Khurshid A. Guru

ICUD-EAU International Consultation on Bladder Cancer 2012: Radical Cystectomy and Bladder Preservation for Muscle-Invasive Urothelial Carcinoma of the Bladder

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.

The Learning Curve of Robot-Assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium

BACKGROUND Robot-assisted radical cystectomy (RARC) has evolved as a minimally invasive alternative to open radical cystectomy for patients with invasive bladder cancer. OBJECTIVE We sought to define the learning curve for RARC by evaluating results from a multicenter, contemporary, consecutive series of patients who underwent this procedure. DESIGN, SETTING, AND PARTICIPANTS Utilizing the International Robotic Cystectomy Consortium database, a prospectively maintained and institutional review board-approved database, we identified 496 patients who underwent RARC by 21 surgeons at 14 institutions from 2003 to 2009. MEASUREMENTS Cut-off points for operative time, lymph node yield (LNY), estimated blood loss (EBL), and margin positivity were identified. Using specifically designed statistical mixed models, we were able to inversely predict the number of patients required for an institution to reach the predetermined cut-off points. RESULTS AND LIMITATIONS Mean operative time was 386 min, mean EBL was 408 ml, and mean LNY was 18. Overall, 34 of 482 patients (7%) had a positive surgical margin (PSM). Using statistical models, it was estimated that 21 patients were required for operative time to reach 6.5h and 8, 20, and 30 patients were required to reach an LNY of 12, 16, and 20, respectively. For all patients, PSM rates of <5% were achieved after 30 patients. For patients with pathologic stage higher than T2, PSM rates of <15% were achieved after 24 patients. CONCLUSIONS RARC is a challenging procedure but is a technique that is reproducible throughout multiple centers. This report helps to define the learning curve for RARC and demonstrates an acceptable level of proficiency by the 30th case for proxy measures of RARC quality.

Complications After Robot-assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium

BACKGROUND Complication reporting is highly variable and nonstandardized. Therefore, it is imperative to determine the surgical outcomes of major oncologic procedures. OBJECTIVE To describe the complications after robot-assisted radical cystectomy (RARC) using a standardized and validated reporting methodology. DESIGN, SETTING, AND PARTICIPANTS Using the International Robotic Cystectomy Consortium (IRCC) database, we identified 939 patients who underwent RARC, had available complication data, and had at least 90 d of follow-up. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Complications were analyzed and graded according to the Memorial Sloan-Kettering Cancer Center (MSKCC) system and were defined and stratified by organ system. Secondary outcomes included identification of preoperative and intraoperative variables predicting complications. Logistic regression models were used to define predictors of complications and readmission. RESULTS AND LIMITATIONS Forty-one percent (n=387) and 48% (n=448) of patients experienced a complication within 30 and 90 d of surgery, respectively. The highest grade of complication was grade 0 in 52%, grade 1-2 in 29%, and grade 3-5 in 19% patients. Gastrointestinal, infectious, and genitourinary complications were most common (27%, 23%, and 17%, respectively). On multivariable analysis, increasing age group, neoadjuvant chemotherapy, and receipt of blood transfusion were independent predictors of any and high-grade complications, respectively. Thirty and 90-d mortality was 1.3% and 4.2%, respectively. As a multi-institutional database, a disparity in patient selection, operating standards, postoperative management, and reporting of complications can be considered a major limitation of the study. CONCLUSIONS Surgical morbidity after RARC is significant when reported using a standardized reporting methodology. The majority of complications are low grade. Strict reporting of complications is necessary to advocate for radical cystectomy (RC) and helps in patient counseling.

Current status of validation for robotic surgery simulators – a systematic review

Little is known on how best to train the future generation of robotic surgeons. It has been postulated that virtual reality (VR) simulators may aid the progression along the learning curve for this rapidly developing surgical technique within a safe training environment. There are several simulators available on the market, the best known is that developed by Intuitive Surgical Inc. The present study provides the first systematic review of all the trails of the various VR robotic platforms. It explores the evidence supporting the effectiveness of the various platforms for feasibility, reliability, validity, acceptability, educational impact and cost‐effectiveness. This article also highlights the deficiencies and future work required to advance robotic surgical training.

Systematic Review and Cumulative Analysis of Perioperative Outcomes and Complications After Robot-assisted Radical Cystectomy

CONTEXT Although open radical cystectomy (ORC) is still the standard approach, laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) have gained popularity. OBJECTIVE To report a systematic literature review and cumulative analysis of perioperative outcomes and complications of RARC in comparison with ORC and LRC. EVIDENCE ACQUISITION Medline, Scopus, and Web of Science databases were searched using a free-text protocol including the terms robot-assisted radical cystectomy or da Vinci radical cystectomy or robot* radical cystectomy. RARC case series and studies comparing RARC with either ORC or LRC were collected. Cumulative analysis was conducted. EVIDENCE SYNTHESIS The searches retrieved 105 papers. According to the different diversion type, overall mean operative time ranged from 360 to 420 min. Similarly, mean blood loss ranged from 260 to 480 ml. Mean in-hospital stay was about 9 d for all diversion types, with consistently high readmission rates. In series reporting on RARC with either extracorporeal or intracorporeal conduit diversion, overall 90-d complication rates were 59% (high-grade complication: 15%). In series reporting RARC with intracorporeal continent diversion, the overall 30-d complication rate was 45.7% (high-grade complication: 28%). Reported mortality rates were ≤3% for all diversion types. Comparing RARC and ORC, cumulative analyses demonstrated shorter operative time for ORC, whereas blood loss and in-hospital stay were better with RARC (all p values <0.003). Moreover, 90-d complication rates of any-grade and 90-d grade 3 complication rates were lower for RARC (all p values <0.04), whereas high-grade complication and mortality rates were similar. CONCLUSIONS RARC can be performed safely with acceptable perioperative outcome, although complications are common. Cumulative analyses demonstrated that operative time was shorter with ORC, whereas RARC may provide some advantages in terms of blood loss and transfusion rates and, more limitedly, for postoperative complication rates over ORC and LRC. PATIENT SUMMARY Although open radical cystectomy (RC) is still regarded as a standard treatment for muscle-invasive bladder cancer, laparoscopic and robot-assisted RC are becoming more popular. Robotic RC can be safely performed with acceptably low risk of blood loss, transfusion, and intraoperative complications; however, as for open RC, the risk of postoperative complications is high, including a substantial risk of major complication and reoperation.

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.

The Role of Laparoscopic and Robotic Cystectomy in the Management of Muscle-Invasive Bladder Cancer With Special Emphasis on Cancer Control and Complications

CONTEXT Minimally invasive radical cystectomy (MIRC) techniques for the treatment of muscle-invasive bladder cancer (BCa) are being increasingly applied. MIRC offers the potential benefits of a minimally invasive approach in terms of reduced blood loss and analgesic requirements whilst striving to provide similar oncologic efficacy to open radical cystectomy (ORC). Whether quicker recovery, shorter hospital stay, and a reduction in complications are routinely achieved with MIRC remains to be proved in prospective comparisons. OBJECTIVE To explore both laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RRC), focusing specifically on the oncologic parameters and comorbidity of the procedures. Reported complications from major centres are identified and categorised via the Clavien system. Positive margins rates, local recurrence, and both cancer-specific survival (CSS) and overall survival rates are assessed. EVIDENCE ACQUISITION A comprehensive electronic literature search was conducted in November 2010 using the Medline database to identify publications relating to laparoscopic, robotic, or minimally invasive radical cystectomy. EVIDENCE SYNTHESIS There are encouraging short- to medium-term results for both LRC and RRC in terms of postoperative morbidity and oncologic outcomes. It seems possible in experienced hands to perform a satisfactory minimally invasive lymphadenectomy regarding lymph node counts and levels of dissection. Positive soft-tissue margins are similar to large open series for T2/T3 disease but inferior for bulky T4 disease. Local recurrence rates and CSS rates seem equivalent to ORC at up to 3 yr of follow-up; however, mature outcome data still need to be presented before definitive comparisons can be made. CONCLUSIONS Robotic and laparoscopic cystectomy has a growing role in the management of muscle-invasive BCa. Long-term oncologic results are awaited, and there are concerns over the ability of MIRC to treat bulky and locally advanced disease, making careful patient selection vital. Forthcoming randomised trials in this area will more fully address these issues.

Consumption of Raw Cruciferous Vegetables is Inversely Associated with Bladder Cancer Risk

Cruciferous vegetables contain isothiocyanates, which show potent chemopreventive activity against bladder cancer in both in vitro and in vivo studies. However, previous epidemiologic studies investigating cruciferous vegetable intake and bladder cancer risk have been inconsistent. Cooking can substantially reduce or destroy isothiocyanates, and could account for study inconsistencies. In this hospital-based case-control study involving 275 individuals with incident, primary bladder cancer and 825 individuals without cancer, we examined the usual prediagnostic intake of raw and cooked cruciferous vegetables in relation to bladder cancer risk. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with unconditional logistic regression, adjusting for smoking and other bladder cancer risk factors. We observed a strong and statistically significant inverse association between bladder cancer risk and raw cruciferous vegetable intake (adjusted OR for highest versus lowest category = 0.64; 95% CI, 0.42-0.97), with a significant trend (P = 0.003); there were no significant associations for fruit, total vegetables, or total cruciferous vegetables. The associations observed for total raw crucifers were also observed for individual raw crucifers. The inverse association remained significant among current and heavy smokers with three or more servings per month of raw cruciferous vegetables (adjusted ORs, 0.46 and 0.60; 95% CI, 0.23-0.93 and 0.38-0.93, respectively). These data suggest that cruciferous vegetables, when consumed raw, may reduce the risk of bladder cancer, an effect consistent with the role of dietary isothiocyanates as chemopreventive agents against bladder cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(4):938–44)

Surgical Margin Status After Robot Assisted Radical Cystectomy: Results From the International Robotic Cystectomy Consortium

PURPOSE Positive surgical margins at radical cystectomy confer a poor prognosis. We evaluated the incidence and predictors of positive surgical margins in patients who underwent robot assisted radical cystectomy for bladder cancer. MATERIALS AND METHODS Using the International Robotic Cystectomy Consortium database we identified 513 patients who underwent robot assisted radical cystectomy, as done by a total of 22 surgeons at 15 institutions from 2003 to 2009. After stratification by age group, gender, pathological T stage, nodal status, sequential case number and institutional volume logistic regression was used to correlate variables with the likelihood of a positive surgical margin. RESULTS Of the 513 patients 35 (6.8%) had a positive surgical margin. Increasing 10-year age group, lymph node positivity and higher pathological T stage were significantly associated with an increased likelihood of a positive margin (p = 0.010, <0.001 and p <0.001, respectively). Gender, sequential case number and institutional volume were not significantly associated with margin positivity. The rate of margin positive disease at cystectomy was 1.5% for pT2 or less, 8.8% for pT3 and 39% for pT4 disease. CONCLUSIONS Positive surgical margin rates at robot assisted radical cystectomy for advanced bladder cancer were similar to those in open cystectomy series in a large, multi-institutional, prospective cohort. Sequential case number, a surrogate for the learning curve and institutional volume were not significantly associated with positive margins at robot assisted radical cystectomy.

Systematic Review and Cumulative Analysis of Oncologic and Functional Outcomes After Robot-assisted Radical Cystectomy

CONTEXT Although open radical cystectomy (ORC) is still the standard approach, laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) are increasingly performed. OBJECTIVE To report on a systematic literature review and cumulative analysis of pathologic, oncologic, and functional outcomes of RARC in comparison with ORC and LRC. EVIDENCE ACQUISITION Medline, Scopus, and Web of Science databases were searched using a free-text protocol including the terms robot-assisted radical cystectomy or da Vinci radical cystectomy or robot* radical cystectomy. RARC case series and studies comparing RARC with either ORC or LRC were collected. A cumulative analysis was conducted. EVIDENCE SYNTHESIS The searches retrieved 105 papers, 87 of which reported on pathologic, oncologic, or functional outcomes. Most series were retrospective and had small case numbers, short follow-up, and potential patient selection bias. The lymph node yield during lymph node dissection was 19 (range: 3-55), with half of the series following an extended template (yield range: 11-55). The lymph node-positive rate was 22%. The performance of lymphadenectomy was correlated with surgeon and institutional volume. Cumulative analyses showed no significant difference in lymph node yield between RARC and ORC. Positive surgical margin (PSM) rates were 5.6% (1-1.5% in pT2 disease and 0-25% in pT3 and higher disease). PSM rates did not appear to decrease with sequential case numbers. Cumulative analyses showed no significant difference in rates of surgical margins between RARC and ORC or RARC and LRC. Neoadjuvant chemotherapy use ranged from 0% to 31%, with adjuvant chemotherapy used in 4-29% of patients. Only six series reported a mean follow-up of >36 mo. Three-year disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates were 67-76%, 68-83%, and 61-80%, respectively. The 5-yr DFS, CSS, and OS rates were 53-74%, 66-80%, and 39-66%, respectively. Similar to ORC, disease of higher pathologic stage or evidence of lymph node involvement was associated with worse survival. Very limited data were available with respect to functional outcomes. The 12-mo continence rates with continent diversion were 83-100% in men for daytime continence and 66-76% for nighttime continence. In one series, potency was recovered in 63% of patients who were evaluable at 12 mo. CONCLUSIONS Oncologic and functional data from RARC remain immature, and longer-term prospective studies are needed. Cumulative analyses demonstrated that lymph node yields and PSM rates were similar between RARC and ORC. Conclusive long-term survival outcomes for RARC were limited, although oncologic outcomes up to 5 yr were similar to those reported for ORC. PATIENT SUMMARY Although open radical cystectomy (RC) is still regarded as the standard treatment for muscle-invasive bladder cancer, laparoscopic and robot-assisted RCs are becoming more popular. Templates of lymph node dissection, lymph node yields, and positive surgical margin rates are acceptable with robot-assisted RC. Although definitive comparisons with open RC with respect to oncologic or functional outcomes are lacking, early results appear comparable.