Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial.

BACKGROUND: BCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer. METHODS: In this phase 3, multicentre, open-label, repeat-dose study done in 33 centres (hospitals and clinics) in the USA, we recruited patients aged 18 years or older, with BCG-unresponsive non-muscle-invasive bladder cancer and an Eastern Cooperative Oncology Group status of 2 or less. Patients were excluded if they had upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis. Eligible patients received a single intravesical 75 mL dose of nadofaragene firadenovec (3 × 1011 viral particles per mL). Repeat dosing at months 3, 6, and 9 was done in the absence of high-grade recurrence. The primary endpoint was complete response at any time in patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour). The null hypothesis specified a complete response rate of less than 27% in this cohort. Efficacy analyses were done on the per-protocol population, to include only patients strictly meeting the BCG-unresponsive definition. Safety analyses were done in all patients who received at least one dose of treatment. The study is ongoing, with a planned 4-year treatment and monitoring phase. This study is registered with ClinicalTrials.gov, NCT02773849. FINDINGS: Between Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53·4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45·5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3-4 study drug-related adverse event (two [1%] of 157 patients, both grade 3), and there were no treatment-related deaths. INTERPRETATION: Intravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state. FUNDING: FKD Therapies Oy.

Impact of radiation on the incidence and management of ureteroenteric strictures: a contemporary single center analysis.

BACKGROUND: Ureteroenteric stricture incidence has been reported as high as 20% after urinary diversion. Many patients have undergone prior radiotherapy for prostate, urothelial, colorectal, or gynecologic malignancy. We sought to evaluate the differences between ureteroenteric stricture occurrence between patients who had radiation prior to urinary diversion and those who did not. METHODS: An IRB-approved cystectomy database was utilized to identify ureteroenteric strictures among 215 patients who underwent urinary diversion at a single academic center between 2016 and 2020. Chart abstraction was conducted to determine the presence of confirmed stricture in these patients, defined as endoscopic diagnosis or definitive imaging findings. Strictures due to malignant ureteral recurrence were excluded (3 patients). Statistical analysis was performed using chi squared test, t-test, and Wilcoxon Rank-Sum Test, logistic regression, and Kaplan-Meier analysis of stricture by cancer type. RESULTS: 65 patients had radiation prior to urinary diversion; 150 patients did not have a history of radiation therapy. Benign ureteroenteric stricture rate was 5.3% (8/150) in the non-radiated cohort and 23% (15/65) in the radiated cohort (p = < 0.001). Initial management of stricture was percutaneous nephrostomy (PCN) in 78% (18/23) and the remaining 22% (5/23) were managed with primary retrograde ureteral stent placement. Long term management included ureteral reimplantation in 30.4% (7/23). CONCLUSIONS: Our study demonstrates a significant increase in rate of ureteroenteric strictures in radiated patients as compared to non-radiated patients. The insult of radiation on the ureteral microvascular supply is likely implicated in the cause of these strictures. Further study is needed to optimize surgical approach such as utilization of fluorescence angiography for open and robotic approaches.

Optimizing Telemedicine Technologic Infrastructure with Animal Models: A Case in Telecystoscopy.

Background: Rapid evolution of telemedicine technology requires procedures in telemedicine to adapt frequently. An example in urology, telecystoscopy, allows certified advanced practice providers to perform cystoscopy, endoscopic examination of the bladder, in rural areas with real-time interpretation and guidance by an off-site urologist. We have previously shown the technological infrastructure for optimized video quality. Introduction: Newer models of cystoscope and coder/decoder (codec) are available with anticipation that components used in our original model will become unavailable. Our objective is to assess the diagnostic ability of two cystoscopes (Storz, Wolf) with old (SX20) and new (DX70) codecs. Materials and Methods: A single urologist performed flexible cystoscopy on an ex vivo porcine bladder. Combinations of cystoscope (Storz vs. Wolf), codec (SX20 vs. DX70), and internet transmission speed were used to create eight distinct recordings. Deidentified videos were reviewed by expert urologist reviewers via electronic survey with questions on video quality and diagnostic ability. A logistic regression model was used to assess the ability to make a diagnosis. Results: Eight transmitted cystoscopy videos were reviewed by 16 urologists. Despite new technology, the Storz cystoscope combined with the SX20 codec (the original combination) provides the best diagnostic capacity. Discussion: Technical infrastructure must be routinely validated to assess the component impact on overall quality because newer is not always better. Should the SX20 become obsolete, ex vivo animal models are safe, inexpensive anatomic models for testing. Conclusions: As technology continues to evolve, procedures in telemedicine must critically scrutinize the impact of new technologic components to uphold quality.

Blinded Comparison of Clarity, Proficiency and Diagnostic Capability of Tele-Cystoscopy Compared to Traditional Cystoscopy: A Pilot Study.

PURPOSE: In order to expand the availability of cystoscopy to underserved areas we have proposed using advanced practice providers to perform cystoscopy with real-time interpretation by the urologist on a telemedicine platform, termed "tele-cystoscopy." The purpose of this study is to have blinded external reviewers retrospectively compare multisite, prospectively collected video data from tele-cystoscopy with the video of traditional cystoscopy in terms of video clarity, practitioner proficiency and diagnostic capability. MATERIALS AND METHODS: Each patient underwent tele-cystoscopy by a trained advanced practice provider and traditional cystoscopy with an onsite urologist. Prospectively collected tele-cystoscopy transmitted video, tele-cystoscopy onsite video and traditional cystoscopy video were de-identified and blinded to external reviewers. Each video was evaluated and rated twice by independent reviewers and diagnostic agreement was quantified. RESULTS: Six tele-cystoscopy encounters were reviewed for a total of 36 assessments. Video clarity, defined by speed of transmission and image resolution, was better for onsite compared to transmitted tele-cystoscopy. Practitioner proficiency for thoroughness of inspection was rated at 92% for tele-cystoscopy and 100% for traditional cystoscopy. Confidence in identification of an abnormality was equivalent. Four of 6 videos had 100% agreement between reviewers for next action taken, indicating high diagnostic agreement. Additionally, provider performing cystoscopy and location did not statistically influence the ability to make a diagnosis or action taken. CONCLUSIONS: This model has excellent completeness of examination, equivalent ability to identify abnormalities and external validation of action taken. This pilot study demonstrates that tele-cystoscopy may expand access to bladder cancer surveillance.

Health Related Quality of Life of Patients with Bladder Cancer in the RAZOR Trial: A Multi-Institutional Randomized Trial Comparing Robot versus Open Radical Cystectomy.

PURPOSE: We evaluated health related quality of life following robotic and open radical cystectomy as a treatment for bladder cancer. MATERIALS AND METHODS: Using the Randomized Open versus Robotic Cystectomy (RAZOR) trial population we assessed health related quality of life by using the Functional Assessment of Cancer Therapy (FACT)-Vanderbilt Cystectomy Index and the Short Form 8 Health Survey (SF-8) at baseline, 3 and 6 months postoperatively. The primary objective was to assess the impact of surgical approach on health related quality of life. As an exploratory analysis we assessed the impact of urinary diversion type on health related quality of life. RESULTS: Analyses were performed in subsets of the per-protocol population of 302 patients. There was no statistically significant difference between the mean scores by surgical approach at any time point for any FACT-Vanderbilt Cystectomy Index subscale or composite score (p >0.05). The emotional well-being score increased over time in both surgical arms. Patients in the open arm showed significantly better SF-8 sores in the physical and mental summary scores at 6 months compared to baseline (p <0.05). Continent diversion (versus noncontinent) was associated with worse FACT-bladder-cystectomy score at 3 (p <0.01) but not at 6 months, and the SF-8 physical component was better in continent-diversion patients at 6 months (p=0.019). CONCLUSIONS: Our data suggests lack of significant differences in the health related quality of life in robotic and open cystectomies. As robotic procedures become more widespread it is important to discuss this finding during counseling.

Predictors of Recurrence, and Progression-Free and Overall Survival following Open versus Robotic Radical Cystectomy: Analysis from the RAZOR Trial with a 3-Year Followup.

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.

Effect of active versus passive void trials on time to patient discharge, urinary tract infection, and urinary retention: a randomized clinical trial.

PURPOSE: We sought to determine the effect of active versus passive voiding trials on time to hospital discharge and rates of urinary tract infection (UTI) and urinary retention (UR). METHODS: We performed a prospective, randomized trial comparing active (AVT) versus passive (PVT) void trials of inpatients requiring urethral catheter removal. Of 329 eligible patients, 274 were randomized to AVT (bladder filled with saline before catheter removal) or PVT (spontaneous bladder filling after catheter removal). Primary outcome was time to hospital discharge. Secondary outcomes were UTI (NSQIP criteria) and UR (requiring repeat catheterization) within 2 weeks of void trial. RESULTS: The median time to void was 18 (5-115) versus 236 (136-360) min in the AVT and PVT groups, respectively (p < 0.0001). However, no difference was seen in comparison of the median time to hospital discharge between AVT [28.4 (13.6-69.3) h] and PVT [30.0 (10.4-75.6) h] cohorts, respectively (p = 0.93). Six (4.8%) and 13 (12.9%) patients developed UTI in the AVT and PVT groups, respectively (p = 0.03). Eleven (8.8%) and 12 (11.9%) patients developed UR in the AVT and PVT groups, respectively (p = 0.36). CONCLUSION: Our study comparing AVT versus PVT demonstrated no difference in time to discharge despite a 3.6 h reduction in time to void associated with AVT. AVT was associated with a 63% reduction in UTI, with no difference seen in UR rates across cohorts. Given the reduction in UTI and technical advantages, our data suggest that AVT should be considered as a recommended technique for void trial protocol. TRIAL REGISTRATION: NCT02886143 (clinicaltrials.gov).

Prostate Cancer Characteristics in the US Preventive Services Task Force Grade D Era: A Single-Center Study and Meta-Analysis.

BACKGROUND: In May 2012, the US Preventive Services Task Force assigned prostate-specific antigen-based screening a grade D recommendation, advising against screening at any age. Our objective was to compare prostate cancer characteristics pre- and post-recommendation with an adjusted analysis of our data and a pooled analysis including other primary data sources. METHODS: We identified all incident prostate cancer diagnoses at our institution from 2007 to 2016. Multivariable log binomial regression was used to determine the relative risk (RR) of metastasis at diagnosis, ≥Gleason Group 4, and high D'Amico risk disease pre- versus post-recommendation. The meta-analysis included primary data studies evaluating these outcomes. RESULTS: At our institution, 287 (44.6%) and 224 (48.8%) patients were diagnosed in the pre- and post-cohorts. The RR of metastatic disease at diagnosis did not differ between groups (p = 0.224), nor did the risk of high D'Amico category disease (p = 0.089). The risk of ≥Gleason Group 4 was 1.58 times higher post-recommendation (p = 0.007). The pooled risk of ≥Gleason Group 4 disease was 1.5 (p < 0.001) post-recommendation and was 1.29 (p = 0.006) for high D'Amico risk disease. CONCLUSIONS: While the number of metastatic cases did not differ after the recommendation, the risk of high-grade cancers increased at both a local and aggregated level.

Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): an open-label, randomised, phase 3, non-inferiority trial.

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%; pnon-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.

Assigning value to preparation for prostate cancer decision making: a willingness to pay analysis.

BACKGROUND: The Personal Patient Profile-Prostate (P3P) is a web-based decision support system for men newly diagnosed with localized prostate cancer that has demonstrated efficacy in reducing decisional conflict. Our objective was to estimate willingness-to-pay (WTP) for men's decisional preparation activities. METHODS: In a multicenter, randomized trial of P3P, usual care group participants received typical preparation for decision making plus referral to publicly-available, educational websites. Intervention group participants received the same, plus online P3P educational media specific to the user's personal preferences and values, and a communication coaching component tailored to race\ethnicity, age and language. WTP data were collected one week after physician consultation. An iterative bidding direct contingent valuation survey format was used, randomly assigning participants to high or low starting values (SV). Tobit models were used to explore associations between SV-adjusted WTP and age, education, marital and work-status, insurance, decision-control preference and decision-making stage. RESULTS: Of 392 participants enrolled, 141 P3P and 107 usual care (UC) provided a WTP value. Men were willing to pay a median $25 (IQR $10-100) for P3P in addition to usual care preparation materials. In the final multivariable tobit regression model, SV, marital status, stage of decision making and income were significantly associated with WTP for P3P. Decision control preference was considered marginally significant (p = 0.11). Men were WTP a median $30 (IQR $10-$200) for usual care material alone. In the final multivariable model, SV, education, and stage of decision making were significantly associated with WTP in usual care. CONCLUSION: WTP was similar for UC and for the addition of P3P to UC decision preparation. The WTP values were associated with demographic and preference variables. Findings can help focus decision support on future patients who would benefit most: those without strong support systems, at earlier stages of decision making, and open to a shared-decision style. TRIAL REGISTRATION: NCT NCT01844999 . Registered May 3, 2013.

Decision Support with the Personal Patient Profile-Prostate: A Multicenter Randomized Trial.

PURPOSE: We evaluated the efficacy of the web based P3P (Personal Patient Profile-Prostate) decision aid vs usual care with regard to decisional conflict in men with localized prostate cancer. MATERIALS AND METHODS: A randomized (1:1), controlled, parallel group, nonblinded trial was performed in 4 regions of the United States. Eligible men had clinically localized prostate cancer and an upcoming consultation, and they spoke and read English or Spanish. Participants answered questionnaires to report decision making stage, personal characteristics, concerns and preferences plus baseline symptoms and decisional conflict. A randomization algorithm allocated participants to receive tailored education and communication coaching, generic teaching sheets and external websites plus a 1-page summary to clinicians (intervention) or the links plus materials provided in clinic (usual care). Conflict outcomes and the number of consultations were measured at 1 month. Univariate and multivariable models were used to analyze outcomes. RESULTS: A total of 392 men were randomized, including 198 to intervention and 194 to usual care, of whom 152 and 153, respectively, returned 1-month outcomes. The mean ± SD 1-month decisional conflict scale (score range 0 to 100) was 10.9 ± 16.7 for intervention and 9.9 ± 18.0 for usual care. The multivariable model revealed significantly reduced conflict in the intervention group (-5.00, 95% CI -9.40--0.59). Other predictors of conflict included income, marital or partner status, decision status, number of consultations, clinical site and D'Amico risk classification. CONCLUSIONS: In this multicenter trial the decision aid significantly reduced decisional conflict. Other variables impacted conflict and modified the effect of the decision aid, notably risk classification, consultations and resources. P3P is an effective adjunct for shared decision making in men with localized prostate cancer.

Robotic-Assisted Surgery for Upper Tract Urothelial Carcinoma: A Comparative Survival Analysis.

BACKGROUND: We performed a comparative survival analysis of patients undergoing robotic-assisted versus laparoscopic or open surgery for upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: Patients diagnosed with non-metastatic UTUC undergoing removal of the kidney and/or ureter were identified using Medicare-linked Surveillance, Epidemiology, and End Results Program data (2004-2013). Patients aged 65-85 years were categorized based on surgical approach (open, laparoscopic, or robotic-assisted). Kaplan-Meier methods were used to determine survival (overall and cancer-specific) and intravesical recurrence rates, the former using a propensity score-weighted model. Independent predictors of survival were determined using multivariable Cox proportional hazards regression analysis. RESULTS: We identified a total of 3801 patients meeting the final inclusion criteria: open (n = 1862), laparoscopic (n = 1624), and robotic (n = 315). Robotic surgery was associated with the shortest length of hospital stay (p < 0.001) but highest in-hospital charges (p < 0.001), with no difference in readmission rates (p = 0.964). No difference was found in overall or cancer-specific survival in the robotic cohort when compared with open or laparoscopic surgery. In addition, no difference in the rate of intravesical recurrence was noted in robotic-assisted laparoscopy compared with the other groups. The sole predictor of improved survival was extent of lymphadenectomy, which was highest in the robotic cohort. CONCLUSIONS: Using a large, population-based cancer database, there was no survival difference when a robotic-assisted approach was utilized in patients undergoing surgery for UTUC. These findings are important with the increased use of robotic surgery in the management of UTUC.

Ileal perforation in the setting of atezolizumab immunotherapy for advanced bladder cancer.

Atezolizumab is a promising immunotherapy for advanced urothelial carcinoma. Like other immune checkpoint inhibitors, it can produce rare immune-related adverse events (IRAEs). Here we present the recent case of a patient with metastatic bladder cancer who developed diarrhea and abdominal pain months after beginning atezolizumab therapy. He presented to our institution with an ileal perforation secondary to atezolizumab-induced enterocolitis. After surgical repair, the patient's condition improved, and he was discharged. We discuss the management of atezolizumab-induced enterocolitis, including the importance of early recognition and intervention to prevent more devastating complications.

Comparison of Renal Cell Carcinoma Surveillance Guidelines: Competing Trade-Offs.

PURPOSE: We estimated the differences in intensity, cost, radiation exposure and cancer control of published surveillance guidelines screening for secondary renal cell carcinoma in patients treated with partial nephrectomy. MATERIALS AND METHODS: We developed a Monte Carlo simulation model to contrast the existing guidelines in terms of cost, radiation exposure and cancer control. Model inputs were extrapolated from the existing literature. Surveillance guidelines were analyzed from the AUA, CUA, EAU and NCCN®. Risk stratification among patients treated with partial nephrectomy was based on tumor characteristics. RESULTS: Expected costs during the 5 years after partial nephrectomy were $587 (CUA), $1,076 (AUA), $1,705 (EAU) and $1,768 (NCCN) for low risk patients, and $903 (CUA), $2,525 (EAU) and $3,904 (AUA and NCCN) for high risk patients. Radiation exposure ranged from 31.41 mSv (CUA) to 104.34 mSv (NCCN) for low risk patients and 46.88 mSv (CUA) to 231.61 mSv (AUA and NCCN) for high risk patients. The EAU and CUA guidelines led to the diagnosis of the highest percentage of low risk patients (more than 95%) while all guidelines diagnosed more than 92% of high risk patients with recurrence. CONCLUSIONS: Renal cell carcinoma surveillance guidelines differ greatly in terms of intensity, cost and radiation exposure. It is important for clinicians to adopt standardized surveillance strategies that limit unnecessary cost and radiation exposure without compromising cancer control.

The RAZOR (randomized open vs robotic cystectomy) trial: study design and trial update.

The purpose of the RAZOR (randomized open vs robotic cystectomy) study is to compare open radical cystectomy (ORC) vs robot-assisted RC (RARC), pelvic lymph node dissection (PLND) and urinary diversion for oncological outcomes, complications and health-related quality of life (HRQL) measures with a primary endpoint of 2-year progression-free survival (PFS). RAZOR is a multi-institutional, randomized, non-inferior, phase III trial that will enrol at least 320 patients with T1-T4, N0-N1, M0 bladder cancer with ≈160 patients in both the RARC and ORC arms at 15 participating institutions. Data will be collected prospectively at each institution for cancer outcomes, complications of surgery and HRQL measures, and then submitted to trial data management services Cancer Research and Biostatistics (CRAB) for final analyses. To date, 306 patients have been randomized and accrual to the RAZOR trial is expected to conclude in 2014. In this study, we report the RAZOR trial experimental design, objectives, data safety, and monitoring, and accrual update. The RAZOR trial is a landmark study in urological oncology, randomizing T1-T4, N0-N1, M0 patients with bladder cancer to ORC vs RARC, PLND and urinary diversion. RAZOR is a multi-institutional, non-inferiority trial evaluating cancer outcomes, surgical complications and HRQL measures of ORC vs RARC with a primary endpoint of 2-year PFS. Full data from the RAZOR trial are not expected until 2016-2017.

Patient positioning and prevention of injuries in patients undergoing laparoscopic and robot-assisted urologic procedures.

Positioning injuries in the perioperative period are one of the inherent risks of surgery, but particularly in robot-assisted urologic surgery, and can result in often unrecognized morbidity. Injuries such as upper or lower extremity peripheral neuropathies occur via neural mechanisms and injuries such as compartment syndrome, rhabdomyolysis, ischemic optic neuropathy, and acute arterial occlusion occur via vascular mechanisms. The risk of injury may be exacerbated by operative and patient-related risk factors. Patient-related risk factors include ASA class and BMI, while surgery-related risk factors include physical orientation of the patient and operative length. These injuries can be prevented or reduced by joint effort of the surgeon, anesthesiologist, and operating room staff.

Cost-Effectiveness Analysis of the Clear Cell Likelihood Score Against Renal Mass Biopsy for Evaluating Small Renal Masses.

OBJECTIVE: To examine the cost-effectiveness of the clear cell likelihood score compared to renal mass biopsy (RMB) alone. METHODS: The clear cell likelihood score, a new grading system based on multiparametric magnetic resonance imaging, has been proposed as a possible alternative to percutaneous RMB for identifying clear cell renal carcinoma in small renal masses and expediting treatment of high-risk patients. A decision analysis model was developed to compare a RMB strategy where all patients undergo biopsy and a clear cell likelihood score strategy where only patients that received an indeterminant score of 3 undergo biopsy. Effectiveness was assigned 1 for correct diagnoses and 0 for incorrect or indeterminant diagnoses. Costs were obtained from institutional fees and Medicare reimbursement rates. Probabilities were derived from literature estimates from radiologists trained in the clear cell likelihood score. RESULTS: In the base case model, the clear cell likelihood score was both more effective (0.77 vs 0.70) and less expensive than RMB ($1629 vs $1966). Sensitivity analysis found that the nondiagnostic rate of RMB and the sensitivity of the clear cell likelihood score had the greatest impact on the model. In threshold analyses, the clear cell likelihood score was the preferred strategy when its sensitivity was greater than 62.7% and when an MRI cost less than $5332. CONCLUSION: The clear cell likelihood score is a more cost-effective option than RMB alone for evaluating small renal masses for clear cell renal carcinoma.

Positioning injuries associated with robotic assisted urological surgery.

PURPOSE: Nerve injury associated with patient positioning during surgery is well documented. With the development of robotic surgery, surgeons are faced with new surgical positioning, requiring attention to ensure patient safety. Published reports that address positioning injury during robotic surgery are sparse and none address the overall incidence. In this study we determine the incidence of positioning injury during robotic assisted urological surgery, identify risk factors and describe the time to resolution of the neurological injury. MATERIALS AND METHODS: We reviewed all adult urological cases at our institution that used the da Vinci® Si and da Vinci Standard® Surgical System from January 2010 to December 2011. We characterized risk factors into the 4 domains of positioning, operative, patient specific and anesthesia related. Within these 4 categories we collected data on 13 specific aspects of patient care to determine their association with positioning injury. RESULTS: Of 334 operations 22 positioning injuries (6.6%) were documented. Of these injuries 13 (59.1%) resolved within 1 month, 4 (18.2%) resolved between 1 and 6 months, and 5 (22.7%) persisted beyond 6 months. We found operative time (p <0.0001), in-room time (p <0.0001) and ASA (American Society of Anesthesiologists) class (p = 0.0033) were significantly associated with injury. CONCLUSIONS: Positioning injuries are under recognized in robotic assisted urological surgery and may persist beyond 6 months. Consideration must be given to counseling patients about the risks of positioning injuries, especially for long operations. Patients with multiple medical comorbidities (ASA class 4) are particularly at risk for these injuries.

India Ink Tattooing of Ureteroenteric Anastomoses.

While upper tract access through the insensate conduit following urinary diversion takes less time and incurs fewer costs than percutaneous kidney access does for the treatment of ureter and kidney pathology, endoscopic ureteroenteric anastomoses (UEA) identification can be difficult. We injected India Ink into the bowel mucosa near the UEA during ileal conduit diversion (IC) to determine the safety and feasibility of ink tattooing. Patients undergoing IC were prospectively randomized to receive ink or normal saline (NS) injections. The injections were placed 1 cm from UEA in a triangular configuration, and loopogram exams and looposcopy were performed to identify reflux (UR), UEA, the tattooing site and strictures in 10 and 11 patients randomized with respect to ink and NS injections, respectively. Ink patients were older (72 vs. 61 years old, p = 0.04) and had a higher Charlson Comorbidity Index (5 vs. 2, p = 0.01). Looposcopy was performed in three ink and four NS patients. Visualization of UEA was achieved in 100% of the ink and 75% of the NS patients (p = 0.26). The ink ureteroenteric anastomotic stricture (UEAS) rate was higher (N = 3 vs. N = 1) and six patients vs. one patients underwent surgery, respectively, for UEAS (p = 0.31). The study was halted early due to safety concerns. Our pilot study demonstrates that ink can be well visualized following injection near UEA during IC. However, the ink cohort had more UEAS than previously cited in the literature and our prior institutional UEAS rate of 6%. While this study sample is small, the higher incidence of UEAS after ink injection led us to question the utility and safety of ink injection following IC.

Disparities in Access to Novel Systemic Therapies in Patients With Urinary Tract Cancer: Propagating Access, Policies and Resources Uniformly.

After several decades of therapeutic stagnation, the treatment of patients with urothelial carcinoma has met a revolutionary wave, anticipated by the advent of immune-checkpoint inhibitors (ICI) and followed by newer therapeutic options in the post-ICI setting. These achievements were made in a very short time-frame, thus making the treatment of this disease particularly susceptible to geographical health disparity due to the differences in healthcare systems and approval processes of the regulatory authorities. Furthermore, additional barriers to access innovative care are represented by a limited coverage of clinical trials availability, that is consistent in focusing on selected geographical areas, across trials and clinical settings. Here, we present the current picture of new drug approvals in urothelial carcinoma worldwide, and we also focus our considerations onto the spectrum of ongoing trial inclusion possibilities, trying to understand what are the current gaps in clinical research and routine practice, identifying a way to move forward.