Introduction Plasmacytoid urothelial carcinoma (PUC) is a rare histologic subtype of urothelial carcinoma of the bladder (BC). Our objective was to characterize treatment patterns and outcomes of PUC, as well as to evaluate the impact of neoadjuvant chemotherapy (NAC) in a large national database and our recent institutional experience. Methods The national cancer database (NCDB) was queried for localized PUC between 2004 and 2020. Patients with PUC from a single institution (Yale School of Medicine) were also incorporated from 2021 onwards to not double-count patients. Primary outcomes were overall survival and treatment trends. Results A total of 146 patients were included, 123 from NCDB and 23 from Yale. Median overall survival (mOS) was 28 [IQR 7.5, 50.3] months, 23 [IQR 8.4, 46.3] months for NCDB and 36 [IQR 4.3, 68.1] for Yale. mOS for patients receiving neoadjuvant chemotherapy (NAC) was 60.0 [28.0, 91.9] vs. 14.8 months [0, 34.3] without NAC, p=0.038, though with wide error margins and borderline statistical significance. Benefit was not preserved on Cox proportional hazard analysis incorporating clinical stage, primary treatment type, and age. Peritoneum was the most common site of metastasis (78.3%), followed by liver and bone. Conclusions Our findings underscore the formidable challenge posed by PUC, emphasizing the limited response to current therapies. Despite higher pT0 rates with NAC, OS benefit remains inconclusive, highlighting the need for more effective treatments.

Introduction Health-related quality of life (HR-QOL) is an important consideration for men on active surveillance (AS) for prostate cancer (PCa). To improve HR-QOL in these patients, “healthy lifestyle” interventions such as diet modification and exercise programs have been proposed. However, a recent randomized control trial of patients on AS found no difference in HR-QOL in those undergoing lifestyle interventions versus those who did not. Notably, this prior study enrolled men with average body mass index (BMI) of 25.9 and high baseline HR-QOL. These authors concluded that the high baseline HR-QOL scores left little room to see significant improvements; a study analyzing those with higher BMI is needed. We therefore assessed the impact of a lifestyle intervention program on HR-QOL in PCa patients with overweight or obesity who are on AS. Methods We assessed HR-QOL of men in the Prostate Cancer Active Lifestyle Study (PALS), a randomized controlled trial of a lifestyle intervention program for PCa patients with overweight/obesity (BMI >25 kg/m2) who are on AS. Men were randomized to a (1) modified Diabetes Prevention Program 6-month diet and exercise intervention with a 7% goal weight loss, versus (2) being provided US Dietary and Physical Activity Guidelines. HR-QOL was assessed at baseline and 6-months with validated questionnaires including: EuroQol 5 Dimension 5 Level (EQ5D5L), Expanded Prostate Cancer Index Short Form 26 (EPIC-SF26), International Prostate Symptom Score (IPSS), and Memorial Anxiety Scale for Prostate Cancer (MAX-PC). Linear regression models evaluated mean differences in questionnaire scores between groups. Analyses were summarized using point estimates of mean differences between assigned treatment groups and two-sided t-tests. Subset analyses were performed using EPIC-SF26 cut-points of 80 which have been shown to correlate with meaningful clinical assessments. Results Between 2016-2020, 100 men (50 in each arm) were randomized and completed the trial. Median age was 67 years and median BMI was 31.5kg/m2 (IQR 26.3 – 39.6). The intervention group experienced a mean weight loss of 7.1%, compared to 1.8% in the control group. At six months, no significant differences were observed between groups in overall EPIC SF-26, IPSS, EQ-5D-5L, or MAX-PC scores compared to baseline (Figure 1). However, in the stratified analysis, those with baseline EPIC SF-26 scores < 80 for “bowel function” and “bowel bother” had significant improvements of 2.3 (95% CI 0.14 – 4.4) and 2.6 points (95% CI 0.14 – 5.0), respectively, in the intervention versus control group at 6-months. Among men with baseline EPIC SF-26 sexual function scores > 80, the intervention was associated with a significant 3.6 point (95% CI 1.0 – 6.1) improvement in sexual function at 6-months (Table 1). Conclusions In this randomized controlled trial of PCa patients with overweight/obesity who are on AS, we found that a modified Diabetes Prevention Program lifestyle intervention program led to improvements in certain HR-QOL domains. Men with high baseline HR-QOL scores for “sexual function”, and low baseline HR-QOL scores for “bowel function” and “bowel bother,” had significant improvements in their respective scores following the lifestyle intervention program. These data suggests that men on AS with overweight/obesity should adopt healthy lifestyle practices to improve their HR-QOL. Such findings are important in the context of the growing obesity epidemic and increasing utilization of active surveillance.

Background Bladder EpiCheck (BE) is a novel methylation-based PCR urine test for the detection of non-muscle invasive bladder cancer (NMIBC) recurrences. Objective We present the results of a North American study evaluating BE and meta-analysis of literature. Methods A prospective, blinded, multicenter study was conducted in North America. Voided urine was collected from NMIBC patients prior to cystoscopic surveillance. BE testing was performed centrally. For the meta-analysis, a PUBMED search was performed to identify all published peer-reviewed clinical studies of BE for NMIBC surveillance. Results In this study, 674 patients were enrolled of which 449 were included. Overall sensitivity was 67% (95%CI 58%-74%), specificity was 84% (80%-88%), PPV was 65% (57%-73%) and NPV was 85% (81%-89%). For high-grade (HG) recurrence, sensitivity was 77% (65%-85%) and NPV was 95% (92%-97%). In patients with negative cystoscopy and cytology at the first study visit, risk of subsequent recurrence in 12 months was 5.3 (2.7–10.3) times higher in patients with positive BE vs. negative BE (p < 0.0001). In patients with negative cystoscopy and equivocal cytology, BE was positive in 75–89% of those with later HG recurrence, with PPV of 42% (15%-72%)-63% (38%-84%). The meta-analysis included 7 studies and 1564 patients. Overall sensitivity was 82% (66–92%), HG sensitivity was 91% (82–95%), specificity was 85% (80–88%), PPV was 60% (55–64%) and HG NPV was 98% (97–99%). Conclusions The consistently strong performance of BE indicate that a positive test could improve timely disease recurrence detection and a negative test could rule-out HG disease. Furthermore, the low rate of false positive results, potentially minimizes unnecessary downstream procedures and patient anxiety.

Background and objective: Many patients with bladder cancer are understaged. Previous work revealed that molecular subtyping using Decipher Bladder improves clinical staging. This multicenter validation study evaluated Decipher Bladder for upstaging in patients who underwent radical cystectomy (RC) without neoadjuvant therapy. Methods: The Decipher Bladder genomic subtyping classifier (GSC; Veracyte, San Diego, CA, USA) was performed on bladder tumor specimens from patients with high-grade, clinically organ-confined (cTa-T2N0M0) urothelial carcinoma who subsequently underwent RC without neoadjuvant chemotherapy. The primary endpoint was pathological upstaging to nonorgan-confined (NOC) disease (pT3+ and/ or N+) at RC. The secondary endpoints included overall survival (OS) and pathological upstaging to MIBC+ disease (pT2+ and/or N+) at RC within clinically non muscle-invasive bladder cancer (cNMIBC) cases. Key findings and limitations: A total of 226 patients (134 cNMIBC [cTa/Tis/T1] and 92 cT2) were analyzed from eight participating institutions. Upstaging to NOC disease was observed in 33% of patients (19% for cNMIBC and 53% for cT2). Molecular subtyping identified 138 luminal and 88 nonluminal tumors. Rates of upstaging to NOC were 41% in nonluminal and 28% in luminal tumors (univariable p = 0.04), which was not independently significant after adjusting for clinical variables. Upstaging to MIBC+ in cNMIBC patients was lower in luminal versus nonluminal tumors (32% vs 51%, multivariable p = 0.03). Patients with nonluminal tumors had worse OS on multivariable analyses (p < 0.05). Limitations include retrospective design and sample size.

BACKGROUND:To evaluate the associations between rheumatoid arthritis (RA) and all-cause (ACM) and cancer-Specific mortality (CSM) in older adults with bladder cancer and examine how frailty may affect these associations. METHODS:Retrospective cohort study derived from the Surveillance Epidemiology and End Results (SEER) cancer registry and linked to Medicare claims data (SEER-Medicare). The cohort consisted of patients ≥ 65 years diagnosed with bladder cancer between 2004 and 2017. RA and frailty status were derived using validated administrative algorithms. ACM and CSM as derived from the SEER registry. RESULTS:Frailty modified the relationship between RA and mortality outcomes (interaction P value for ACM: .002 and for CSM: .007). We observed that RA was associated with a higher risk of CSM (aHR 1.17, 95% CI, 1.01-1.35) and ACM (aHR 1.12, 95% CI, 1.05-1.20) in nonfrail patients. In frail patients with bladder cancer, RA was not independently associated with CSM (aHR 0.81, 95% CI, 0.62-1.06) or ACM (aHR 0.93, 95% CI, 0.83-1.05). CONCLUSION:Frailty is associated with adverse health outcomes. As people are living longer, it is becoming increasingly prevalent among patients with chronic conditions such as RA. We observed that RA is associated with increased risk of ACM and CSM among nonfrail older adults with bladder cancer. The lack of an association between RA and mortality in frail patients with RA suggests that the effect of frailty on mortality may overpower the effect that RA may exert-this information can help prognosticate outcomes in patients with bladder cancer, RA, and frailty.

BACKGROUNDWe rapidly implemented a telemedicine Multidisciplinary Urologic Cancer Clinic (MDUCC) at the University of Washington/Seattle Cancer Care Alliance during the peak of the COVID-19 Public Health Emergency to maintain our ability to provide multidisciplinary cancer care. We report our experiences though assessment of patient-reported outcomes from our telemedicine MDUCC.METHODSVideo visits with a urologic oncologist, medical oncologist, and radiation oncologist were conducted in the same format as our in-person MDUCC. We prospectively collected patient demographic and clinical data. Patients were invited to complete a post-visit survey that assessed satisfaction, provider trust, travel time, and costs of the telemedicine visit. We estimated travel distances and times from each patient's home to our clinic.RESULTSAmong invited patients, twenty-four patients completed a survey after their telemedicine MDUCC visit. Twenty patients (83%) were at home during the visit. Most (85%)were men, Caucasian (79%), and were being seen in our Bladder Cancer MDUCC (83%). All twenty-four patients responded that they would be willing to have future appointments via telemedicine; eighteen patients (75%) strongly agreed that the encounter was high quality; 19 patients strongly agreed that they were satisfied with their visit. Patients saved an estimated average one-way travel distance of 145 miles and one-way travel time of 179 minutes to convene a telemedicine visit.CONCLUSIONSTelemedicine MDUCCs are feasible and effective in providing access to multidisciplinary urologic cancer care. Patient satisfaction was high, and many patients were spared a substantial travel burden. Telemedicine may continue to be leveraged to improve access to multidisciplinary urologic cancer care.FUNDINGThis project is supported by a 2019 Conquer Cancer Young Investigator Award & a Swim Across America Seattle Cancer Care Alliance Young Investigator Award, both to Dr. Gadzinski.Micro AbstractDuring the 2020 pandemic, we implemented telemedicine in our multidisciplinary urologic cancer clinic (MDUCC) to mitigate the spread of COVID-19. We invited our telemedicine cohort to complete surveys assessing factors like patient satisfaction and estimated visit costs. We found patient satisfaction remained high and the cost burden was diminished, highlighting the great potential utility of virtual care in cancer treatment.

Introduction Frailty describes multidimensional vulnerability to stressors. In patients with bladder cancer, frailty predicts an increased risk of treatment-related complications and mortality. A critical limitation of the frailty literature lies in the many ways frailty is measured. Relying on one frailty instrument to label a patient as “frail” risks oversimplifying a patient's vulnerability profile, failing to identify specific vulnerabilities (e.g. nutritional vs. cognitive vs. psychological vs. functional frailty) that may be clinically actionable. Current guidelines recommend using a comprehensive geriatric assessment (CGA) to quantify frailty across domains of physical function, mental health/cognition, nutrition, multimorbidity, and social supports in older and medically complex adults. However, the CGA provides so much data that it can be challenging to synthesize into a single assessment and integrate into busy clinical practice. Herein, we propose a novel CGA-derived Frailty Spider Plot. This approach synthesizes the discrete CGA-identified vulnerabilities into a single, clinically useful frailty profile. Methods Patients with urothelial cancer were prospectively enrolled from a multidisciplinary bladder cancer clinic between 9/2020 and 7/2021. After providing informed consent, participants completed a CGA incorporating validated assessments of frailty, functional status, multimorbidity, nutrition, cognition, and mental health, augmented with computed tomography-derived assessments of muscle mass and adiposity. We quantified the interdependence and relationships of different frailty instruments and domains using Spearman Correlation Coefficients to measure the degree to which the instruments conveyed similar or discrete data regarding patients’ risk factors. Frailty measures for each patient were then visualized using spider plots to discriminate individual frailty phenotypes. Each spoke represented a specific frailty instrument from the CGA, grouped by frailty domains. Nodes of the spoke were determined by predefined validated thresholds for each geriatric assessment. Outer ring values corresponded to higher degrees of frailty for each instrument (Figure). Results The cohort included 67 patients (median age 71 years, 16.4% female). This population was medically complex with ASA class ≥III in 55.2%, ECOG PS ≥3 in 25.4%, and Charlson Comorbidity Index;≥3 in 54%. Most patients had muscle-invasive bladder cancer (77.6%; cN+ and M1 in 20.9% and 7.6%, respectively). The CGA identified key vulnerabilities beyond a standard risk assessment with 31.4% vulnerable-to-moderately frail (Clinical Frailty Scale), 23.9% at risk for falls, 13.4% and 7.5% with mild and moderate-to-severe depression, respectively, 3% with mild/moderate dementia, 34% at risk for malnutrition, and 6% malnourished. The majority of frailty measures were weakly correlated (ρ<|0.5|) across instruments with the exception of Clinical Frailty Scale/Timed-up-and-Go (ρ=0.7, p<0.0001), Mini-Mental/Grip strength (ρ=0.61, p<0.001), and albumin/skeletal muscle index (ρ=0.51, p=0.01). To illustrate, two patients’ Frailty spider plots are presented in the Figure, demonstrating the specific and unique vulnerabilities within respective domains between individuals. Conclusions In this prospective observational cohort, a CGA identified key vulnerabilities. Here, we demonstrate that the different domains communicate discrete information regarding an individual's specific risk profile that would be oversimplified if we rely on the nomenclature of frail/not frail. Notably, even within a domain, different instruments demonstrated low correlations, thus contributing distinct insights regarding a patient's individual vulnerability profile. We present a novel approach to synthesize these numerous data points in a single visual depiction that demonstrates the driving components of frailty (e.g. physical function, multimorbidity, nutrition, mental health/cognition) that could be targeted by personalized prehabilitation interventions. This approach maintains the specificity of the data provided by a CGA. Future work will evaluate the most relevant risk assessment instruments to best predict salient clinical outcomes and develop more parsimonious Frailty spider plots for evaluation and validation in clinical practice.

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I (MP15)1 May 2024MP15-02 A LNCRNA-BASED CLASSIFIER IDENTIFIES HIGH GRADE T1 BLADDER CANCER PATIENTS WITH EXCELLENT OUTCOMES AFTER RADICAL CYSTECTOMY Yair Lotan, Joep J. de Jong, James Proudfoot, Sia Daneshmand, Robert Svatek, Vikram Narayan, Shreyas Joshi, Roger Li, Brant Inman, Jonathan Wright, Paras Shah, and Ewan Gibb Yair LotanYair Lotan , Joep J. de JongJoep J. de Jong , James ProudfootJames Proudfoot , Sia DaneshmandSia Daneshmand , Robert SvatekRobert Svatek , Vikram NarayanVikram Narayan , Shreyas JoshiShreyas Joshi , Roger LiRoger Li , Brant InmanBrant Inman , Jonathan WrightJonathan Wright , Paras ShahParas Shah , and Ewan GibbEwan Gibb View All Author Informationhttps://doi.org/10.1097/01.JU.0001009500.87761.bf.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In select patients with high grade (HG) clinical T1 non-muscle-invasive bladder cancer (NMIBC) radical cystectomy (RC) is a recommended therapy. However, even after radical surgery patients may experience disease recurrence, increasing the risk of cancer-related mortality. In previous work, a long non-coding RNA (lncRNA)-based classifier was developed to identify patients with favorable biology and excellent prognosis after RC in patients with muscle-invasive bladder cancer (MIBC). Here, we further evaluate this classifier in a cohort of patients with HG clinical T1 and T2 urothelial bladder tumors undergoing RC only. METHODS: Microarray data was analyzed from bladder tumor specimens resected transurethrally (TURBT) in two cohorts (MOLI n=206, MOLII n=200) of patients with high grade cT1-T2 N0M0 UC who subsequently underwent RC without neoadjuvant chemotherapy (NAC). Molecular subtypes were determined using the Decipher Bladder genomic subtyping classifier (GSC) [Seiler 2017, Batista da Costa 2019] and a lncRNA-based classifier was used to identify patients with good outcomes [de Jong et al, 2019]. The primary endpoints were overall survival (OS) and cancer specific mortality (CSM), quantified by Kaplan-Meier and cumulative incidence plots, respectively. RESULTS: In the MOLII cohort, molecular subtyping identified 51 (cT1=37, cT2=13) luminal-type FGFR3 active (FGFR3+) cases with high FGFR3, SHH and p53 pathway activity, and lower EMT hallmark scores. At five years, the freedom from event (FFE) rates for OS in the full cohort were 87% and 54% for FGFR3+ and FGFR3-, respectively. By stage, the T1 FGFR3+ patients had 97% vs 57% FFE rates compared to FGFR3- patients. In T2 patients, the FFE rate was 69% for FGFR3+ and 51% for FGFR3- tumors. For CSM, the event rates for the full cohort were 11% and 30% for FGFR3+ and FGFR3- cases, respectively. By stage, for T1 tumors, the rates were 0% for FGFR3+ and 21% for FGFR3-, compared to 31% and 38% for FGFR3- in T2 tumors. Similar patterns were seen for the MOLI cohort, but with less separation in event rates. CONCLUSIONS: Application of a lncRNA-based classifier to two cystectomy cohorts revealed that FGFR3+ patients with cT1 disease have excellent outcomes after RC, suggesting these less aggressive tumors are both organ-confined and readily cured with surgery alone. These findings represent a first step towards identifying cT1 patients with less favorable biology that may warrant systemic treatment before radical surgery. Source of Funding: Veracyte © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e229 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Yair Lotan More articles by this author Joep J. de Jong More articles by this author James Proudfoot More articles by this author Sia Daneshmand More articles by this author Robert Svatek More articles by this author Vikram Narayan More articles by this author Shreyas Joshi More articles by this author Roger Li More articles by this author Brant Inman More articles by this author Jonathan Wright More articles by this author Paras Shah More articles by this author Ewan Gibb More articles by this author Expand All Advertisement PDF downloadLoading ...

579 Background: Frailty in bladder cancer predicts increased complications and mortality. Measuring frailty is challenging because relying on one frailty instrument risks oversimplifying patients’ multidimensional vulnerability profiles. Current guidelines recommend using a comprehensive geriatric assessment (CGA) to quantify frailty across domains of physical function, mental health/cognition, nutrition, and multimorbidity in older adults. However, the CGA’s extensive data can be hard to synthesize and integrate into busy clinical practice. We propose a novel CGA-derived Frailty Spider Plot, synthesizing CGA-identified vulnerabilities into a clinically useful frailty profile. Methods: Urothelial cancer patients, prospectively enrolled between 9/2020 and 7/2021 in a multidisciplinary bladder cancer clinic, completed a CGA incorporating validated assessments of functional status, multimorbidity, nutrition, cognition, and mental health, augmented with CT-derived assessments of muscle mass and adiposity. Spearman Correlation Coefficients were used to quantify relationships between frailty tools and domains. Novel Frailty Spider plots were then created to visualize individuals’ distinct frailty phenotypes. The CGA instruments, grouped by domain, were the spokes of the plot, with each node determined by validated thresholds. Outer ring values indicated greater frailty. Results: The cohort included 67 patients (median age 71, 16.4% female), most with muscle-invasive bladder cancer (77.6%; cN+: 20.9%, M1: 7.6%). The CGA identified 31.4% vulnerable-to-moderately frail, 23.9% at risk for falls, 13.4% with mild depression, 7.5% with moderate-severe depression, 3% with mild/moderate dementia, 34% at risk for malnutrition, and 6% malnourished. Frailty measures were generally weakly correlated (rho <|0.5|). Individuals’ specific risk profiles were plotted on the novel Frailty spider plot which visually distinguished patients according to their frailty phenotypes. For instance, a patient with a high risk Mini-nutritional Assessment score, hypoalbuminema, and sarcopenic skeletal muscle mass, is distinguished with a Spider plot dominated by nutritional frailty spokes. Conclusions: In this prospective observational cohort, a CGA identified key vulnerabilities beyond a standard risk assessment. Frailty domains provide unique risk insights beyond relying on simple frail/not frail nomenclature. Notably, even within a domain, instruments had low correlations, contributing distinct insights into a patient’s vulnerability profile. Our novel Spider plot approach visually synthesizes this data in a single depiction of the predominant components of frailty that can be targeted by personalized prehabilitation interventions. Future work will refine risk assessment instruments to best predict clinical outcomes, creating parsimonious Frailty spider plots for clinical use.

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation II (MP35)1 May 2024MP35-18 AGREEMENT BETWEEN TRANSURETHRAL RESECTION OF BLADDER TUMOR (TURBT) AND RADICAL CYSTECTOMY (RC) PATHOLOGY IN PATIENTS WITH BLADDER CANCER SUBTYPE HISTOLOGY Dimitra Rafailia Bakaloudi, Elizabeth L. Koehne, Dimitrios Makrakis, Leonidas N. Diamandopoulos, Petros Grivas, Brian R. Winters, Lawrence D. True, Maria S. Tretiakova, Sarah P. Psutka, Sarah K. Holt, Gore L. John, Daniel W. Lin, George R. Schade, Yaw Nyame, Andrew C. Hsieh, John K. Lee, Todd Yezefski, Jessica Hawley, Michael T. Schweizer, Heather H. Cheng, Evan Y. Yu, Funda Vakar-Lopez, Bruce R. Montgomery, and Jonathan Wright Dimitra Rafailia BakaloudiDimitra Rafailia Bakaloudi , Elizabeth L. KoehneElizabeth L. Koehne , Dimitrios MakrakisDimitrios Makrakis , Leonidas N. DiamandopoulosLeonidas N. Diamandopoulos , Petros GrivasPetros Grivas , Brian R. WintersBrian R. Winters , Lawrence D. TrueLawrence D. True , Maria S. TretiakovaMaria S. Tretiakova , Sarah P. PsutkaSarah P. Psutka , Sarah K. HoltSarah K. Holt , Gore L. JohnGore L. John , Daniel W. LinDaniel W. Lin , George R. SchadeGeorge R. Schade , Yaw NyameYaw Nyame , Andrew C. HsiehAndrew C. Hsieh , John K. LeeJohn K. Lee , Todd YezefskiTodd Yezefski , Jessica HawleyJessica Hawley , Michael T. SchweizerMichael T. Schweizer , Heather H. ChengHeather H. Cheng , Evan Y. YuEvan Y. Yu , Funda Vakar-LopezFunda Vakar-Lopez , Bruce R. MontgomeryBruce R. Montgomery , and Jonathan WrightJonathan Wright View All Author Informationhttps://doi.org/10.1097/01.JU.0001009372.61513.54.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: TURBT is the primary diagnostic procedure for bladder cancer (BC) and helps determine subsequent care. However, its pathology interpretation may be limited by cautery artifact, lack of spatial orientation of tumor pieces, and sampling bias, especially in cases of incomplete resection. Accurately identifying bladder cancer subtype histology (SH) on TURBT such as plasmacytoid, sarcomatoid and micropapillary is critical to inform clinical decisions. We compared the concordance between TURBT and RC pathology of patients with SH of BC. METHODS: We retrospectively examined TURBT and RC pathology reports of patients who underwent RC at our institutional database from 2010-2022. All slides were reviewed by a GU pathologist. We included patients with pure SH as well as mixed histologies (e.g., urothelial carcinoma with SH present) in either TURBT and RC specimens. Cohen's kappa coefficient was used to determine the degree of agreement between TURBT and RC SH. Agreement was characterized as slight, fair, moderate, substantial, or almost perfect for kappa=0-0.2, 0.21-0.4, 0.41-0.6, 0.61-0.8, and 0.81-1, respectively. Negative kappa values are interpreted as no agreement. RESULTS: From a total of 1161 RC performed, we identified 464 (40%) patients with any amount of SH present on either TURBT or RC. At TURBT, 427 (92%) had SH reported and 59% of these were confirmed at cystectomy. In contrast, 291 RC specimens had SH reported and 56% of these SH were reported on the paired TURBT. We found a high level of agreement (kappa range: 0.5-0.75) between TURBT and RC in pure non-urothelial histology (pure squamous cell carcinoma, pure adenocarcinoma, pure small cell/neuroendocrine carcinoma). In contrast, we found fair (plasmacytoid, small cell, sarcomatoid, squamous) or slight (micropapillary, adenocarcinoma) agreement between TURBT and RC in pts with a mix of urothelial carcinoma and SH (kappa range: 0.1-0.4). CONCLUSIONS: We found low agreement of pathologic detection between TURBT and RC for mixed urothelial carcinoma with subtype histology. In contrast, high level of agreement was noted in pure non-UC histology. Future efforts are needed to develop reliable diagnostic tools for accurate characterization of SH in UC to better inform management. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e588 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Dimitra Rafailia Bakaloudi More articles by this author Elizabeth L. Koehne More articles by this author Dimitrios Makrakis More articles by this author Leonidas N. Diamandopoulos More articles by this author Petros Grivas More articles by this author Brian R. Winters More articles by this author Lawrence D. True More articles by this author Maria S. Tretiakova More articles by this author Sarah P. Psutka More articles by this author Sarah K. Holt More articles by this author Gore L. John More articles by this author Daniel W. Lin More articles by this author George R. Schade More articles by this author Yaw Nyame More articles by this author Andrew C. Hsieh More articles by this author John K. Lee More articles by this author Todd Yezefski More articles by this author Jessica Hawley More articles by this author Michael T. Schweizer More articles by this author Heather H. Cheng More articles by this author Evan Y. Yu More articles by this author Funda Vakar-Lopez More articles by this author Bruce R. Montgomery More articles by this author Jonathan Wright More articles by this author Expand All Advertisement PDF downloadLoading ...

OBJECTIVE:To further evaluate a genomic classifier (GC) in a cohort of patients undergoing radical cystectomy (RC), as long non-coding RNA (lncRNA)-based genomic profiling has suggested utility in identifying a distinct tumour subgroup corresponding to a favourable prognosis in patients with bladder cancer. PATIENTS AND METHODS:Transcriptome-wide expression profiling using Decipher Bladder was performed on transurethral resection of bladder tumour samples from a cohort of patients with high-grade, clinically organ-confined (cTa-T2N0M0) urothelial carcinoma (UC) who subsequently underwent RC without any neoadjuvant therapy (n = 226). The lncRNA-based luminal favourable status was determined using a previously developed GC. The primary endpoint was overall survival (OS) after RC. Secondary endpoints included cancer-specific mortality and upstaging at RC. RESULTS:In the study, 134 patients were clinical non-muscle-invasive bladder cancer (cTa/Tis/T1) and 92 patients were cT2. We identified 60 patients with luminal favourable subtype, all of which showed robust gene expression patterns associated with less aggressive bladder cancer biology. On multivariate analysis, patients with the luminal favourable subtype (vs without) were significantly associated with lower odds of upstaging to pathological (p)T3+ disease (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.12-0.82; P = 0.02), any upstaging (OR 0.41, 95% CI 0.20-0.83; P = 0.01), and any upstaging and/or pN+ (OR 0.50, 95% CI 0.25-1.00; P = 0.05). Luminal favourable bladder cancer was significantly associated with better OS (hazard ratio 0.33, 95% CI 0.15-0.74; P = 0.007). CONCLUSIONS:This study validates the performance of the GC for identifying UCs with a luminal favourable subtype, harbouring less aggressive tumour biology.

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I (MP15)1 May 2024MP15-07 MOLECULAR SUBTYPING FOR PREDICTING NON-ORGAN CONFINED DISEASE AND SURVIVAL OUTCOMES AFTER RADICAL CYSTECTOMY IN CLINICAL HIGH-GRADE T1 AND T2 BLADDER CANCER PATIENTS Yair Lotan, Joep J. de Jong, James Proudfoot, Sia Daneshmand, Robert Svatek, Vikram Narayan, Shreyas Joshi, Roger Li, Brant Inman, Jonathan Wright, Paras Shah, and Ewan Gibb Yair LotanYair Lotan , Joep J. de JongJoep J. de Jong , James ProudfootJames Proudfoot , Sia DaneshmandSia Daneshmand , Robert SvatekRobert Svatek , Vikram NarayanVikram Narayan , Shreyas JoshiShreyas Joshi , Roger LiRoger Li , Brant InmanBrant Inman , Jonathan WrightJonathan Wright , Paras ShahParas Shah , and Ewan GibbEwan Gibb View All Author Informationhttps://doi.org/10.1097/01.JU.0001009500.87761.bf.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Accurate clinical staging bladder cancer represents a significant clinical challenge as many patients are upstaged to non-organ confined (NOC) disease (pT3+ and/or N+) at radical cystectomy (RC). A prior multicenter trial found that molecular subtyping could improve clinical staging and for predicting patient outcomes. This study is an independent multicenter evaluation of the Decipher Bladder Genomic Subtyping Classifier (GSC) for predicting upstaging and outcomes on a cohort of patients with clinical T1 and T2 bladder cancer who underwent radical cystectomy without neoadjuvant therapy. METHODS: Microarray data was analyzed from bladder tumor specimens resected transurethrally from a cohort of patients with high grade cT1-T2 N0M0 UC who subsequently underwent RC without NAC (n=200). Molecular subtypes were determined using the Decipher Bladder GSC Seiler 2017, Batista da Costa 2019]. The primary endpoint was pathological upstaging to non-organ confined disease (pT3+ and/or N+), while the secondary endpoints were cancer specific mortality (CSM) and overall survival (OS). RESULTS: In the patient cohort, 108 and 92 patients were clinical T1 and T2, respectively. The overall rate of upstaging to NOC was 31% for cT1 and 69% for cT2 patients. Molecular subtyping identified 117 luminal tumors, 16 infiltrated luminal, 48 basal, 15 claudin-low tumors and 4 neuroendocrine-like (NE-like). Non-luminal tumors (infiltrated luminal, basal, claudin-low, NE-like), were upstaged to NOC disease at a rate of 42.2%, compared to 30.8% for luminal tumors (p=0.1). For cT1 luminal tumors, the rates of upstaging were 18% compared to 27% for cT1 non-luminal tumors. Within cT2 tumors, upstaging rates were similar at 41% and 47% for luminal and non-luminal tumors, respectively. Kaplan-Meier analysis revealed significantly improved survival outcomes (both OS and CSM) for patients with luminal tumors versus non-luminal tumor patients within the cT2 patient subgroup. CONCLUSIONS: Molecular subtyping suggests that luminal tumors harbor a less aggressive disease state reflected by lower rates of upstaging compared to non-luminal tumors. Critically, luminal tumors in the cT2 population showed a significantly improved outcomes compared to non-luminal tumors, even in the absence of systemic chemotherapy. Source of Funding: Veracyte © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e231 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Yair Lotan More articles by this author Joep J. de Jong More articles by this author James Proudfoot More articles by this author Sia Daneshmand More articles by this author Robert Svatek More articles by this author Vikram Narayan More articles by this author Shreyas Joshi More articles by this author Roger Li More articles by this author Brant Inman More articles by this author Jonathan Wright More articles by this author Paras Shah More articles by this author Ewan Gibb More articles by this author Expand All Advertisement PDF downloadLoading ...

Purpose: Active surveillance is a safe and effective strategy for men with lower-risk prostate cancer who want to avoid local therapy; however, many patients on active surveillance progress to active treatment (eg, prostatectomy or radiation). We hypothesized that apalutamide would decrease active surveillance attrition rates through downstaging low-grade tumors. Materials and Methods: This was an open-label, single-arm, phase II study testing 90 days of oral apalutamide 240 mg daily in men with low- to intermediate-risk prostate cancer on active surveillance. The primary objective was to determine the percentage of patients with a negative biopsy immediately following treatment. Secondary objectives were to assess long-term clinical outcomes, quality of life, safety, and biomarkers of response/resistance. Results: Twenty-three patients enrolled and 22 completed 90 days of apalutamide with post-treatment biopsy. Fifteen (65%) had Grade Group 1 disease, and all others had Grade Group 2 disease. Seven (30%) had favorable- to intermediate-risk disease. Of 22 evaluable patients, 13 (59%) had no residual cancer on post-treatment biopsy. The median time to first positive biopsy was 364 days (95% CI: 91-742 days). The impact of apalutamide on quality of life was minimal and transient. Decipher risk classifier revealed a greater number of negative post-treatment biopsies in those with higher baseline genomic risk score (P = .01). Conclusions: The negative repeat biopsy rate following 90 days of apalutamide was high in men with prostate cancer followed on active surveillance. Apalutamide was safe, well tolerated, and had minimal impact on quality of life. Randomized studies evaluating the effects of apalutamide in men enrolled on active surveillance are warranted.

You have accessJournal of UrologyCME1 Apr 2023MP65-01 RISK FACTORS FOR PARASTOMAL HERNIATION: A SURVEILLANCE, EPIDEMIOLOGY AND END RESULTS-MEDICARE DATA ANALYSIS Diboro Kanabolo, Sarah Holt, Jonathan Wright, and George Schade Diboro KanaboloDiboro Kanabolo More articles by this author , Sarah HoltSarah Holt More articles by this author , Jonathan WrightJonathan Wright More articles by this author , and George SchadeGeorge Schade More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003323.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A frequent complication of stoma creation is parastomal herniation (PSH), defined as any palpable bulge or radiologic defect containing bowel in the parastomal region. Reported incidence rates are up to 50% for patients in the 24 months following ileal conduit (IC) surgery. To better understand risk factors for PSH in those undergoing cystectomy and ileal conduit (RC/IC) procedure, we examined a contemporary cohort of patients through combined Surveillance, Epidemiology and End Results-Medicare data (SEER-MD). METHODS: Using SEER-MD, patients with PSH after cystectomy and IC were identified. This was performed using CPT codes to identify surgery patients and subsequent diagnostic the new ICD-10 PSH specific code (K43.5) post-surgery, for those with surgery between 2015 and 2019. Risk factors of interest included: race, sex, socioeconomic status, marital status, COPD, smoking, obesity status, neoadjuvant chemotherapy administration, and tumor stage. An adjusted Cox Proportional-Hazards model was utilized for statistical analysis, enabling assessment of time to PSH from receipt of surgery and to account for censored patients. RESULTS: Of 1,838 patients identified as having undergone RC/IC, 132 patients (7 %) developed PSH in the followup period. The median time to PSH was 11.5 months (IQR: 6.5-18.7 months). The greatest risk factor in our cohort of patients for development of PSH was obesity (HR 2.05, 95% CI 1.48-2.98). The lowest socioeconomic quartile was also associated with greater risk of PSH (HR 1.49, 95% CI 1.01-2.22). Sex, COPD diagnosis, gender, race, smoking status, neoadjuvant chemotherapy, and tumor stage were not significantly associated with risk of PSH, although the female sex, Black/Hispanic race, and pT4 lesions showed elevated HR estimates. Marital status of “Divorced/Separated/Widowed” was significantly associated with PSH (HR 1.66, 95% CI 1.04-2.66) vs. “Married”, however due to a large portion of “unknown” marital status in our cohort, this finding may not be clinically meaningful. CONCLUSIONS: While the SEER-MD incidence rate is far below 50%, this reflects a mutable coding process subject to variation in capture by provider. With the available cohort, our model demonstrated an increased risk of PSH for obese and low SES patients undergoing RC/IC surgery. Both weight loss prevention strategies and careful symptom monitoring must be pursued in this population. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e890 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Diboro Kanabolo More articles by this author Sarah Holt More articles by this author Jonathan Wright More articles by this author George Schade More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyCME1 May 2022PD53-09 ANTIBODY DRUG CONJUGATES AND VARIANT HISTOLOGY MUSCLE-INVASIVE BLADDER CANCER: ARE THE TARGETS PRESENT IN PRIMARY AND/OR METASTATIC TUMORS? Fady Ghali, Martine Roudier, Funda Vakar-Lopez, Jose Garcia, Yan Wang, Gavin Ha, Petros Grivas, John Lee, Evan Yu, Bruce Montgomery, Andrew Hsieh, Jonathan Wright, and Hung-Ming Lam Fady GhaliFady Ghali More articles by this author , Martine RoudierMartine Roudier More articles by this author , Funda Vakar-LopezFunda Vakar-Lopez More articles by this author , Jose GarciaJose Garcia More articles by this author , Yan WangYan Wang More articles by this author , Gavin HaGavin Ha More articles by this author , Petros GrivasPetros Grivas More articles by this author , John LeeJohn Lee More articles by this author , Evan YuEvan Yu More articles by this author , Bruce MontgomeryBruce Montgomery More articles by this author , Andrew HsiehAndrew Hsieh More articles by this author , Jonathan WrightJonathan Wright More articles by this author , and Hung-Ming LamHung-Ming Lam More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002630.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Nectin-4 and Trop-2 are cell surface targets of novel humanized monoclonal antibody-drug conjugates, Enfortumab-vedotin (EV) and Sacituzumab govitecan (SG), respectively. These agents are FDA-approved for locally advanced/metastatic urothelial cancer (UC), however their wider role in the treatment of variant histology bladder cancer (BC) is unknown. We describe the expression level and sub-cellular localization of Nectin-4 and TROP-2 via immunostaining in histologic variants of BC within primary and matched metastatic samples. METHODS: Immunohistochemistry for Nectin-4 and TROP-2 was performed (using Abcam 192033 and 214488 respectively) on matched primary and metastatic tumor samples from patients with metastatic BC collected via rapid autopsy. Staining was scored by intensity (0-3) and multiplied by % of positive cells resulting in a range of 0-300 H-score. Membranous and cytoplasmic staining were separately evaluated for each sample. RESULTS: A total of 68 samples from 20 patients were collected and analyzed, of which 27 were urothelial carcinoma (UC), 17 plasmacytoid (PUC), 19 Squamous cell carcinoma (SCC), and 5 neuroendocrine (NE); 11 samples were collected from primary tumor sites, 20 from lymph node (LN) and 37 from various metastatic sites; 17 of 20 patients (85%) had received systemic chemotherapy and 35% had received immunotherapy. No patient had received EV or SG. Table 1 demonstrates mean membranous and cytoplasmic H-score levels as well as % positive rates for Nectin-4 and TROP-2. Nectin-4 localized primarily in the cytoplasm rather than the membrane in PUC and SCC for LN and metastatic sites, while primary tumors demonstrated relatively even Nectin-4 distribution between membrane and cytoplasm. TROP-2 was expressed at equivalent levels in both membrane and cytoplasm for both PUC and SCC, and the high expression was conserved from primary to metastases. CONCLUSIONS: Nectin-4 and TROP-2 are highly expressed in UC and variant histology BC, both at primary and metastatic sites, but not in NE histology. Whether differences in membranous vs cytoplasmic localization affects response to EV or SG is unknown. The implications of these findings on treatment response for variant histology BC warrant further study in clinical trials, which we are launching. Source of Funding: N/A © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e913 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Fady Ghali More articles by this author Martine Roudier More articles by this author Funda Vakar-Lopez More articles by this author Jose Garcia More articles by this author Yan Wang More articles by this author Gavin Ha More articles by this author Petros Grivas More articles by this author John Lee More articles by this author Evan Yu More articles by this author Bruce Montgomery More articles by this author Andrew Hsieh More articles by this author Jonathan Wright More articles by this author Hung-Ming Lam More articles by this author Expand All Advertisement PDF downloadLoading ...

INTRODUCTION:µ-Opioid-receptor antagonists are a standard component of enhanced recovery after surgery (ERAS) pathways following radical cystectomy (RC) as they reduce ileus and shorten length of stay (LOS). Prior studies have used alvimopan; however, naloxegol is a less expensive medication in the same class. We compared differences in postoperative outcomes between patients receiving alvimopan or naloxegol following RC. METHODS:We retrospectively reviewed all patients undergoing RC over 20 months at an academic center during which standard practice transitioned from using alvimopan to naloxegol, while maintaining all other components of our ERAS pathway. We utilized bivariate comparisons as well as negative binomial and logistic regression to compare return of bowel function, rates of ileus and LOS following RC. RESULTS:Of 117 eligible patients, 59 (50%) received alvimopan and 58 (50%) received naloxegol. There were no differences in baseline clinical, demographic or perioperative factors. Median postoperative LOS was 6 days in each group (p=0.3). Time to flatus (2 versus 2 days, p=0.2) and ileus (14% versus 17%, p=0.6) were similar between the alvimopan and naloxegol groups, respectively. In multivariable models controlling for patient and surgical factors, µ-opioid antagonist agent was associated with neither LOS nor ileus. Cost difference was -$344.20/day, equivalent to a $2,065.20 savings over a 6-day hospital stay with naloxegol. CONCLUSIONS:In patients undergoing RC managed with a standard ERAS pathway, there were no differences in postoperative recovery based on the use of alvimopan versus naloxegol. Substitution of naloxegol for alvimopan may allow for significant cost savings without compromising outcomes.

Abstract Introduction: Although studies using mixed insurance populations suggest that chemotherapy use in men with advanced penile cancer (PC) is low, it is unclear what regimens are being utilized. In this study, we use a database of insured patients to better understand specific chemotherapy utilization in men with PC. Methods: This is a retrospective cohort study of patients with stage IIIB or IV PC in the Surveillance, Epidemiology, and End Results-Medicare database (2004–2015). Standard of care (SOC) chemotherapy was defined by the National Comprehensive Cancer Network® guidelines: 4 cycles of paclitaxel, ifosfamide and cisplatin or 5-fluorouracil with cisplatin in the neoadjuvant, adjuvant or primary setting. We calculated what proportion of patients receive SOC or any chemotherapy within 2 years of diagnosis and analyzed what factors were associated with receiving chemotherapy. Results: Our study included 147 patients—48 stage IIIB and 99 stage IV. Of these patients, 49 (33%) received chemotherapy. Less than 5% of men received SOC. About 10% received SOC chemotherapy but an insufficient number of cycles. Married men were more likely to undergo chemotherapy (OR 3.4, 95% CI 1.5–7.8). Less than 5% of the 24 Black or Hispanic patients received chemotherapy compared to 37% of white patients (p <0.001). Conclusions: Only a third of men with stage IIIB/IV PC underwent chemotherapy. Less than 5% of men received complete guideline-based regimens. Whether this is driven primarily by patient or provider factors is unknown, although social determinants of health may play a role. These data highlight the difficulty for patients with PC to get chemotherapy.