Rutveej Patel

Controversies in Robotics: Open Versus Robotic Radical Cystectomy

Open radical cystectomy (ORC) remains the gold standard for treatment of muscle-invasive bladder cancer and certain cases of high-risk noninvasive bladder cancer. However, ORC is associated with significant morbidity, and there is promise of improved outcomes with the emergence of minimally invasive surgery. Because of the increased adoption of robotic radical cystectomy (RRC), we sought to review the current literature on the robotic approach. We explored the surgical techniques, perioperative and postoperative complications, oncologic and functional outcomes, and quality of life of patients with RRC versus ORC. Current data appear to favor RRC in perioperative outcomes and patient recovery, although RRC continues to be associated with longer surgical times and higher costs. Oncologic data are also promising, however data on long-term oncologic outcomes are insufficient. To date, there is evidence of similar functional outcomes between RRC and ORC continence, but there is a paucity of rigorous, standardized studies on health-related quality of life for continent versus incontinent diversion. Even as use of RRC steadily grows, there is a lack of consensus on the type of approach and urinary diversion that is optimal. We assessed the influence of surgeon experience on the totally intracorporeal urinary diversion and its feasibility to be widely adopted. We aimed to answer the question of whether there are significant benefits to RRC, and furthermore, of the effect of the approach on the choice of urinary diversion.

Regional Cost Variations of Robot-Assisted Radical Prostatectomy Compared With Open Radical Prostatectomy

INTRODUCTION The purpose of the study was to evaluate the cost differences between robot-assisted radical prostatectomy (RARP) and open radical prostatectomy (ORP) in various census regions of the United States because RARP has been reported to be more expensive than ORP with significant regional cost variations in radical prostatectomy (RP) cost across the United States. PATIENTS AND METHODS International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify patients with prostate cancer who underwent RARP or ORP from the Nationwide Inpatient Sample (NIS) database from 2009 to 2011. Hospital costs were compared using the Wilcoxon rank sum test and multivariable linear regression analysis adjusting for age, sex, race, comorbidities, and hospital characteristics. RESULTS From the NIS database, 24,636 RARP and 13,590 ORP procedures were identified and evaluated. The lowest cost overall was in the South; the highest cost RARP was in the West and for ORP in the Northeast. In multivariable analysis, adjusted according to patient and hospital characteristics, RARP was 43.3% more costly in the Midwest, 37.2% more costly in the South, and 39.1% more costly in the West (P < .0001 for all). In contrast, the cost for RARP in the Northeast was 12.8% less than for ORP (P < .0001). CONCLUSION Cost for RP significantly varies within the nation and in most regions it is significantly greater for RARP than for ORP. ORP in the Northeast is more costly than RARP. Further research is needed to delineate the reason for these differences and to optimize the cost of RP.

Pharmacokinetics, pharmacodynamics and clinical efficacy of abiraterone acetate for treating metastatic castration-resistant prostate cancer

Introduction: Androgen signaling axis (ASA) continues to play a crucial role in castration-resistant prostate cancer (CRPC). One of the proposed mechanisms is the activation of ASA by adrenal and intratumoral androgens. Targeted therapy to deplete such androgen sources should be effective in treating men with CRPC. Areas covered: Abiraterone acetate (AA) is a selective irreversible inhibitor of CYP 17. It is orally administered and is converted to its active metabolite abiraterone by the liver. Increased adrenocorticotrophic hormone drive, however, results in increased risks of hypertension and hypokalemia. In Phase III trials, AA with prednisone was shown to improve survivals in men with metastatic CRPC (mCRPC). The overall tolerability and safety profiles were acceptable. Expert opinion: It is now accepted that CRPC is not independent of androgen signaling, and targeted therapies to suppress ASA have recently been developed. With multiple high-level evidences of efficacy and safety, AA is considered a breakthrough in the treatment of mCRPC. Current clinical challenge, however, is to better delineate the mechanisms of the disease progression for developments of resistance to targeted therapies. Identification of the drug-resistance patterns would allow better patient selection for each treatment modality.

Pharmacokinetic drug evaluation of atezolizumab for the treatment of locally advanced or metastatic urothelial carcinoma.

ABSTRACT Introduction: Muscle invasive bladder cancer (MIBC) is difficult to manage for patients who progress during or after initial chemotherapy regimens. Current regimens offer low response rates with high toxicities. The advent of immune checkpoint inhibitors may represent a new opportunity for effective management of these patients. Areas covered: Atezolizumab is an engineered humanized monoclonal immunoglobulin G1 antibody that binds selectively to PD-L1 and prevents its interaction with PD-1 and B7-1. It is administered intravenously and is given every 3 weeks as long as there is no evidence of tumor progression. Phase I trials confirmed antitumor activity of atezolizumab in patients with advanced or metastatic urothelial carcinoma. Phase II trials showed an improved response rate and a longer durable response than current conventional therapy. Phase III trials are currently underway with an estimated accrual end date of 2017. Expert opinion: MIBC is a high-risk disease, and after progression on current chemotherapy regimens, second-line treatments leave much to be desired. Emerging evidence of efficacy and safety and a recent accelerated approval by the FDA presents atezolizumab as a promising treatment option. Current clinical challenges include the details of disease progression and determining where immune checkpoint inhibition will reside in the treatment algorithm.

Intracrine androgen biosynthesis in renal cell carcinoma

Background:Renal cell carcinoma (RCC) is one of the most lethal genitourinary cancers. The presence of androgen receptor (AR) in RCC has recently been shown to be associated with higher tumour stage irrespective of gender. Because the clinical context of androgens in female RCC patients is similar to that of prostate cancer patients undergoing androgen-deprivation therapy, mechanisms underlying the emergence of castration-resistant prostate cancer (CRPC) may be at play in AR-positive RCC cells. Therefore, we hypothesized that AR-positive RCC has intratumoral steroidogenesis and that anti-androgen therapy may result in tumour suppression.Methods:Mice were injected with an AR-positive RCC cell line. When tumours became palpable, surgical castration was performed and tumour volume was measured. Using ELISA, the levels of intracellular testosterone and dihydrotesterone were measured in AR-positive human RCC cell lines. Lastly, male mice containing xenografts were treated with enzalutamide or abiraterone acetate (AA) for 3 weeks to measure tumour volume.Results:We first observed in vivo that castration retards the growth of AR-positive RCC tumour xenograft in mice. Next, AR-positive human RCC cell lines and tissues were found to have elevated levels of testosterone and dihydrotestosterone and express key enzymes required for intracellular androgen biosynthesis. A mouse xenograft study with AR-positive RCC cell line using the commonly used anti-androgen therapies showed significant tumour suppression (P<0.01).Conclusions:Intracrine androgen biosynthesis is a potential source of androgen in AR-positive RCC and that the androgen signaling axis is a potential target of intervention in RCC.

Long-Term Outcomes of Using Hyaluronic Acid-Carboxymethylcellulose Adhesion Barrier Film on the Neurovascular Bundle

INTRODUCTION/OBJECTIVE We hypothesize that the use of hyaluronic acid-carboxymethylcellulose (HACM) adhesion barrier at the neurovascular bundle may hasten the return of erectile function after robot-assisted laparoscopic prostatectomy. MATERIALS AND METHODS A retrospective review identified 462 consecutive patients who underwent a nerve-sparing prostatectomy between 2009 and 2012. The first 246 patients were administered the barrier film, while the next 216 patients, the control group, did not receive HACM. Postoperative erectile function and oncologic outcomes were compared. Independent t-test and Kaplan-Meier analysis were conducted, p < 0.05 was considered significant. RESULTS The two groups were well matched, without significant differences in age, weight, operative time, prostate size, preoperative prostate-specific antigen, sexual health inventory for men (SHIM), or AUA symptom scores. The mean SHIM was significantly higher for the experimental group at 6 months (6.39 vs 4.75, p = 0.008), 9 months (7.32 vs 5.44, p = 0.006), 1 year (8.52 vs 6.90, p = 0.049), and 18 months (10.01 vs 7.60, p = 0.018). This effect was not noted beyond 18 months. A subgroup analysis of patients with initial SHIM scores 22 or greater demonstrated a higher rate of return to the preoperative SHIM score for the barrier film group, 23% vs 12% (p = 0.046). There was no significant difference in biochemical recurrence between groups, with a median follow-up duration of 18 months. CONCLUSIONS HACM application at the neurovascular bundle during prostatectomy may decrease the time to return of erectile function, with improved SHIM at 6 to 18 months after surgery. This effect is more pronounced in patients with better baseline erectile function. There is no significant effect on biochemical recurrence.

MP60-08 INTRACRINE ANDROGEN BIOSYNTHESIS IN RENAL CELL CARCINOMA

INTRODUCTION AND OBJECTIVES: We previously reported that high MET and matriptase expression in RCC cells in bone metastasis indicates their importance in bone metastasis (Mukai et al. Hum Cell, 2015). MET is a high-affinity receptor tyrosine kinase of hepatocyte growth factor (HGF). HGF is secreted as an inactive singlechain precursor, which requires proteolytic activation for conversion to an active form. Matriptase is the most efficient known cellular activator of pro-HGF. Furthermore, activation of matriptase is regulated by HGF activator inhibitor (HAI). In this study, we employed a previously reported mouse model of bone metastasis (Strube et al. Clin Exp Metastasis, 2010) to clarify the significance of the matriptase-induced HGF/MET signaling axis in RCC bone metastasis. METHODS: Luciferase-transfected 786-O cells were injected into the left cardiac ventricle of female nude mice (5 weeks old). After 6 weeks, we confirmed the formation of bone metastasis by whole-body bioluminescent imaging, and extracted specimens. Expression of matriptase, MET and HAI was analyzed by PCR, immunohistochemistry (IHC) and immunoblots. Phosphorylation of MET was also investigated. Based on the result, we produced HAI-2 (specific inhibitor of matriptase) stable knock down (KD) 786-O cells, and analyzed the difference of expression in each molecule, cell-migration assay and invasion assay. RESULTS: Expression of matriptase was increased significantly in bone metastasis compared with parent cell line, and we confirmed increased phosphorylation of MET in bone metastasis. On the other hand, decreased expression of HAI-2 was observed in bone metastasis. Interestingly, increased matriptase expression was observed by HAI-2 KD in 786-O cells. In addition, invasive activity was increased significantly by knock down of HAI-2. CONCLUSIONS: These results have suggested that matriptase contributes to the HGF-dependent MET activation in the pericellular microenvironment of bone metastasis in RCC. In addition, upregulation of matriptase and downregulation of HAI-2 may have important roles in their progression.

MP04-05 DECLINING USE OF CONTINENT DIVERSIONS FOR BLADDER CANCER

INTRODUCTION AND OBJECTIVES: The effect of non-muscle invasive bladder cancer (NMIBC) on health-related quality of life (HRQOL) is poorly understood. We evaluated changes in HRQOL in patients with a new diagnosis of NMIBC compared with the general population using the Surveillance Epidemiology and End Results (SEER) Medicare Health Outcomes Survey (MHOS) database. METHODS: We identified 325 Medicare beneficiaries diagnosed with NMIBC between initial and 2-year follow-up using SEERMHOS data (1998-2013). NMIBC patients who underwent cystoscopy with biopsy or transurethral resection of bladder tumor(s) for bladder cancer were propensity matched 1:5 to non-cancer controls (n1⁄41685). Changes from baseline in the physical component score (PCS) and mental component score (MCS), which are normalized to between 0-100, where 50 represents the US population mean, were compared between NMIBC patients and non-cancer controls with c testing and multivariate linear regression analysis. We secondarily assessed differences in urinary symptoms on post-diagnosis surveys with univariate and multivariate models. RESULTS: Pre-diagnosis, mean PCS (39.94 vs 39.54, p 1⁄4 0.71) and mean MCS (52.03 vs 52.17, p 1⁄4 0.82) scores were similar between NMIBC patients and matched non-cancer controls. Postdiagnosis, NMIBC patients had a significantly greater decrease in PCS compared with controls (-2.87 (95% CI -3.87, -1.86) vs. -1.47 (95% CI -1.93, -1.02), p 1⁄4 0.02). Conversely, mean MCS change did not vary between groups (-1.79 (95% CI -2.76, -0.81) vs. -0.72 (95% CI -1.21, -0.23), p 1⁄4 0.09). With respect to urinary function, NMIBC pts were more likely to have worsening of urinary leakage (38.0 % vs 18.7 %, p1⁄4 < 0.01), require physician intervention for urinary symptoms (33.9 % vs 13.7 %, p1⁄4 <0.01 ), and receive treatment for urine leakage (31.6 % vs 12.0 %, p1⁄4 <0.01 ) compared with non-cancer controls (p 1⁄4 <0.01). CONCLUSIONS: The diagnosis of NMIBC is associated with a significant decrease in physical HRQOL, including a significant impact on urinary symptoms and leakage. Further efforts to prospectively evaluate HRQOL in patients with NMIBC should be pursued to inform and improve patient counseling.

MP75-18 COMPARISON OF COSTS AND OUTCOMES OF PERCUTANEOUS NEPHROLITHOTOMY BASED ON PERCUTANEOUS ACCESS

1 symptomatic ipsilateral pleural effusion requiring thoracocentesis. Other complications occurred in 9 patients (11.8%) which included bleeding requiring transfusion (1), fever (4), urinary retention (2), and syncope (2). CONCLUSIONS: Compared to historical controls, our approach to upper tract PCNL utilizing a nephrostomy tube free approach resulted in an overall low thoracic complication rate and facilitated hospital discharge.