Eric Wallen

Prospective Randomized Controlled Trial of Robotic versus Open Radical Cystectomy for Bladder Cancer: Perioperative and Pathologic Results

BACKGROUND In recent years, surgeons have begun to report case series of minimally invasive approaches to radical cystectomy, including robotic-assisted techniques demonstrating the surgical feasibility of this procedure with the potential of lower blood loss and more rapid return of bowel function and hospital discharge. Despite these experiences and observations, at this point high levels of clinical evidence with regard to the benefits of robotic cystectomy are absent, and the current experiences represent case series with limited comparisons to historical controls at best. OBJECTIVE We report our results on a prospective randomized trial of open versus robotic-assisted laparoscopic radical cystectomy with regard to perioperative outcomes, complications, and short-term narcotic usage. DESIGN, SETTING, AND PARTICIPANTS A prospective randomized single-center noninferiority study comparing open versus robotic approaches to cystectomy in patients who are candidates for radical cystectomy for urothelial carcinoma of the bladder. Of the 41 patients who underwent surgery, 21 were randomized to the robotic approach and 20 to the open technique. INTERVENTION Radical cystectomy, bilateral pelvic lymphadenectomy, and urinary diversion by either an open approach or by a robotic-assisted laparoscopic technique. MEASUREMENTS The primary end point was lymph node (LN) yield with a noninferiority margin of four LNs. Secondary end points included demographic characteristics, perioperative outcomes, pathologic results, and short-term narcotic use. RESULTS AND LIMITATIONS On univariate analysis, no significant differences were found between the two groups with regard to age, sex, body mass index, American Society of Anesthesiologists classification, anticoagulation regimen of aspirin, clinical stage, or diversion type. Significant differences were noted in operating room time, estimated blood loss, time to flatus, time to bowel movement, and use of inpatient morphine sulfate equivalents. There was no significant difference in regard to overall complication rate or hospital stay. On surgical pathology, in the robotic group 14 patients had pT2 disease or higher; 3 patients had pT3/T4 disease; and 4 patients had node-positive disease. In the open group, eight patients had pT2 disease or higher; five patients had pT3/T4 disease; and seven patients had node-positive disease. The mean number of LNs removed was 19 in the robotic group versus18 in the open group. Potential study limitations include the limited clinical and oncologic follow-up and the relatively small and single-institution nature of the study. CONCLUSIONS We present the results of a prospective randomized controlled noninferiority study with a primary end point of LN yield, demonstrating the robotic approach to be noninferior to the open approach. The robotic approach also compares favorably with the open approach in several perioperative parameters.

Molecular Stratification of Clear Cell Renal Cell Carcinoma by Consensus Clustering Reveals Distinct Subtypes and Survival Patterns

Clear cell renal cell carcinoma (ccRCC) is the predominant RCC subtype, but even within this classification, the natural history is heterogeneous and difficult to predict. A sophisticated understanding of the molecular features most discriminatory for the underlying tumor heterogeneity should be predicated on identifiable and biologically meaningful patterns of gene expression. Gene expression microarray data were analyzed using software that implements iterative unsupervised consensus clustering algorithms to identify the optimal molecular subclasses, without clinical or other classifying information. ConsensusCluster analysis identified two distinct subtypes of ccRCC within the training set, designated clear cell type A (ccA) and B (ccB). Based on the core tumors, or most well-defined arrays, in each subtype, logical analysis of data (LAD) defined a small, highly predictive gene set that could then be used to classify additional tumors individually. The subclasses were corroborated in a validation data set of 177 tumors and analyzed for clinical outcome. Based on individual tumor assignment, tumors designated ccA have markedly improved disease-specific survival compared to ccB (median survival of 8.6 vs 2.0 years, P = 0.002). Analyzed by both univariate and multivariate analysis, the classification schema was independently associated with survival. Using patterns of gene expression based on a defined gene set, ccRCC was classified into two robust subclasses based on inherent molecular features that ultimately correspond to marked differences in clinical outcome. This classification schema thus provides a molecular stratification applicable to individual tumors that has implications to influence treatment decisions, define biological mechanisms involved in ccRCC tumor progression, and direct future drug discovery.

Robotic Radical Cystectomy for Bladder Cancer: Surgical and Pathological Outcomes in 100 Consecutive Cases

PURPOSE Radical cystectomy remains the most effective treatment for patients with localized, invasive bladder cancer and recurrent noninvasive disease. Recently some surgeons have begun to describe outcomes associated with less invasive surgical approaches to this disease such as laparoscopic or robotic assisted techniques. We report our maturing experience with 100 consecutive cases of robotic assisted laparoscopic radical cystectomy with regard to perioperative results, pathological outcomes and surgical complications. MATERIALS AND METHODS A total of 100 consecutive patients (73 male and 27 female) underwent robotic radical cystectomy and urinary diversion at our institution from January 2006 to January 2009 for clinically localized bladder cancer. Outcome measures evaluated included operative variables, hospital recovery, pathological outcomes and complication rate. RESULTS Mean age of this cohort was 65.5 years (range 33 to 86). Of the patients 61 underwent ileal conduit diversion, 38 received a neobladder and 1 had no urinary diversion (renal failure). Mean operating room time for all patients was 4.6 hours (median 4.3) and mean surgical blood loss was 271 ml (median 250). On surgical pathology 40% of the cases were pT1 or less disease, 27% were pT2, 13% were pT3/T4 disease and 20% were node positive. Mean number of lymph nodes removed was 19 (range 8 to 40). In no case was there a positive surgical margin. Mean days to flatus were 2.1, bowel movement 2.8 and discharge home 4.9. There were 41 postoperative complications in 36 patients with 8% having a major complication (Clavien grade 3 or higher) and 11% being readmitted within 30 days of surgery. At a mean followup of 21 months 15 patients had disease recurrence and 6 died of disease. CONCLUSIONS We report a relatively large and maturing experience with robotic radical cystectomy for the treatment of bladder cancer providing acceptable surgical and pathological outcomes. These results support continued efforts to refine the surgical management of high risk bladder cancer.

Neoadjuvant Clinical Trial With Sorafenib for Patients With Stage II or Higher Renal Cell Carcinoma

PURPOSE The multitargeted tyrosine kinase inhibitor sorafenib is used for the treatment of advanced-stage renal cell carcinoma. However, the safety and efficacy of this agent have yet to be evaluated in the preoperative period, where there may be potential advantages including tumor downstaging. This prospective trial evaluates the safety and feasibility of sorafenib in the preoperative setting. PATIENTS AND METHODS Thirty patients with clinical stage II or higher renal masses, selected based on their candidacy for nephrectomy, underwent preoperative treatment with sorafenib. Toxicities, surgical complications, and tumor responses were monitored. RESULTS Of the thirty patients enrolled, 17 patients had localized disease and 13 had metastatic disease. After a course of sorafenib therapy (median duration, 33 days), a decrease in primary tumor size (median, 9.6%) and radiographic evidence of loss of intratumoral enhancement, quantified using a methodology similar to Choi criteria (median, 13%), was also observed. According to Response Evaluation Criteria in Solid Tumors, of the 28 patients evaluable for response, two patients had a partial response and 26 had stable disease, with no patients progressing on therapy. Toxicities from sorafenib were similar to that expected with this class of medication. All patients were able to proceed with nephrectomy and no surgical complications related to sorafenib administration were observed. CONCLUSION The administration of preoperative sorafenib therapy can impact the size and density of the primary tumor and appears safe and feasible. Further studies are required to determine if preoperative systemic therapy improves outcomes in patients undergoing nephrectomy for renal cell carcinoma.

Comparison of mid-lobe versus lateral systematic sextant biopsies in the detection of prostate cancer

OBJECTIVE Systematic sextant biopsies are a powerful tool in the diagnosis of prostate cancer. Interpretation of the histopathologic results of these biopsies plays a central role in treatment decisions. This biopsy approach was originally described as sampling the prostate in the mid-lobe, parasagittal plane at the apex, mid-gland, and base, bilaterally. Morphometric analysis of prostate specimens has revealed that most clinically significant cancers are mainly located in the posterolateral aspect of the gland, not the mid-lobe. We sought to determine if cancer detection could be improved by obtaining more laterally placed biopsies. MATERIALS AND METHODS Forty-one patients underwent transrectal ultrasound with mid-lobe sextant as well as lateral sextant biopsies. Biopsy specimens were evaluated for Gleason grade and length of cancer present in each core. The mid-lobe and lateral biopsy results were then compared. RESULTS Thirteen of 41 patients (31.7%) were found to have no cancer on either biopsy set. Cancer was detected by both the mid-lobe and the lateral biopsies in 19 patients (46.3%). In 6 patients (14.6%), only the lateral biopsies revealed cancer, and in 3 patients (7.3%), only the mid-lobe biopsies revealed cancer. CONCLUSIONS Laterally-placed systematic sextant biopsies may yield an improved diagnosis rate in patients with palpable nodularity in the lateral aspect of the prostate, patients without any palpable abnormalities but with elevated PSA levels, and in those patients undergoing repeat biopsies.

Analysis of intracorporeal compared with extracorporeal urinary diversion after robot-assisted radical cystectomy: Results from the international robotic cystectomy consortium

BACKGROUND Intracorporeal urinary diversion (ICUD) has the potential benefits of a smaller incision, reduced pain, decreased bowel exposure, and reduced risk of fluid imbalance. OBJECTIVE To compare the perioperative outcomes of patients undergoing extracorporeal urinary diversion (ECUD) and ICUD following robot-assisted radical cystectomy (RARC). DESIGN, SETTING, AND PARTICIPANTS We reviewed the database of the International Robotic Cystectomy Consortium (IRCC) (18 international centers), with 935 patients who had undergone RARC and pelvic lymph node dissection (PLND) between 2003 and 2011. INTERVENTION All patients within the IRCC underwent RARC and PLND as indicated. The urinary diversion was performed either intracorporeally or extracorporeally. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Demographic data, perioperative outcomes, and complications in patients undergoing ICUD or ECUD were compared. All patients had at least a 90-d follow-up. The Fisher exact test was used to summarize categorical variables and the Wilcoxon rank sum test or Kruskal-Wallis test for continuous variables. RESULTS AND LIMITATIONS Of 935 patients who had RARC and PLND, 167 patients underwent ICUD (ileal conduit: 106; neobladder: 61), and 768 patients had an ECUD (ileal conduit: 570; neobladder: 198). Postoperative complications data were available for 817 patients, with a minimum follow-up of 90 d. There was no difference in age, gender, body mass index, American Society of Anesthesiologists grade, or rate of prior abdominal surgery between the groups. The operative time was equivalent (414 min), with the median hospital stay being marginally longer for the ICUD group (9 d vs 8 d, p=0.086). No difference in the reoperation rates at 30 d was noted between the groups. The 90-d complication rate was not significant between the two groups, but a trend favoring ICUD over ECUD was noted (41% vs 49%, p=0.05). Gastrointestinal complications were significantly lower in the ICUD group (p ≤ 0.001). Patients with ICUD were at a lower risk of experiencing a postoperative complication at 90 d (32%) (odds ratio: 0.68; 95% confidence interval, 0.50-0.94; p=0.02). Being a retrospective study was the main limitation. CONCLUSIONS Robot-assisted ICUD can be accomplished safely, with comparable outcomes to open urinary diversion. In this cohort, patients undergoing ICUD had a relatively lower risk of complications.

Robotic-Assisted Laparoscopic Intracorporeal Urinary Diversion

BACKGROUND Recent small case series have now been reported for robotic-assisted laparoscopic radical cystectomy (RALRC). In most of these series, the urinary diversion has been performed in an extracorporeal fashion. There have been few case reports of an intracorporeal diversion and little description of the technique of such a procedure. OBJECTIVE In this paper, we report our initial experience with robotic-assisted laparoscopic intracorporeal urinary diversion, describing stepwise the surgical procedure itself and evaluating perioperative and pathologic outcomes of this novel procedure. DESIGN, SETTING, AND PARTICIPANTS We studied a single-institution case series of patients undergoing robotic-assisted cystectomy and intracorporeal urinary diversion for clinically localized urothelial carcinoma of the bladder (n=10) or for a noncompliant dysfunctional bladder refractory to more conservative management (n=2). Historical comparisons are also made to a consecutive case series of 20 patients undergoing robotic radical cystectomy and extracorporeal urinary diversion. SURGICAL PROCEDURE RALRC and intracorporeal urinary diversion, including ileal conduit (n=9) and orthotopic ileal neobladder (n=3). MEASUREMENTS The stepwise operative procedure is described in detail. Outcome measures evaluated in this series included operative variables, hospital recovery, and complication rate. Comparisons were made to a contemporaneous series of 20 patients who underwent a robotic cystectomy with extracorporeal diversion during this time period (from an experience of >100 robotic cystectomy patients since 2005). RESULTS AND LIMITATIONS Twelve patients (mean age: 60.9 yr) underwent an intracorporeal diversion. Mean operating-room time of all patients was 5.3h, and mean surgical blood loss was 221ml. Mean time to flatus, bowel movement, and hospital discharge was 2.2 d, 3.2 d, and 4.5 d, respectively. Eleven of the 12 patients were discharged on or before postoperative day 5. There were six postoperative complications in five patients (42%), with one complication being Clavien grade 3 or higher. The major limitations of the study are the small sample size and the nonrandomized nature of the compared treatment groups (intracorporeal vs extracorporeal), which limits the ability to directly compare the techniques at a high level of scientific confidence. CONCLUSIONS Our initial experience with robotic-assisted laparoscopic intracorporeal diversion appears to be favorable with acceptable operative and short-term clinical outcomes.

Cost Analysis of Robotic Versus Open Radical Cystectomy for Bladder Cancer

PURPOSE Recently robotic approaches to cystectomy have been reported, and while clinical and oncological efficacy continues to be evaluated, potential financial costs have not been clearly evaluated. In this study we present a financial analysis using current cost structures and clinical outcomes for robotic and open cystectomy for bladder cancer. MATERIALS AND METHODS The financial costs of robotic and open radical cystectomy were categorized into operating room and hospital components, and further divided into fixed and variable costs for each. Fixed operating room costs for open cases involved base cost as well as disposable equipment costs while robotic fixed costs included the amortized machine cost as well as equipment and maintenance. Variable operating room costs were directly related to length of surgery. Variable hospital costs were directly related to transfusion requirement and length of stay. The means of the prior 20 cases of robotic and open cystectomy were used to perform a comparative cost analysis. RESULTS Mean fixed operating room costs for robotic cases were

Preoperative tyrosine kinase inhibition as an adjunct to debulking nephrectomy.

1,634 higher than for open cases. Operating room variable costs were also higher by a difference of

Ror2, a developmentally regulated kinase, promotes tumor growth potential in renal cell carcinoma

570, directly related to increased operating room time. Hospital costs were nearly identical for the fixed component while variable costs were