OBJECTIVE:To describe the oncological outcomes for patients with newly diagnosed bladder cancer, as long-term oncological outcomes and natural history of different initial subtypes of diagnoses of bladder cancer are understudied. PATIENTS AND METHODS:This was a prospective, multicentre population-based cohort study, where newly diagnosed patients with bladder cancer from 1995 to 1996 in Stockholm County, Sweden were followed. The primary outcome was cancer-specific mortality (CSM), separately analysed for low-grade non-muscle-invasive bladder cancer (NMIBC Low), high-grade non-muscle-invasive bladder cancer (NMIBC High), and muscle-invasive bladder cancer (MIBC). We used cumulative incidence with competing risk to assess survival outcomes. RESULTS:In total, 526 patients were included, 396 had NMIBC. Out of 102 patients with T1, 37% died of bladder cancer during the 25-year follow-up. The rate of CSM for NMBIC Low was 3%, NMIBC High 26%, and MIBC 71%, respectively. For the operated patients with MIBC, the 5-year CSM was 39%. Of the 178 patients with NMIBC High, 22% progressed to MIBC, 10% had lymph node progression, and 17% progressed to metastatic disease during the follow-up. The main limitation of the study is that it was established 30 years ago. CONCLUSION:In this population-based study, we found that patients with NMIBC High had a persistent risk of CSM up to 25 years from the initial diagnosis, more specifically in patients with T1 tumours. The study demonstrates the importance for optimal treatment for selective high-risk T1 patients with long life expectancy, and high risk of progression.

PURPOSE The purpose of this study was to elucidate the relationship between the tumor microenvironment (TME) and cellular diversity in bladder cancer (BLCA) progression, leveraging single-cell RNA sequencing (scRNA-seq) data to identify potential prognostic biomarkers and construct a prognostic model for BLCA. METHODS We analyzed scRNA-seq data of normal and tumor bladder cells from the Gene Expression Omnibus (GEO) database to uncover crucial markers within the bladder TME. The study compared gene expression in normal versus tumor bladder cells, identifying differentially expressed genes. These genes were subsequently assessed for their prognostic significance using patient follow-up data from The Cancer Genome Atlas. Prognostic models were constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression analyses, focusing on eight genes of interest. The predictive performance of the model was also tested against additional GEO data sets (GSE31684, GSE13507, and GSE32894). RESULTS The prognostic model demonstrated reliable prediction of patient outcomes. Validation through gene set enrichment analysis and immune cell infiltration assessment supported the model's efficacy. The results from both the univariate and multivariate analyses suggest that the risk score is an independent prognostic factor with a hazard ratio of 2.97 (95% CI, 2.28 to 3.9, P < .001). In the validation cohort, the AUC at 1, 2, and 3 years is 0.74, 0.74, and 0.72, respectively. CONCLUSION Our findings proposed biomarkers with prognostic potential, laying the groundwork for future in vitro validation and therapeutic exploration. This contributes to a deeper understanding of the genes associated with bladder TME and may improve prognostic precision in BLCA management.

BACKGROUND AND OBJECTIVES:Pituitary adenomas (PAs) are the most common intrasellar tumor. Clinically relevant adenomas have a prevalence of 1 per 1000 in the general population. Transsphenoidal surgery (TSS) is the most common surgical treatment and is the first-line management for most PAs. Most patients fare well postoperatively, but a subset of patients experience a prolonged length of stay (PLOS). In this article, we aim to identify demographic and clinical factors associated with PLOS after TSS for PA. METHODS:Patients with sellar pathologies surgically treated at a single tertiary center from March 1, 2009, to May 31, 2020, were retrospectively reviewed. All patients older than 18 years receiving nonemergent endoscopic TSS for pituitary adenoma were included. Clinical and demographic characteristics were analyzed using χ 2 -tests and student t -tests. For those factors with a P -value less than .01, multivariate logistic regression and negative binomial regression models were constructed to estimate the adjusted odds of PLOS across predictive factors. RESULTS:A total of 301 patients were included in the study. This cohort had an average age of 54.65 ± 15.06 years and an average body mass index of 29.47 ± 6.69. The median length of stay was 54.9 hours [25th-75th percentiles: 43.5-72.9]. Postoperative cerebrospinal fluid leak ( P < .01), postoperative diabetes insipidus (DI) ( P < .01), increased surgery duration ( P = .01), and elevated maximal tumor dimension ( P = .01) were predictive of PLOS in logistic regression. Increased surgery duration, previous pituitary radiation, intraoperative complications, and postoperative DI (all P < .01) were associated with increased rate of PLOS in negative binomial regression. CONCLUSION:Patients undergoing endoscopic TSS for PA resection demonstrate prolonged lengths of stay if they have higher tumor burden, have lengthier surgeries with intraoperative complications, or develop postoperative complications such as cerebrospinal fluid leak or DI. Careful monitoring of these factors will allow for better resource optimization, reducing costs to both the hospital and the patient.

Background: Enhanced recovery after surgery (ERAS) has significantly decreased the morbidity associated with radical cystectomy. However, infectious complications including sepsis, urinary tract (UTIs), wound (WIs), and intra-abdominal (AIs) infections remain common. Objective: To assess whether intracorporeal urinary diversion (ICUD) and antibiogramdirected antimicrobial prophylaxis would decrease infections after robotic-assisted radical cystectomy (RARC). Design, setting, and participants: A retrospective analysis was performed of a prospectively maintained database of patients undergoing RARC between 2014 and 2022 at a tertiary care institution, identifying two groups based on adherence to a prospectively implemented modified ERAS protocol for RARC: modified-ERAS-ICUD and antibiogram-directed ampicillin-sulbactam, gentamicin, and fluconazole prophylaxis were utilized (from January 2019 to present time), and unmodified-ERAS-extracorpor eal urinary diversion (UD) and guideline-recommended cephalosporin-based prophylaxis regimen were utilized (from November 2014 to June 2018). Patients receiving other prophylaxis regimens were excluded. Intervention: ICUD and antibiogram-directed infectious prophylaxis. Outcome measurements and statistical analysis: The primary outcome was UTIs within 30 and 90 d postoperatively. The secondary outcomes were WIs, AIs, and sepsis within 30 and 90 d postoperatively, and Clostridioides difficile infection (CDI) within 90 d postoperatively. Results and limitations: A total of 396 patients were studied (modified-ERAS: 258 [65.2%], unmodified-ERAS: 138 [34.8%]). UD via a neobladder was more common in the modified-ERAS cohort; all other intercohort demographic differences were not statistically different. Comparing cohorts, modified-ERAS had significantly reduced rates of 30-d (7.8% vs 15.9%, p = 0.027) and 90-d UTIs (11.2% vs 25.4%, p = 0.001), and 30-d WIs (1.2% vs. 8.7%, p < 0.001); neither group had a WI after 30 d. Rates of AIs, sepsis, and CDI did not differ between groups. On multivariate regression, the modified-ERAS protocol correlated with a reduced risk of UTIs and WIs (all p < 0.01). The primary limitation is Conclusions: Utilization of ICUD and antibiogram-based prophylaxis correlates with sigPatient summary: In this study of infections after robotic radical cystectomy for bladder cancer, we found that intracorporeal (performed entirely inside the body) urinary diversion and an institution-specific antibiogram-directed antibiotic prophylaxis regimen led to fewer urinary tract infections and wound infections at our institution. (c) 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The combination of sequential intravesical gemcitabine and docetaxel (Gem/Doce) chemotherapy has been considered a feasible option for BCG (Bacillus Calmette-Guérin) treatment in non-muscle invasive bladder cancer (NMIBC), gaining popularity during BCG shortage period. We seek to determine the efficacy of the treatment by comparing Gem/Doce induction alone vs induction with maintenance, and to evaluate the treatment outcomes of two different dosage protocols. A bi-center retrospective analysis of consecutive patients treated with Gem/Doce for NMIBC between 2018 and 2023 was performed. Baseline characteristics, risk group stratification (AUA 2020 guidelines), pathological, and surveillance reports were collected. Kaplan–Meier survival analysis was performed to detect Recurrence-free survival (RFS). Overall, 83 patients (68 males, 15 females) with a median age of 73 (IQR 66–79), and a median follow-up time of 18 months (IQR 9–25), were included. Forty-one had an intermediate-risk disease (49

Introduction: Pituitary adenomas (PA) are the most common intrasellar tumor and have a prevalence of a prevalence of 17%, and transsphenoidal surgical approach (TSA) is the most common surgical treatment. Most patients fare well postoperatively, but a subset of patients experience a prolonged length of stay (PLOS). The aim of this study was to identify demographic and clinical factors associated with PLOS following TSA for PA.

Introduction: While the prognostic value of immune system biomarkers has been well explored, role of cancer associated macrophages in bladder cancer(BC) is unclear due to lack of consistent results, coupled with tissue nonspecific transcriptomic signature. Methodology: Data acquisition from 3,936 patients of The Cancer Genome Atlas (TCGA) in addition to Gene Expression Omninus (GEO) data sets GSE13507, GSE16945, GSE48277, GSE32894, GSE149582, as well as European Genotype Phenotype EGAS000001004507 was obtained. Tumor associated macrophages M1 and M2 were defined utilizing 188 and 159 gene expression profiles via xCell computational algorithm. To obtain bladder tissue residence macrophage signatures, scRNA seq was performed on tissue collected from surgical resection of 5 HG bladder cancer patients and 2 healthy controls. CellRanger software package with default parameters was utilized giving a total of 8,068 cells. FindAllMarkers was utilized for integration of DEG genes (cancer vs control) among the cluster and identification of BC macrophage specific markers. Endpoint of OS were measured in months from the time of cystectomy to follow up. Results: Surprisingly, presence of M1 infiltration was found to be associated with improved OS in two out of eight cohorts only (GSE32894, GSE70691, p<0.001), while the remainder detected no significant difference. Similarly, no association with OS was detected among all 8 cohorts with M2 infiltration. To improve our understanding of tissue specific markers of macrophage population in bladder, we then analyzed macrophage clusters detected within scRNAseq of BC patients compared to healthy. Gene ontology enrichment analysis of functions within tumor specific macrophages demonstrated an exaggerated expression of mTORC1 signaling, PI3K/AKT/mTOR signaling, TGF beta and EGF receptor pathways compared to non-cancer controls. Reanalysis of 22 tissue specific markers for M1/M2 infiltration showed no difference in any of the 8 cohorts with M1 high vs low infiltration. Similarly, addition of M2 infiltration as predictive marker yielded no further associations with OS in all but one cohort (GSE32894, p=0.00041), where high M2 tumor presence was associated with improved OS. Conclusion: Our study represents the largest TAMs evaluation of BC across 8 cohorts with additional scRNA seq exploration of tissue specific signatures, demonstrating no association with OS in bladder cancer. Citation Format: Laura Bukavina, Spencer Bell, Daniel Geynisman, Ilaha Isali, Daniel Ranti, John Sfakianos, Henkel Valentine, Adam Calaway, Alexander Kutikov, Andres Correa, Robert Uzzo, Lee Ponsky, Philip Abbosh. Macrophage transcriptomic signature validation in scRNA seq and overall survival differences in urothelial carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5141.

Single-port (SP) robot-assisted laparoscopic partial nephrectomy (RAPN) is a promising new technique. The aim of this study was to compare surgical and oncological outcomes of SP-RAPN to the multi-port (MP) surgical platform. This is a retrospective, cohort-based study involving patients undergoing SP-RAPN between 2019 and 2020 at a single institution. Demographic, preoperative, surgical, and postoperative outcomes data were gathered and compared to a 1-to-1 matched MP cohort. A total of 50 SP and 50 matched MP cases were included. Length of surgery and ischemia time were not statistically significant between the two cohorts; however, estimated blood loss (EBL) was significantly lower in the SP group than in the MP (IQR 25–50 vs. IQR 50–100 mL, p = 0.002). No differences were seen in regard to the 30-day readmission rate, surgical margin status, pain scores, and complications between the two approaches. We found no statistically significant differences in positive margins, pain score, length of stay, or readmission rate between matched SP and MP patients. These data support the viability of the SP technique as an alternative to MP-RAPN when in the hands of experienced surgeons.

OBJECTIVE To characterize first and second recurrence patterns using 26 years of cohort-level follow-up and microsimulation modeling.METHODS Patients diagnosed with nonmuscle-invasive bladder cancer in Stockholm County between 1995 and 1996 were included. Clinical, pathological, and longitudinal follow-up data were gathered. Logistic regressions, Kaplan Meier curves, and Cox proportional hazards models were run to generate assumptions for a microsimulation model, simulating first and second recurrence and progression for 10,000 patients.RESULTS Three hundred eighty-six patients were included: 67.4% were male; > 50% were TaLG; and 37.5% were American Urological Association high-risk. Median time to recurrence was 300 days. Three patients had missing data. Cohort follow-up has been carried out for 26 years. For simulated firstrecurrences, low-risk patients recurred at 56.6% over 15 years of follow-up, with 2.2% muscleinvasive (MI) progression; intermediate-risk patients recurred at 62.8%, with 4.3% MI progression; high-risk patients recurred at 48.7% over 15 years, with MI progression at 14.3%. For second recurrences, 70.7%, 75.7%, and 84.7% of low, medium, and high-risk patients recurred. No patients were seen to have first recurrences after 9 years, with low, but notable, rates beyond 5 years.CONCLUSION These data suggest that low-, intermediate-, and high-risk patients without recurrence at 5 years may be potentially transitioned to less invasive monitoring.

CD40 is a central co-stimulatory receptor implicated in the development of productive anti-tumor immune responses across multiple cancers, including bladder cancer. Despite strong preclinical rationale, systemic administration of therapeutic agonistic antibodies targeting the CD40 pathway have demonstrated dose limiting toxicities with minimal clinical activity to date, emphasizing an important need for optimized CD40-targeted approaches, including rational combination therapy strategies. Here, we describe an important role for the endogenous IL-15 pathway in contributing to the therapeutic activity of CD40 agonism in orthotopic bladder tumors, with upregulation of trans-presented IL-15/IL-15Rα surface complexes, particularly by cross-presenting cDC1s, and associated enrichment of activated CD8 T cells within the bladder tumor microenvironment. In bladder cancer patient samples, we identify DCs as the primary source of IL-15, however, they lack high levels of IL-15Rα at baseline. Using humanized immunocompetent orthotopic bladder tumor models, we demonstrate the ability to therapeutically augment this interaction through combined treatment with anti-CD40 agonist antibodies and exogenous IL-15, including the fully-human Fc-optimized antibody 2141-V11 currently in clinical development for the treatment of bladder cancer. Combination therapy enhances the crosstalk between Batf3-dependent cDC1s and CD8 T cells, driving robust primary anti-tumor activity and further stimulating long-term systemic anti-tumor memory responses associated with circulating memory-phenotype T and NK cell populations. Collectively, these data reveal an important role for IL-15 in mediating anti-tumor CD40 agonist responses in bladder cancer and provide key proof-of-concept for combined use of Fc-optimized anti-CD40 agonist antibodies and agents targeting the IL-15 pathway. These data support expansion of ongoing clinical studies evaluating anti-CD40 agonist antibodies and IL-15-based approaches to evaluate combinations of these promising therapeutics for the treatment of patients with bladder cancer.

Objective: We aimed to compare perioperative and oncologic outcomes for patients undergoing robotic-assisted radical cystectomy (RARC) with intracorporeal ileal conduit (IC) and neobladder (NB) urinary diversion.Methods: Patients undergoing RARC with intracorporeal urinary diversion between January 2017 and January 2022 at the Icahn School of Medicine at Mount Sinai, New York, NY, USA were indexed. Baseline demographics, clinical characteristics, perioperative, and oncologic out-comes were analyzed. Survival was estimated with Kaplan-Meier plots.Results: Of 261 patients (206 [78.9%] male), 190 (72.8%) received IC while 71 (27.2%) received NB diversion. Median age was greater in the IC group (71 [interquartile range, IQR 65-78] years vs. 64 [IQR 59-67] years, p<0.001) and BMI was 26.6 (IQR 23.2-30.4) kg/m(2). IC group was more likely to have prior abdominal or pelvic radiation (15.8% vs. 2.8%, p=0.014). American Association of Anesthesiologists scores were comparable between groups. The IC group had a higher proportion of patients with pathological tumor stage 2 (pT2) tumors (34 [17.9%] vs. 10 [14.1%], p=0.0 08) and pathological node stages pN2-N3 (28 [ 14.7%] vs. 3 [4.2%], p<0.001). The IC group had less median operative time (272 [IQR 246-306] min vs. 341 [IQR 303-378] min, p<0.001) and estimated blood loss (250 [150-500] mL vs. 325 [200-575] mL, p=0.00 2). Thirty-and 9 0-day complication rates were 44.4% and 50.2%, respectively, and comparable between groups. Clavien-Dindo grades 3-5 complications occurred in 27 (10.3%) and 34 (13.0%) patients within 30 and 90 days, respectively, with com-parable rates between groups. Median follow-up was 324 (IQR 167-552) days, and comparable between groups. Kaplan-Meier estimate for overall survival at 24 months was 89% for the IC cohort and 93% for the NB cohort (hazard ratio 1.23, 95% confidence interval 1.05-2.42, p=0.02). Kaplan-Meier estimate for recurrence-free survival at 24 months was 74% for IC and 87% for NB (hazard ratio 1.81, 95% confidence interval 0.82-4.04, p=0.10).Conclusion: Patients undergoing intracorporeal IC urinary diversion had higher postoperative cancer stage, increased nodal involvement, similar complications outcomes, decreased over-all survival, and similar recurrence-free survival compared to patients undergoing RARC with intracorporeal NB urinary diversion.2023 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier B.V.

Abstract Introduction: We aim to assess the transcriptomic features of the single cell level to identify intracellular pathogens in patients with high grade bladder cancer. Methodology: CellRanger and Alevin were utilized to extract cell barcodes and unique molecular identifiers. After quality control, reads were aligned with human reference genome with Kraken2 for species level identification of bacteria. Contaminants (false positives) were removed based on higher frequencies and negative control (reference control) of 2,491 sterile cell experiments. Seuret Findmarkers, scIntegrate, and scDensity Plot were utilized to normalize the data, cluster the cells, and calculate markers in each cluster of differentially expressed genes between the two conditions. We focused our analysis on Pseudomonas aeruginosa due to high urogenital virulence, and immunomodulation capabilities by pattern recognition receptors and inflammasome. Results: We identified presence of three over-represented intracellular taxa in tissue biopsies of patients with BC compared to healthy controls (after false discovery rate correction and cross validation of contaminants). Patients with history of high-grade BC demonstrated increased presence of Aeromonas (175,473 reads, 54%), Pseudomonas (75,002 reads, 26.73%), and Bacillus (15,410 reads, 5.49%) in their tissue samples, not visualized in healthy controls (counts <10). Among 8,324 cells (across 7 patients), classical CD14+ monocyte subtype was most likely to be exposed to Pseudomonas species (4150/5069, 81.8%), followed by non-classical CD16+ monocytes (722/1040, 69.4%), and CD8+ Tcells (348/680, 51.1%). (Figure 1A-C). Relative gene expression level between exposed and non-exposed monocytes demonstrated total 25 upregulated genes, with increased expression GNBL21 (aka: RACK1, log10 4.1), MALAT1(log10 3.7), TCEB2(log10 2.9) (increasing proliferation, migration, and reduction of cell autophagy) compared to non-infected, and normal controls. Pseudomonas involvement of non-monocyte cells (CD8+, CD4+Th17, CD4+ naïve) was associated with disease progression (2/5 patients), as well as increased expression of IFI6/27(interferon alpha inducible protein 6 &27), ITAC (interferon inducible T cell alpha-chemoattractant). Conclusion: Altogether, our analysis depicted the distribution of intracellular bacteria not previously recognized within tumor microenvironment utilizing scRNAseq, and revealed overexpression of RACK1 in Pseudomonas positive cells, associated with apoptosis resistance. Citation Format: Laura Bukavina, Mohit Sindhani, Henkel Valentine, Daniel Ranti, Kirtishri Mishra, Alexander Kutikov, Shilpa Gupta, John Sfakiano, Mahmoud Ghannoum, Mauricio Retuerto, Andres Correa, Robert Uzzo, Philip Abbosh. Identification of intratumor pathogens from single-cell RNA sequencing, cellular dysfunction and immune response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5891.

BACKGROUND: For decades, immunotherapies have been integral for the treatment and management of bladder cancer, with immune checkpoint inhibitors (ICIs) transforming patient care in recent years. However, response rates are poor to T cell-targeted ICIs such as programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) blocking antibodies, framing a critical need for complementary immunotherapies. Promising strategies involve harnessing the activation potential of natural killer (NK) cells. They quickly exert their antitumor activity via signaling through germline-encoded activating receptors and are rapidly sensitized to new tissue microenvironments via their regulation by polymorphic HLA class I, KIR and NKG2A receptors. OBJECTIVE: In this review, we examined the roles of currently available NK-targeted antitumor treatment strategies such as engineered viral vectors, small-molecule IMiDs, NK agonist antibodies, interleukins, and chimeric antigen receptor (CAR) NK cells, and their potential for improving the efficacy of immunotherapy in the treatment of bladder cancer. METHODS: Through review of current literature, we summarized our knowledge of NK cells in solid tumors and hematologic malignancies as their roles pertain to novel immunotherapies already being applied to the treatment of bladder cancer or that offer rationale for considering as potential novel immunotherapeutic strategies. RESULTS: NK cells play a critical role in shaping the tumor microenvironment (TME) that can be exploited to improve T cell-targeted immunotherapies. CONCLUSIONS: Emerging evidence suggests that NK cells are a prime target for improving antitumor functions in immunotherapies for the treatment of bladder cancer. Further research into profiling NK cells in settings of immunotherapies for bladder cancer could help identify patients who might maximally benefit from NK cell-targeted immunotherapies and the various approaches for exploiting their antitumor properties.

Introduction: Perioperative management of patients undergoing radical cystectomy and urinary diversion utilizing both open and minimally invasive techniques have routinely included the use of drains in the operative field. We herein demonstrate the safety of roboticassisted radical cystectomy (RARC) without the routine use of postoperative drains. Methods: Patients who underwent drainless RARC with intracorporeal urinary diversion between 2017 and 2022 at our institution were reviewed. Baseline and clinical characteristics as well as perioperative and postoperative outcomes were analyzed. The primary study outcome was incidence of postoperative urinary leak or intra-abdominal infectious collections within 90 days of RARC. A univariate and multivariable logistic regression analysis was performed to determine associations between study variables and the primary outcome. Results: Of 381 patients, 298 (78.2%) were male and median age and BMI were 68 (63, 76) and 26.2 [23.0, 29.8], respectively. Overall 30 and 90-day complication rates were 39.6% and 50.4%, respectively. Twenty-one (5.5%) patients experienced a urine leak or intraabdominal infectious collections. Sub-group analysis of patients who experienced the primary outcome demonstrated median postoperative day of presentation was day 19, and this group required 16 total additional procedures. On multivariable logistic regression analysis, only prior radiation therapy was associated with the development of the primary outcome of urinary leak or intra-abdominal infectious collection (odds ratio: 15.12, 95% confidence interval [1.52-156.8], p = 0.02). Conclusion: Drainless RARC with totally intracorporeal urinary diversion achieved competitive perioperative and complications outcomes compared to prior open and robotic series. In the context of a larger enhanced recovery after surgery protocol in RARC patients, the routine use of drains may be safely omitted. (c) 2023 Published by Elsevier Inc.

You have accessJournal of UrologyCME1 Apr 2023MP66-11 PREFERENCE SIGNALING IN THE UROLOGY MATCH: IMPACT AND USAGE TRENDS Ralph Grauer, Daniel Ranti, Kirsten Greene, Michael Gorin, Mani Menon, and Saša Zorc Ralph GrauerRalph Grauer More articles by this author , Daniel RantiDaniel Ranti More articles by this author , Kirsten GreeneKirsten Greene More articles by this author , Michael GorinMichael Gorin More articles by this author , Mani MenonMani Menon More articles by this author , and Saša ZorcSaša Zorc More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003329.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Analyzing behavior from the implementation of signals during the American Urological Association (AUA) urology match will help clarify applicant/program signal usage and trends. METHODS: Using verified data from the match as well as survey data reported by applicants and programs, a logistic regression was performed on applicant factors associated with obtaining a residency interview: age, gender, degree (MD or DO), distribution of signals, US senior status, minority status, Latino status, IMG status, presence of a home urology program, AUA geographic section, and USMLE Step 1 score. We described signal distribution strategies stratified by program competitiveness and program behavior upon receipt of signals with respect to interviewing/ranking applicants. RESULTS: A total of 2,659 signals were sent by 553 candidates submitting rank lists for 364 positions at 142 programs. Programs received a median of 352 applications and were signaled to a median of 16 times each (IQR: 8–26). In a logistic regression predicting interview status, we found that geographic proximity (OR 3.25, 95% CI, 2.05–5.15; p=0.001), and signal status (OR 6.04, 95% CI, 3.50–10.40; p<0.001) were predictive of receiving an interview. Using multiple imputation to broadening the dataset, male gender (OR: 0.64, 95% CI, 0.45–0.92; p=0.039) and IMG status (OR: 0.35, 95% CI, 0.15–0.81; p=0.036) were negatively predictors, while MD degree (OR 2.36, 95% CI, 1.27–4.36; p=0.023), and US senior status (OR 1.91, 95% CI, 1.13–3.23; p=0.039), were positive predictors. CONCLUSIONS: We analyzed trends of the newly added signals. We reportedstrategies for signal dispersal, factors associated with obtaining interviews, and how signals informed program interviewing/ranking decisions. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e936 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ralph Grauer More articles by this author Daniel Ranti More articles by this author Kirsten Greene More articles by this author Michael Gorin More articles by this author Mani Menon More articles by this author Saša Zorc More articles by this author Expand All Advertisement PDF downloadLoading ...

You have accessJournal of UrologyCME1 May 2022PD12-05 SPATIAL TRANSCRIPTOMICS PROVIDES EVIDENCE FOR ALTERNATIVE CHECKPOINT AXES IN BCG-TREATED NMIBC Daniel Ranti, Yuanshuo Wang, Jorge Daza, Sanjana Shroff, Kristin Beaumont, Amir Horowitz, and John Sfakianos Daniel RantiDaniel Ranti More articles by this author , Yuanshuo WangYuanshuo Wang More articles by this author , Jorge DazaJorge Daza More articles by this author , Sanjana ShroffSanjana Shroff More articles by this author , Kristin BeaumontKristin Beaumont More articles by this author , Amir HorowitzAmir Horowitz More articles by this author , and John SfakianosJohn Sfakianos More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002538.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recurrence in BCG treated non-muscle invasive bladder cancer is significant. Disruption of the PD-1:PD-L1 axis via checkpoint inhibitors has shown promise, however studies show PD-L1 resistance may explain ∼25% of recurrence. Antitumor immunity is critical in clearing recurrent tumors, and evidence supports HLA-E/NKG2A as a key checkpoint in NK clearance of tumors and CD8 T-cell infiltration. We used spatial sequencing (STseq) to visualize interactions between tumor, stroma, and immune cells, and to investigate the molecular signatures associated with NK and T cells interacting with tumor. METHODS: STseq was performed on a specimen from 1 BCG-resistant NMIBC case. Slides were processed and imaged according to the Visium 10X protocol. Cell lineages were defined by Robertson AG et al. (Cell. 2017). Visium spots with >90th percentile of a linage signature were labelled as high-signature spots. Spots with multiple signatures, representing the plasticity across tumor lineages as well as the presence of NK or T cells, were annotated accordingly (Fig. 1A). We identified immune cells in and immediately surrounding tumor cells using NK, mutual NK and CD8 T cell, and tumor cell markers. Combined score of all listed genes and HLA-E were visualized (Fig. 1B). A differential gene expression analysis, scaled column-wise, was performed to understand the relationship between immune markers and tumor lineages (Fig. 1C). RESULTS: Neuronal tumor cells had the second highest observed co-expression of NK and CD8 T cell signatures and similarly expressed high levels of HLA-E. However, “neuronal” tumors lacked expression of PD-L1. We also observed NK and/or CD8 T cells infiltrating nests of other lineage subtypes, such as “p53”, but lacking activation signals. Lastly, preferential infiltration of “immune” tumor cell nests by NK and/or CD8 T cells was seen in areas of higher expression of HLA-E and CD274 (PD-L1). CONCLUSIONS: These results suggest overlapping non-redundant mechanisms of evasion. Our analysis confirms preferential infiltration of immune tumor cell nests by NK and/or CD8 T cells where expression of HLA-E and PD-L1 is higher, and that interactions between tumor immune cells is heterogeneous within samples. This suggests that HLA-E could be a secondary inhibitory axis of BCG resistance via NK mediated HLA-E:NKG2A. Source of Funding: NA © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e196 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel Ranti More articles by this author Yuanshuo Wang More articles by this author Jorge Daza More articles by this author Sanjana Shroff More articles by this author Kristin Beaumont More articles by this author Amir Horowitz More articles by this author John Sfakianos More articles by this author Expand All Advertisement PDF DownloadLoading ...

You have accessJournal of UrologyCME1 May 2022PD14-07 LONG-TERM CYSTOSCOPY SURVEILLANCE OF PATIENTS WITH NON-RECURRING NMIBC: IDENTIFYING THE POINT OF DIMINISHING RETURNS Daniel Ranti, Ralph Grauer, Yuanshuo Wang, Linda Dey, Lotta Renström, Gunnar Steinbeck, Abolfazl Hosseini, Peter Wiklund, Reza Mehrazin, John Sfakianos, and Nikhil Waingankar Daniel RantiDaniel Ranti More articles by this author , Ralph GrauerRalph Grauer More articles by this author , Yuanshuo WangYuanshuo Wang More articles by this author , Linda DeyLinda Dey More articles by this author , Lotta RenströmLotta Renström More articles by this author , Gunnar SteinbeckGunnar Steinbeck More articles by this author , Abolfazl HosseiniAbolfazl Hosseini More articles by this author , Peter WiklundPeter Wiklund More articles by this author , Reza MehrazinReza Mehrazin More articles by this author , John SfakianosJohn Sfakianos More articles by this author , and Nikhil WaingankarNikhil Waingankar More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002546.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Non-muscle invasive bladder cancer (NIMBC) is a heterogenous disease with high rates of disease recurrence up to 70%. The current AUA recommendations include initial close surveillance, followed by annual cystoscopies for 5 years, and thereafter based on shared decision making. In part due to the intense surveillance and cost of regular cystoscopies, bladder cancer has become the most expensive cancer to treat per capita in the United States. Approximately, 60% of costs are due to surveillance and treatment of recurrence. This abstract sought to analyze long-term recurrence of NMIBC to inform surveillance choices. METHODS: NMIBC patients were identified from a population-based dataset including all patients diagnosed with bladder cancer in Stockholm County between 1995-96. Demographics (gender, age at diagnosis) and clinical and treatment data (initial histology, tumor grade, tumor stage, focality, size, recurrence information, and mortality) were gathered. The starting point of our analysis was first diagnosis, and the stopping point was either date of recurrence or date of last follow-up. A random survival forest was run with tumor size, number of tumors, grade, stage, sex, and age at diagnosis as covariates. Risk groups were defined as the combination of grade (high, low) and stage (Tis, Ta, T1). A cumulative hazards curve for each risk group was created, and timepoint hazards were estimated via the derivative of the cumulative hazards. RESULTS: Median follow-up was 10 years, and median age at diagnosis was 71. There were 212 TaLG, 110 T1HG, 72 TaHG and 11 TisHG patients. Median time to recurrence was 283 days for TaLG; 190 days for TaHG; 119 days for T1HG; and 114 days for TisHG. Recurrence rates were 59.4% for TaLG, 66.7% for TaHG, 72.7% for T1HG and 27% for TisHG. Alive patients under surveillance without a recurrence were 9 for TisHG; 159 for TaLG; 57 for TaHG; and 84 for T1HG. Tumor number was the strongest predictor of recurrence (coefficient = 0.071) followed by tumor size (0.045). After 6 years, all patients showed low risk of recurrence. CONCLUSIONS: Tumor number was most predictive of recurrence, and after 6 years, all patients without disease carried low risk for recurrence. These findings suggest that surveillance cystoscopy, particularly in those with unifocal tumors and no recurrences, may be unnecessary beyond 6 years after diagnosis in select patients. Source of Funding: N/A © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e258 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Daniel Ranti More articles by this author Ralph Grauer More articles by this author Yuanshuo Wang More articles by this author Linda Dey More articles by this author Lotta Renström More articles by this author Gunnar Steinbeck More articles by this author Abolfazl Hosseini More articles by this author Peter Wiklund More articles by this author Reza Mehrazin More articles by this author John Sfakianos More articles by this author Nikhil Waingankar More articles by this author Expand All Advertisement PDF DownloadLoading ...

Background: The European Association of Urology guidelines recommend the use of imaging, biomarkers, and risk calculators in men at risk of prostate cancer. Risk predictive calculators that combine multiparametric magnetic resonance imaging with prebiopsy variables aid as an individualized decision-making tool for patients at risk of prostate cancer, and advanced neural networking increases reliability of these tools. Objective: To develop a comprehensive risk predictive online web-based tool using magnetic resonance imaging (MRI) and clinical data, to predict the risk of any prostate cancer (PCa) and clinically significant PCa (csPCa) applicable to biopsy-naïve men, men with a prior negative biopsy, men with prior positive low-grade cancer, and men with negative MRI. Design, setting, and participants: Institutional review board–approved prospective data of 1902 men undergoing biopsy from October 2013 to September 2021 at Mount Sinai were collected. Outcome measurements and statistical analysis: Univariable and multivariable analyses were used to evaluate clinical variables such as age, race, digital rectal examination, family history, prostate-specific antigen (PSA), biopsy status, Prostate Imaging Reporting and Data System score, and prostate volume, which emerged as predictors for any PCa and csPCa. Binary logistic regression was performed to study the probability. Validation was performed with advanced neural networking (ANN), multi-institutional European cohort (Prostate MRI Outcome Database [PROMOD]), and European Randomized Study of Screening for Prostate Cancer Risk Calculator (ERSPC RC) 3/4. Results and limitations: Overall, 2363 biopsies had complete clinical information, with 57.98% any cancer and 31.40% csPCa. The prediction model was significantly associated with both any PCa and csPCa having an area under the curve (AUC) of 81.9% including clinical data. The AUC for external validation was calculated in PROMOD, ERSPC RC, and ANN for any PCa (0.82 vs 0.70 vs 0.90) and csPCa (0.82 vs 0.78 vs 0.92), respectively. This study is limited by its retrospective design and overestimation of csPCa in the PROMOD cohort. Conclusions: The Mount Sinai Prebiopsy Risk Calculator combines PSA, imaging and clinical data to predict the risk of any PCa and csPCa for all patient settings. With accurate validation results in a large European cohort, ERSPC RC, and ANN, it exhibits its efficiency and applicability in a more generalized population. This calculator is available online in the form of a free web-based tool that can aid clinicians in better patients counseling and treatment decision-making. Patient summary: We developed the Mount Sinai Prebiopsy Risk Calculator (MSP-RC) to assess the likelihood of any prostate cancer and clinically significant disease based on a combination of clinical and imaging characteristics. MSP-RC is applicable to all patient settings and accessible online.