David Golombos

Determinants of nocturia severity in men, derived from frequency-volume charts

Abstract Objective. Nocturia may be characterized by indices derived from the frequency–volume chart (FVC). The objective of this study was to determine how these parameters relate to the severity of nocturia in men with and without lower urinary tract symptoms (LUTS). Materials and methods. A retrospective analysis of FVCs was performed in two cohorts of men: those presenting with LUTS in a New York ambulatory urology clinic and those from the longitudinal population-based Krimpen study. Nocturnal urine volume (NUV), nocturia index (Ni), nocturnal polyuria index (NPi), nocturnal maximal voided volume (nMVV) and sleep duration were derived from FVCs. Comparisons were made using Spearman’s rank correlation coefficient between actual number of nightly voids (ANV) and the other diary parameters. Results. Eighty-eight consecutive men who presented with LUTS completed a 24 h FVC [median age 70 years, interquartile range (IQR) 64.5–74.5, median ANV 2, IQR 1.5–4]. Nocturnal voiding frequency and volume were analyzed in 1082 community-dwelling men (median age 61 years, IQR 56.1–66.4, range 49.4–78.2; median ANV 1.5, IQR 1.0–2.0, range 0–4.5). Both cohorts demonstrated strong correlations between nocturia severity (represented as ANV) and Ni (0.797, 0.658 for cohorts 1 and 2, respectively). There were moderate correlations between nocturia severity and NPi (0.545, 0.394), NUV (0.463, 0.432) and sleep duration (0.306, 0.272). The nMVV correlated poorly with nocturia severity (0.159, 0.146). Conclusions. Treatment of nocturia should aim to match nocturnal urine production with bladder capacity. Given the lack of known effective pharmacotherapy for low bladder volume, the first attempt nocturia treatment could focus on volume reduction.

MP54-06 IMPACT OF SURGICAL VOLUME ON SURVIVAL FOLLOWING RARC IN A LARGE, NATIONAL COHORT

physical capacity (86%), followed by improvement of incontinence (81%) and reduction of mental distress (31%). During FT 25.9% of patients had a urinary tract infection requiring antibiotics and 8.6% had a symptomatic metabolic acidosis. Only 18.1% were under antithrombotic medication at the beginning of FT. Antibiotic use decreased from 19.8% to 17.3%. Incontinence pad use increased from 2.14 to 2.55 pads per day on average. At the end of FT, patients indicated improvement of incontinence, physical capacity and mental distress in 60.5%, 74.1% and 30.86%. CONCLUSIONS: Compared to the preand perioperative management of BC, there is a scarcity of studies investigating FT of BC. A multitude of significantly different FT models have been implemented in different countries. Both from the economic as well as medical point of view high-quality FT must be strived for. Our study gives insights into the current state of FT in Germany and shows both benefits as well as unsolved challenges.

MP54-20 DO MEN WITH A HISTORY OF PROSTATE CANCER HAVE WORSE BLADDER CANCER OUTCOMES?

cancer is a controversial issue with contradictory findings concerning ureteral FS and very few data concerning urethral FS. Moreover, previous reports aimed to assess the impact of positive FS on oncological outcomes but none have compared the impact of FS vs. no FS on oncological ouctomes. The objective of this study was to evaluate the impact of urethral and ureteral FS use on oncological outcomes after radical cystectomy for bladder cancer. METHODS: All patients who underwent a radical cystectomy for bladder cancer between 1995 and 2015 were included in a singlecenter retrospective study. The use of ureteral and urethral FS varied according to surgeons preference (routine for some, never for others) but not according to the tumors’ characteristics. Patients were divided into different groups according to the use of ureteral and/or urethral FS (FS vs. no FS). Preoperative data and the rate of positive margins were compared between groups. The prognostic factors for cancer-specific survival (CSS) and recurrence-free survival (RFS) were sought in univariate analysis using the log-rank test and in multivariate analysis using a cox regression model. RESULTS: Out of 329 patients included in this study, ureteral FS were performed in 132 (40%) and urethral FS in 183 (56%) respectivley respectively. Thirteen urethral FS were positive (7.1%) resulting in 10 additional urethrectomy. Fourteen ureteral FS (10.6%) were invaded resulting in 8 additional ureteral resections and 1 nephroureterectomy. The use of urethral FS was associated with a decrease in positive margins rate (6% vs. 23%; RR 1⁄4 0.27; p <0.0001). Conversely, the use of ureteral FS had no impact on the rate of positive margins (12% vs.14%; RR 1⁄4 0.85; p 1⁄4 0.58). The use of ureteral FS had no impact on survival whereas the routine use of urethral FS was a prognostic factor for RFS and CSS in univariate (5-years RFS: 51.5% vs. 32%; p <0.0001 and 5-year CSS: 65.1% vs. 50.5%) and multivariate analysis (HR 1⁄4 1.7; p1⁄4 0.003 and HR1⁄41.4; p1⁄40.04 respectively). CONCLUSIONS: This study is the first to asses the impact of urethral and ureteral FS use on oncological outcomes after radical cystectomy. The routine use of urethral FS was associated with adecreased rate of positive surgical margins and improved recurrence-free survival and cancer-specific survival. Conversely, the use of ureteral frozen section had no impact on oncological outcomes.

PD20-09 SURGICAL APPROACH DOES NOT IMPACT POSITIVE MARGIN RATE IN PARTIAL NEPHRECTOMY FOR LARGE RENAL MASSES

INTRODUCTION AND OBJECTIVES: Utilization of partial nephrectomy (PNx) has expanded to include treatment of an increasing number of renal masses 4cm by various surgical approaches. Recent evidence has suggested risk of recurrence with positive surgical margin (PSM) is increased in the presence of high-risk features, including stage T2. While surgical approach has been associated with PSM in PNx for small renal masses (<4 cm), its impact on margin status for large renal masses is unclear. METHODS: Using the National Cancer Data Base (NCDB), we identified patients undergoing PNx for clinical T1b and T2a renal cell carcinoma (RCC) from 2011 to 2013. Primary outcome was surgical margin status. Multivariable regression modeling was performed to identify patient, facility, and surgical factors, including surgical approach (open, laparoscopic, or robotic) on PSM in patients undergoing PNx. RESULTS: Of 7495 undergoing PNx for cT1b and T2a renal masses from 2011 to 2013, 504 (6.72%) had PSM. On multivariable analysis, age > 60 years (OR 1.57 [95% CI 1.01-2.44] p1⁄40.048), African American race (OR1.52 [95%CI 1.06-2.17] p1⁄40.023), education level (OR 1.48 [95% CI 1.03-2.14] p1⁄40.034), rural setting (OR 4.82 [95% CI 2.459.46] p<0.01), mixed histology (OR 1.84 [95% CI 1.04-3.24] p1⁄40.035), undifferentiated tumor grade (OR2.42 [95%CI 1.26-4.65] p<0.01), aswell as having surgery performed at a non-academic facility (OR 1.57 [95% CI 1.15-2.15] p<0.01) were associated with PSM. Surgical approach (laparoscopic and robotic vs. open) (p1⁄40.119 and p1⁄40.437, respectively) and stage (T2a vs. T1b) (p1⁄40.182) were not associated with PSM. CONCLUSIONS: Surgical approach is not independently associated with increased risk of PSM for large renal masses, which is contrary to previous reports pertaining to cT1a lesions. Surgery at an academic facility was protective against having a positive margin. These data are important given the unclear oncologic significance of margin status in these tumors.

MP48-09 INTEGRIN SIGNALING MODULATION DEMONSTRATES POTENTIAL THERAPEUTIC STRATEGY IN BLADDER CANCER USING THREE-DIMENSIONAL ORGANOID CULTURE

INTRODUCTION AND OBJECTIVES: Integrin signaling plays an important role in cellular proliferation and migration via interactions with extracellular matrix proteins. Prior studies indicate that integrin signaling facilitates tumor invasion and metastasis, and there are several ongoing clinical trials using agents that modulate this pathway. We recently identified clonal enrichment in mutations in the integrin cell surface interactions pathways in advanced urothelial carcinoma. An ideal strategy for investigating integrin signaling is via 3D organoid culture, maintaining intercellular interactions that replicate the epithelial microenvironment. We hypothesize that pharmacologic integrin signaling modulation will impair organoid growth in bladder cancer cells and demonstrate a therapeutic utility for this approach. METHODS: RT4 human bladder cancer cell line was used as well as a second cell line established from a patient-derived bladder cancer sample (PM748). Cells were grown in 3D organoid culture as previously described. For in vitro integrin modulation, defactinib, an orally-bioavailable selective inhibitor of focal adhesion kinase (FAK, a convergent and conserved enzyme activated by integrin ligand binding), was used. SDS-PAGE and immunoblotting were performed to show in vitro FAK inhibition. Single cell suspensions and organoids were plated in the presence of various concentrations of defactinib to determine the impact on organoid formation and regression. RESULTS: Defactinib caused a dose-dependent decrease in autophosphorylation of FAK for both cell lines, demonstrating effective FAK inhibition. 3D culture of single cells with defactinib produced a dose-dependent decrease in organoid size after 96 hours (mean size for DMSO only, 100nM, 1uM, and 10uM were 128um, 75um, 48um, and 26um, respectively; p<0.0001 versus DMSO for all dilutions). Established organoids showed a dose-dependent regression in size after 72 hours of defactinib exposure (mean size for DMSO, 100nM, 1uM, and 10uM were 225um, 96um, 70um, and 34um, respectively; p<0.0001 versus DMSO). Experiments utilizing Crispr-Cas9-mediated FAK knock-out as well as in vivo studies with FAK inhibitors in xenograft models are currently underway. CONCLUSIONS: Integrin modulation via FAK inhibition with defactinib causes both inhibition of organoid formation as well as regression of formed organoids, and the effects are seen at concentrations well below the cytotoxic range for the drug. This study suggests a utility for these agents in bladder cancer treatment.

MP96-16 ASSOCIATION OF TRAVEL DISTANCE, SOCIOECONOMIC STATUS, AND REFERRAL INSTITUTION ON DELAY TO DEFINITIVE SURGERY IN PATIENTS WITH BLADDER CANCER

INTRODUCTION AND OBJECTIVES: Hospital acquired conditions are a significant source of patient morbidity and mortality and have been targeted by recent legislation as achievable target for quality improvement. Here, we aim to define the rates of 3 most of the most common hospital acquired conditions (HACs); surgical site infection (SSI) , urinary tract infection (UTI) , and venous thromboembolism (VTE) in patients who undergo major urologic surgery over a period of time encompassing the implementation of the Hospital Acquired Condition Reduction program. METHODS: Using American College of Surgeons National Surgical Quality Improvement Program data, we determined rates of HACs in patients undergoing major inpatient urologic surgery from 2005 to 2012. Rates were stratified by procedure type and approach (open vs. laparoscopic/robotic). Multivariable logistic regression was used to determine the association between [insert independent variable of interest] and HACs. RESULTS: We identified 39,257 patients undergoing major urologic surgery, of whom 2300 (5.8%) had at least one hospital acquired condition. UTI (2.58%) was the most common, followed by SSI (2.46%) and VTE (0.68%). Multivariable logistic regression analysis demonstrated that open surgical approach, diabetes, obesity, hypertension, congestive heart failure, BMI>30, and length of stay were associated with higher likelihood of HAC. When controlling for surgical approach, patients undergoing prostatectomy had the lowest predicted probability of HAC (PP 0.04, p<0.05) compared to patients undergoing upper tract surgery (PP 0.06) or cystectomy and retroperitoneal lymph node dissection (PP 0.02) We observed a non-significant secular trend of decreasing rates of HAC from 7.4% to 5.8% HAC’s during the study period, which encompassed the implementation of the CMS Hospital Acquired Condition Reduction Program. CONCLUSIONS: HACs occurred at a rate of 5.8% during major urologic surgery, and are significantly affected by procedure type and patient health status. The rate of HAC appeared unaffected by national reduction program in this cohort. Better understanding of the nonmodifiable factors associated with HACs is critical in developing effective reduction programs.

PD10-09 HEALTH CARE DISPARITIES AND POST DISCHARGE COMPLICATIONS IN PATIENTS UNDERGOING RADICAL CYSTECTOMY

were stratified into groups based on their distance from UNMH. Fisher tests and odds ratios were used to compare groups. RESULTS: One hundred fifty seven were compliant with follow up while 68 were not. Patients were more likely to be compliant who lived within 40 miles (OR: 4.45, CI: 2.03 e 9.61, P 1⁄4 0.0002), 30 miles (OR: 3.83, CI: 2.05 e 7.16, P < 0.0001), and 20 miles (OR: 3.83 CI: 2.09 e 7.02, P < 0.0001) of our institution. In contrast, those living within 15 miles of UNMH were not statistically different than all other patients living farther away (OR: 0.66, CI: 0.37-1.19, P1⁄40.17). CONCLUSIONS: Urolithiasis is a common problem in the southwest United States, and the need for comprehensive follow up care is crucial for treatment. To our knowledge, this is the first study of its kind to show how distance from point of care relates to compliance in stone disease. Patients living greater than 20 miles from our center demonstrated significantly decreased compliance. Stone disease is distressing to patients and economically costly, and our study highlights the need for further research in strategies to improve compliance.

MP21-12 PCA3 AND T2:ERG ADD FURTHER PREDICTIVE AND CLINICAL BENEFIT TO THE DETECTION OF PROSTATE CANCER IN MEN OF VARIOUS AGES IN THE EARLY DETECTION RESEARCH NETWORK (EDRN)

underwent PSA screening decreased from 52.2% to 46.9% (p1⁄40.01). Survey year 2013 vs. 2010 was associated with decreased odds of screening (OR 0.74, 95% CI 0.66-0.83); the interaction term for age and survey year was not significant. Men with higher self reported health status were no more likely to undergo screening than their less healthy counterparts. CONCLUSIONS: Our results suggest a nationwide impact of the 2012 USPSTF statement on discouraging PSA screening despite their physician’s recommendation for screening, although this was restricted to men aged 50-64. Widespread media coverage and greater awareness of the implications of PSA screening may underlie this phenomenon.