;Anne Sales,&nbsp;Ted Skolarus,&nbsp;Kristian Stensland","doi":"10.1016/j.urolonc.2024.12.024","DOIUrl":"10.1016/j.urolonc.2024.12.024","url":null,"abstract":"<div><h3>Introduction</h3><div>Clinical trials should reflect the population affected by the disease under study. While urologic cancers occur more frequently in men, there is still a significant incidence in women. Whether women are proportionately represented in urologic oncology clinical trials is not known. Ensuring representative enrollment is crucial for the generalizability of trial outcomes and addressing potential gender disparities in treatment efficacy and safety. This analysis examines enrollment of women in urologic oncology clinical trials compared to the estimated incidence of these cancers among women.</div></div><div><h3>Methods</h3><div>Enrollment demographics were extracted from the Aggregate Analysis of ClinicalTrials.gov database for bladder and kidney cancer trials registered since 1/1/2007. Trials with results reported were included. The proportion of female enrollees in each trial was calculated from aggregate result tables. Trials were then coded by cancer type, and descriptive statistics were calculated for proportion of women enrolled for trials of each cancer type. These proportions were compared to the proportion of incident cancers estimated by the American Cancer Society.</div></div><div><h3>Results</h3><div>There were 590 cancer trials included in the analysis, with 414 kidney and 176 bladder trials. The median proportion of women in kidney cancer trials was 29% (IQR 23-37%), with a mean of 31%. The expected proportion based on estimated proportional incidence of kidney cancer in women is 36%. Among bladder cancer trials, the median proportion of women was 22% (IQR 16-30%), with a mean of 25%, which is similar to the estimated proportional incidence of bladder cancer in women (24%).</div></div><div><h3>Conclusions</h3><div>The proportion of women enrolled in kidney cancer clinical trials is below what is expected based on annual incident proportions, falling short by approximately 1 in 14 women with kidney cancer. Meanwhile, bladder cancer trials enrolled the expected proportion of women with bladder cancer. Further work is needed to ensure adequate representation of women in kidney cancer trials, especially for advanced and metastatic settings. While women are not currently underserved in bladder cancer trials, efforts should continue to maintain representative enrollment of women to ensure equitable and effective urologic cancer treatment across sexes and genders.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Page 9"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509782","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":"HYDROXYCHLOROQUINE INCREASES TUMOR SUPPRESSOR PAR-4 LEVELS IN PATIENTS WITH OLIGOMETASATIC PROSTATE CANCER: RESULTS FROM A PHASE-2 TRIAL","authors":"Patrick Hensley,&nbsp;Andrew James,&nbsp;Ravshan Burikhanov,&nbsp;Zhengyan Huang,&nbsp;Zin Myint,&nbsp;Don Cohen,&nbsp;Donglin Yan,&nbsp;Akosua Adu,&nbsp;Leigh Anne Faul,&nbsp;Ning Li,&nbsp;Peng Wang,&nbsp;Stephen Strup,&nbsp;William St Clair,&nbsp;Vivek Rangnekar","doi":"10.1016/j.urolonc.2024.12.069","DOIUrl":"10.1016/j.urolonc.2024.12.069","url":null,"abstract":"<div><h3>Introduction</h3><div>In oligometastatic prostate cancer (OMPC), delaying time to initiation of androgen deprivation therapy (ADT) may have oncologic and quality of life benefits. Additionally, there is an emerging role for metastatic/primary tumor site-directed therapy for patients with OMPC. Prostate apoptosis response-4 (PAR-4) is a potent tumor suppressor, facilitating apoptosis in prostate cancer cells. Hydroxychloroquine (HCQ) has been identified to be a potent inducer of PAR-4 secretion and downstream tumor inhibition in preclinical models and Phase I trials. We present a single institution Phase II trial assessing induction of PAR-4 levels in the plasma of patients in response to HCQ administration in combination with radiation therapy (RT) for OMPC.</div></div><div><h3>Methods</h3><div>Men with OMPC (≤5 synchronous metastatic lesions) following primary tumor treatment were eligible. Patients received 400 mg HCQ daily for 2 weeks prior to metastatic site-directed RT and 400 mg HCQ daily for 90 days post-radiation. Plasma samples were collected on Day 0, 14, 30, 60, and 90. The primary endpoint was induction of ≥50% serum PAR-4 expression above baseline level within 90 days of treatment initiation. We hypothesized that over half of patients would exhibit ≥50% induction of serum PAR-4 expression.</div></div><div><h3>Results</h3><div>Nineteen participants met inclusion criteria and were treated with 90 days of HCQ and RT to oligometastatic lesions. Median age was 68 years (range 55-77), the majority of patients were Caucasian (94%), and the median baseline PSA was 6.30 ng/ml (range 0.99 to 27.80). Prior primary tumor treatment included radiation therapy in 26%, radical prostatectomy in 32%, and radical prostatectomy with radiation in 42%. Eleven patients (58%) showed ≥50% increase in plasma PAR-4 above baseline levels (p=0.0006). This was associated with a concomitant PSA decline at 6-months (mean -0.98 ng/ml, 95% CI -6.61 to 4.65) and 12-months (mean -7.21 ng/ml, 95% CI -12.45 to -1.97). At 12-month follow-up, seven patients (37%) were free from ADT and median progression-free survival was 9.3 months (95% CI 6.4 to N/A). Twelve patients (63%) reported at least one adverse event, with 2 patients (11%) experiencing grade 3 toxicity.</div></div><div><h3>Conclusions</h3><div>Oral administration of HCQ is well tolerated and effectively induces plasma expression of the potent tumor suppressor PAR-4 in patients with OMPC. Given the promising findings, further investigation into possible radiosensitizing and anti-tumor benefits of HQC in a larger cohort of OMPC is necessary.</div></div>","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Pages 27-28"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509870","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":"SAFETY AND EFFICACY OF OUTPATIENT ROBOTIC RETROPERITONEAL LYMPH NODE DISSECTION FOR STAGE 2 NONSEMINOMATOUS GERM CELL TUMOR PATIENTS WITH/WITHOUT NEOADJUVANT CHEMOTHERAPY","authors":"Mehrdad Alemozaffar,&nbsp;Jennifer Lee","doi":"10.1016/j.urolonc.2024.12.089","DOIUrl":"10.1016/j.urolonc.2024.12.089","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Retroperitoneal lymph node dissection (RPLND) is a complex surgical procedure typically performed at high volume tertiary centers for testicular germ cell cancer. Historically an open approach has been utilized but since the first reported robotic RPLND (rRPLND) in 2006, this approach has gained popularity offering possible advantages including less operative blood loss and earlier recovery particularly. While early reports were primarily in patients with stage 1 disease, increased experience has expanded rRPLND to patients with more advanced disease and in the post-chemotherapy setting. We report our experience at a single large tertiary center and assess the safety and efficacy of outpatient rRPLND in patients with Stage 2 nonseminomatous germ cell tumor (NSGCT) disease who had and had not undergone neoadjuvant chemotherapy.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;A retrospective analysis was conducted on patients who underwent outpatient rRPLND at a single tertiary center from January 2021-July 2024. Appropriate templated dissection and utilization of nerve-sparing was performed in accordance with NCCN guidelines. Data collected included the patient's age, body mass index (BMI), pathology, surgical time, estimated blood loss, length of stay, intraoperative complications (iAE CLASSIC Grade &gt; 1), postoperative complications (Clavien Dindo &gt; 2), and 30 day readmissions.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Twenty patients were identified who underwent outpatient rRPLND. The median demographics included age 31 years (range 20 - 71 years) and BMI 28 kg/m2 (range 20.2 - 42 kg/m2). Primary tumor laterality consisted of 45% (n=9) left, and 55% (n=11) right side. Clinical stages included 7 (35%) Stage 2A NSGCT, 9 (45%) Stage 2B NSGCT, 4 (20%) Stage 2C. Eighty five percent of patients had neoadjuvant chemotherapy (n = 17). The median operative time was 165 minutes (range 85 - 267 minutes). The median estimated blood loss was 55 mL (range 5 -300 mL). Two intraoperative class Grade 2 complications were observed. One venotomy requiring primary closure and one small bowel enterotomy which was primarily repaired. Postoperative complications included one case of cellulitis treated with antibiotics and one case of chylous ascites requiring readmission that resolved following drain placement (Clavien Dindo 2 and 3, respectively). This was the only readmission.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;rRPLND can be safely and effectively performed as an outpatient procedure in patients with Stage 2 NCGCT who have or have not received neoadjuvant chemotherapy. When performed as an outpatient surgery there was an acceptable rate of readmission and postoperative complications similar to historic controls. Further research is needed to identify factors that contribute to appropriate patient selection for rRPLND. Longer term follow up is needed to assess long-term oncologic outcomes and preservation of ejaculatory function compared t","PeriodicalId":23408,"journal":{"name":"Urologic Oncology-seminars and Original Investigations","volume":"43 3","pages":"Pages 35-36"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509944","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}