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505 Background: TAR-200 is a novel intravesical drug delivery system designed to provide a continuous, slow release of gemcitabine within the bladder. Prolonged gemcitabine exposure over days, instead of hours, such as with current standard intravesical installations, may achieve more efficient and effective tumor response. We report on the safety and tolerability of TAR-200 in patients with non-muscle–invasive bladder cancer (NMIBC). Methods: In this phase 1b, open-label, prospective study, patients with a papillary recurrence after prior histologically proven, intermediate risk (IR)-NMIBC received two 1-week TAR-200 dosing cycles over a 4- to 6-week period. The study used a marker lesion/ablation design. Cystoscopy was performed to assess for recurrent papillary disease and for complete transurethral resection of the residual bladder tumor. The primary outcome was safety of TAR-200. Secondary outcomes were tolerability, pharmacokinetics, preliminary efficacy, and immunohistochemistry. Results: In total, 12 patients received TAR-200 treatment. Insertion and removal of TAR-200 was uneventful. No TAR-200-related serious adverse events (AEs) occurred. Four patients had no TAR-200-associated AEs; the remainder had varying degrees of AEs (all grade ≤2 [CTCAEv4.0]), mainly consisting of low-grade urinary urgency, urinary frequency, and dysuria, with no delay in the treatment schedule. Two patients refused a second dosing cycle due to urinary urgency and frequency. Plasma gemcitabine concentrations remained below the lower limit of detection. Five of 12 patients (42%) had complete response (CR); of these, 4 had a pathologic CR and 1 had CR based on visual assessment (with no biopsy available for pathologic assessment). Conclusions: In this small, phase 1 series, TAR-200 appears to be safe and well tolerated in patients with IR-NMIBC. Clinical trial information: NCT02720367 .

Summary 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.

Introduction:To assess and improve quality of care, the Commission on Cancer developed 3 evidence-based quality measures for the treatment of muscle invasive bladder cancer. We sought to as...

Introduction The treatment landscape for patients with metastatic hormone-sensitive prostate cancer (mHSPC) has changed dramatically in the past five years, despite little change in the preceding 20 years. Such rapid change can make it difficult for clinicians to remain abreast of the current literature and synthesize the relevant data to inform evidence-based treatment decisions. Methodology We performed a narrative, comprehensive review of treatment options for patients with mHSPC as of December 31, 2019. Specifically, we focused on phase II and III randomized controlled trials assessing the role of chemotherapy, novel androgen axis targeting agents, local-(prostate) directed therapy, and metastasis-directed therapy. Results The data support a survival benefit with the addition of four different agents to androgen deprivation among men with newly diagnosed prostate cancer-docetaxel, abiraterone acetate, enzalutamide, and apalutamide. While not directly compared, the efficacy of these agents appears similar. That said, there are differences in their toxicity profiles and notable differences in cost between agents. Although analyses encompassing men with low- and high-volume metastases failed to demonstrate a significant survival benefit for radiotherapy treatment to the prostate, new data demonstrates a benefit for men with low-volume metastatic disease. Ongoing trials will assess whether this applies to local surgical treatment. Similarly, metastasis-directed therapy appears beneficial among carefully selected patients. Conclusion Treatment options for patients with mHSPC are rapidly changing following years of stagnation. A number of systemic therapies offer benefit without significant clinical differences between them. The role for local treatment of the prostate as well as metastatic sites continues to evolve.

A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders). While baseline titers did not predict treatment response, 3-mo titer800 was associated with a higher likelihood of durable response (p = 0.026). Peak post-treatment titers800 were noted in 42 (89%) responders versus 26 (59%) nonresponders (p = 0.001; assay sensitivity, 89%; negative predictive value, 78%). Moreover, 22 (47%) responders compared with eight (18%) nonresponders had a combination of peak post-treatment titers800 and peak antibody fold change8 (p = 0.004; assay specificity, 82%; positive predictive value, 73%). A majority of responders continued to have post-treatment antibody titers800 after the first 6 mo of therapy. In conclusion, serum antiadenovirus antibody quantification may serve as a novel predictive marker for nadofaragene firadenovec response durability. Future studies will focus on large-scale validation and clinical utility of the assay. PATIENT SUMMARY: This study reports on a planned secondary analysis of a phase 3 multicenter clinical trial that established the benefit of nadofaragene firadenovec, a novel intravesical gene therapeutic, for the treatment of patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer. Prospective assessment of serum anti-human adenovirus type-5 antibody levels of patients in this trial indicated that a combination of post-treatment titers and fold change from baseline can predict treatment efficacy. While this merits additional validation, our findings suggest that serum antiadenovirus antibody levels can serve as an important predictive marker for the durability of therapeutic response to nadofaragene firadenovec.

INTRODUCTION AND OBJECTIVE:The standard of care for patients with muscle-invasive bladder cancer (MIBC) consists of neoadjuvant chemotherapy and radical cystectomy (RC) or chemoradiotherapy (CRT). ...

INTRODUCTION AND OBJECTIVE:Nadofaragene firadenovec is a recombinant adenoviral vector-based intravesical therapeutic that delivers a copy of human IFNα2b gene to urothelial cells. A recent phase 3...

Objectives To investigate the relationship between gender, body mass index (BMI), and prognosis in renal cell carcinoma (RCC) patients. Materials and Methods We retrospectively reviewed 1353 patients with RCC who underwent a partial or radical nephrectomy between 1988 and 2015. The association among sex, BMI, stage, grade, overall survival (OS), and recurrence-free survival (RFS) was analyzed. Results The median age of the patients was 59.4 ± 11.9 years. Female patients had proportionally lower grade tumors than male patients (Grade I-II in 75.5% vs. 69.3% in women and men, respectively, P = 0.022). There was no relationship between Fuhrman grade and BMI when substratified by gender (p > 0.05). There was a nonsignificant trend toward more localized disease in female patients (p = 0.058). There was no relationship between T stage and BMI when stratified by gender (p > 0.05). Patients with higher BMI had significantly better OS (p = 0.0004 and P = 0.0003) and RFS (P = 0.0209 and P =0.0082) whether broken out by lower 33rd or 25th percentile. Male patients with higher BMI had significantly better OS and RFS rates. However, there was no relationship between BMI and OS or RFS for female patients (P > 0.05). Multivariate analysis of the entire cohort demonstrated that a BMI in the lower quartile independently predicts OS (hazard ratio 1.604 [95% confidence interval: 1.07-2.408], P = 0.022) but not RFS (P > 0.05). When stratified by gender, there was no relationship between BMI and either OS or RFS (P > 0.05). Conclusions Increasing BMI was associated with RCC prognosis. However, the clinical association between BMI and oncologic outcomes may be different between men and women.

Contains fulltext : 251844.pdf (Publisher’s version ) (Open Access) OBJECTIVES: Neoadjuvant chemotherapy and radical cystectomy (RC) are underutilized standards of care for the treatment of muscle-invasive bladder cancer (MIBC) due to high patient burden from systemic toxicities and postoperative complications, respectively. TAR-200 is a novel intravesical drug delivery system developed to release gemcitabine into the bladder urine continuously, resulting in distribution of drug into stromal layers of the bladder. The primary aim of the TAR-200-101 study was to evaluate the safety of TAR-200 in patients with MIBC prior to RC (NCT02722538). METHODS AND MATERIALS: This phase I, open-label study was conducted across 6 US and European sites. Eligible patients were aged ≥18 years with histologically confirmed T2a-T3b N0-N1 M0 urothelial cancer and had refusal or were ineligible to receive cisplatin-based combination chemotherapy. Two arms were enrolled serially. Patients in Arm 1 had residual tumor >3 cm after transurethral resection of bladder tumor (TURBT); those in Arm 2 had undergone maximal TURBT (residual tumor

Earlier studies on the cost of muscle-invasive bladder cancer treatments are limited to short-term costs of care. We determined the 2- and 5-year costs associated with trimodal therapy (TMT) vs. radical cystectomy (RC).We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Total Medicare costs at 2 and 5 years following RC vs. TMT were compared using inverse probability of treatment-weighted propensity score models.A total of 2,537 patients aged 66 to 85 years were diagnosed with clinical stage T2-4a muscle-invasive bladder cancer. Total median costs for patients that received no definitive treatment(s) were $73,780 and $88,275 at 2-and 5-years. Costs were significantly higher for TMT than RC at 2-years ($372,839 vs. $191,363, Median Difference $127,815, Hodges-Lehmann Estimate (H-L) 95% Confidence Interval (CI), $112,663-$142,966) and 5-years ($424,570 vs. $253,651, Median Difference $124,466, H-L 95% CI, $105,711-$143,221). TMT had higher outpatient costs than RC (2-years: $318,221 vs. $100,900; 5-years: $367,092 vs. $146,561) with significantly higher costs with radiology, medications, pathology/laboratory, and other professional services. RC had higher inpatient costs than TMT (2-years: $62,240 vs. $33,631, Median Difference $-29,174, H-L 95% CI, $-32,364-$-25,984; 5-years: $75,499 vs. $45,223, Median Difference $-29,843, H-L 95% CI, $-33,905-$-25,781).The excess spending associated with trimodal therapy vs. radical cystectomy was largely driven by outpatient expenditures. The relatively high long-term trimodal therapy costs are prime targets for cost containment strategies to optimize future value-based care.

PURPOSE Provide evidence- and expert-based recommendations for optimal use of imaging in advanced prostate cancer. Due to increases in research and utilization of novel imaging for advanced prostate cancer, this guideline is intended to outline techniques available and provide recommendations on appropriate use of imaging for specified patient subgroups. METHODS An Expert Panel was convened with members from ASCO and the Society of Abdominal Radiology, American College of Radiology, Society of Nuclear Medicine and Molecular Imaging, American Urological Association, American Society for Radiation Oncology, and Society of Urologic Oncology to conduct a systematic review of the literature and develop an evidence-based guideline on the optimal use of imaging for advanced prostate cancer. Representative index cases of various prostate cancer disease states are presented, including suspected high-risk disease, newly diagnosed treatment-naïve metastatic disease, suspected recurrent disease after local treatment, and progressive disease while undergoing systemic treatment. A systematic review of the literature from 2013 to August 2018 identified fully published English-language systematic reviews with or without meta-analyses, reports of rigorously conducted phase III randomized controlled trials that compared ≥ 2 imaging modalities, and noncomparative studies that reported on the efficacy of a single imaging modality. RESULTS A total of 35 studies met inclusion criteria and form the evidence base, including 17 systematic reviews with or without meta-analysis and 18 primary research articles. RECOMMENDATIONS One or more of these imaging modalities should be used for patients with advanced prostate cancer: conventional imaging (defined as computed tomography [CT], bone scan, and/or prostate magnetic resonance imaging [MRI]) and/or next-generation imaging (NGI), positron emission tomography [PET], PET/CT, PET/MRI, or whole-body MRI) according to the clinical scenario.

TPS4586 Background: The standard of care for patients with muscle-invasive bladder cancer (MIBC) consists of neoadjuvant chemotherapy and radical cystectomy (RC) or chemoradiotherapy (CRT). However, RC is associated with potential morbidity or mortality from the procedure. TAR-200 is an intravesical drug-delivery system designed for the local continuous release of gemcitabine within the bladder. Cetrelimab is an investigational immunoglobulin G4 anti–programmed cell death protein-1 antibody. In patients with MIBC, this clinical trial will evaluate whether combination treatment with intravesical TAR-200 and systemic cetrelimab will result in enhanced local and systemic antitumor activity versus concurrent CRT. Methods: SunRISe-2 (NCT04658862) is a prospective, multicenter, open-label, randomized phase 3 study evaluating the efficacy and safety of intravesical TAR-200 plus systemic cetrelimab versus CRT in participants with MIBC. Eligible participants are aged ³18 years with an ECOG performance status of 0, 1, or 2, and histologically proven, cT2-T4a, N0, M0 urothelial carcinoma of the bladder diagnosed within 90 days of the randomization date, and who refuse or are ineligible for RC. Approximately 550 participants will be randomized in a 1:1 ratio and with stratification by 2 factors: transurethral resection of bladder tumor screening results (visibly complete vs incomplete) and screening tumor stage (T0 vs Ta/T1/Tis vs T2-T4a). Participants in Arm 1 will receive intravesical TAR-200 every 3 weeks for the first 18 weeks on study; and, beginning at week 24, every 12 weeks through study year 3. Cetrelimab will be dosed every 3 weeks until month 18. Participants in Arm 2 will receive standard of care CRT (with either cisplatin or gemcitabine, for up to 6 weeks). A primary disease assessment will be performed at week 18 to evaluate treatment response in both arms. Subsequent assessments (axial imaging and cystoscopy) will occur at week 24 and every 12 weeks thereafter through study year 2, and then every 24 weeks through study year 5. The primary endpoint is bladder intact event-free survival. Key secondary endpoints include metastasis-free survival, overall survival, overall response rate (at week 18), and safety and tolerability. Other/exploratory end points include assessments of cancer-specific survival, time to symptomatic progression, pharmacokinetics, immunogenicity, health-related quality of life, healthcare resource utilization, and biomarkers. Participants are being enrolled at approximately 272 study sites worldwide. The study opened for enrollment in December 2020. Clinical trial information: NCT04658862.

INTRODUCTION AND OBJECTIVES:There is a paucity of data regarding the predictive value of clinical staging on pathological outcomes in primary urethral carcinoma (PUC). Therefore, we aimed to analys...

BACKGROUND: To evaluate the impact of salvage therapy (ST) on overall survival (OS) in recurrent primary urethral cancer (PUC). PATIENTS: A series of 139 patients (96 men, 43 women; median age = 66, interquartile range: 57–77) were diagnosed with PUC at 10 referral centers between 1993 and 2012. The modality of ST of recurrence (salvage surgery vs. radiotherapy) was recorded. Kaplan-Meier analysis with log-rank was used to estimate the impact of ST on OS (median follow-up = 21, interquartile range: 5–48). RESULTS: The 3-year OS for patients free of any recurrence (I), with solitary or concomitant urethral recurrence (II), and nonurethral recurrence (III) was 86.5%, 74.5%, and 48.2%, respectively (P = 0.002 for I vs. III and II vs. III; P = 0.55 for I vs. II). In the 80 patients with recurrences, the modality of primary treatment of recurrence was salvage surgery in 30 (37.5%), salvage radiotherapy (RT) in 8 (10.0%), and salvage surgery plus RT in 5 (6.3%) whereas 37 patients did not receive ST for recurrence (46.3%). In patients with recurrences, those who underwent salvage surgery or RT-based ST had similar 3-year OS (84.9%, 71.6%) compared to patients without recurrence (86.7%, P = 0.65), and exhibited superior 3-year OS compared to patients who did not undergo ST (38.0%, P < 0.001 compared to surgery, P = 0.045 to RT-based ST, P = 0.29 for surgery vs. RT-based ST). CONCLUSIONS: In this study, patients who underwent ST for recurrent PUC demonstrated improved OS compared to those who did not receive ST and exhibited similar survival to those who never developed recurrence after primary treatment.

There are growing concerns regarding the overtreatment of localized prostate cancer. It is also relatively unknown whether there has been increased uptake of observational strategies for disease management. We assessed the temporal trend in observation of clinically localized prostate cancer, particularly in men with low risk disease, who were young and healthy enough to undergo treatment.We performed a retrospective cohort study using the SEER-Medicare database in 66,499 men with localized prostate cancer between 2004 and 2009. The main study outcome was observation within 1 year after diagnosis. We performed multivariable analysis to develop a predictive model of observation adjusting for diagnosis year, age, risk and comorbidity.Observation was performed in 12,007 men (18%) with a slight increase with time from 17% to 20%. However, there was marked increase in observation from 18% in 2004 to 29% in 2009 in men with low risk disease. Men 66 to 69 years old with low risk disease and no comorbidities had twice the odds of undergoing observation in 2009 vs 2004 (OR 2.12, 95% CI 1.73-2.59). Age, risk group, comorbidity and race were independent predictors of observation (each p0.001), in addition to diagnosis year.We identified increasing use of observation for low risk prostate cancer between 2004 and 2009 even in men young and healthy enough for treatment. This suggests growing acceptance of surveillance in this group of patients.

Physician-led perioperative surgical home models are developing as a method for improving the American health care system. These models are novel, team-based approaches that help to provide continuity of care throughout the perioperative period. Another avenue for improving care for surgical patients is the use of enhanced recovery after surgery pathways. These are well-described methods that have shown to improve perioperative outcomes. An established perioperative surgical home model can help implementation, efficiency, and adherence to enhanced recovery after surgery pathways. For these reasons, the Tennessee Valley Healthcare System, Nashville Veterans Affairs Medical Center created an Anesthesiology Perioperative Care Service that provides comprehensive care to surgical patients from their preoperative period through the continuum of their hospital course and postdischarge follow-up. In this brief report, we describe the development, implementation, and preliminary outcomes of the service.

Objective To evaluate predictors of understaging in patients with presumed non-muscle-invasive bladder cancer (NMIBC) identified on transurethral resection of bladder tumour (TURBT) who underwent radical cystectomy (RC) with attention to the role of a restaging TURBT. Patients and Methods We retrospectively evaluated 279 consecutive patients with clinically staged T1 (cT1) disease after TURBT who underwent RC at our institution from April 2000 to July 2011. In all, 60 of these cT1 patients had undergone a restaging TURBT before RC. The primary outcome measure was pathological staging of ≥T2 disease at the time of RC. Results In all, 134 (48.0%) patients were understaged. Of the 60 patients who remained cT1 after a restaging TURBT, 28 (46.7%) were understaged. Solitary tumour (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.25–0.76, P = 0.004) and fewer prior TURBTs (OR 0.84, 95% CI 0.71–1.00, P = 0.05) were independent risk factors for understaging. Conclusions Despite the overall improvement in staging accuracy linked to restaging TURBTs, the risk of clinical understaging remains high in restaged patients found to have persistent T1 urothelial carcinoma who undergo RC. Solitary tumour and fewer prior TURBTs are independent risk factors for being understaged. Incorporating these predictors into preoperative risk stratification may allow for augmented identification of those patients with clinical NMIBC who stand to benefit most from RC.

In March 2010, the Patient Protection and Affordable Care Act as well as its amendments were signed into law. This sweeping legislation was aimed at controlling spiraling healthcare costs and redressing significant disparities in healthcare access and quality. Cancer diagnoses and their treatments constitute a large component of rising healthcare expenditures and, not surprisingly, the legislation will have a significant influence on cancer care in the United States. Because genitourinary malignancies represent an impressive 25% of all cancer diagnoses per year, this legislation could have a profound impact on urologic oncology. To this end, we will present key components of this landmark legislation, including the proposed expansion to Medicaid coverage, the projected role of Accountable Care Organizations, the expected creation of quality reporting systems, the formation of an independent Patient-Centered Outcomes Research Institute, and enhanced regulation on physician-owned practices. We will specifically address the anticipated effect of these changes on urological cancer care. Briefly, the legal ramifications and current barriers to the statutes will be examined.

Purpose: Salvage robotic assisted laparoscopic prostatectomy is a treatment option for certain patients with recurrent prostate cancer after primary therapy. Data regarding patient selection, complication rates and cancer outcomes are scarce. We report the largest, single institution series to date, to our knowledge, of salvage robotic assisted laparoscopic prostatectomy.Materials and Methods: We reviewed our database of 4,234 patients treated with robotic assisted laparoscopic prostatectomy at Vanderbilt University and identified 34 men who had surgery after the failure of prior definitive ablative therapy. Each patient had biopsy proven recurrent prostate cancer and no evidence of metastases. The primary outcome measure was biochemical failure.Results: Median time from primary therapy to salvage robotic assisted laparoscopic prostatectomy was 48.5 months with a median preoperative prostate specific antigen of 3.86 ng/ml. Most patients had Gleason scores of 7 or greater on preoperative biopsy, although 1...

Context New guidelines of the International Consultation on Urological Diseases for the treatment of muscle-invasive bladder cancer (MIBC) have recently been published. Objective To provide a comprehensive overview of the current role of radical cystectomy (RC) in MIBC. Evidence acquisition A detailed Medline analysis was performed for original articles addressing the role of RC with regard to indication, timing, surgical extent, perioperative morbidity, oncologic outcome, and follow-up. The analysis also included radiation-based bladder-preserving strategies. Evidence synthesis The major findings are presented in an evidence-based fashion and are based on large retrospective unicenter and multicenter series with some prospective data. Conclusions Open RC is the standard treatment for locoregional control of MIBC. Delay of RC is associated with reduced cancer-specific survival. In males, standard RC includes the removal of the bladder, prostate, seminal vesicles, and distal ureters; in females, RC includes an anterior pelvic exenteration including the bladder, entire urethra and adjacent vagina, uterus, and distal ureters. A procedure sparing the urethra and the urethra-supplying autonomous nerves can be performed in case of a planned orthotopic neobladder. Further technical variations (ie, seminal-sparing or vaginal-sparing techniques) aimed at improving functional outcomes must be weighed against the risk of a positive margin. Laparoscopic surgery is promising, but long-term data are required prior to accepting it as an option equivalent to the open procedure. Lymphadenectomy should remove all lymphatic tissue around the common iliac, external iliac, internal iliac, and obturator region bilaterally. Complications after RC should be reported according to the modified Clavien grading system. In selected patients with MIBC, bladder-preserving therapy with cystectomy reserved for tumor recurrence represents a safe and effective alternative to immediate RC.

Hospital volume and surgeon volume are each associated with outcomes after complex oncological surgery. However, the interplay between hospital and surgeon volume, and their impact on these outcomes has not been well characterized. We studied the relationship between surgeon and hospital volume, and overall mortality after radical cystectomy.The SEER (Surveillance, Epidemiology and End Results)-Medicare linked database was used to identify 7,127 patients with urothelial carcinoma of the bladder who underwent radical cystectomy from 1992 to 2006. Hospital volume and surgeon volume were expressed by tertile. The primary outcome measure was overall survival. Covariates included age, Charlson comorbidity index, stage, grade, node count, node density, number of positive nodes, urinary diversion and year of surgery. Multivariate analyses using generalized linear multilevel models were used to determine the independent association between hospital and surgeon volume and survival.When hospital volume or surgeon volume was included in the multivariate model, a significant volume-survival relationship was observed for each. However, when both were in the model, hospital volume attenuated the impact of surgeon volume on mortality while the significant hospital volume-mortality relationship persisted (HR 1.18, 95% CI 1.08-1.30, p0.01). In addition, the adjusted 3-year probability of survival was significantly correlated with hospital volume in each distinct surgeon volume stratum while survival was not correlated with surgeon volume in each hospital volume stratum.After adjustment for patient and disease characteristics, the relationship between surgeon volume and survival after radical cystectomy is accounted for by hospital volume. In contrast, hospital volume remained an independent predictor of survival, suggesting that structure and process characteristics of high volume hospitals drive long-term outcomes after radical cystectomy.

Introduction: We aimed to evaluate the relative prognostic impact of the most common variant histologies on disease-specific survival (DSS) in patients undergoing radical cystectomy. Materials and Methods: The Surveillance, Epidemiology, and End Result database was used to identify patients who underwent radical cystectomy for bladder cancer from 1990 to 2007. Patients with urothelial cell carcinoma (UCC), squamous cell carcinoma (SCC), adenocarcinoma (AC), sarcoma, small cell carcinoma, signet ring carcinoma, and spindle cell carcinoma were included in the study. Multivariable analysis was performed using Cox proportional hazards model to assess independent predictors of disease-specific survival (DSS). Mortality rates were estimated using Kaplan–Meier analyses. Results: A total of 14,130 patients met inclusion criteria with the following histologies: UCC (90.1%), SCC (4.6%), AC, (2.3%), sarcoma (0.8%), small cell carcinoma (0.8%), signet ring carcinoma (0.5%), and spindle cell carcinoma (0.9%). Three-year DSS was most favorable in patients with UCC (63.7%; 95% confidence interval [62.9%–64.8%]) and AC (65.3% [59.3%–70.6%]), whereas 3-year DSS was the least favorable for small cell carcinoma (41.6% [31.3%–51.6%]) and sarcoma (45.4% [35.1%–55.1%]). In the multivariable analysis, independent predictors of DSS were age, marital status, grade, T-stage, N-stage, and variant histology. With respect to UCC, there was an increased risk of disease-specific death associated with all variants except AC. Sarcoma and spindle cell carcinoma were associated with the highest risk of death. Conclusions: With the exception of AC, the most common variant bladder cancer histologies are all independently associated with worse DSS relative to UCC in patients undergoing radical cystectomy.

Diabetes mellitus is a systemic disease estimated to affect 7% of the US population. Patients with diabetes cannot properly regulate glucose in the body secondary to insulin deficiency or insulin resistance. The resultant hyperglycemic environment leads to a variety of complications, including diabetic cystopathy, which refers to the effects of diabetes on the bladder. The clinical presentation of diabetic cystopathy varies dramatically. Patients may be asymptomatic, or have a wide variety of voiding complaints. On urodynamic testing, cystopathy is characterized by a hyposensate, acontractile detrusor muscle. In some patients, urgency and involuntary detrusor activity predominate. Diagnosis is made with history and physical examination as well as urodynamic evaluation. Treatment is guided by urodynamic findings. This review focuses on diagnosis and treatment of diabetic cystopathy, emphasizing pathophysiology and recent developments in our understanding of the effects of diabetes on the bladder.

PURPOSE: To evaluate risk factors for survival in a large international cohort of patients with primary urethral cancer (PUC). METHODS: A series of 154 patients (109 men, 45 women) were diagnosed with PUC in ten referral centers between 1993 and 2012. Kaplan–Meier analysis with log-rank test was used to investigate various potential prognostic factors for recurrence-free (RFS) and overall survival (OS). Multivariate models were constructed to evaluate independent risk factors for recurrence and death. RESULTS: Median age at definitive treatment was 66 years (IQR 58–76). Histology was urothelial carcinoma in 72 (47 %), squamous cell carcinoma in 46 (30 %), adenocarcinoma in 17 (11 %), and mixed and other histology in 11 (7 %) and nine (6 %), respectively. A high degree of concordance between clinical and pathologic nodal staging (cN+/cN0 vs. pN+/pN0; p < 0.001) was noted. For clinical nodal staging, the corresponding sensitivity, specificity, and overall accuracy for predicting pathologic nodal stage were 92.8, 92.3, and 92.4 %, respectively. In multivariable Cox-regression analysis for patients staged cM0 at initial diagnosis, RFS was significantly associated with clinical nodal stage (p < 0.001), tumor location (p < 0.001), and age (p = 0.001), whereas clinical nodal stage was the only independent predictor for OS (p = 0.026). CONCLUSIONS: These data suggest that clinical nodal stage, whereas clinical nodal stage is a critical parameter for outcomes in PUC.

BACKGROUND To investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC). PATIENTS AND METHODS A series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5-48). RESULTS Neoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005). CONCLUSION In this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH.

The treatment and management of advanced urothelial carcinoma of the bladder is a considerable therapeutic challenge. Prospective, randomized clinical trial data demonstrate a survival advantage for those patients that receive neoadjuvant chemotherapy prior to radical cystectomy. Despite the overall survival benefits, results from both institutional and administrative datasets suggest that historical use of a neoadjuvant chemotherapy paradigm is remarkably low. This review will evaluate the recent trends in pre-operative chemotherapy utilization that suggest small, but progressively increased use–currently on the order of 20% of radical cystectomy patients. Additionally, this analysis will explore the various processes and structural barriers that preclude its receipt such as patient age and comorbidity, as well as physician preference, delay to potentially curable surgery, geographic region, distance to treatment facility, and socioeconomic status.

To evaluate predictors of understaging in patients with presumed non-muscle-invasive bladder cancer (NMIBC) identified on transurethral resection of bladder tumour (TURBT) who underwent radical cystectomy (RC) with attention to the role of a restaging TURBT.We retrospectively evaluated 279 consecutive patients with clinically staged T1 (cT1) disease after TURBT who underwent RC at our institution from April 2000 to July 2011. In all, 60 of these cT1 patients had undergone a restaging TURBT before RC. The primary outcome measure was pathological staging of ≥T2 disease at the time of RC.In all, 134 (48.0%) patients were understaged. Of the 60 patients who remained cT1 after a restaging TURBT, 28 (46.7%) were understaged. Solitary tumour (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.25-0.76, P = 0.004) and fewer prior TURBTs (OR 0.84, 95% CI 0.71-1.00, P = 0.05) were independent risk factors for understaging.Despite the overall improvement in staging accuracy linked to restaging TURBTs, the risk of clinical understaging remains high in restaged patients found to have persistent T1 urothelial carcinoma who undergo RC. Solitary tumour and fewer prior TURBTs are independent risk factors for being understaged. Incorporating these predictors into preoperative risk stratification may allow for augmented identification of those patients with clinical NMIBC who stand to benefit most from RC.

Radical cystectomy (RC) is associated with significant blood loss and transfusion requirement. We performed a prospective, randomized trial to compare blood loss, operative time, and cost using 2 different and commonly employed approaches to tissue ligation and division during RC: mechanical (stapler device) and electrosurgical (heat-sealing device).Eighty patients undergoing RC for urothelial bladder carcinoma were randomized to use of either an Endo GIA Stapler or Impact LigaSure device for tissue ligation and division. Primary outcomes were blood loss, operative time, and device costs. Data were analyzed with Wilcoxon rank sum test and Welch 2-sample t test.There were no significant demographic or preoperative differences between the cohorts. Mean estimated blood loss was similar between the electrosurgical (687 ml) and stapler (708 ml) arms (P = 0.850). There were no significant differences between cohorts when comparing operative times or transfusion requirement. There was a significant increase in the mean number of adjunctive suture ligatures used in the stapling device arm (3.0 vs. 1.5, P = 0.047). Total device costs were significantly lower with the LigaSure compared with the GIA Stapler ($625.00 vs. $1490.10, P0.001). There were no complications attributable to either device.This prospective, randomized study demonstrates no significant difference in blood loss, transfusion requirement, or safety between mechanical vs. electrosurgical control of the vascular pedicles. The LigaSure device, however, is significantly less costly than the GIA Stapler and required fewer additional measures for hemostasis.

Georgios Gakis*, Tuebingen, Germany; Sia Daneshmand, Los Angeles, CA; Jason A. Efstathiou, Boston, MA; Bedeir Ali-El-Dein, Mansoura, Egypt; Jan Hrbacek, Prague, Czech Republic; Kirk A. Keegan, Nashville, TN; Sigolene Galland, Rebecca Clayman, Boston, MA; Lars Weissbach, Hamburg, Germany; Johannes Brunner, Regensburg, Germany; Harras B. Zaid, Nashville, TN; Tilman Todenhofer, Tuebingen, Germany; Michael Rink, Hamburg, Germany; Hans-Martin Fritsche, Regensburg, Germany; Sam S. Chang, Nashville, TN; Marko Babjuk, Prague, Czech Republic; George Thalmann, Bern, Switzerland; Arnulf Stenzl, Tuebingen, Germany

To evaluate the current literature for processes of care and outcomes of multimodal therapies for muscle-invasive urothelial carcinoma of the bladder.Treatments for high-risk bladder cancer remain an active area of investigation. Despite evidence of the benefits, the use of chemotherapy, either neoadjuvant or adjuvant, remains underutilized. Given patient preference or baseline comorbidities, multimodal bladder-preserving strategies have been employed by several institutions, with rates of overall survival similar to radical cystectomy series. Late complications associated with these treatments were recently described. Future management strategies for solid tumors will incorporate a personalized approach based upon molecular diagnostic tools to predict risk of recurrence, progression, and response to specific therapeutic agents.Multimodal paradigms for muscle-invasive urothelial carcinoma have demonstrated favorable clinical outcomes relative to radical cystectomy alone. Further work through properly conducted randomized trials and accurate individual-level risk assessments will facilitate the determination of the optimal candidates and timing for these treatments.