G. Wilding

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.

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.

Lymphadenectomy at the time of robot‐assisted radical cystectomy: results from the International Robotic Cystectomy Consortium

What’s known on the subject? and What does the study add?

A phase I study to determine the safety, pharmacokinetics and pharmacodynamics of a dual VEGFR and FGFR inhibitor, brivanib, in patients with advanced or metastatic solid tumors.

BACKGROUND This study was designed to determine the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of brivanib in patients with advanced/metastatic solid tumors. PATIENTS AND METHODS Ninety patients enrolled in this two-part, phase I open-label study of oral brivanib alaninate. The primary objectives of this study were (in part A) dose-limiting toxicity, maximum tolerated dose (MTD) and the lowest biologically active dose level and (in part B) the optimal dose/dose range. The secondary objectives of this study were preliminary evidence of antitumor activity, PK and PD. RESULTS Across part A (open-label dose escalation and MTD) and part B (open-label dose optimization), 68 patients received brivanib alaninate. Brivanib demonstrated a manageable toxicity profile at doses of 180-800 mg. Most toxic effects were mild. Systemic exposure of the active moiety brivanib increased linearly ≤1000 mg/day. The MTD was 800 mg/day. Forty-four patients were treated at the MTD: 20 with 800 mg continuously, 11 with 800 mg intermittently and 13 with 400 mg b.i.d. doses. Partial responses were confirmed in two patients receiving brivanib ≥600 mg. Dynamic contrast-enhanced magnetic resonance imaging demonstrated statistically significant decreases in parameters reflecting tumor vascularity and permeability after multiple doses in the 800-mg continuous q.d. and 400-mg b.i.d. dose cohorts. CONCLUSION In patients with advanced/metastatic cancer, brivanib demonstrates promising antiangiogenic and antitumor activity and manageable toxicity at doses ≤800 mg orally q.d., the recommended phase II study dose.

Biological effects and clinical significance of lenalidomide-induced tumour flare reaction in patients with chronic lymphocytic leukaemia: in vivo evidence of immune activation and antitumour response.

Lenalidomide has demonstrated impressive antileukaemic effects in patients with chronic lymphocytic leukaemia (CLL). The mechanism(s) by which it mediates these effects remain unclear. Clinically, CLL patients treated with lenalidomide demonstrate an acute inflammatory reaction, the tumour flare reaction that is suggestive of an immune activation phenomenon. Samples from CLL patients treated with lenalidomide were used to evaluate its effect on the tumour cell and components of its microenvironment (immune cellular and cytokine). Lenalidomide was unable to directly induce apoptosis in CLL cells in vitro, however it modulated costimulatory (CD80, CD83, CD86) surface molecules on CLL cells in vitro and in vivo. Concurrently, we demonstrated that NK cell proliferation was induced by lenalidomide treatment in patients and correlated with clinical response. Cytokine analysis showed increase in levels of TNF‐α post‐lenalidomide treatment, consistent with acute inflammatory reaction. Furthermore, the basal cytokine profile (high IL‐8, MIG, IP‐10 and IL‐4 levels and low IL‐5, MIP1a, MIP1b, IL12/p70) was predictive of clinical response to lenalidomide. Collectively, our correlative studies provide further evidence that the antileukaemic effect of lenalidomide in CLL is mediated not only through modulation of the leukaemic clone but also through elements of the tumour microenvironment.

Does previous robot-assisted radical prostatectomy experience affect outcomes at robot-assisted radical cystectomy? Results from the international robotic cystectomy consortium

OBJECTIVES To evaluate the effect of previous robot-assisted radical prostatectomy (RARP) case volume on the outcomes of robot-assisted radical cystectomy. Little is known regarding the effect of previous robotic surgical experience on the implementation and execution of robot-assisted radical cystectomy. METHODS Using the International Robotic Cystectomy Consortium database, 496 patients were identified who had undergone robot-assisted radical cystectomy by 21 surgeons at 14 institutions from 2003 to 2009. The surgeons were divided into 4 groups according to their previous RARP experience (≤ 50, 51-100, 101-150, and > 150 cases). The overall operative time, blood loss, lymph node yield, pathologic stage, and surgical margin status were compared among the 4 groups using chi-square analysis. RESULTS The mean operative time was 386 minutes (range 178-827). The mean estimated blood loss was 408 mL (range 25-3500). The operative time and blood loss were both significantly associated with previous RARP experience (P < .001). The mean lymph node count was 17.8 nodes (range 0-68). Lymph node yield and increased pathologic stage were significantly associated with previous RARP experience (P < .001). Finally, 34 (7.0%) of the 482 patients had a positive surgical margin. Margin status was not significantly associated with previous RARP experience (P = .089). CONCLUSIONS Previous RARP case volume might affect the operative time, blood loss, and lymph node yield at robot-assisted radical cystectomy. In addition, surgeons with increased RARP experience operated on patients with more advanced tumors. Previous RARP experience, however, did not appear to affect the surgical margin status.

International Robotic Radical Cystectomy Consortium: A way forward.

Robot-assisted radical cystectomy (RARC) is an emerging operative alternative to open surgery for the management of invasive bladder cancer. Studies from single institutions provide limited data due to the small number of patients. In order to better understand the related outcomes, a world-wide consortium was established in 2006 of patients undergoing RARC, called the International Robotic Cystectomy Consortium (IRCC). Thus far, the IRCC has reported its findings on various areas of operative interest and continues to expand its capacity to include other operative modalities and transform it into the International Radical Cystectomy Consortium. This article summarizes the findings of the IRCC and highlights the future direction of the consortium.

International radical cystectomy consortium: A way forward

Robot-assisted radical cystectomy (RARC) is an emerging operative alternative to open surgery for the management of invasive bladder cancer. Studies from single institutions provide limited data due to the small number of patients. In order to better understand the related outcomes, a world-wide consortium was established in 2006 of patients undergoing RARC, called the International Robotic Cystectomy Consortium (IRCC). Thus far, the IRCC has reported its findings on various areas of operative interest and continues to expand its capacity to include other operative modalities and transform it into the International Radical Cystectomy Consortium. This article summarizes the findings of the IRCC and highlights the future direction of the consortium.

Population-based analysis of cancer control of partial nephrectomy for high-risk localized renal cell carcinoma.

385 Background: Partial nephrectomy (PN) has reported equivalent oncologic outcomes with superior renal function outcomes when compared to radical nephrectomy (RN) for treatment of localized renal cell carcinoma (RCC). Whether PN provides adequate cancer control in high risk disease is unclear. To clarify, survival outcomes were compared between those who underwent RN and PN for high risk RCC. METHODS Using the Surveillance, Epidemiology, and End Results database patients with RCC who underwent PN or RN for a localized tumor ≤ 7cm were identified. Cancer-specific (CSS) and overall survival (OS) were compared between those with high risk disease (defined as poorly or undifferentiated grade and/or pathologic stage T3) who underwent PN or RN. RESULTS Of 51,183 patients with localized RCC ≤ 7cm, 24.9% had high risk disease, 85.2% and 14.8% of which underwent RN and PN, respectively. Five-year CSS was superior in the PN group vs. the RN group (93.3% vs. 86.0%, p<0.001). On multivariable analysis undergoing RN was no longer predictive of CSS (HR 1.23, p=0.08). Similarly, 5-year OS was superior in the PN versus RN group (79.5% vs. 70.1%, p<0.001). RN remained independently associated with poor OS on multivariable analysis (HR 1.16, p=0.031). Propensity analysis accounting for factors affecting selection for type of nephrectomy produced similar results. RN did not influence CSS but portended a 20% increased risk of death from all causes (p=0.008). CONCLUSIONS In patients with high risk RCC, partial nephrectomy is associated with improved OS and does not compromise cancer control as compared to radical nephrectomy.

International Robotic Radical Cystectomy Consortium

Robot-assisted radical cystectomy (RARC) is an emerging operative alternative to open surgery for the management of invasive bladder cancer. Studies from single institutions provide limited data due to the small number of patients. In order to better understand the related outcomes, a world-wide consortium was established in 2006 of patients undergoing RARC, called the International Robotic Cystectomy Consortium (IRCC). Thus far, the IRCC has reported its findings on various areas of operative interest and continues to expand its capacity to include other operative modalities and transform it into the International Radical Cystectomy Consortium. This article summarizes the findings of the IRCC and highlights the future direction of the consortium.