David Paulucci

Heterogeneity in renal cell carcinoma

INTRODUCTION In recent years, molecular characterization of renal cell carcinoma has facilitated the identification of driver genes, specific molecular pathways, and characterization of the tumor microenvironment, which has led to a better understanding of the disease. This comprehension has revolutionized the treatment for patients with metastatic disease, but despite these advancements many patients will develop resistance leading to treatment failure. A primary cause of this resistance and subsequent treatment failure is tumor heterogeneity. We reviewed the literature on the mechanisms of tumor heterogeneity and its clinical implications. METHODS A comprehensive literature search was performed using the MEDLINE/PubMed Index. RESULTS Intertumor and intratumor heterogeneity is possibly a reason for treatment failure and development of resistance. Specifically, the genetic profile of a renal tumor differs spatially within a tumor as well as among patients. Genomic mutations can change temporally with resistant subclones becoming dominant over time. CONCLUSIONS Accounting for intratumor and intertumor heterogeneity with better sampling of cancer tissue is needed. This will hopefully lead to improved identification of driver mutations and actionable targets. Only then, we can move past the one-size-fits-all approach toward personalized treatment based on each individual׳s molecular profile.

Robot-assisted partial nephrectomy: continued refinement of outcomes beyond the initial learning curve.

To evaluate trends in peri‐operative outcomes of 250 consecutive cases beyond the initial learning curve (LC) of robot‐assisted partial nephrectomy (RAPN) among multiple surgeons.

Selective arterial clamping does not improve outcomes in robot-assisted partial nephrectomy: a propensity-score analysis of patients without impaired renal function.

To assess the benefit of selective arterial clamping (SAC) as an alternative to main renal artery clamping (MAC) during robot‐assisted partial nephrectomy (RAPN) in patients without underlying chronic kidney disease (CKD).

Predictors of biochemical recurrence in pT3b prostate cancer after radical prostatectomy without adjuvant radiotherapy

Men with pathologic evidence of seminal vesicle invasion (SVI) at radical prostatectomy (RP) have higher rates of biochemical recurrence (BCR) and mortality. Adjuvant radiotherapy (XRT) has been shown to increase freedom from BCR, but its impact on overall survival is controversial and it may represent overtreatment for some. The present study, therefore, sought to identify men with SVI at higher risk for BCR after RP in the absence of adjuvant XRT.

Predicting Complications Following Robot-Assisted Partial Nephrectomy with the ACS NSQIP® Universal Surgical Risk Calculator

Purpose: We evaluated the predictive value of the ACS NSQIP® (American College of Surgeons National Surgical Quality Improvement Program®) surgical risk calculator in a tertiary referral cohort of patients who underwent robot‐assisted partial nephrectomy. Materials and Methods: We queried our prospectively maintained, multi‐institutional database of patients treated with robot‐assisted partial nephrectomy and input the preoperative details of 300 randomly selected patients into the calculator. Accuracy of the calculator was assessed by the ROC AUC and the Brier score. Results: The observed rate of any complication in our cohort was 14% while the mean predicted rate of any complication using the calculator was 5.42%. The observed rate of serious complications (Clavien score 3 or greater) was 3.67% compared to the predicted rate of 4.89%. Low AUC and high Brier score were calculated for any complication (0.51 and 0.1272) and serious complications (0.55 and 0.0352, respectively). The calculated AUC was low for all outcomes, including venous thromboembolism (0.67), surgical site infection (0.51) and pneumonia (0.44). Conclusions: The ACS NSQIP risk calculator poorly predicted and discriminated which patients would experience complications after robot‐assisted partial nephrectomy. These findings suggest the need for a more tailored outcome prediction model to better assist urologists risk stratify patients undergoing robot‐assisted partial nephrectomy and counsel them on individual surgical risks.

Utilization of the Robotic Surgical Platform for Radical Nephrectomy: A National Comparison of Trends for Open, Laparoscopic and Robotic Approaches

Introduction: The robotic platform in surgery has been widely adopted as it facilitates complex surgical reconstructions such as renorrhaphy during partial nephrectomy. Although the robotic approach to radical nephrectomy has higher costs and a lack of perioperative and oncologic evidence, the use of robotic platforms for radical nephrectomy is increasing. We evaluated a national database to explain the increased use of robotic radical nephrectomy despite a lack of perioperative and oncologic evidence. Methods: The current retrospective cohort study used NIS (Nationwide Inpatient Sample) to identify patients who underwent radical nephrectomy from the last quarter of 2008 through 2010. We investigated hospital and patient specific factors associated with the robotic approach to radical nephrectomy, including hospital volume of robotic partial nephrectomy and robot‐assisted radical prostatectomy. Results: Of the 124,462 radical nephrectomies 4.7% were performed robotically. The median cost of robotic radical nephrectomy was

Use of Partial Nephrectomy after Acquisition of a Surgical Robot: A Population Based Study

1,324 to

Robot-assisted partial nephrectomy for large renal masses: a multi-institutional series.

2,759 higher than that of open and laparoscopic radical nephrectomy. No differences in complications, length of stay, blood transfusion rates or mortality were found between laparoscopic and robotic radical nephrectomy. However the rate of open and laparoscopic radical nephrectomy decreased during the study period while the use of robotic radical nephrectomy increased almost fourfold. At hospitals in the middle or highest tertile of robotic partial nephrectomy the procedure was more likely to be performed. Patients younger than 60 years were less likely to undergo the surgery than those older than 80 years (p <0.001). Robotic radical nephrectomy was less likely to be done at large and medium medical centers (p <0.05). The hospital volume of robot‐assisted radical prostatectomy did not predict that of robotic radical nephrectomy. Conclusions: Although increased median costs and equivalent outcomes (perioperative and oncologic) question the benefit of robotic radical nephrectomy, its use is increasing. Robotic radical nephrectomy is more likely to be done at medium‐high volume robotic centers for partial nephrectomy. This nationwide overtreatment and inefficiency may reflect the use of robotic radical nephrectomy as a training tool to facilitate the robotic learning curve and the proliferation of robotic partial nephrectomy.

Genomic differences between black and white patients implicate a distinct immune response to papillary renal cell carcinoma

Introduction: The advent of robotics may promote the dissemination of partial nephrectomy, and allow patients to experience survival and functional benefits compared to radical nephrectomy. Therefore, we assessed the impact of hospital acquisition of a robotic surgery platform on the rate of partial nephrectomy recorded in a nationwide database. Methods: We identified 53,364 patients with a diagnosis of localized renal cell carcinoma who underwent extirpative surgery from 2006 to 2012 using the Perspective database. Procedures were categorized based on extent of surgery (radical nephrectomy vs partial nephrectomy), approach (open, laparoscopic, robotic) and hospital ownership of a surgical robot. Changes in the proportion of partial nephrectomies performed over time and the effect of acquiring a surgical robot on the proportion of partial nephrectomies performed were assessed with multivariable logistic regression. Results: Overall 40,147 (75.2%) radical nephrectomies and 13,217 (24.8%) partial nephrectomies were performed between 2006 and 2012. The proportion of hospitals using a surgical robot for renal cancer surgery increased from 1.8% in the first quarter of 2006 to 47.7% by the end of 2012. Partial nephrectomy use ranged from 19.1% to 31.2%. More robotic hospitals performed partial nephrectomy than nonrobotic hospitals (29.6% vs 18.0%, p <0.001). After acquisition of a surgical robot the partial nephrectomy rate increased from 16.4% to 34.3% (p <0.001). Hospitals with a robot were more likely to use partial nephrectomy than radical nephrectomy (OR 1.464, CI 1.39–1.54, p <0.001). Conclusions: While laparoscopic partial nephrectomy remains a challenging operation, this study demonstrates that hospital ownership of a surgical robot is associated with increased use of partial nephrectomy in the treatment of localized renal masses.

Analysis of the Transperitoneal Approach to Robot-Assisted Laparoscopic Partial Nephrectomy for the Treatment of Anterior and Posterior Renal Masses

To compare peri‐operative outcomes after robot‐assisted partial nephrectomy (RAPN) for cT2a (7 to <10 cm) to cT1 tumours.