PURPOSE: Previous studies have shown robot assisted radical cystectomy (RARC) to have comparable perioperative outcomes to open radical cystectomy. There are few reports that have examined the oncologic results of RARC, specifically with respect to lymph node-positive patients. We report the outcomes of pathologic node-positive patients who have undergone RARC with medium-term follow-up. MATERIALS AND METHODS: A total of 275 patients underwent RARC at 2 institutions for invasive bladder cancer between April 2005 and June 2009. We examined the 50 patients with lymph node-positive disease. Oncologic outcomes, overall, and recurrence-free survival were analyzed and compared with the open literature. RESULTS: Mean (median) clinical follow-up in this cohort was 42 (39.5) months (range 16-75 months). The mean (median) number of lymph nodes (LN) removed was 18 (17.5)(range 5-35), and mean (median) number of positive LN was 3 (2)(range 1-12). Mean lymph node density was 18%. Seventeen (34%) patients had ≤ pT(2) disease and 33 (66%) pT(3)/T(4) disease. At this follow-up, 29 patients have recurred, and 22 patients have died of disease. Mean (median) time to recurrence was 10 (9) months. The estimated overall survival at 36 and 60 months was 55%, and 45%, respectively. The recurrence-free survival at 36 and 60 months was 43%, and 39%, respectively. Thirty-three (66%) patients had an LN density <20%. The estimated overall survival at 36 months of patients with a lymph node density of <20% was higher than those with a lymph node density >20%, though the difference was not statistically significant. A total of 58% of patients received chemotherapy in this cohort. The use of chemotherapy was associated with a statistically significant (P = 0.033) improvement in overall survival, with an overall survival of 68% at 36 months compared with 36% for the patients who did not receive any chemotherapy. CONCLUSIONS: The oncologic outcomes of patients with lymph node-positive bladder cancer treated with robot assisted radical cystectomy (RARC) compare favorably to previous published studies of open radical cystectomy at medium-term (mean follow-up of 42 months). As our follow-up increases, we expect to continue to accurately define the long-term clinical suitability and oncologic success of this procedure in this high-risk population.

Study Type - Therapy (patterns of practice) Level of Evidence 2b What's known on the subject? and What does the study add? Claims-based analyses suggest unexplained and potentially problematic variation in treatment intensity adherence to guidelines-recommended care in NMIBC. Previous physician surveys prior to the contemporary Clinical Practice Guidelines (CPGs) reported associations between variation in NMIBC care and practice type, years in practice, and other physician-related factors. In the largest physician survey addressing the management of NMIBC, and the first to examine these questions after the promulgation of contemporary CPGs, US urologists report grade-specific utilization consistent with CPG recommendations, at rates higher than suggested by recent claims-based analyses. As with prior studies, practice type and years in practice were significantly associated with variation in practices. Further research is needed to reconcile these findings with administrative claims data. OBJECTIVES: •  To determine self-reported practices of use of intravesical chemo- and immunotherapy for patients with non-muscle-invasive bladder cancer (NMIBC) •  To evaluate the extent to which respondent characteristics were associated with any observed variation. Guidelines recommend intravesical therapy (IVT) in the management of NMIBC, but recent claims-based analyses suggest exceedingly low rates of use of some of these therapies. MATERIALS AND METHODS: •  An electronic survey was developed by members of the Bladder Cancer Advocacy Network (BCAN) to elicit self-reported use of management strategies for NMIBC. •  The survey was circulated to urologists via the American Urological Association, Society for Urologic Oncology and Large Urology Group Practice Association distribution lists. •  In all, 512 respondents completed the survey. RESULTS: •  In all, 63% reported routine perioperative mitomycin-c (MMC) after transurethral resection of bladder tumour (80% academic vs 54% private practice, P < 0.001). •  Whereas 5% of respondents reported routine induction therapy with all new low-grade (LG) diagnoses, 99% reported routinely doing so in new high-grade (HG) cases; most commonly with single-agent bacille Calmette-Guérin (BCG)(94% vs 9% BCG/interferon and 5% MMC). •  Reported induction therapy was higher in the setting of high-volume (77%) or frequently recurrent (44%) LG disease. •  In all, 89% reported routinely using maintenance therapy for HG vs 29% for LG disease. •  Routine biopsy after BCG, even with normal cystoscopy, was endorsed by 28%(39% academic vs 22% private practice, P < 0.001). CONCLUSIONS: •  Urologists report grade-specific use of IVT for NMIBC, at rates higher than suggested in some claims-based analyses. •  Further study is needed to corroborate these self-reported patterns of care with lower rates of use suggested by claims-based analyses.

Objective: To perform a cost-comparison of three approaches to partial nephrectomy (PN): open (OPN), hand-assisted laparoscopic (HALPN), and robot-assisted (RAPN). Subjects and Methods: We retrospectively evaluated cost and clinical data from patients undergoing OPN, HALPN, and RAPN from 2007 to 2010 (n=89). Baseline demographic data, patient comorbidities, R.E.N.A.L. nephrometry score, and perioperative outcomes were assessed. Costs and subcosts from the OR and hospital were evaluated using non-parametric statistical analyses. Results: Patient demographics and tumor characteristics were similar between HALPN and RAPN, while OPN patients had more comorbidities and more difficult-to-resect tumors. Thus, HALPN and RAPN were directly compared, while OPN were excluded from the analysis. No difference was found in overall costs between HALPN and RAPN ($13560 vs $13439, p=0.29). OR costs were higher for RAPN ($7276 v $5708, p=0.0001) due to higher robotic capital and reusable equipment costs which outweighed higher disposable costs in the HALPN group. OR time-related costs were similar between groups. RAPN patients had a shorter length of stay (LOS) which decreased post-op hospital costs ($4371 v $5984, p=0.002). Conclusions: No difference in overall cost was found between RAPN and HALPN. Robot allocation, OR equipment use, and LOS are important determinants of total cost. Further study regarding recovery and quality of life may reveal added benefits to minimally-invasive approaches and increase utilization of nephron-sparing surgery.

Abstract Purpose: Recently, some surgeons have begun to describe single-institution case series with less invasive surgical approaches to bladder cancer such as laparoscopic or robotic-assisted techniques. We report on a multi-institutional, multi-surgeon experience with robotic radical cystectomy with regard to operative and pathologic outcomes and complications to evaluate the feasibility and reproducibility of this technique in a large cohort of patients. Subjects and Methods: Two hundred twenty-seven patients (178 males and 49 females) underwent a robotic cystectomy and urinary diversion at one of four institutions. Operative outcomes, pathological results, and complications of this combined case series are herein reported. Results: Mean age of this cohort was 67.1 years (range, 33-86 years) with a mean American Society of Anesthesiologists score of 2.7 (range, 2-4). One hundred sixty-eight patients (74%) underwent ileal conduit diversion, 58 (26%) underwent orthotopic ileal neobladder, and 1 patient (<1%) had no diversion (end-stage renal disease). The urinary diversion was performed extracorporeally in 97% cases, with 7 patients (3%) undergoing an intracorporeal diversion. Mean operating room time of all patients was 5.5 hours, and mean surgical blood loss was 256 mL. On surgical pathology, 120 (53%) patients had pT2 or less disease, 35 (15%) had pT3/T4 disease, and 46 (20%) had N+ disease. The mean number of lymph nodes removed was 18 (range, 3-52). There was a positive surgical margin in 5 cases-all with pT3-4 disease. Mean time to discharge was 5.5 days (median, 5 days), with 70% of patients discharged on postoperative day 5 or sooner. Sixty-eight patients (30%) experienced complications, with 7% having Clavien grade 3 or higher. On multivariate analysis, decreased age and increased American Society of Anesthesiologists score were predictors of higher Clavien complication score, with younger patients more likely to undergo neoadjuvant chemotherapy prior to surgery. Conclusion: A multi-institutional experience with robotic radical cystectomy appears to demonstrate acceptable operative and pathologic outcomes, thus helping to validate the previously reported single-institution case series. Ultimately, oncologic follow-up of these patients will remain as the most important measure of therapeutic success.

BACKGROUND Clear cell renal cell carcinoma (ccRCC) displays molecular and histologic heterogeneity. Previously described subsets of this disease, ccA and ccB, were defined based on multigene expression profiles, but it is unclear whether these subgroupings reflect the full spectrum of disease or how these molecular subtypes relate to histologic descriptions or gender. OBJECTIVE Determine whether additional subtypes of ccRCC exist and whether these subtypes are related to von Hippel-Lindau (VHL) inactivation, hypoxia-inducible factor (HIF) 1 and 2 expression, tumor histology, or gender. DESIGN, SETTING, AND PARTICIPANTS Six large, publicly available ccRCC gene expression databases were identified that cumulatively provided data for 480 tumors for meta-analysis via meta-array compilation. MEASUREMENTS Unsupervised consensus clustering was performed on the meta-arrays. Tumors were examined for the relationship of multigene-defined consensus subtypes and expression signatures of VHL mutation and HIF status, tumor histology, and gender. RESULTS AND LIMITATIONS Two dominant subsets of ccRCC were observed. However, a minor third cluster was revealed that correlated strongly with a wild type (WT) VHL expression profile and indications of variant histologies. When variant histologies were removed, ccA tumors naturally divided by gender. This technique is limited by the potential for persistent batch effect, tumor sampling bias, and restrictions of annotated information. CONCLUSIONS The ccA and ccB subsets of ccRCC are robust in meta-analysis among histologically conventional ccRCC tumors. A third group of tumors was identified that may represent a new variant of ccRCC. Within definitively clear cell tumors, gender may delineate tumors in such a way that it could have implications regarding current treatments and future drug development.

UNLABELLED What's known on the subject? and What does the study add? Robot-assisted radical cystectomy is an increasingly used method for surgical extirpation for clinically localized, muscle-invasive urothelial cartinoma. This study reviews its technique and associated preoperative and oncological outcomes. OBJECTIVE •  To assess peri-and postoperative outcomes of robot-assisted radical cystectomy (RARC) with pelvic lymph node dissection (PLND) and urinary diversion for the treatment of bladder cancer. MATERIALS AND METHODS •  We review our previously described surgical technique for RARC and its development over recent years, with an accompanied video illustration. •  We also focus on peri- and postoperative outcomes of RARC and compare this with the 'gold standard' of open RC. RESULTS •  RARC has been steadily growing since 2003, with acceptable peri-and postoperative outcomes. •  Most studies report decreased blood loss, return of bowel function, and shorter length of hospital stay. Furthermore, complication rates have been shown to be similar to that of open series. •  Most importantly, oncological outcomes appear to be favourable in terms of margin status, LND and disease-specific survival, although data may be affected by the lack of long-term results and a randomized clinical trial assessing overall survival. CONCLUSIONS •  RARC with PLND and urinary diversion is an increasingly used strategy in the treatment armamentarium for bladder cancer. •  Perioperative and oncological outcomes from existing data have been favourable thus far, but are limited by relatively short follow-up. •  Randomized clinical trials with extended patient follow-up are needed to fully assess outcomes related to RARC.

INTRODUCTION:: The utility of a preoperative mechanical bowel preparation prior to bowel surgery has recently been questioned. The purpose of this study is to compare the perioperative outcomes between patients undergoing cystectomy with urinary diversion with or without preoperative mechanical bowel preparation. METHODS:: Seventy patients underwent radical cystectomy and urinary diversion between May 2008 and August 2009 for bladder cancer. The first cohort of patients (n = 37) underwent cystectomy and diversion during the period May 2008-December 2008 and underwent a preoperative mechanical bowel preparation including a clear liquid diet, magnesium citrate solution, and an enema before surgery. The second cohort of patients underwent surgery during the period of January 2009-August 2009 (n=33). These patients were given a regular diet before surgery and did not undergo a mechanical bowel preparation except for the enema before surgery was performed to decrease rectal/colonic distention. Outcome measures included gastrointestinal and overall complications, and perioperative outcomes including recovery of bowel function. RESULTS:: There were no differences with regard to recovery of bowel function, time to discharge, or overall complication rates between the 2 groups. More specifically, the rate of GI complications was not different in prepped patients vs. nonprepped patients (22% vs. 15%; P = 0.494). There were no occurrences of bowel anastomotic leak, fistula, abscess, peritonitis, or surgical site infection in either group. One perioperative death occurred in the nonprepped group secondary to cardiovascular complications. CONCLUSIONS:: Preoperative mechanical bowel preparation prior to radical cystectomy with urinary diversion does not demonstrate any significant advantage in perioperative outcomes, including gastrointestinal complications. Further studies aimed at measuring patient satisfaction and larger randomized trials will be beneficial in evaluating the role of mechanical bowel preparation prior to urinary diversion.

OBJECTIVES:: Epidermal growth factor receptor (EGFR) and HER-2 tyrosine kinases may be involved in activation of androgen receptor and progression of prostate cancer. They represent potential therapeutic targets in prostate cancer. Lapatinib is an oral inhibitor of EGFR and HER-2. The objective of this study is to assess the preliminary clinical efficacy of lapatinib in the therapy of castration-resistant prostate cancer. METHODS:: In this multicenter, open-label trial, patients with rising PSA on androgen deprivation therapy and not having received chemotherapy were eligible. They were treated with lapatinib at a dose of 1,500 mg once daily. The primary end point was a >50% confirmed PSA decline from baseline; safety, tolerability, and time to PSA progression were secondary outcomes. RESULTS:: Twenty-nine patients enrolled in the study had a median age of 73 years and a baseline PSA of 21.6 ng/ml. Seven patients had no radiologic evidence of metastatic disease, while the remaining patients had bone or measurable disease or both. Treatment was well tolerated with only grade 3 treatment-related toxicities being diarrhea (14%) and rash (3%). One of 21 evaluable patients had >50% reduction in PSA, while another patient had 47% reduction in PSA with an ongoing duration of response of 45+ months. The median time to PSA progression was 29 days. CONCLUSIONS:: Lapatinib showed single agent activity in a small subset of unselected patients with castration-resistant prostate cancer, as measured by PSA. Future trials should explore a trial design with time-to-event end points and predictive biomarkers and a combination with other agents.