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Sacituzumab govitecan (SG) is an antibody-drug conjugate (ADC) targeting TROP2, which has recently been approved for treatment-refractory metastatic urothelial cancer (UC). However, the variability of TROP2 expression across different bladder cancer (BC) subtypes, as well as after enfortumab vedotin (EV) exposure, remains unknown. Using gene expression data from four clinical cohorts with1400 patient samples of muscle-invasive BC and a BC tissue microarray, we found that TROP2 mRNA and protein are highly expressed across basal, luminal, and stroma-rich subtypes, but depleted in the neuroendocrine subtype. In addition, TROP2 mRNA levels are correlated with NECTIN4 mRNA but are more highly expressed than NECTIN4 mRNA in patient cohorts and BC cell lines. Moreover, CRISPR/Cas9-mediated knockdown of TROP2 demonstrates that its expression is one factor governing SG sensitivity. After prolonged EV exposure, cells can downregulate NECTIN4, leading to EV resistance, but retain TROP2 expression and remain sensitive to SG, suggesting nonoverlapping resistance mechanisms to these ADCs. While our findings warrant further validation, they have significant implications for biomarker development, patient selection, and treatment sequencing in the clinic as well as clinical trial design and stratification for metastatic BC patients. PATIENT SUMMARY: In this report, we investigated the expression levels of the drug target TROP2 across different molecular subtypes of bladder cancer in multiple patient cohorts and cell lines. We found high levels of TROP2 in most subtypes except in the neuroendocrine subtype. Overall, TROP2 gene expression is higher than NECTIN4 gene expression, and cells resistant to enfortumab vedotin (EV), a NECTIN4-targeting antibody-drug conjugate, remain sensitive to sacituzumab govitecan (SG). Our findings suggest that SG may be effective across most bladder cancer subtypes, including the bladder cancers previously treated with EV.

To examine stakeholder perspectives regarding the lack of in-person externships and transition to a virtual urology residency interview format. The unprecedented disruption from the COVID-19 pandemic forced an abrupt pivot to a "virtual" Urology Match for the 2021 cycle. We aim for our study to inform ongoing deliberations on the future of the Urology Match.Following Urology Match day in February 2021, two surveys were distributed by the Society of Academic Urologists to all applicants and program directors (PDs) who participated in the 2021 Urology Match.Overall, 192 of 481 applicants (40%) and 63 of 160 PDs (39%) responded. Most applicants (67%) were satisfied with their match outcomes, although unmatched applicants were significantly more likely to be unsatisfied than matched applicants (98% vs 9%, P.0001). Most PDs were equally (79%) or more satisfied (13%) with their match outcomes compared with prior years. Nearly all applicants (93%) and PDs (94%) recommended retaining an in-person externship option. Most applicants (61%) and PDs (71%) felt their outcomes would not have changed with in-person interviews. Applicants and PDs were evenly split as to whether interviews should be conducted in-person or virtually in the future.The vast majority of applicants and PDs recommended retaining in-person externships for future match cycles despite high costs. In contrast, there was ambivalence amongst both groups of stakeholders regarding the format of interviews for future match cycles. We recommend virtual interviews moving forward to help alleviate the financial burden placed on applicants and increase equity.

Association between NECTIN4 mRNA expression and clinical characteristics in the Seiler cohort for (A) sex (p

The p values from pairwise comparisons amongst the molecular subtypes for each cohort using the Wilcoxon rank-sum test are shown.

Purpose:Enfortumab vedotin (EV) is an antibody–drug conjugate (ADC) targeting NECTIN4 (encoded by the PVRL4/NECTIN4 gene) approved for treatment-refractory metastatic urothelial cancer. Factors that mediate sensitivity or resistance to EV are unknown. In this study, we sought to (i) examine heterogeneity of NECTIN4 gene expression across molecular subtypes of bladder cancer and (ii) determine whether NECTIN4 expression mediates EV sensitivity or resistance.Experimental Design:Molecular subtyping and NECTIN4 expression data from seven muscle-invasive bladder cancer clinical cohorts (n = 1,915 total specimens) were used to assess NECTIN4 expression across molecular subtypes. The outcome of the transcriptomic analysis was relative NECTIN4 expression in the consensus molecular subtypes of bladder cancer. Expression of NECTIN4 was validated in bladder cancer cell lines. NECTIN4 was stably overexpressed or knocked down in basal and luminal bladder cancer cell lines and EV drug sensitivity assays were performed, as measured by cell proliferation and clonogenic assays.Results:NECTIN4 expression is heterogenous across molecular subtypes of bladder cancer and significantly enriched in luminal subtypes. NECTIN4 expression is positively correlated with luminal markers GATA3, FOXA1, and PPARG across all cohorts. NECTIN4 expression is both necessary and sufficient for EV sensitivity in luminal and basal subtypes of urothelial bladder cancer cells. Downregulation of NECTIN4 leads to EV resistance.Conclusions:Sensitivity to EV is mediated by expression of NECTIN4, which is enriched in luminal subtypes of bladder cancer. These findings may have implications for biomarker development, patient selection, and the inclusion of molecular subtyping in ongoing and future EV clinical trials.See related commentary by Teo and Rosenberg, p. 4950

Introduction:Excessive trainee debt continues to be a problem. Little is known about how debt influences future practice decisions. We sought to examine the correlation between educational ...

Coronavirus disease (COVID-19) has profoundly impacted residency training and education. To date, there has not been any broad assessment of urological surgery residency changes and concerns during the COVID-19 pandemic.The Society of Academic Urologists distributed a questionnaire to urology residency program directors on March 30, 2020 exploring residency program changes related to the COVID-19 pandemic. Descriptive statistics are presented. A qualitative analysis of free response questions was undertaken. A post hoc analysis of differences related to local COVID-19 incidence is described.The survey was distributed to 144 residency programs with 65 responses for a 45% response rate. Reserve staffing had started in 80% of programs. Patient contact time had decreased significantly from 4.7 to 2.1 days per week (p0.001). Redeployment was reported by 26% of programs. Sixty percent of programs reported concern that residents will not meet case minimums due to COVID-19. Wellness activities centered on increased communication. All programs had begun to use videoconferencing and the majority planned to continue. Programs in states with a higher incidence of COVID-19 were more likely to report resident redeployment (48% vs 11%, p=0.002) and exposure to COVID-19 positive patients (70% vs 40%, p=0.03), and were less likely to report concerns regarding exposure (78% vs 97%, p=0.02) and personal protective equipment availability (62% vs 89%, p=0.02).As of April 1, 2020 the COVID-19 pandemic had resulted in significant changes in urology residency programs. These findings inform a rapidly changing landscape and aid in the development of best practices.

Although relative value units are used to measure physician productivity, research has demonstrated incongruencies between relative value units and actual surgeon work effort. We sought to determine whether this variation extends across surgical specialties.A retrospective review of surgical cases was conducted using the 2017 American College of Surgeons National Surgical Quality Improvement Program database. For each case, we identified the primary Current Procedural Terminology, surgical specialty, total relative value units, and 5 alternative measures of work effort. We then examined the correlation between a Current Procedural Terminology's mean total relative value unit and work effort. Finally, we constructed a multivariable linear regression model to evaluate the association between surgical specialty and the expected mean total relative value unit adjusting for work effort and patient characteristics.A total of 876,515 cases met the inclusion criteria. Overall, median operative time correlated well with mean total relative value unit (R = 0.85), though it was lowest for cardiac surgery (R = 0.51) and highest for otolaryngology (R = 0.97). Neurosurgery had the greatest increase in mean total relative value unit per hour of operative time (12.9/h). Mean total relative value unit correlated modestly with length of stay (R = 0.58) and serious adverse events (R = 0.61) and weakly with readmission (R = 0.42) and mortality (R = 0.29). When holding these metrics constant, the multivariable model showed mean total relative value units differed according to surgical specialty alone. Compared with general surgery, neurosurgery and cardiac surgery earned 3.41 to 3.61 additional mean total relative value units (P.05), while orthopedics, otolaryngology, thoracic, urology, and vascular surgery received fewer mean total relative value units (-1.84 to -4.43, P.05).Surgeon productivity is increasingly measured using relative value units. While mean total relative value units correlate well with operative time, they may not reflect other aspects of work effort. Differences in mean total relative value units by surgical specialty demonstrate potential inequities in the determination of physician productivity.

Objectives To determine whether implicit gender bias exists in the urology residency application process, we compared linguistic differences in letters of recommendation submitted for male and female applicants. Methods Letters of recommendation were abstracted from residency applications to a urology residency program. Linguistic Inquiry and Word Count, a validated text analysis software program, characterized the linguistic content of the letters. Analyzed letters were compared according to gender of the applicant using multivariable analysis, examining the association of applicant gender, letter writer and letter characteristics. Multivariable analysis was also performed to determine the association of letter characteristics with matching into a urology residency. Results Of 460 letters evaluated, letters for male applicants are written in a more authentic tone compared to letters written for female applicants. Letters written for male applicants contain significantly more references to personal drive, work, and power than letters written for female applicants. Significant differences are maintained on multivariable analysis when controlling for race and Step 1 score of the applicant. Letters with references to power were significantly more likely to be associated with an applicant who matched into urology than an applicant who didn't match. Conclusions Significant linguistic differences exist among letters of recommendation written for men and women applying into urology, suggesting that gender bias may permeate resident recruitment. These differences may affect the likelihood of women matching into urology.

BackgroundImmune checkpoint inhibitors (ICI) can achieve durable responses in a subset of patients with locally advanced or metastatic urothelial carcinoma (aUC). The use of tumor genomic profiling in clinical practice may help suggest biomarkers to identify patients most likely to benefit from ICI.MethodsWe undertook a retrospective analysis of patients treated with an ICI for aUC at a large academic medical center. Patient clinical and histopathological variables were collected. Responses to treatment were assessed for all patients with at least one post-baseline scan or clear evidence of clinical progression following treatment start. Genomic profiling information was also collected for patients when available. Associations between patient clinical/genomic characteristics and objective response were assessed by logistic regression; associations between the characteristics and progression-free survival (PFS) and overall survival (OS) were examined by Cox regression. Multivariable analyses were performed to identify independent prognostic factors.ResultsWe identified 119 aUC patients treated with an ICI from December 2014 to January 2020. Genomic profiling was available for 78 patients. Overall response rate to ICI was 29%, and median OS (mOS) was 13.4 months. Favorable performance status at the start of therapy was associated with improved OS (HR 0.46, p=0.025) after accounting for other covariates. Similarly, the presence of a TERT promoter mutation was an independent predictor of improved PFS (HR 0.38, p=0.012) and OS (HR 0.32, p=0.037) among patients who had genomic profiling available. Patients with both a favorable performance status and a TERT promoter mutation had a particularly good prognosis with mOS of 21.1 months as compared with 7.5 months in all other patients (p=0.03).ConclusionsThe presence of a TERT promoter mutation was an independent predictor of improved OS in a cohort of aUC patients treated with an ICI who had genomic data available. Most of the clinical and laboratory variables previously shown to be prognostic in aUC patients treated with chemotherapy did not have prognostic value among patients treated with an ICI. Genomic profiling may provide important prognostic information and affect clinical decision making in this patient population. Validation of these findings in prospective patient cohorts is needed.

Critical evaluation of minimally invasive techniques for bladder cancer has emerged in the last 5 years, with several single and multi-institutional case series, randomized controlled trials, and systematic reviews devoted to the discussion of outcomes following robotic-assisted radical cystectomy (RARC). Potential advantages to the robotic technique exist, and despite the arguably steep learning curve, the approach is rapidly becoming more familiar in the field of urologic oncology. This chapter describes the evidence which shows that RARC appears to have acceptable oncologic efficacy when compared to ORC for high-grade invasive bladder cancer. Offering advantages of decreased pain, early recovery, and reduced blood loss in addition to better cosmesis, RARC appears to be an excellent procedure with increasing use in academic and nonacademic centers. Ultimately, the choice of the technique should be tailored to patient characteristics, expertise, and experience of the surgeon and availability of technology.

Objective To determine whether patient-reported health status, more so than comorbidity, influences treatment in men with localized prostate cancer. Methods Using Surveillance, Epidemiology, and End Results data linked with Medicare claims and CAHPS surveys, we identified men aged 65-84 diagnosed with localized prostate cancer from 2004 to 2013 and ascertained their National Cancer Institute (NCI) comorbidity score and patient-reported health status. Adjusting for demographics and cancer risk, we examined the relationship between these measures and treatment for the overall cohort, low-risk men aged 65-74, intermediate/high-risk men aged 65-74, and men aged 75-84. Results Among 2724 men, 43.0% rated their overall health as Excellent/Very Good, while 62.7% had a comorbidity score of 0. Beyond age and cancer risk, patient-reported health status was significantly associated with treatment. Compared to men reporting Excellent/Very Good health, men in Poor/Fair health less often received treatment (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.56-0.90). Younger men with intermediate/high-risk cancer in Good (OR 0.60, 95% CI 0.41-0.88) or Fair/Poor (OR 0.49, 95% CI 0.30-0.79) health less often underwent prostatectomy vs radiation compared to men in Excellent/Very Good health. In contrast, men with NCI comorbidity score of 1 more often received treatment (OR 1.37, 95% CI 1.11-1.70) compared to men with NCI comorbidity score of 0. Conclusion Patient-reported health status drives treatment for prostate cancer in an appropriate direction whereas comorbidity has an inconsistent relationship. Greater understanding of this interplay between subjective and empiric assessments may facilitate more shared decision-making in prostate cancer care.

To analyze differences in length of stay, opioid use, and other perioperative outcomes in patients undergoing radical cystectomy with urinary diversion who received either liposomal bupivacaine (LB) or epidural analgesia.This was a single center, retrospective cohort study of patients undergoing open radical cystectomy with urinary diversion from 2015-2019 in the early recovery after surgery (ERAS) pathway. Patients received either LB or epidural catheter analgesia for post-operative pain control. LB was injected at the time of fascial closure to provide up to 72 hours of local analgesia. The primary outcome was post-operative length of stay. Secondary outcomes were post-operative opioid use, time to solid food, time to ambulation, and direct hospitalization costs. Multivariable Cox proportional hazards regression was used to determine associations between analgesia type and discharge.LB use was independently associated with shorter post-operative length of stay compared to epidural use (median (IQR) 4.9 days (3.9-5.8) vs 5.9 days (4.9-7.9), P.001), less total opioid use (mean 188.3 vs 612.2 OME, P.001), earlier diet advancement (mean 1.6 vs 2.4 days, P.001), and decreased overall direct costs ($23,188 vs $29,628, P.001). 45% of patients who received LB were opioid-free after surgery, none in the epidural group. On multivariable Cox proportional hazards regression modeling, LB use was independently associated with earlier discharge (HR 2.1, IQR 1.0-4.5).Use of LB in open radical cystectomy is associated with reduced LOS, less opioid exposure, and earlier diet advancement.

Purpose Urachal adenocarcinoma is a rare type of primary bladder adenocarcinoma that comprises less than 1% of all bladder cancers. The low incidence of urachal adenocarcinomas does not allow for an evidence-based approach to therapy. Transcriptome profiling of urachal adenocarcinomas has not been previously reported. We hypothesized that an in-depth molecular understanding of urachal adenocarcinoma would uncover rational therapeutic strategies. Patients and Methods We performed targeted exon sequencing and global transcriptome profiling of 12 urachal tumors to generate a comprehensive molecular portrait of urachal adenocarcinoma. A single patient with an MSH6 mutation was treated with the anti–programmed death-ligand 1 antibody, atezolizumab. Results Urachal adenocarcinoma closely resembles colorectal cancer at the level of RNA expression, which extends previous observations that urachal tumors harbor genomic alterations that are found in colorectal adenocarcinoma. A subset of tumors was found to have alterations in genes that are associated with microsatellite instability ( MSH2 and MSH6) and hypermutation ( POLE). A patient with an MSH6 mutation was treated with immune checkpoint blockade, which resulted in stable disease. Conclusion Because clinical trials are next to impossible for patients with rare tumors, precision oncology may be an important adjunct for treatment decisions. Our findings demonstrate that urachal adenocarcinomas molecularly resemble colorectal adenocarcinomas at the level of RNA expression, are the first report, to our knowledge, of MSH2 and MSH6 mutations in this disease, and support the consideration of immune checkpoint blockade as a rational therapeutic treatment of this exceedingly rare tumor.

Objective: To assess the feasibility of enrollment and collecting PRO data as part of routine clinical urologic care for bladder and prostate cancer patients and examine overall patterns and racial variations in PRO use and symptom reports over time. Subjects/Patients and Methods: We recruited 76 patients (n=29 Black and n=47 White) with prostate or bladder cancer at a single, comprehensive cancer center. The majority of prostate cancer patients had intermediate risk (57%) disease and underwent either radiation or prostatectomy. Over half (58%) of bladder cancer patients had muscle invasive disease and underwent cystectomy. Patients were asked to complete PRO symptom surveys using their preferred mode [web- or phone-based interactive voice response (IVR)]. Symptom summary reports were shared with providers during visits. Surveys were completed at three time points and assessed urinary, sexual, gastrointestinal, anxiety/depression, and sleep symptoms. Feasibility of enrollment and survey completion were calculated, and linear mixed effects models estimated differences in outcomes by race and time. Results: 63% of study participants completed all PRO measures at all three time points. Black patients were more likely to select IVR as their survey mode (40% vs 13%, p

To explore the relationship between research time during urologic training and career academic success.We included urologists graduating residency between 2002 and 2008 from 36 programs affiliated with a top 50 hospital for urology as ranked by the United States News and World Report, and collected research time during residency, fellowship training, current appointment (private practice, assistant professor, associate professor, professor, chair), national institutes of health (NIH) grant accrual, NIH R01 grant accrual, and current H-index in Scopus database. Publication output during and after residency was identified through the PubMed database.In our cohort of 543 urologists, 66.3% of graduating trainees pursued private practice. Increasing residency research time was associated with increased publication count (P.001), pursuit of professor positions (P.001), and NIH funding (P.001). One year of dedicated research increased the odds of being in the top 10th percentile of publication output during residency (odds ratio [OR]: 5.7, 95% confidence interval [CI]: 2.7-12.1), pursuing a fellowship (OR: 2.0, 95% CI: 1.3-3.1), promotion to professor (OR: 4.9, 95% CI: 2.0-12.2), obtaining a NIH grant (OR: 6.2, 95% CI: 2.3-16.5), and decreased the odds of pursuing private practice (OR: 0.4, 95% CI: 0.3-0.6). As amount of time dedicated to research in urologic residency increased from 3-4 to 6-12 months, OR increased for career academic success metrics.Although a minority of trainees enter academics, dedicated time for research in urologic residency is associated with career academic success, with more research time associated with increased publication output, academic appointments, and grant funding.

Background The emergence of the coronavirus disease (COVID-19) pandemic in March 2020 created unprecedented challenges in the provision of scheduled ambulatory cancer care. As a result, there has been a renewed focus on video-based telehealth consultations as a means to continue ambulatory care. Objective The aim of this study is to analyze the change in video visit volume at the University of California, San Francisco (UCSF) Comprehensive Cancer Center in response to COVID-19 and compare patient demographics and appointment data from January 1, 2020, and in the 11 weeks after the transition to video visits. Methods Patient demographics and appointment data (dates, visit types, and departments) were extracted from the electronic health record reporting database. Video visits were performed using a HIPAA (Health Insurance Portability and Accountability Act)-compliant video conferencing platform with a pre-existing workflow. Results In 17 departments and divisions at the UCSF Cancer Center, 2284 video visits were performed in the 11 weeks before COVID-19 changes were implemented (mean 208, SD 75 per week) and 12,946 video visits were performed in the 11-week post–COVID-19 period (mean 1177, SD 120 per week). The proportion of video visits increased from 7%-18% to 54%-72%, between the pre– and post–COVID-19 periods without any disparity based on race/ethnicity, primary language, or payor. Conclusions In a remarkably brief period of time, we rapidly scaled the utilization of telehealth in response to COVID-19 and maintained access to complex oncologic care at a time of social distancing.

BACKGROUND The emergence of the coronavirus disease (COVID-19) pandemic in March 2020 created unprecedented challenges in the provision of scheduled ambulatory cancer care. As a result, there has been a renewed focus on video-based telehealth consultations as a means to continue ambulatory care. OBJECTIVE The aim of this study is to analyze the change in video visit volume at the University of California, San Francisco (UCSF) Comprehensive Cancer Center in response to COVID-19 and compare patient demographics and appointment data from January 1, 2020, and in the 11 weeks after the transition to video visits. METHODS Patient demographics and appointment data (dates, visit types, and departments) were extracted from the electronic health record reporting database. Video visits were performed using a HIPAA (Health Insurance Portability and Accountability Act)-compliant video conferencing platform with a pre-existing workflow. RESULTS In 17 departments and divisions at the UCSF Cancer Center, 2284 video visits were performed in the 11 weeks before COVID-19 changes were implemented (mean 208, SD 75 per week) and 12,946 video visits were performed in the 11-week post–COVID-19 period (mean 1177, SD 120 per week). The proportion of video visits increased from 7%-18% to 54%-72%, between the pre– and post–COVID-19 periods without any disparity based on race/ethnicity, primary language, or payor. CONCLUSIONS In a remarkably brief period of time, we rapidly scaled the utilization of telehealth in response to COVID-19 and maintained access to complex oncologic care at a time of social distancing.

BackgroundThe emergence of the coronavirus disease 2019 (COVID-19) pandemic in March 2020 created unprecedented challenges in the provision of scheduled ambulatory cancer care. As a result, there has been a renewed focus on video consultations as a means to continue ambulatory care.ObjectiveTo analyze the change in video visit volume at the University of California, San Francisco (UCSF) Comprehensive Cancer Center in response to COVID-19 and compare demographics/appointment data from January 1, 2020 and in the 11 weeks after transition to video visits.MethodsPatient demographics and appointment data (dates, visit types, and departments) were abstracted from the Electronic Health Record reporting database. Video visits were performed using a HIPAA-compliant video conferencing platform with a pre-existing workflow.ResultsIn 17 departments and divisions at the UCSF Cancer Center, 2,284 video visits were performed in the 11 weeks before COVID-19 changes with an average (SD) of 208 (75) per week and 12,946 video visits were performed in the 11 week post-COVID-19 period with an average (SD) of 1,177 (120) per week. The proportion of video visits increased from 7-18% to 54-72%, between the pre- and post-COVID-19 periods without any disparity based on race/ethnicity, primary language, or payor.ConclusionsIn a remarkably brief period of time, we rapidly scaled the utilization of telehealth in response to COVID-19 and maintained access to complex oncologic care at a time of social distancing.

Objective Financial toxicity (FT) has been defined as the patient-level impact of the costs of cancer care. Our objective was to better characterize FT among bladder cancer patients as well as oncologic, demographic and insurance characteristics related to FT. Methods We conducted a cross-sectional survey of the Bladder Cancer Advocacy Network Patient Survey Network using the validated COST (COmprehensive Score for financial Toxicity) questionnaire. Our primary outcome was relative degree of FT, with lower COST scores corresponding to worse FT. Wilcoxon rank sum tests and multiple regression were used to evaluate differences in demographic, diagnostic and treatment characteristics as they related to degree of FT. Results Among 226 patients, median age was 68 years with 64% male, 83% married, and 49% with Medicare with supplemental insurance. Respondents reported an average of 65 months since diagnosis, with 62% reporting noninvasive disease. Mean COST was 28.4 (range 0–44). On multivariable analysis, patients who were younger, with a household annual income less than $50,000, not retired, or with insurance that was neither Medicare nor employer paid were significantly more likely to have worse FT. A majority of respondents (63.5%) agreed or strongly agreed that they would be interested in discussing cost in the context of their treatment preferences, independent of COST score (P = 0.24). Conclusions A national cross-sectional survey demonstrated high prevalence of FT which was worse among younger patients with lower incomes, not retired, and without employer-paid or Medicare insurance. Most patients preferred to discuss treatment costs with their bladder cancer provider.

PURPOSE: The RAZOR (Randomized Open versus Robotic Cystectomy) trial revealed noninferior 2-year progression-free survival for robotic radical cystectomy. This update was performed with extended followup for 3 years to determine potential differences between the approaches. We also report 3-year overall survival and sought to identify factors predicting recurrence, and progression-free and overall survival. MATERIALS AND METHODS: We analyzed the per protocol population of 302 patients from the RAZOR study. Cumulative recurrence was estimated using nonbladder cancer death as the competing risk event and the Gray test was applied to assess significance in differences. Progression-free survival and overall survival were estimated by the Kaplan-Meier method and compared with the log rank test. Predictors of outcomes were determined by Cox proportional hazard analysis. RESULTS: Estimated progression-free survival at 36 months was 68.4% (95% CI 60.1–75.3) and 65.4% (95% CI 56.8–72.7) in the robotic and open groups, respectively (p=0.600). At 36 months overall survival was 73.9% (95% CI 65.5–80.5) and 68.5% (95% CI 59.8–75.7) in the robotic and open groups, respectively (p=0.334). There was no significant difference in the cumulative incidence rates of recurrence (p=0.802). Patient age greater than 70 years, poor performance status and major complications were significant predictors of 36-month progression-free survival. Stage and positive margins were significant predictors of recurrence, and progression-free and overall survival. Surgical approach was not a significant predictor of any outcome. CONCLUSIONS: This analysis showed no difference in recurrence, 3-year progression-free survival or 3-year overall survival for robotic vs open radical cystectomy. It provides important prospective data on the oncologic efficacy of robotic radical cystectomy and high level data for patient counseling.

Summary Background Radical cystectomy is the surgical standard for invasive bladder cancer. Robot-assisted cystectomy has been proposed to provide similar oncological outcomes with lower morbidity. We aimed to compare progression-free survival in patients with bladder cancer treated with open cystectomy and robot-assisted cystectomy. Methods The RAZOR study is a randomised, open-label, non-inferiority, phase 3 trial done in 15 medical centres in the USA. Eligible participants (aged ≥18 years) had biopsy-proven clinical stage T1–T4, N0–N1, M0 bladder cancer or refractory carcinoma in situ. Individuals who had previously had open abdominal or pelvic surgery, or who had any pre-existing health conditions that would preclude safe initiation or maintenance of pneumoperitoneum were excluded. Patients were centrally assigned (1:1) via a web-based system, with block randomisation by institution, stratified by type of urinary diversion, clinical T stage, and Eastern Cooperative Oncology Group performance status, to receive robot-assisted radical cystectomy or open radical cystectomy with extracorporeal urinary diversion. Treatment allocation was only masked from pathologists. The primary endpoint was 2-year progression-free survival, with non-inferiority established if the lower bound of the one-sided 97·5% CI for the treatment difference (robotic cystectomy minus open cystectomy) was greater than −15 percentage points. The primary analysis was done in the per-protocol population. Safety was assessed in the same population. This trial is registered with ClinicalTrials.gov, number NCT01157676. Findings Between July 1, 2011, and Nov 18, 2014, 350 participants were randomly assigned to treatment. The intended treatment was robotic cystectomy in 176 patients and open cystectomy in 174 patients. 17 (10%) of 176 patients in the robotic cystectomy group did not have surgery and nine (5%) patients had a different surgery to that they were assigned. 21 (12%) of 174 patients in the open cystectomy group did not have surgery and one (1%) patient had robotic cystectomy instead of open cystectomy. Thus, 302 patients (150 in the robotic cystectomy group and 152 in the open cystectomy group) were included in the per-protocol analysis set. 2-year progression-free survival was 72·3% (95% CI 64·3 to 78·8) in the robotic cystectomy group and 71·6% (95% CI 63·6 to 78·2) in the open cystectomy group (difference 0·7%, 95% CI −9·6% to 10·9%; p non-inferiority =0·001), indicating non-inferiority of robotic cystectomy. Adverse events occurred in 101 (67%) of 150 patients in the robotic cystectomy group and 105 (69%) of 152 patients in the open cystectomy group. The most common adverse events were urinary tract infection (53 [35%] in the robotic cystectomy group vs 39 [26%] in the open cystectomy group) and postoperative ileus (33 [22%] in the robotic cystectomy group vs 31 [20%] in the open cystectomy group). Interpretation In patients with bladder cancer, robotic cystectomy was non-inferior to open cystectomy for 2-year progression-free survival. Increased adoption of robotic surgery in clinical practice should lead to future randomised trials to assess the true value of this surgical approach in patients with other cancer types. Funding National Institutes of Health National Cancer Institute.

Purpose: Costly surveillance and treatment of bladder cancer can lead to financial toxicity, a treatment related financial burden. Our objective was to define the prevalence of financial toxicity among patients with bladder cancer and identify delays in care and its effect on health related quality of life.Materials and Methods: We identified patients with bladder cancer in the University of North Carolina Health Registry/Cancer Survivorship Cohort. Financial toxicity was defined as agreement with having “to pay more for medical care than you can afford.” Health related quality of life was measured using general and cancer specific validated questionnaires. Statistical analyses were performed using the Fisher exact test and the Student t-test.Results: A total of 138 patients with bladder cancer were evaluated. Median age was 66.9 years, 75% of the patients were male and 89% were white. Of the participants 33 (24%) endorsed financial toxicity. Participants who were younger (p = 0.02), black (p = 0.01), rep...

Pressure on physicians to increase productivity is rising in parallel with administrative tasks, regulations, and the use of electronic health records (EHRs). Physician extenders and clinical pathways are already in use to increase productivity and reduce costs and burnout, but other strategies are required. We evaluated whether implementation of medical scribes in an academic urology clinic would affect productivity, revenue, and patient/provider satisfaction. Six academic urologists were assigned scribes for 1 clinic day per week for 3 months. Likert-type patient and provider surveys were developed to evaluate satisfaction with and without scribes. Matched clinic days in the year prior were used to evaluate changes in productivity and physician/hospital charges and revenue. After using scribes for 3 months, providers reported increased efficiency (p value = 0.03) and work satisfaction (p value = 0.03), while seeing a mean 2.15 more patients per session (+ 0.96 return visits, + 0.99 new patients, and + 0.22 procedures), contributing to an additional 2.6 wRVUs, $542 in physician charges, and $861 in hospital charges per clinic session. At a gross collection rate of 36%, actual combined revenue was + $506/session, representing a 26% increase in overall revenue. At a cost of $77/session, the net financial impact was + $429 per clinic session, resulting in a return-to-investment ratio greater than 6:1, while having no effect on patient satisfaction scores. Additionally, with scribes, clinic encounters were closed a mean 8.9 days earlier. Implementing medical scribes in academic urology practices may be useful in increasing productivity, revenue, and provider satisfaction, while maintaining high patient satisfaction.

Introduction In this study we holistically describe and characterize the current state of urology practice by evaluating compensation, workload and practice factors as they relate to our demographic makeup as a specialty. Methods We collaborated with the American Urological Association to query its domestic membership of practicing urologists regarding socioeconomic, workforce and quality of life issues. The survey consisted of 26 questions and took approximately 13 minutes to complete. A total of 733 responders had complete data for the factors statistically analyzed in the study. Results Mean yearly compensation for urologists surveyed was $404,755 and median compensation was $380,000 (IQR $300,000–480,000). Female respondents had a significantly lower median yearly compensation vs males ($318,422 vs $400,000) on univariate and multivariate analysis. Respondents reported a median of 60 work hours per week (IQR 50–60) and the median number of call days per month was 7 (IQR 5–10). Of the respondents 62% indicated that they use advanced practice providers in their practice. In addition, 30% reported employed status, 49% reported self-employed status and 21% reported academic status. Overall 20% of respondents plan to retire within 5 years and 40% within 10 years. Conclusions Higher income was associated with greater job satisfaction and hourly wage appeared to decrease at increased work hours per week. Several workplace and demographic factors drive compensation, number of hours worked per week, number of call days per month and job satisfaction.

Background: PVSRIPO, a novel intratumoral viral immunotherapy, infects cells via CD155, which is widely expressed on solid tumors and antigen-presenting cells (APC). Infection is lethal in malignant cells, but a unique, activating, nonlethal infection of local APCs yields type-I/III interferon (IFN)-dominant inflammation with subsequent anti-tumor T-cell priming and activation. In preclinical models, PVSRIPO-dependent inflammation upregulated the PD-1/L1 pathway, and greater anti-tumor response was observed with PVSRIPO + anti-PD-1/L1 (αPD-1/L1). Promising clinical activity with PVSRIPO monotherapy was observed in patients (pts) with recurrent glioblastoma and advanced αPD-1–refractory melanoma (Desjardins 2018 NEJM, Beasley 2021 JITC). Collectively, these results warrant further clinical investigation of PVSRIPO ± αPD-1/L1. Trial design, objectives, and eligibility criteria: LUMINOS-103 (NCT04690699) is a phase (Ph) 1/2, open-label, multi-center, single-arm basket trial evaluating repeat administration of PVSRIPO ± αPD-1/L1 in adults with solid tumors. Trial objectives are to assess the safety and tolerability of PVSRIPO monotherapy in each cohort in Ph 1 and the safety, tolerability, and antitumor efficacy of PVSRIPO + αPD-1/L1 in each cohort in Ph 2. The first two study cohorts include pts with muscle-invasive bladder cancer being treated in the neoadjuvant setting (A) and pts with metastatic bladder cancer being treated in the 1st/2nd line setting (B); these cohorts have been described previously (Inman 2021 Virtual AACR Annual Meeting). Cohort C includes pts with resectable, locally advanced head and neck squamous cell carcinoma (HNSCC) being treated in the neoadjuvant setting; Cohort D includes pts with recurrent/metastatic HNSCC with a PD-L1 Combined Positive Score ≥1 being treated in the 1st line setting. Eligibility: HNSCC pts must have histologically or cytologically proven SCC of the oral cavity, oropharynx, hypopharynx, or larynx. All pts must have prior and boosted PV immunization and tumors amenable to injection and biopsy. Key exclusion criteria: Requirement for oxygen supplementation, systemic or intratumoral therapy ≤6 months prior to the first dose of study drug, CNS metastases requiring immediate treatment, systemic immunosuppressive medications ≤4 weeks prior to the first dose of study drug, and severe active comorbidities. Pts who are HIV+, HBV+ or HCV+ are eligible provided they meet certain criteria. Endpoints: Primary endpoints include safety (all), tolerability (all), surgical complication rate (A, C), pathologic treatment effect/response (A, C), and objective response rate (B, D). Secondary endpoints include overall survival (all), pathologic downstaging and relapse-free survival (A, C), duration of response and progression-free survival (B, D), and assessment of tumor/blood biomarkers (all). Citation Format: Brant A. Inman, Matthew I. Milowsky, Raj S. Pruthi, Marshall Posner, Melissa J. Polasek, Shannon R. Morris, Lori Mixson, Kristin Orr, Elizabeth M. H. Woodson, Andrea T. Kelly, W. Garrett Nichols, Arjun V. Balar. LUMINOS-103: A basket trial evaluating the safety and efficacy of PVSRIPO and PVSRIPO in combination with anti-PD-1/L1 checkpoint inhibitors in patients with advanced solid tumors [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P045.

BackgroundPVSRIPO, a novel intratumoral viral immunotherapy, infects cells via CD155, which is widely expressed on solid tumors and antigen-presenting cells (APC). Infection is lethal in malignant cells, but a unique, activating, nonlethal infection of local APCs yields type-I/III interferon (IFN)-dominant inflammation with subsequent anti-tumor T-cell priming and activation resulting in anti-tumor efficacy. In preclinical models, PVSRIPO-dependent inflammation upregulated the PD-1/L1 pathway, and greater anti-tumor response was observed with PVSRIPO + anti-PD-1/L1 (αPD-1/L1). Promising clinical activity with PVSRIPO monotherapy was observed in patients with recurrent glioblastoma and advanced αPD-1–refractory melanoma.1 2 Collectively, these results warrant further clinical investigation of PVSRIPO ± αPD-1/L1.MethodsLUMINOS-103 (NCT04690699) is a phase (Ph) 1/2, open-label, multi-center, single-arm basket trial evaluating repeat administration of PVSRIPO ± αPD-1/L1 in adults with solid tumors. Trial objectives are to assess the safety and tolerability of PVSRIPO monotherapy in each cohort in Ph 1 and the safety, tolerability, and antitumor efficacy of PVSRIPO + αPD-1/L1 in each cohort in Ph 2. The first two study cohorts include patients with muscle-invasive bladder cancer being treated in the neoadjuvant setting (A) and patients with metastatic bladder cancer being treated in the 1st/2nd line setting (B); these cohorts have been described previously.3 Cohort C includes patients with resectable, locally advanced head and neck squamous cell carcinoma (HNSCC) being treated in the neoadjuvant setting; Cohort D includes patients with recurrent/metastatic HNSCC with a PD-L1 Combined Positive Score ≥1 being treated in the 1st line setting. Eligibility: HNSCC patients must have histologically or cytologically-proven SCC of the oral cavity, oropharynx, hypopharynx, or larynx. All patients must have prior and boosted PV immunization and tumors amenable to injection and biopsy. Key exclusion criteria: Requirement for oxygen supplementation, systemic or intratumoral therapy ≤6 months prior to the first dose of study drug, CNS metastases requiring immediate treatment, systemic immunosuppressive medications ≤4 weeks prior to the first dose of study drug, and severe active comorbidities. Patients who are HIV+, HBV+ or HCV+ are eligible provided they meet certain criteria. Primary endpoints include safety (all cohorts), tolerability (all cohorts), surgical complication rate (A, C), pathologic treatment effect/response (A, C), and objective response rate (B, D). Secondary endpoints include overall survival (all cohorts), pathologic downstaging and relapse-free survival (A, C), duration of response and progression-free survival (B, D), and assessment of tumor/blood biomarkers (all cohorts).Trial RegistrationClinicalTrials.gov: NCT04690699ReferencesDesjardins A, et al. Recurrent glioblastoma treated with recombinant poliovirus. N Engl J Med 2018;379(2):150–161.Beasley GM, et al. Phase I trial of intratumoral PVSRIPO in patients with unresectable, treatment-refractory melanoma. J Immunother Cancer 2021;9(4):e002203.Inman BA, et al. LUMINOS-103: A basket trial evaluating the safety and efficacy of PVSRIPO in patients with advanced solid tumors. Cancer Res 2021;81(13_Suppl):Abstract nr CT242.Ethics ApprovalThe study has been approved by the central Institutional Review Board (IRB), WCG (Study# 1310534) and will be approved by all local IRBs and other required committees, as applicable. The study will be conducted in accordance with the provisions of the Declaration of Helsinki and the Good Clinical Practice guidelines of the International Conference on Harmonization. All patients will provide written informed consent.

Background: The recombinant poliovirus (PV):rhinovirus chimera, PVSRIPO, is a novel non-neurovirulent, intratumoral (IT) immunotherapy showing promising clinical activity in patients (pts) with recurrent glioblastoma and advanced anti-PD-1 refractory melanoma (Desjardins 2018 NEJM, Beasley 2020 SITC). PVSRIPO targets CD155 (PV receptor), expressed on most solid tumors (including bladder cancer [BC]) and antigen presenting cells (APCs) of the tumor microenvironment (TME). PVSRIPO infection results in inflammatory-mediated destruction of tumor cells but non-lethal lingering infection in TME APCs. This leads to a type-I/III interferon-dominant inflammation and ultimately, tumor antigen-specific T cell activation and recruitment (Brown 2017 Sci Transl Med), potentiated by immunologic recall to intratumoral replicating virus via prior vaccination. Induction of type-1 IFN dominant inflammation and compensatory activation of the PD-1:PD-L1 immune checkpoint (IC) pathway support investigation of PVSRIPO in combination with PD-1/L1 IC inhibitors. PVSRIPO+anti-PD-1 therapy resulted in greater anti-tumor response than either agent in immunologically cold mouse tumor models. Trial design, objectives, and eligibility criteria: LUMINOS-103 (NCT04690699) is a phase 1/2, open-label, multi-center, single-arm basket trial evaluating repeat administration of PVSRIPO (2×108 TCID50/mL)±anti-PD-1/L1 therapy in adults with solid tumors. Trial objectives are to evaluate the safety, tolerability, and anti-tumor activity of the combination in pts with solid tumors, beginning with muscle invasive bladder cancer (MIBC). The first arm will include pts in 2 cohorts: MIBC undergoing cystectomy (A); and unresectable locally advanced/metastatic BC (B). Safety/tolerability of PVSRIPO IT injections via cystoscopy will be evaluated in phase 1, Cohort A, and proceed to phase 2, where PVSRIPO+anti-PD-1/L1 therapy will be assessed in both cohorts. Eligible BC pts must refuse/be ineligible for cisplatin (A) or platinum-based therapy (B), have prior and boost PV immunization, and have measurable tumors (B) amenable to injection. Key exclusion criteria: other anti-cancer therapies ≤3 weeks, CNS metastases requiring active radiotherapy or steroids ≤14 days, systemic immunosuppressives ≤4 weeks, and severe active comorbidities. Endpoints: Primary endpoints include safety and tolerability and pathologic complete response (A) or overall response rate (B). Secondary endpoints: overall survival (both cohorts); for A, pathologic downstaging (p≤T2) and relapse-free survival; for B, duration of response and progression-free survival. Exploratory endpoints: assessment of tumor/blood biomarkers; measurement of disease by itRECIST. The trial will open US enrollment ≈ Q2 2021; results will inform later-stage trials in promising indications. Citation Format: Brant A. Inman, Arjun V. Balar, Matthew I. Milowsky, Raj S. Pruthi, Melissa J. Polasek, Shannon R. Morris, Lori Mixson, Kristin Orr, Elizabeth M. Woodson, Andrea True Kelly, Garrett Nichols. LUMINOS-103: A basket trial evaluating the safety and efficacy of PVSRIPO in patients with advanced solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT242.

Introduction Projections suggest a significant shortage of urologists coupled with an increasing burden of urological disease due to an aging population. To meet this need, urologists have increasingly partnered with advanced practice providers. However, to this point the advanced practice provider workforce has not been comprehensively evaluated. Understanding the impact of advanced practice providers on the urology workforce is essential to maximize collaborative care as we strive for value and quality in evolving delivery models. Methods A 29-item, web based survey was administered to advanced practice providers identified by the AUA (American Urological Association), UAPA (Urological Association of Physician Assistants) and SUNA (Society of Urologic Nurses and Associates), querying many aspects of their practice. Results A total of 296 advanced practice providers completed the survey. Advanced practice nurses comprised 62% of respondents while physician assistants comprised the remaining 38%. More than two-thirds of the respondents were female and median age was 46 years. Only 6% reported having participated in formal postgraduate urological training. Advanced practice providers were evenly divided between institutional and private practice settings, and overwhelmingly in urban or suburban environments. The majority of advanced practice providers practice in the ambulatory setting (74%) and characterize their practice as general urology (72%). Overall 81% reported performing procedures independently, with 63% performing some procedures considered to be of moderate or high complexity. Conclusions Advanced practice providers are active in the provision of urological care in many roles, including complex procedures. Given future workforce needs, advanced practice providers will likely assume additional responsibilities. As roles shift we must ensure we have the necessary educational and training opportunities to equip this vital part of our workforce.

Objective To understand the role of Advanced Practice Providers (APPs) in urologic procedural care and its change over time. As the population ages and the urologic workforce struggles to meet patient access demands, the role of APPs in the provision of all aspects of urologic care is increasing. However, little is currently known about their role in procedural care. Materials and Methods Commonly performed urologic procedures were linked to Current Procedural Terminology (CPT) codes from 1994 to 2012. National Medicare Part B beneficiary claims frequency was identified using Physician Supplier Procedure Summary Master Files. Trends were studied for APPs, urologists, and all other providers nationally across numerous procedures spanning complexity, acuity, and technical skill set requirements. Results Between 1994 and 2012, annual Medicare claims for urologic procedures by APPs increased dramatically. Cystoscopy increased from 24 to 1820 (+7483%), transrectal prostate biopsy from 17 to 834 (+4806%), complex Foley catheter placement from 471 to 2929 (+522%), urodynamics testing from 41 to 9358 (+22,727%), and renal ultrasound from 18 to 4500 (+24,900%) Conclusion We found dramatic growth in the provision of urologic procedural care by APPs over the past 2 decades. These data reinforce the known expansion of the APP role in urology and support the timeliness of ongoing collaborative multidisciplinary educational efforts to address unmet needs in education, training, and guideline formation to maximize access to urologic procedural services.

To analyze the effects of a decision aid on improving patients' and family members' information giving and question asking during consultations for prostate cancer treatment decision-making.This study is a secondary analysis of archived audio-recorded real-time consultation visits with participants from a randomized clinical trial. Participants were randomly assigned into three groups: TD-intervention targeted patient-only; TS-intervention targeted patients and family members; and control-a handout on staying healthy during treatment. We conducted content analysis using a researcher-developed communication coding system. Using SAS 9.3, we conducted Chi-square/Fisher's exact test to examine whether information giving and question asking among patients and family members varied by groups when discussing different content/topics.Compared with those in the TS and control groups, significantly higher percentages of participants in the TD group demonstrated information giving in discussing topics about diagnosis, treatment options, risks and benefits, and preferences; and engaged in question asking when discussing diagnosis, watchful waiting/active surveillance, risks and benefits, and preferences for treatment impacts.Information support and communication skills training for patients were effective in improving communication during treatment decision-making consultations.Providing information about prostate cancer and communication skills training empower patients and their family members.

Context Gender-specific functional and health-related quality of life (HRQOL) outcomes following radical cystectomy (RC) for bladder cancer (BCa) remain unclear, with many studies excluding women from the study population. Objective To better characterize female-specific functional outcomes following RC and urinary diversion for BCa. Evidence acquisition We performed a critical review of PubMed/Medline and Embase in August 2015 according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Outcomes of interest included urinary function (for orthotopic neobladder), sexual function, bowel function, and quality of life. Excluded were nonbladder malignancies, RCs performed for neurogenic bladder dysfunction, and patients with exposure to radiation therapy prior to surgery. Forty-five publications were selected for inclusion in this analysis. Evidence synthesis Included reports addressed urinary function (34 studies), sexual function (11 studies), and HRQOL (9 studies). All studies had a high risk of bias and ranged significantly in sample size, inclusion criteria, and follow-up time, precluding meaningful meta-analysis. Daytime incontinence approximated 20%, nighttime incontinence 20%, and hypercontinence 10–20%. Sexual function appeared to be better among those patients undergoing genitalia-sparing RC, but generally poor outcomes were noted among those undergoing routine RC. Only 40% of studies assessed sexual function using standardized instruments. HRQOL differences between diversion types appeared to be minimal, whereas comparisons with the general population revealed significant differences in emotional problems, role functioning, fatigue, and appetite. Conclusions Functional outcomes among women undergoing RC for BCa are poorly studied with limitations regarding use of validated questionnaires, heterogeneous patient populations, and small sample sizes. Collaborative efforts will be needed to better define functional outcomes among this poorly studied patient population. Patient summary We reviewed functional outcomes following cystectomy among women with bladder cancer. We found that urinary, sexual, and bowel function and quality of life are poorly studied among women, with function ranging significantly across studies.

Computed tomography (CT) has limited diagnostic accuracy for staging of muscle-invasive bladder cancer (MIBC). [Twenty-one patients with MIBC with planned radical cystectomy were enrolled. Two teams of radiologists reviewed FDG-PET/MRI scans to determine: (1) presence of primary bladder tumor; and (2) lymph node involvement and distant metastases. FDG-PET/MRI was compared with cystectomy pathology and computed tomography (CT).Eighteen patients were included in the final analysis, most (72.2%) of whom received neoadjuvant chemotherapy. Final pathology revealed 10 (56%) patients with muscle invasion and only 3 (17%) patients with lymph node involvement. Clustered analysis of FDG-PET/MRI radiology team reads revealed a sensitivity of 0.80 and a specificity of 0.56 for detection of the primary tumor with a sensitivity of 0 and a specificity of 1.00 for detection of lymph node involvement when compared with cystectomy pathology. CT imaging demonstrated similar rates in evaluation of the primary tumor (sensitivity, 0.91; specificity, 0.43) and lymph node involvement (sensitivity, 0; specificity, 0.93) when compared with pathology.This pilot single-institution experience of FDG-PET/MRI for preoperative staging of MIBC performed similar to CT for the detection of the primary tumor; however, the determination of lymph node status was limited by few patients with true pathologic lymph node involvement. Further studies are needed to evaluate the potential role for FDG-PET/MRI in the staging of MIBC.

INTRODUCTION AND OBJECTIVES:The advantage of health-related quality of life (HRQoL) in continent (C) urinary diversions (UD) over non-continent (NC) UD remains controversial. We compared outcomes b...

INTRODUCTION AND OBJECTIVES:Health-related quality of life (HRQoL) can be significantly affected following radical cystectomy (RC) and factors affecting it have not been well studied in this popula...

Background Preventable complications and readmissions after cystectomy may be detectable via postoperative monitoring of patient-reported outcomes (PROs). However, no study has defined meaningful PROs or the use of mobile communication devices (mobile health [mHealth]) to capture them. The objectives of this study were to determine which high-priority PROs influence patients' perioperative experience, what processes influence these outcomes, how patients and caregivers differ in their experiences, and how mHealth might be used to improve outcomes. Methods Forty-five semistructured, in-depth interviews were conducted with readmitted cystectomy patients, caregivers, and providers with an interview guide that addressed perioperative education, symptoms, function, and the potential for mHealth interventions. Among 15 patients, 10 had an interviewed partner. A thematic analysis of interviews conducted with readmitted patients, caregivers, and providers was performed to examine processes that affected perioperative care and readmission and to determine how mHealth interventions might be implemented. Results Readmitted patients and caregivers ranged in age from 33 to 78 years and were diverse in race and stage. The providers included a diverse representation of physicians, nurses, and other specialists. Cystectomy preoperative education was overwhelming and lacked personalization, and this contributed to a fundamental lack of knowledge regarding normal and abnormal symptoms after surgery. Three connecting themes were identified: 1) cystectomy education overload, 2) a need to define normal symptoms, and 3) education with incremental learning through mHealth. Conclusions A personalized mHealth intervention addressing themes of education overload, the definition of normality, and incremental learning could be realized through mHealth technology and provide the right information for the right patient at the right time.

e16510 Background: Patients (pts) with muscle-invasive bladder cancer (MIBC) ineligible for cisplatin-based chemotherapy have no standard systemic therapy options and are prioritized for radical cystectomy (RC) alone. This prospective clinical trial investigated the safety and efficacy of escalating doses of neoadjuvant atezolizumab (N-ATZ) prior to RC in MIBC pts. Methods: This is a single-institution, phase II trial of escalating doses of N-ATZ (1200 mg IV every 3 weeks) in pts with MIBC. Key inclusion criteria were resectable urothelial carcinoma of the bladder (T2-T4a,N0-1,M0) and inability to receive cisplatin-based treatment (eGFR < 60 mL/min, G≥2 neuropathy/hearing loss, pt decision). Pts with high-risk disease at RC were eligible to receive adjuvant ATZ for up to 16 total doses. Pts were followed for up to 2 years following RC. Primary efficacy endpoint was pathologic complete response (pCR; pT0N0). Secondary endpoints were safety of treatment, rate of pathologic downstaging (≤pT1N0), response based on PD-L1 status, and overall survival (OS) and recurrence-free survival (RFS) at 1 and 2 years from RC. Results: A total of 20 pts were enrolled and sequentially treated with one (n=6), two (n=5), and three (n=9) cycles of N-ATZ prior to RC. Median age was 69 (range 61-81), 75% were male and 85% Caucasian. Pts were cisplatin-ineligible due to low GFR (35%), hearing loss (25%) or neuropathy (10%); the rest refused cisplatin (30%). Most pts had pT2 disease (80%); the remainder, pT3/pT4 (15%/5%), and 10% had cN1. Among 17 pts with available tumor PD-L1 status, 76% had PD-L1 positive (CPS≥10) tumors. pCR was observed in 2 pts (10%) with 1 and 2 ATZ doses, whereas pathologic downstaging was observed in 5 pts (25%) across all 3 doses (Table). All pts completed intended treatment and RC within the trial-defined timeframe. Perioperative TRAEs of any grade occurred in 75%, but only 10% had G3 TRAEs (diarrhea, fecal incontinence). There were no G4/G5 events. Median follow-up from RC was 23.6 months and 75% were still followed at the time of data cutoff in 2/2021. Among evaluable pts, 1-year RFS and OS were 72% and 94% while 2-year RFS and OS were 64% and 69%. PD-L1 positive pts had superior OS (logrank p=0.06) and RFS (p=0.10) relative to PD-L1 negative pts. Conclusions: N-ATZ was well tolerated at all three dose levels and did not delay or prevent surgery. As few as 1 to 2 ATZ doses resulted in pathologic downstaging, including pCR. Although pCR rate in this trial was lower than expected, most pts had a durable recurrence-free period and all evaluable pts with tumor downstaging were alive and recurrence-free at 2 years following RC. Increased tumor PD-L1 expression was suggestive of improved outcomes and further biomarker analyses are ongoing. Clinical trial information: NCT02451423. [Table: see text]

463 Background: Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) targeting Nectin-4 (encoded by the PVRL4/NECTIN4 gene ) approved for treatment-refractory metastatic urothelial cancer. Factors that mediate sensitivity or resistance to EV are unknown. In the present study, we sought to 1) examine heterogeneity of NECTIN4 gene expression across molecular subtypes of bladder cancer and 2) determine if Nectin-4 expression mediates EV sensitivity or resistance. Methods: NECTIN4 expression data from seven muscle-invasive bladder cancer clinical cohorts (n = 1912 total patients) were used to compare relative NECTIN4 expression across molecular subtypes. The outcome of the gene expression analysis was relative NECTIN4 expression in the consensus molecular subtypes of bladder cancer. Expression of NECTIN4 was validated in multiple bladder cancer cell lines. NECTIN4 was stably over-expressed or knocked down in basal (TCCSUP and UMUC-3) and luminal (HT-1376, HT-1197 and UMUC-9) bladder cancer cell lines, respectively, and EV dose-response assays were performed, as measured by cell proliferation and clonogenic assays. Results: NECTIN4 expression is heterogenous across molecular subtypes of bladder cancer and significantly enriched in luminal subtypes (p < 0.001). NECTIN4 expression is positively correlated with the luminal markers GATA3, FOXA1, and PPARG across cohorts (Spearman’s rank correlation r = 0.57, p < 0.0001 for GATA3, r = 0.37, p < 0.0001 for FOXA1, and r = 0.56, p < 0.0001 for PPARG). NECTIN4 expression is both necessary and sufficient for EV sensitivity in luminal and basal subtypes of urothelial bladder cancer cells. Downregulation of NECTIN4 led to EV resistance, and EV-resistant cell lines expressed decreased levels of Nectin-4. Conclusions: Results of this pre-clinical study suggest that sensitivity to EV is mediated by expression of NECTIN4, which is significantly enriched in luminal subtypes of bladder cancer. Downregulation of NECTIN4 leads to resistance to EV. These findings have implications for biomarker development, patient selection and the inclusion of molecular subtyping in ongoing and future EV clinical trials. Further investigation into Nectin-4 loss as a mechanism of resistance in patients treated on EV is warranted.

476 Background: Reliable predictive markers are lacking in patients (pts) with locally advanced or metastatic urothelial carcinoma (aUC) treated with immune checkpoint inhibitors (ICI). We sought to determine whether specific genomic alterations could be used to predict overall survival (OS) in this patient population. Methods: We undertook a retrospective cohort study of pts with aUC who received ICI and underwent genomic profiling by next-generation sequencing (NGS). All patients underwent NGS using commercially available platforms (e.g. Foundation Medicine, Strata, Invitae), or testing on the CLIA-certified institutional panel UCSF500. Associations between the 20 most frequently altered genes and OS were first examined by Cox regression. Genes with a p

442 Background: For patients (pts) with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy (cisplatin), the standard of care option is radical cystectomy (RC) alone. This prospective clinical trial investigated the safety and efficacy of escalating doses of atezolizumab (ATZ) as neoadjuvant therapy prior to RC in pts with non-metastatic urothelial cancer. Methods: This single-arm, single institution, phase II trial investigated the administration of one (n = 6), two (n = 5) or three (n = 9) cycles of ATZ (1200 mg IV given every 3 weeks) in pts with MIBC who are either ineligible for or refused cisplatin prior to RC. Key inclusion criteria were urothelial carcinoma of the bladder (T2-T4a,N0-1,M0) and inability to receive cisplatin-based treatment (eGFR < 60 mL/min, G≥2 neuropathy/hearing loss, pt decision). Pts with high-risk disease ( > pT2 or LN+) at the time of RC were eligible to receive adjuvant ATZ for up to 16 total cycles. Primary efficacy endpoint was pathologic complete response (pCR; pT0N0). Important secondary endpoints were safety of treatment, rates of pathologic downstaging and biomarker assessments in serial tissue samples. Pts were followed for up to 2 years following RC. Results: Among 20 pts with MIBC, median age was 69 (range 61-81) and 75% were male. Most commonly pts were cisplatin-ineligible due to low GFR (35%), hearing loss (25%) or neuropathy (10%); remainder refused cisplatin (30%). At trial enrollment, pT2, pT3, and pT4 was present in 80%, 15%, and 5% of pts and 10% had enlarged pelvic lymph nodes ( > 10 mm) on scans. All pts completed intended treatment cycles and all had RC within the defined timeframe ( > 3 weeks from last and < 12 weeks from first treatment). pCR at RC was 10% (2/20 pts), and was observed in pts receiving 1 and 2 cycles of ATZ. Pathologic downstaging (≤pT1N0) was achieved in 25% (5/20 pts) and observed across all three dose levels. Adjuvant ATZ was given to 8 pts. TRAEs of any grade during perioperative period occurred in 75% and G3 TRAEs in 10% (diarrhea, fecal incontinence). There were no G4 or G5 events. Median follow-up from the time of RC was 21.4 months at the time of data cutoff in 10/2020. Among evaluable pts, 1-year RFS and OS were 71% and 94% while 2-year RFS and OS were 64% and 75%. Conclusions: This prospective trial supports the safety and efficacy of ATZ as neoadjuvant therapy in MIBC. Although pCR and rates of downstaging were lower than what was previously reported in comparable neoadjuvant trials of checkpoint inhibitors in MIBC, pCRs in this trial were seen even in pts receiving only 1-2 doses of ATZ. Many pts had a durable recurrence-free period and all 4 evaluable pts who had pathologic downstaging were alive and disease free at 2 years post RC. Translational and biomarker work from this study is also being pursued. Clinical trial information: NCT02451423.

Men with clinically localized prostate cancer face an archetypal "preference sensitive" treatment decision. A shared decision making process incorporating patient values and preferences is paramount. We evaluated the benefit of a novel decision making application, and investigated associations between patient preferences and treatment choice.We used a novel, web based application that provides education, preference measurement and personalized decision analysis for patients with newly diagnosed prostate cancer. Preferences are measured using conjoint analysis. The application ranks treatment options according to their "fit" (expected value) based on clinical factors and personal preferences, and serves as the basis for shared decision making during the consultation. We administered the decisional conflict scale before and after completion of the application. Additionally, we compared post-visit perceptions of shared decision making between a baseline "usual care" cohort and a cohort seen after the application was integrated into clinical practice.A total of 109 men completed the application before their consultation, and had decisional conflict measured before and after use. Overall decisional conflict decreased by 37% (p0.0001). Analysis of the decisional conflict subscales revealed statistically significant improvements in all 5 domains. Patients completing the decision making application (33) felt more included in (88% vs 57%, p=0.01) and jointly responsible for (94% vs 52%, p0.0001) the decision about further treatment compared to those receiving usual care (24). More patients who completed the application strongly agreed that different treatment options were discussed (94% vs 74%, p=0.02).Implementation of this web based intervention was associated with decreased decisional conflict and enhanced elements of shared decision making.

Objective To forecast the size and composition of the urologist and urology advanced care provider (ACP; nurse practitioner, physicians' assistant) workforce over the next 20 years. Methods Current urologist workforce was estimated from the American Board of Urology certification data and the 2014 American Urological Association (AUA) Census. Incoming workforce was estimated from the American Board of Urology and AUA residency match data. Estimates of the ACP workforce were extracted from the 2012 AUA Physician Survey. Full-time equivalent (FTE) calculations were based on a 2014 urology workforce survey. Workforce projections were created using a stock and flow population model with multiple alternative forecast scenarios. Results Slight growth in overall (urologist + ACP) workforce FTEs is expected, from 14,792 in 2015 to 15,160 in 2035. A significant decline in urologist FTEs is likely, from 11,221 in 2015 to 8859 in 2035. ACPs should increase markedly, from 8,710 in 2015 to 15,369 in 2035. Female urologists should increase by 2035, from the current 7.0% to 18.6% of urologist workforce. Alternate scenarios were evaluated, with forecasted FTEs in 2035 ranging from 14,066 to 17,675. In 2035, workforce shortage predictions range from 12% to 46%. Conclusion With a decrease in urologists over the coming decades, urologists and ACPs may not meet future demand. This forecast highlights the need for discussion and planning among leadership in the field to find creative solutions for this impending workforce shortage.

Background Renal cell carcinoma forming a venous tumor thrombus (VTT) in the inferior vena cava (IVC) has a poor prognosis. Recent investigations have been focused on prognostic markers of survival. Thrombus consistency (TC) has been proposed to be of significant value but yet there are conflicting data. The aim of this study is to test the effect of IVC VTT consistency on cancer specific survival (CSS) in a multi-institutional cohort. Methods The records of 413 patients collected by the International Renal Cell Carcinoma–Venous Thrombus Consortium were retrospectively analyzed. All patients underwent radical nephrectomy and tumor thrombectomy. Kaplan–Meier estimate and Cox regression analyses investigated the impact of TC on CSS in addition to established clinicopathological predictors. Results VTT was solid in 225 patients and friable in 188 patients. Median CSS was 50 months in solid and 45 months in friable VTT. TC showed no significant association with metastatic spread, pT stage, perinephric fat invasion, and higher Fuhrman grade. Survival analysis and Cox regression rejected TC as prognostic marker for CSS. Conclusions In the largest cohort published so far, TC seems not to be independently associated with survival in RCC patients and should therefore not be included in risk stratification models. J. Surg. Oncol. 2016;114:764–768. © 2016 Wiley Periodicals, Inc.

Introduction There is little information on job satisfaction in the extant literature in urology. The purpose of this study is to examine 1) the current state of job satisfaction among urologists in the United States, and 2) the demographic and work place factors that have the greatest influence on satisfaction. Methods We collaborated with AUA (American Urological Association) to query its domestic membership of practicing urologists regarding socioeconomic, work force and quality of life issues. A total of 848 responses were collected for a total response rate of 13%. Linear regression models were used to evaluate bivariable and multivariable associations with job satisfaction scores on a 1 to 5 scale. Results Of providers 70% reported being satisfied, 63% reported that they would choose medicine again and 83% would choose urology again. Age and job satisfaction did not demonstrate a linear association on statistical analysis but rather a U-shaped relationship. On bivariate analysis significant factors associated with higher job satisfaction included younger and older age, higher income (p = 0.047), fewer call days (p = 0.006), fellowship training (p = 0.006) and academic practice (overall p = 0.002). On multivariate analysis age (younger and older ages) and academic practice remained significant predictors of job satisfaction (p = 0.01) as did higher income (p = 0.038). Conclusions The current study helps describe the current state of job satisfaction among American urologists and examined work place factors that influence satisfaction. Income, hours worked, academic practice and age each have a significant impact on job satisfaction for the practicing urologist. Keeping abreast of the drivers of job satisfaction is critical to ensure that urologists continue to care for patients, perform research, educate future physicians and provide service to their communities.

Introduction: Computed tomography (CT) has limited diagnostic accuracy for staging of muscle-invasive bladder cancer (MIBC). [18F] Fluorodeoxyglucose positron emission tomography (FDG-PET)/magnetic resonance imaging (MRI) is a novel imaging modality incorporating functional imaging with improved soft tissue characterization. This pilot study evaluated the use of preoperative FDG-PET/MRI for staging of MIBC. Patients and Methods: Twenty-one patients with MIBC with planned radical cystectomy were enrolled. Two teams of radiologists reviewed FDG-PET/MRI scans to determine: (1) presence of primary bladder tumor; and (2) lymph node involvement and distant metastases. FDG-PET/MRI was compared with cystectomy pathology and computed tomography (CT). Results: Eighteen patients were included in the final analysis, most (72.2%) of whom received neoadjuvant chemotherapy. Final pathology revealed 10 (56%) patients with muscle invasion and only 3 (17%) patients with lymph node involvement. Clustered analysis of FDG-PET/MRI radiology team reads revealed a sensitivity of 0.80 and a specificity of 0.56 for detection of the primary tumor with a sensitivity of 0 and a specificity of 1.00 for detection of lymph node involvement when compared with cystectomy pathology. CT imaging demonstrated similar rates in evaluation of the primary tumor (sensitivity, 0.91; specificity, 0.43) and lymph node involvement (sensitivity, 0; specificity, 0.93) when compared with pathology. Conclusions: This pilot single-institution experience of FDG-PET/MRI for preoperative staging of MIBC performed similar to CT for the detection of the primary tumor; however, the determination of lymph node status was limited by few patients with true pathologic lymph node involvement. Further studies are needed to evaluate the potential role for FDG-PET/MRI in the staging of MIBC. © 2020 Elsevier Inc.In this pilot study, preoperative staging with [18F] fluorodeoxyglucose-positron emission tomography/magnetic resonance imaging in muscle-invasive bladder cancer detected the primary bladder tumor; however, the determination of lymph node status was limited by few patients with pathologic lymph node involvement. Additional studies are needed to evaluate the potential role for [18F] fluorodeoxyglucose-positron emission tomography/magnetic resonance imaging in the staging of bladder cancer.