Table S2. Differentially expressed genes between the upper and lower four TMB quintiles.

Survival outcomes by pathologic stage. A, RFS. B, OS. CI, confidence interval.

RFS by TMB. A, Upper TMB quintile (TMB-upper) vs. lower four TMB quintiles (TMB-lower). B, TMB ≥ 10 Mut/Mb (TMB-hi) vs. TMB < 10 Mut/Mb (TMB-lo). CI, confidence interval.

Abstract Objectives To investigate how patient‐specific factors, including race and socioeconomic status, impact time to treatment initiation (TTI) for patients with small renal masses (SRMs). Materials and Methods We retrospectively reviewed 275 patients with SRMs ≤ 4 cm at Atrium Health Carolinas Medical Center who underwent treatment for their renal mass. TTI was defined by the time between office visit (TTI‐OV) or between initial imaging (TTI‐Imaging) and procedure date. Statistical analysis was employed to determine patient‐specific factors associated with TTI. Results We found that TTI was significantly associated with race as Black patients experienced longer TTI than non‐Hispanic White patients (OV: HR = 0.637, 95% CI [0.479–0.848], p = 0.0048; Imaging: HR = 0.541, 95% CI [0.402–0.727], p = 0.0002). TTI, however, was not significantly associated with socioeconomic status as defined by Area Deprivation Index, income or insurance status. TTI‐OV was also significantly associated with procedure year, and TTI‐Imaging was associated with procedure year, Charlson Comorbidity Index (CCI) and tumour size when first seen on imaging. On multivariable analysis, TTI‐Imaging was not independently associated with race (p = 0.1775), suggesting procedure year, CCI and tumour size are more significant predictors of TTI. Conclusion Black patients experienced a treatment delay from initial clinical presentation to procedure, but treatment delays from initial imaging identification to procedure may be tied more strongly to clinical factors.

PURPOSE:The survival rate for the majority of patients with non-muscle invasive bladder cancer (NMIBC) is favorable; however, the rates of recurrence and progression to muscle-invasive bladder cancer are important surrogate endpoints for overall prognosis, as these are major determinants of long-term outcome. The recurrence and progression probability rates depend on several clinical and pathologic factors. Therefore, the ability to predict risk of recurrence and progression and treating the disease appropriately is important. This Guideline provides a risk-stratified clinical framework for the management of NMIBC. MATERIALS AND METHODS:During the 2025 update, a modified version of the Guideline search strategy was used to conduct a systematic search of Ovid MEDLINE and Embase for new evidence published between May 2023 and December 2025. The modified search added keywords for newly added therapeutic agents in accordance with the updated populations, interventions, comparators, and outcomes. The systematic search identified 2933 studies, of which 71 studies met inclusion criteria following title and abstract screening. Full-text review resulted in 38 studies being included in the final evidence base. RESULTS:Updates were made to NMIBC risk stratification and statements on biomarkers, subtype histologies, transurethral resection, intravesical therapy, Bacillus Calmette-Guérin maintenance, enhanced cystoscopy, and future directions. Revisions were made to the methodology and reference sections as appropriate. CONCLUSIONS:The Guideline updates herein seek to improve clinicians' ability to evaluate and treat patients with NMIBC based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care.

Figure S1. Survival outcomes for entire study cohort.

OS by TMB. A, Upper TMB quintile (TMB-upper) vs. lower four TMB quintiles (TMB-lower). B, TMB ≥ 10 Mut/Mb (TMB-hi) vs. TMB < 10 Mut/Mb (TMB-lo). CI, confidence interval.

Abstract Pathologic complete response (pCR) after cisplatin-based neoadjuvant chemotherapy (NAC) is associated with improved outcomes in muscle-invasive bladder cancer (MIBC), but genomic predictors of benefit remain unvalidated. Based on observations in lung cancer, we hypothesized that patients with MIBC with high tumor mutational burden (TMB) would be unlikely to benefit from NAC, indicated by residual disease after cystectomy. Pretreatment tumor specimens from patients treated with cisplatin-based NAC were analyzed using Tempus xT/xR platforms. Sample size was prespecified by statistical design. High TMB was defined as the upper TMB quintile within the cohort. Correlation of TMB values and genomic variants with outcomes was performed using logistic regression, Cox proportional hazards models, and Kaplan–Meier techniques. Ninety-one patients were included, with a median follow-up of 63.6 months. pCR occurred in 31.9%. Median TMB was 8.9 mutations per megabase (Mut/Mb). Contrary to the prespecified hypothesis, higher TMB was associated with more favorable outcomes. Patients in the upper TMB quintile had a numerically higher pCR rate (47.4% vs. 27.8%; P = 0.165) and improved relapse-free survival (RFS)/overall survival [OS; hazard ratio (HR), 0.456; P = 0.08 and HR, 0.495; P = 0.16]. Using a clinically relevant cutoff, TMB ≥ 10 Mut/Mb was associated with higher pCR [43.6% vs. 23.1%; odds ratio (OR), 0.39; P = 0.044] and improved RFS (HR, 0.330; P < 0.001) and OS (HR, 0.388; P = 0.013). Exploratory analyses showed a trend toward enrichment of mismatch repair alterations (OR, 3.57; P = 0.087) in TMB-high tumors. Baseline TMB ≥ 10 Mut/Mb was associated with improved pathologic response and survival in MIBC treated with cisplatin-based NAC and warrants prospective evaluation in contemporary perioperative regimens. Significance: In MIBC treated with cisplatin-based neoadjuvant chemotherapy, we found that baseline TMB ≥10 Mut/Mb was associated with higher pCR rates and improved RFS and OS. These findings support the prospective study of TMB as a prognostic biomarker in contemporary perioperative treatment regimens.

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy IV (PD61)1 May 2024PD61-12 SAME-DAY DISCHARGE FOLLOWING ROBOTIC PROSTATECTOMY: STANDARDIZATION AND SAFETY EVALUATION Emily H. Roebuck, Winston Salem, Lila McGrath, Justin T. Matulay, Peter E. Clark, and Stephen B. Riggs Emily H. RoebuckEmily H. Roebuck , Winston SalemWinston Salem , Lila McGrathLila McGrath , Justin T. MatulayJustin T. Matulay , Peter E. ClarkPeter E. Clark , and Stephen B. RiggsStephen B. Riggs View All Author Informationhttps://doi.org/10.1097/01.JU.0001009352.31737.3d.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Average length of stay following robot-assisted laparoscopic prostatectomy (RALP) ranges from 24-48 hours. In August 2022, our institution implemented a same day discharge (SDD) protocol for patients undergoing RALP. Here, we describe our standardized program and aim to characterize early outcomes among patients undergoing RALP with SDD to assess safety and feasibility of adoption. METHODS: This is a retrospective cohort study of patients who underwent RALP at our institution between August 2022-July 2023. Preoperative screening metrics for inclusion and our standardized SDD protocol are outlined in Figure 1. Patients were excluded from analysis if they stayed ≥1 night following surgery. Primary outcomes included rate of emergency department (ED) visits within 24 hours of surgery, 30-day readmissions rates, and complication rates. Additionally, we evaluated operational components including length of PACU stay and compliance with POD1 virtual visit. Descriptive statistics were used to assess outcomes. RESULTS: Among 85 patients who underwent RALP during this time, 79/85 (93%) were discharged the same day as surgery. Six patients required ≥1 night stay due to postoperative hypotension (2), poor pain control (1), lack of transportation (1), and unidentified reasons (2). SDD patients tended to be between 50-70 years old (88.6%) and of ASA class 3 (79.7%). Average length of surgery was 4.34 hours with an average EBL of 157.3 mL. Phase I PACU times ranged from 0.78 to 7.2 hours (mean 1.8 hours). Following discharge, 67/79 patients (84.8%) were compliant with POD1 virtual visit. Three patients presented to the ED within 24 h of surgery, one of whom was readmitted. Reasons for ED visit included postoperative atrial fibrillation, wound concerns, and syncope. Overall, 30-day readmission rate was 10% (8/79), with an average time to readmission of 12 days. 4/79 patients had Clavien-Dindo complications grades II (2), IIIa and IIIb. CONCLUSIONS: In this study, we present a standardized workflow for SDD following RALP. Additionally, our findings demonstrate that SDD is a safe alternative to overnight stay following RALP. Further studies are needed to elucidate preoperative risk stratification and identify poor SDD candidates for appropriate tailoring of protocol driven care. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1284 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Emily H. Roebuck More articles by this author Winston Salem More articles by this author Lila McGrath More articles by this author Justin T. Matulay More articles by this author Peter E. Clark More articles by this author Stephen B. Riggs More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyEducation Research III (PD60)1 May 2024PD60-05 ASSESSING THE EFFICACY OF A NOVEL LONGITUDINAL RESIDENT CLINIC: PROOF OF CONCEPT Samuel J. Ivan, Mackenzie L. Needham, Nicholas B. Koch, S. Lee Guice, Manish N. Patel, Ornob P. Roy, Alison C. Keenan, Peter E. Clark, and Stephen B. Riggs Samuel J. IvanSamuel J. Ivan , Mackenzie L. NeedhamMackenzie L. Needham , Nicholas B. KochNicholas B. Koch , S. Lee GuiceS. Lee Guice , Manish N. PatelManish N. Patel , Ornob P. RoyOrnob P. Roy , Alison C. KeenanAlison C. Keenan , Peter E. ClarkPeter E. Clark , and Stephen B. RiggsStephen B. Riggs View All Author Informationhttps://doi.org/10.1097/01.JU.0001009460.27205.df.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Our institution developed a novel longitudinal resident clinic (LRC) in 2021 in which residents, with faculty supervision, assume primary management of patients over a continuous four-year period. The LRC design mimics general urology practice by establishing longitudinal follow-up with a general urology patient cohort and aims to increase resident confidence in ambulatory urologic practice. We audited the LRC to assess continuity of care and distribution of consult diagnoses and surgical cases. METHODS: We performed a retrospective chart review of LRC patients between 9/29/2022 and 6/29/2023 for office consults and 10/26/22 to 10/30/23 for surgical cases. During this time five residents (Post Grad Years 2-5) saw patients in bi-weekly half-day clinics. We report longitudinal care, defined as an additional in-person follow-up visit with the consulting resident, as well as surgical continuity of care defined by resident participation in a surgical case posted through the LRC. We also report consult diagnosis and surgical case distribution and frequency. RESULTS: Outpatient consultations in the LRC totaled 124 for the period of interest. Of these patients, 67.7% completed a follow-up visit. Reasons for no follow-up included visit not scheduled, cancelled, or follow-up not indicated. Of patients who completed follow-up, 78.6% had that visit with the same consulting resident, which we considered successful longitudinal follow-up. During the study period, 42 surgical cases were posted through the LRC. Of these, 47.6% included participation by the posting resident while 76% included any resident. There were 27 unique consult diagnoses after grouping similar diagnoses and 10 different surgical cases. The most common diagnoses and cases are listed in Table 1. CONCLUSIONS: Longitudinal care was achieved with 78.6% of patients returning for follow-up with the same resident. Surgical continuity, however, was limited to 47.6% of cases. The LRC clinic demonstrated a range of presenting complaints and surgical cases, but their diversity should be improved to further model general practice. Referral patterns to subspecialty physicians in a tertiary care practice may explain these patterns. These findings demonstrate alignment with LRC stated aims and highlight areas for improvement. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1274 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Samuel J. Ivan More articles by this author Mackenzie L. Needham More articles by this author Nicholas B. Koch More articles by this author S. Lee Guice More articles by this author Manish N. Patel More articles by this author Ornob P. Roy More articles by this author Alison C. Keenan More articles by this author Peter E. Clark More articles by this author Stephen B. Riggs More articles by this author Expand All Advertisement PDF downloadLoading ...

Benign prostatic hyperplasia (BPH) may decrease patient quality of life and often leads to acute urinary retention and surgical intervention. While effective treatments are available, many BPH patients do not respond or develop resistance to treatment. To understand molecular determinants of clinical symptom persistence after initiating BPH treatment, we investigated gene expression profiles before and after treatments in the prostate transitional zone of 108 participants in the Medical Therapy of Prostatic Symptoms (MTOPS) Trial. Unsupervised clustering revealed molecular subgroups characterized by expression changes in a large set of genes associated with resistance to finasteride, a 5α-reductase inhibitor. Pathway analyses within this gene cluster found finasteride administration induced changes in fatty acid metabolism, amino acid metabolism, immune response, steroid hormone metabolism, and kinase activity within the transitional zone. We found that patients without this transcriptional response were highly likely to develop clinical progression, which is expected in 13.2% of finasteride-treated patients. Importantly, a patient's transcriptional response to finasteride was associated with their pre-treatment kinase expression. Further, we identified novel expression signatures of finasteride resistance among the transcriptionally responded patients. These patients showed different gene expression profiles at baseline and increased prostate transitional zone volume compared to the patients who responded to the treatment. Our work suggests molecular mechanisms of clinical resistance to finasteride treatment that could be potentially helpful for personalized BPH treatment as well as new drug development to increase patient drug response.

Introduction: The effect of individual non-narcotic analgesics in cystectomy enhanced recovery after surgery (ERAS) is unknown. Additionally, many non-narcotic medications are associated with side effects pertinent to the cystectomy population. To better understand the actual use and utility of these medications, we sought to characterize the association between non-narcotic medications and milligram morphine equivalent (MME) narcotic score during the postoperative inpatient stay. Methods: We reviewed 260 consecutive ERAS cystectomy patients. The MME impact of non-narcotic compliance and cumulative dose of medication received was evaluated separately with general linear models. We also assessed relationship of non-narcotic compliance to patient reported pain score, length of stay (LOS), and time to return of bowel function (ROBF) and performed manual review of postoperative documentation to identify reasons for medication noncompliance. Results: Compliance with postoperative acetaminophen, gabapentin, and ketorolac was low. There was an inverse relationship between ketorolac dose and MME on postoperative day 1 (-0.026 MME/mg; P = 0.004) and postoperative day 2 (-0.33 MME/mg; P < 0.001). Compliance with ketorolac was associated with lower MME on postoperative day 1 (26.1 MME v. 33.6 MME; P = 0.023). There were no such associations identified with gabapentin or acetaminophen. Gabapentin compliance was associated with earlier ROBF (3.7 days v. 4.3 days; P = 0.006). Ketorolac compliance was associated with lower pain score on POD1 (3.25 VAS v. 4.07 VAS; P = 0.019) and POD2 (3.05 VAS v. 3.85 VAS; P = 0.040) There was no association between medication compliance and LOS. The most common reasons identified for non-compliance with gabapentin and ketorolac were renal function concerns (38% and 40% respectively), bleeding concerns with ketorolac (20%) and concerns for neurologic adverse effect with gabapentin (16%). Conclusion: Compliance with non-narcotic medications in our ERAS cystectomy protocol was poor. There was a modest association with ketorolac and postoperative MME but no association with gabapentin or acetaminophen. Further study will clarify the role of these medications for cystectomy patients. Component specific analysis of protocolized care is valuable and may alter care pathways. (c) 2024 Published by Elsevier Inc.

IntroductionMen with advanced germ cell tumors (GCT) treated with chemotherapy are at high risk of venous thromboembolism (VTE). Predictors of VTE may identify patients who would benefit from prophylactic anticoagulation.Patients and MethodsMen with advanced GCT (Stage IS, II, III) treated with chemotherapy were identified at two centers. High genomic risk was defined from a 5 single nucleotide polymorphism (SNP) germline panel. Logistic regression was used to evaluate the impact of genomic risk on VTE within six months of chemotherapy initiation. Orthogonal Projection to Latent Structures Discriminant Analysis (OPLS-DA) was used to build models to predict VTE based on clinical variables and an 86 SNP panel.ResultsThis 123-patient cohort experienced a VTE rate of 26% with an incidence of high genomic risk of 21%. Men with high genomic risk did not have a significantly higher VTE rate (31%, 8/26) than men with low genomic risk (25%, 24/97), unadjusted OR 1.4 (95% CI 0.5–3.5, p=0.54). Incorporation of clinical variables (Khorana score, N3 status and elevated LDH) resulted in adjusted OR 2.1 (95% CI 0.7–6.5, p=0.18). A combined model using clinical variables and 86 SNPs performed similarly (AUC 0.77) compared to clinical variables alone (AUC 0.72).ConclusionsA previously established 5-SNP panel was not associated with VTE among patients with GCT receiving chemotherapy. However, multivariable models based on clinical variables alone warrant further validation to inform prophylactic anticoagulation strategies.MicroAbstractVTE occurs at a high rate in men with germ cell tumors treated with curative intent chemotherapy. A 5-SNP genetic risk panel was not significantly associated with VTE in a retrospective cohort of 123 patients. Clinical variables alone with or without a broad 86 SNP panel did successfully identify a high-risk population who warrant further study of prophylactic anticoagulation.Clinical Practice PointsMen with advanced germ cell tumors (GCT) treated with chemotherapy are at high risk of venous thromboembolism (VTE). We analyzed 123 patients with advanced GCT treated with cisplatin-based chemotherapy to evaluate the association between VTE and a 5 gene single nucleotide polymorphism (SNP) panel that has previously been associated with VTE risk. While no significant association between VTE and the 5-SNP panel was found, we did show that clinical variables are a powerful predictor of VTE. Additionally, a broad 86 SNP panel did provide additional benefit when combined with clinical variables for VTE risk stratification using a novel machine learning model. These results emphasize that VTE is a common issue in this population and strategies to reduce the risk of VTE, such as with prophylactic anticoagulation, are urgently needed. We propose a prospective clinical trial of prophylactic anticoagulation in this high-risk group, which would be practice changing if it were shown to reduce the risk of VTE in this population of patients undergoing curative intent treatment.

PURPOSE:To prevent avoidable treatment and make more informed care decisions about small renal masses, the use of renal mass biopsies has increased since the early 2000s. In April 2017, Atrium Health Carolinas Medical Center began requiring biopsies before all percutaneous thermal ablation procedures for renal masses. We aim to determine the effect of this preablation biopsy mandate on small renal mass treatment decisions.MATERIALS AND METHODS:Our study is a retrospective analysis of a prospectively managed database designed to track patients with small renal masses presented at the Kidney Tumor Program from 2000-2020. We separated patients into 2 cohorts (pre- and postmandate) based on the initial encounter date, excluding those from April 2017-April 2018 to allow for implementation of the mandate. We also excluded patients with masses >4 cm.RESULTS:Overall, we found no significant difference between the pre- and postmandate cohorts, with race as an exception. Implementation of the mandate coincided with an increase in biopsies for both ablation and nonablation treatment pathways (P < .001, P = .01). Renal mass biopsy rates increased in all socioeconomic groups except the lowest quartile. Additionally, Black/Hispanic patients had the highest biopsy rate. We found significant changes in treatment decisions between our cohorts: surgery decreased 24% (P < .001), active surveillance increased 28% (P < .001), and patients with no follow-up decreased 8% (P = .03).CONCLUSIONS:Our data indicate that a preablation renal mass biopsy mandate is associated with the wider use of biopsies for all small renal mass patients, fewer surgical interventions, and an increase in active surveillance.

e16520 Background: Galectin-1 (Gal-1) and Galectin-3 (Gal-3) are carbohydrate binding proteins which regulate cellular adhesion, proliferation, and apoptosis in solid tumors . Prior studies have reported that Gal-3 expression is associated with non-muscle invasive UC progression to muscle invasive disease. Therefore, we assessed whether UC Gal-1 and Gal-3 protein expression in cystectomy specimens was prognostic for overall survival (OS) or recurrence free survival (RFS). Methods: Tissue microarrays (TMA) were generated from chemotherapy naïve cystectomy specimens. Biopsies included benign urothelium, noninvasive papillary UC (Ta), UC in situ (Tis), and invasive UC (p1-pT4: INV). Gal-1 and Gal-3 IHC expression was scored by intensity (0-3) and % of cells staining positive (0-100). An H-score (product of % and intensity) was utilized for analysis. Clinical data including pathologic T stage, N stage, surgical margins, tumor size, and Charlson Comorbidity Index (CCI) were included in multivariable analysis. Results: 656 biopsies were evaluated from 301 patients. 198 (30%) were from benign urothelium, 28 (4%) Ta, 178 (27%) Tis, and 252 (38%) were INV. With a median follow up of 64 months, median OS was 47.5 mo and median RFS was 38.4 mo. Gal-1 H-score was significantly higher in INV specimens than non-INV specimens, and the inverse relationship was found with Gal-3 (median Gal-1 H-score was 0 across non-invasive tissue types and 200 in invasive, p < 0.01 and median Gal-3 score was 270 across non-invasive tissue types and 70 in invasive, p < 0.01). In multivariable analysis, T stage, N stage, margins, tumor size, PCV pre-op and CCI score were prognostic of OS and RFS. Gal-1 and Gal-3 H-scores were not predictive of RFS (Gal-1: HR 1.0, p = 0.67, Gal-3: HR 1.0, p = 0.25) or OS (Gal-1: HR 1.0, p = 0.71, Gal-3: HR 1.0, p = 0.37). Intra-tumoral Gal-1 and Gal-3 expression heterogeneity was observed. 203 (67%) patients had 2 or more tissue specimens and of these, 99 (49%) had discordant H-scores at the same level of invasion. Conclusions: In this cohort, both Gal-1 and Gal-3 expression correlated with biopsy T stage; however, the highest intra-tumor H-score per specimen did not independently predict for RFS or OS. This result differs from prior observations from smaller cohorts that showed an association between Gal-3 expression and RFS, suggesting that intra-tumoral Gal-1/Gal-3 heterogeneity may confound the study of Gal-1 and Gal-3 as a potential biomarker in UC. The biological significance of intra-tumoral Gal heterogeneity in UC merits further investigation.