Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial.

PURPOSE: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. MATERIALS AND METHODS: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF). RESULTS: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. CONCLUSIONS: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.

Impact of iodide ions on the speciation of radiolytic transients in molten LiCl-KCl eutectic salt mixtures.

The fate of fission-product iodine is critical for the deployment of next generation molten salt reactor technologies, owing to its volatility and biological impacts if it were to be released into the environment. To date, little is known on how ionizing radiation fields influence the redox chemistry, speciation, and transport of iodine in high temperature molten salts. Here we employ picosecond electron pulse irradiation techniques to elucidate for the first time the impact of iodide ions (I-) on the speciation and chemical kinetics of the primary radiation-induced transient radicals generated in molten chloride salt mixtures (eS- and Cl2˙-) as a function of temperature (400-700 °C). In the presence of I- ions (≥ 1 wt% KI in LiCl-KCl eutectic), we find that the transient spectrum following the electron pulse is composed of at least three overlapping species: the eS- and the Cl2˙- and ICl˙- radical anions, for which a deconvoluted spectrum of the latter is reported here for the first time in molten salts. This new transient spectrum was consistent with gas phase density functional theory calculations. The lifetime of the eS- was unaffected by the addition of I- ions. The newly observed interhalogen radical anion, ICl˙-, exhibited a lifetime on the order of microseconds over the investigated temperature range. The associated chemical kinetics indicate that the predominate mechanism of ICl˙- decay is via reaction with the Cl2˙- radical anion. The iodine containing product of this reaction is expected to be ICl2-, which will have implications for the transport of fission-product iodine in MSR technologies.

Complete Description of the LaCl3-NaCl Melt Structure and the Concept of a Spacer Salt That Causes Structural Heterogeneity.

Lanthanides are important fission products in molten salt reactors, and understanding their structure and that of their mixtures is relevant to many scientific and technological problems including the recovery and separation of rare earth elements using molten salt electrolysis. The literature on molten salts and specifically on LaCl3 and LaCl3-NaCl mixtures is often fragmented, with different experiments and simulations coinciding in their explanation for certain structural results but contradicting or questioning for others. Given the very practical importance that actinide and lanthanide salts have for energy applications, it is imperative to arrive at a clear unified picture of their local and intermediate-range structure in the neat molten state and when mixed with other salts. This article aims to unequivocally answer a set of specific questions: is it correct to think of long-lived octahedral coordination structures for La3+? What is the nature as a function of temperature of networks and intermediate-range order particularly upon dilution of the trivalent ion salt? Is the so-called scattering first sharp diffraction peak (FSDP) for neat LaCl3 truly indicative of intermediate-range order? If so, why is there a new lower-q peak when mixed with NaCl? Are X-ray scattering and Raman spectroscopy results fully consistent and easily described by simulation results? We will show that answers to these questions require that we abandon the idea of a most prominent coordination state for M3+ ions and instead think of multiple competing coordination states in exchange due to significant thermal energy in the molten state.

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.

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.

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.

Implementation of medical scribes in an academic urology practice: an analysis of productivity, revenue, and satisfaction.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Implementing medical scribes in academic urology practices may be useful in increasing productivity, revenue, and provider satisfaction, while maintaining high patient satisfaction.

Integrating Patient Preference into Treatment Decisions for Men with Prostate Cancer at the Point of Care.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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% (p <0.0001). 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%, p <0.0001) 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). CONCLUSIONS: Implementation of this web based intervention was associated with decreased decisional conflict and enhanced elements of shared decision making.

Gender Differences in Compensation, Job Satisfaction and Other Practice Patterns in Urology.

PURPOSE: The proportion of women in urology has increased from less than 0.5% in 1981 to 10% today. Furthermore, 33% of students matching in urology are now female. In this analysis we characterize the female workforce in urology compared to that of men with regard to income, workload and job satisfaction. MATERIALS AND METHODS: We collaborated with the American Urological Association to survey its domestic membership of practicing urologists regarding socioeconomic, workforce and quality of life issues. A total of 6,511 survey invitations were sent via e-mail. The survey consisted of 26 questions and took approximately 13 minutes to complete. Linear regression models were used to evaluate bivariable and multivariable associations with job satisfaction and compensation. RESULTS: A total of 848 responses (660 or 90% male, 73 or 10% female) were collected for a total response rate of 13%. On bivariable analysis female urologists were younger (p <0.0001), more likely to be fellowship trained (p=0.002), worked in academics (p=0.008), were less likely to be self-employed and worked fewer hours (p=0.03) compared to male urologists. On multivariable analysis female gender was a significant predictor of lower compensation (p=0.001) when controlling for work hours, call frequency, age, practice setting and type, fellowship training and advance practice provider employment. Adjusted salaries among female urologists were $76,321 less than those of men. Gender was not a predictor of job satisfaction. CONCLUSIONS: Female urologists are significantly less compensated compared to male urologists after adjusting for several factors likely contributing to compensation. There is no difference in job satisfaction between male and female urologists.

Preoperatively misclassified, surgically removed benign renal masses: a systematic review of surgical series and United States population level burden estimate.

PURPOSE: A significant proportion of renal masses removed for suspected malignancy are histologically benign with the probability inversely proportional to lesion size. To our knowledge the number of preoperatively misclassified benign renal masses treated with nephrectomy is currently unknown. Given the increasing incidence and decreasing average size of renal cell carcinoma, this burden is likely increasing. We estimated the population level burden of surgically removed, preoperatively misclassified benign renal masses in the United States. MATERIALS AND METHODS: We systematically reviewed the literature for studies of pathological findings of renal masses removed for suspected renal cell carcinoma based on preoperative imaging through July 1, 2014. We excluded studies that did not describe benign pathology and with masses not stratified by size, and in which pathology results were based on biopsy. SEER data were queried for the incidence of surgically removed renal cell carcinomas in 2000 to 2009. RESULTS: A total of 19 studies of tumor pathology based on size met criteria for review. Pooled estimates of the proportion of benign histology in our primary analysis (American studies only and 1 cm increments) were 40.4%, 20.9%, 19.6%, 17.2%, 9.2% and 6.4% for tumors less than 1, 1 to less than 2, 2 to less than 3, 3 to less than 4, 4 to 7 and greater than 7, respectively. The estimated number of surgically resected benign renal masses in the United States from 2000 to 2009 increased by 82% from 3,098 to 5,624. CONCLUSIONS: These estimates suggest that the population level burden of preoperatively misclassified benign renal masses is substantial and increasing rapidly, paralleling increases in surgically resected small renal cell carcinoma. This study illustrates an important and to our knowledge previously unstudied dimension of overtreatment that is not directly quantified in contemporary surveillance data.

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.

Nutritional predictors of complications following radical cystectomy.

PURPOSE: To determine the impact of preoperative nutritional status on the development of surgical complications following cystectomy using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). METHODS: We performed a retrospective review of the NSQIP 2005-2012 Participant Use Data Files. ACS-NSQIP collects data on 135 variables, including pre- and intraoperative data and 30-day postoperative complications and mortality on all major surgical procedures at participating institutions. Preoperative albumin (<3.5 or >3.5 g/dl), weight loss 6 months before surgery (>10 %), and body mass index (BMI) were identified as nutritional variables within the database. The overall complication rate was calculated, and predictors of complications were identified using multivariable logistic regression models. RESULTS: A total of 1,213 patients underwent cystectomy for bladder cancer between 2005 and 2012. The overall 30-day complication rate was 55.1 % (n = 668). While 14.7 % (n = 102) had a preoperative albumin <3.5 g/dL, 3.4 % had >10 % weight loss in the 6 months prior to surgery and the mean BMI was 28 kg/m(2). After controlling for age, sex, medical comorbidities, medical resident involvement, operation year, operative time, and prior operation, only albumin <3.5 g/dl was a significant predictor of experiencing a postoperative complication (p = 0.03). This remained significant when albumin was evaluated as a continuous variable (p = 0.02). CONCLUSIONS: Poor nutritional status measured by serum albumin is predictive of an increased rate of surgical complications following radical cystectomy. This finding supports the importance of preoperative nutritional status in this population and highlights the need for the development of effective nutritional interventions in the preoperative setting.

Resident involvement and experience do not affect perioperative complications following robotic prostatectomy.

PURPOSE: Most urologic training programs use robotic prostatectomy (RP) as an introduction to teach residents appropriate robotic technique. However, concerns may exist regarding differences in RP outcomes with resident involvement. Our objective was therefore to evaluate whether resident involvement affects complications, operative time, or length of stay (LOS) following RP. METHODS: Using the National Surgical Quality Improvement Program database (2005-2011), we identified patients who underwent RP, stratified them by resident presence or absence during surgery, and compared hospital LOS, operative time, and postoperative complications using bivariable and multivariable analyses. A secondary analysis comparing outcomes of interest across postgraduate year (PGY) levels was also performed. RESULTS: A total of 5,087 patients who underwent RPs were identified, in which residents participated in 56%, during the study period. After controlling for potential confounders, resident present and absent groups were similar in 30-day mortality (0.0 vs. 0.2%, p = 0.08), serious morbidity (1.8 vs. 2.1%, p = 0.33), and overall morbidity (5.1 vs. 5.4%, p = 0.70). While resident involvement did not affect LOS, operative time was longer when residents were present (median 208 vs. 183 min, p < 0.001). Similar findings were noted when assessing individual PGY levels. CONCLUSIONS: Regardless of PGY level, resident involvement in RPs appears safe and does not appear to affect postoperative complications or LOS. While resident involvement in RPs does result in longer operative times, this is necessary for the learning process.

Robot-assisted retroperitoneal lymph node dissection in testicular cancer.

Robotic surgical techniques are now being applied in the setting of retroperitoneal lymphadenectomy (RPLND) for testicular cancer. While laparoscopic RPLND has not been widely accepted, reports of robot assisted RPLND (RARPLND) are emerging. This manuscript will review the application of RPLND for testicular cancer, evolution of minimally invasive techniques, the controversies, and current status of RARPLND.

Preoperative imaging for staging bladder cancer.

Accurate preoperative staging of bladder cancer is essential in determining the extent of disease and optimal treatment. The current gold standard of transurethral resection of bladder tumor (TURBT) followed by computed tomography (CT) imaging provides excellent staging specificity, but often understages the disease, leading to pathologic upstaging and adverse outcomes in patients undergoing radical cystectomy. Newer imaging modalities, such as multiparametric magnetic resonance (MR) imaging and positron emission tomography (PET) combined with CT or MR provides promising imaging alternatives which may improve accuracy of staging both local and distant disease.

Practical tips for safe and efficient robotic cystectomy.

Robotic-assisted radical cystectomy (RARC) is a challenging procedure that potentially offers the patient decreased perioperative morbidity. With careful patient selection and attention to surgical detail, one can learn to efficiently and safely perform RARC with extracorporeal diversion. As one develops further expertise with RARC, patient selection criteria can be liberalized and intracorporeal diversion can be performed. The accumulated experience of our institution and other high-volume institutions are reviewed with attention to the technical details that yield a safe and efficient robotic cystectomy.

Economic impact of training and career decisions on urological surgery.

PURPOSE: Medical students and residents make career decisions at a relatively young age that have significant implications for their future income. While most of them attempt to estimate the impact of these decisions, there has been little effort to use economic principles to illustrate the impact of certain variables. MATERIALS AND METHODS: The economic concept of net present value was paired with available Medical Group Management Association and Association of American Medical Colleges income data to calculate the value of career earnings based on variations in the choice of specialty, an academic vs a private practice career path and fellowship choices for urology and other medical fields. RESULTS: Across all specialties academic careers were associated with lower career earnings than private practice. However, among surgical specialties the lowest difference in value between these 2 paths was for urologists at only $334,898. Fellowship analysis showed that training in pediatric urology was costly in forgone attending salary and it also showed a lower future income than nonfellowship trained counterparts. An additional year of residency training (6 vs 5 years) caused a $201,500 decrease in the value of career earnings. CONCLUSIONS: Choice of specialty has a dramatic impact on future earnings, as does the decision to pursue a fellowship or choose private vs academic practice. Additional years of training and forgone wages have a tremendous impact on monetary outcomes. There is also no guarantee that fellowship training will translate into a more financially valuable career. The differential in income between private practice and academics was lowest for urologists.

Sarcopenia as a predictor of complications and survival following radical cystectomy.

PURPOSE: Patients undergoing radical cystectomy face substantial but highly variable risks of major complications. Risk stratification may be enhanced by objective measures such as sarcopenia. Sarcopenia (loss of skeletal muscle mass) has emerged as a novel biomarker associated with adverse outcomes in many clinical contexts relevant to cystectomy. Based on these data we hypothesized that sarcopenia would be associated with increased 30-day major complications and mortality after radical cystectomy for bladder cancer. MATERIALS AND METHODS: We performed a retrospective study of patients treated with radical cystectomy at our institution from 2008 to 2011. Sarcopenia was assessed by measuring cross-sectional area of the psoas muscle (total psoas area) on preoperative computerized tomography. Cutoff points were developed and evaluated using ROC curves to determine predictive ability in men and women for outcomes of major complications and survival. RESULTS: Of 224 patients with bladder cancer 200 underwent preoperative computerized tomography within 1 month of surgery. Total psoas area was calculated with a mean score of 712 and 571 cm2/m2 in men and women, respectively. A clear association was noted between major complications and lower total psoas area in women using a cutoff of 523 cm2/m2 to define sarcopenia (AUC 0.70). Sarcopenia was not significantly associated with complications in men. There was a nonsignificant trend of sarcopenia with worse 2-year survival. CONCLUSIONS: Sarcopenia in women was a predictor of major complications after radical cystectomy. Further research confirming sarcopenia as a useful predictor of complications would support the development of targeted interventions to mitigate the untoward effects of sarcopenia before cancer surgery.

Muscle-invasive bladder cancer: evaluating treatment and survival in the National Cancer Data Base.

OBJECTIVE: To evaluate the association between patterns of care and patient survival for the treatment of muscle-invasive bladder cancer (MIBC) using a large, national database. PATIENTS AND METHODS: We identified a cohort of 36,469 patients with MIBC (stage II) from 1998 to 2010 from the National Cancer Data Base. Patients were stratified into four treatment groups: radical cystectomy, chemo-radiation, other therapy, or no treatment. Overall survival (OS) among the groups was evaluated using Kaplan-Meier analysis and the log rank test. A multivariable Cox proportional hazards model was fit to evaluate the association between treatment groups and OS. RESULTS: In all, 27% of patients received radical cystectomy, 10% chemo-radiation, 61% other therapy and 2% no treatment. Unadjusted Kaplan-Meier analysis showed significant differences by treatment group, with cystectomy having the greatest median OS (48 months) followed by chemo-radiation (28 months), other therapy (20 months), and no treatment (5 months). When controlling for multiple covariates, the OS for cystectomy was similar to that for chemo-radiation (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.98, 1.12), but superior to other therapy (HR 1.42; 95% CI 1.35, 1.48), and no treatment (HR 2.40; 95% CI 2.12, 2.72). The OS time for chemo-radiation was superior to other therapy and no treatment. CONCLUSIONS: Radical cystectomy and chemo-radiation are significantly underused despite a substantial survival benefit compared with other therapies or no treatment. Future studies are needed to optimise care delivery and improve outcomes for patients with MIBC.