RATE OF ACTIVE SURVEILLANCE AS A MANAGEMENT STRATEGY FOR T1A RENAL MASSES: RESULTS FROM THE NATIONAL CANCER DATABASE

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1 RATE OF ACTIVE SURVEILLANCE AS A MANAGEMENT STRATEGY FOR T1A RENAL MASSES: RESULTS FROM THE NATIONAL CANCER DATABASE Da David Jiang MD*, Ann C Martinez Acevedo BS*, Ryan Kopp MD, Mark Garzotto MD, Michael Conlin MD, Christopher Amling MD, and Jen-Jane Liu, MD Portland, OR (Presentation to be made by Jen-Jane Liu) Objectives: Over the past two decades, the management of small renal masses (SRM) has significantly shifted. Since the 2009 AUA guideline, surveillance becomes acceptable management for certain patients with SRMs. Our goal is to evaluate contemporary practice patterns of active surveillance (AS) in the management of clinical T1a renal masses from a national database that captures approximately 70% of all cancer diagnoses in the United States. Methods: We identified patients diagnosed with clinical stage T1a renal cell carcinoma between 2010 and 2013 from the National Cancer Data Base (NCDB). We compared the rates of AS vs any intervention (eg. any type of ablation, or partial or radical nephrectomy). Trends in the rate of AS over time were assessed with Pearson s correlation coefficient. We identified clinical and socioeconomic factors predicative of receipt of AS, including age, race, insurance status, mean county income, geographical region, tumor size, facility type and volume, distance to treatment facility, and Charslson Comorbidity Index (CCI) using logistic regression modeling. Results: We identified 47,834 patients with clinical stage T1a renal cell carcinoma during the study period. 1,252 were followed with AS vs 43,779 who underwent intervention (4,339 had IR ablation and 35,423 had surgery, with 24,249 (68%) undergoing partial nephrectomy and 11,174 (32%) radical nephrectomy). Average age was 63 years, and average CCI was 0.4. On multivariable analysis, significant predictors of receiving AS included age greater than 75 years (OR 4.0 [ ]), African American race (OR 1.4 [ ]), and insurance type (Medicare (OR 2.2 [ ]), other government insurance (OR 1.5 [ ]), or no insurance (OR 2.1 [ ])). Tumor size > 2.5 cm (OR 1.7 [ ]) was a significant predictor for receiving treatment with ablation or surgery. Rates of AS increased by year: 2.23% in 2010, 2.53% in 2011, 2.86% in 2012, 3.34% in 2013 (p < 0.001). In the elderly population (age 75), the rate of active surveillance was higher and increased over time from 6.55% in 2010 to 9.1% in 2013 (p=0.032). Conclusions: Although AS is an accepted treatment modality for clinical T1a renal masses and is even recommended for patients with limited life expectancy and/or significant medical comorbidities, rates of AS are still very low, even among elderly patients. Age 75 or greater was the strongest predictor of receiving AS, whereas size greater than 2.5cm was most predictive of intervention. Non-medical socioeconomic factors influenced the utilization of AS compared to intervention with ablation or surgery. Socioeconomic indicators such as white race and private insurance were associated with increased likelihood of intervention. Source of Funding: none References: Campbell SC, Novick AC, Belldegrun A, et al. Guideline for management of the clinical T1 renal mass. J Urol. 2009;182:

2 TRENDS IN SURGICAL MANAGEMENT OF T1A RENAL MASSES: RESULTS FROM THE NATIONAL CANCER DATABASE Da David Jiang MD*, Ann C Martinez Acevedo BS*, Ryan Kopp MD, Mark Garzotto MD, Michael Conlin MD, Christopher Amling MD, and Jen-Jane Liu, MD Portland, OR (Presentation to be made by Dr. Jen-Jane Liu) Objective: The management of small renal masses (SRMs) has changed over the past two decades with the diffusion of minimally invasive techniques and increasing acceptance of thermal ablation and active surveillance as treatment modalities. Nephron-sparing surgery and thermal ablation reduce the risk of renal insufficiency. We evaluate contemporary practice patterns in the management of T1a renal masses in a national database that captures 70% of all cancer diagnoses in the United States. Methods: We identified patients with clinical stage T1a renal cell carcinoma between 2004 and 2013 from the National Cancer Data Base (NCDB) treated with surgery (partial vs total nephrectomy) or thermal ablation (cryotherapy, radiofrequency, or microwave). Rates of surgery and ablation over the study period were assessed for trend using Pearson s correlation coefficient. We identified socioeconomic and clinical factors predictive of treatment type, including advanced age ( 75 years), race, insurance status, county mean income, region of the USA, tumor size, facility type and volume, distance to treating facility, Charlson Comorbidity Index (CCI), and tumor size with logistic regression modeling. We also performed subset analysis of patients who underwent surgery for tumors 2.5 cm to identify predictive factors for receipt of partial nephrectomy. Results: We identified 72,923 patients that met our inclusion criteria. 7,621 (10%) underwent ablation and 65,302 (90%) had surgery. Rates of thermal ablation increased early in the study period, from 5.2% in 2004 to 10.6% in 2006, and then stabilized at 11% in 2013 (p<0.001). On multivariable analysis, significant predictors of receiving ablation included age 75 years (OR 2.7 [ ]), insurance type (Medicare insurance (OR 1.9 [ ]), other government insurance (OR 1.5 [ ])), West coast location (Or 1.16 [ ], and treatment at a high volume facility (OR 1.6 [ ] ). Independent predictors of surgical treatment were African-American race (OR 1.11 [ ]), higher median income (OR 1.2 [ ]) and tumor size > 2.5 cm (OR 1.5 [ ]). Among surgery patients, 26,781 (40%) had radical nephrectomy and 40,124 (60%) had partial nephrectomy. Significant predictors of partial nephrectomy include younger age (OR 1.3 [ ]), higher volume facilities and academic centers (OR 2.4 [ ] and 1.4 [ ] respectively), residence in a high income county (OR 1.3 [ ] for highest quartile), and increased distance to treatment center (OR 1.03 [ ] for every 100 miles). Predictors of radical nephrectomy include African American race (OR 1.4 [ ], Hispanic race (OR 1.3 [ ]), insurance type (Medicare (OR 1.5 [ ]) or other government (OR 1.14[ ]) insurance), CCI > 2 (OR 1.4 [ ]), and Central or West region (OR 1.1 [ ] and OR 1.2 [ ] respectively). When just focusing on surgical treatment patterns for renal masses 2.5cm (N = 31,929), 22,820 (71%) had partial nephrectomy, and 9,109 (29%) had radical nephrectomy. Conclusions: Utilization of thermal ablation techniques is increasing. Patients over 75 years old, with smaller tumors, those with government insurance, and treated at high volume centers were more likely to undergo ablation compared to surgery. In our subset analysis of patients who had definitive surgery; the majority of patients are undergoing partial nephrectomy for T1a tumors, however the rate of radical nephrectomy was still 29% for tumors less than 2.5cm, suggesting suboptimal usage of nephron-sparing techniques. Younger age, white race, private insurance, higher income county, higher volume and academic centers, and longer distance to treatment center were all predictive of receipt of partial nephrectomy. Although utilization of nephron-sparing treatments is increasing over time, non-clinical sociodemographic factors still appear to influence management decisions, with a significant percentage of patients still undergoing radical nephrectomy for very small tumors. Source of Funding: none

3 TRIFECTA OUTCOMES OF ROBOTIC PARTIAL NEPHRECTOMY IN A COMMUNITY HOSPITAL SETTING Matthew N. Simmons, Timothy Krigbaum, Michelle Fitts, Andrew D. Neeb Urology Specialists of Oregon, Bend, OR Introduction: This analysis evaluated trifecta outcomes for robotic partial nephrectomy (RPN) surgery conducted in a community hospital setting. Methods: Patient data was reviewed for 69 patients who underwent RPN from January 2013 through February Complications, oncologic and functional outcomes were assessed. GFR was calculated using the MDRD2 equation from creatinine measurements obtained post-operatively and at >30d after RPN. DAP nephrometry scoring was used to measure tumor complexity. Trifecta was defined as negative margins, <10% decrease in GFR >30d after RPN, and absence of complications. Results: Mean operative time was 1.9 hours (±0.7), and mean operative blood loss was 257ml (±182). Mean hospital stay was 2.8 days (±1). There were no positive margins. 82% of tumors were stage pt1a, 13% were pt1b, 1% were pt2 and 3% were pt3a. Complications occurred in 5 patients (7%): 4 were Grade 1-2 (6%) and 1 was Grade 3 (1%). There was one post-op bleed managed with bedrest, and one delayed urine leak managed with ureteral stent and percutaneous drain placement. Nadir GFR was on average 89% (±17%) of pre-op GFR, and late GFR was 96% (±9). Mean DAP nephrometry score was 5.8 (±1.5) with 43%, 45% and 12% of tumors being classified as low, intermediate and high complexity, respectively. The trifecta rate for the cohort was 69%. Conclusions: Trifecta rates in this community hospital practice rival those of major academic referral centers. In the past, most surgeries in the community consisted of open radical nephrectomy. The introduction of RPN has resulted in decreased morbidity in the community by facilitating use of laparoscopic technique and preservation of renal function.

4 BOILING HISTOTRIPSY ABLATION OF RENAL CARCINOMA PRODUCES SIGNIFICANT CHANGES IN THE IMMUNE SYSTEM Wayne G Brisbane, MD, Tatiana D. Khokhlova, PhD, Stella Whang, BS, Kayla Gravelle, BS, Yak-Nam Wang, PhD, Venu Pillarisetty, MD, Joo Ha Hwang, MD, PhD, W. Conrad Liles, MD, Vera Khokhlova, PhD, Michael Bailey, PhD, George R. Schade, MD: Seattle WA (Presentation to be made by Dr. Wayne Brisbane) Objective: Evidence suggests focused ultrasound (FUS) tumor ablation may stimulate an anti-tumor immune response. We have been developing the FUS technique boiling histotripsy (BH) as a non-invasive treatment for renal carcinoma (RCC). Previously, we have shown short-term changes in systemic and local cytokines, as well as tumor infiltration of CD8+ T cells following BH. We aimed to characterize the long-term immune response to BH RCC tumor ablation in the Eker rat model. Methods: RCC bearing genotyped Eker rats (Tsc2 heterozygotes) and syngeneic wild type (WT) non-tumor bearing rats were randomly assigned to transcutaneous BH or a sham US procedure targeting ~0.5 cc of RCC or non-tumor bearing normal kidney. BH was delivered with a 1.5 MHz US-guided small animal FUS system (VIFU-2000, Alpinion) operated at duty cycle of 1-2%, ms pulses, W electric power. Following treatment, rats were recovered, underwent serial US surveillance, and survived for 7, 14, or 56 days. Following euthanasia, bilateral kidneys, tumor draining lymph nodes (TDLN), and spleen were collected. Flow cytometry was performed on processed tissues to analyze for changes in circulating and local immune cell populations. Results: At 14 days post-treatment, significant changes in the immune system were observed following BH vs. sham treatment (see Figure). BH treatment was associated with increases in splenic antigen presenting CD11c+ dendritic cells irrespective of tumor status (RCC: 3.4-fold (p=0.048), kidney: 2.3-fold (p=0.03) vs. sham). Conversely, BH treatment was associated with several RCC specific changes in T-lymphocyte populations. Specifically, BH RCC treatment resulted in significant alterations in cytotoxic CD8+ T-cell populations not observed with treatment of normal kidney including significant differences in CD8+CD62L-CD44+ effector memory cell (3.0-fold, p<0.01), central memory CD8+CD62L+CD44- cell (7.0-fold, p <0.01), and CD8+CD62L+CD44+ naïve cell populations (0.4-fold, p=0.01) in TDLNs. Similarly, BH RCC treatment was associated with small changes in CD4+ T-cell populations with a near significant 1.9-fold (p=0.08) increase in central memory CD4+CD62L+CD44- cells in TDLNs. Conclusion: These data represent the first quantitative analysis of the immune response to BH and hint at an RCC specific response. Ongoing analysis of tumor infiltrating lymphocytes, cytokines, and longer-term 56-day survival will shed further light on the immune response to BH treatment. Further studies, will evaluate the antigen specificity of this response and if it can improve clinically relevant outcomes. Funding: Focused Ultrasound Foundation, Urology Care Foundation, and NIH K01EB and R01CA

5 NON-INVASIVE DIAGNOSIS OF RENAL CELL CARCINOMA SUBTYPES Andrew Bergersen, MD; Elinora Price*; Bobby Kalb*, MD; and Benjamin R Lee, MD: Tucson, AZ (Presentation to be made by Dr. Andrew Bergersen) Introduction and Objectives: Renal cell carcinoma (RCC) is the 7 th highest incidence cancer in the US, and its incidence has been steadily increasing over the past years. Due to the increasing use of cross-sectional imaging, most renal masses are identified incidentally. These lesions tend to be smaller and it ~20-30% of these lesions are benign. Given the potential benign nature of a significant proportion of these masses, accurate diagnosis prior to initiating treatment is becoming more important. In addition, prior to starting tyrosine kinase therapy, assessing histology in the advanced setting is crucial in differentiating clear cell histology from other types. AUA guidelines now recommend biopsy under certain conditions, including when there is suspicion of lymphoma, abscess, or metastases to the kidney, to confirm diagnosis in the setting of bilateral renal masses, and to establish diagnosis prior to initiating treatment for presumed metastatic RCC. However, biopsies are not without complications. For this reason, we evaluated the possible use of MRI to assess tumor characteristics radiographically. The purpose of this study is to demonstrate the ability of MRI to non-invasively differentiate among the RCC subtypes to guide patient counseling and management. Methods: We conducted a retrospective chart review of all patients who underwent partial or radical nephrectomy for suspected malignancy at our institution between Preoperative radiologic diagnoses obtained on MRI were compared with corresponding post-operative final histology on pathological specimen. Preoperative MRI tumor assessment was completed and recorded prior to surgical pathology outcome assessment. Results: Of the 93 patients identified as receiving either partial or radical nephrectomy, 43 underwent preoperative MRI tumor assessment at our institution. Based on the appearance on T2 post-gadolinium enhancement, clear cell RCC histology appeared markedly different compared to papillary RCC. Of those patients with histological subtype indicated in their radiology report, 90% were correctly identified as clear cell type histology, and 80% were correctly identified as papillary. At least 76% of subtypes were accurately identified (with the misidentification more likely to occur in rarer RCC forms such as chromophobe). Conclusions: Prediction of RCC histology by MRI may aid in counseling patients with significant comorbidities and may aid decision making on presurgical planning. Further optimization of MRI imaging protocols may hold the promise of even greater accuracy of non-invasive tumor assessment. A prospective study is planned. Source of Funding: None.

6 EFFECT OF SURGICAL APPROACH ON RECEIPT AND QUALITY OF LYMPH NODE DISSECTION AND SHORT AND LONG TERM SURVIVAL IN UPPER TRACT UROTHELIAL CARCINOMA: RESULTS FROM NATIONAL CANCER DATABASE Hamed Ahmadi, MD; Ann Martinez Acevedo, MS*, Michael Conlin, MD; Mark Garzotto, MD; Ryan Kopp, MD; Christopher Amling, MD; Jen-Jane Liu, MD; Portland, Oregon (Presentation to be made by Hamed Ahmadi, MD) Objectives: Performance of lymph node dissection (LND) is variable during nephroureteroctomy (NU), despite the known survival benefit of LND in bladder cancer. Surgical approach may have an effect on receipt and quality of LND during NU. Specifically, an open surgical approach (ONU) may facilitate performance of LND compared to laparoscopic NU (LNU), and robotic nephroureteroctomy (RNU) may also facilitate performance of LND due to improved dexterity. This study examines receipt and quality of LND as well as short and long term survival among different surgical approaches for NU. Methods: The National Cancer Database (NCDB) was queried for patients with upper tract urothelial carcinoma (clinical stage T2, N0 M0) who underwent NU between 2004 and The cohort was categorized based on surgical approach (ONU, LNU, or RNU). Performance of lymph node dissection (LND) and LN yield (LNY) were determined. LNY was also divided into quartiles and the top quartile was selected as the reference value. Predictors of LND performance and LNY and effect of surgical approach on short and long term survival were evaluated using multivariable logistic regression modeling. Results: 14,084 patients were identified; 44% underwent ONU, 36% LNU, and 20% RNU. 3,444 (25%) patients underwent LND. Patients who underwent RNU were more likely to have LND compared to ONU and LNU (31, 27, and 18%, respectively). Median LNY was 3 (range 1-75). Median LNY was similar between ONU and RNU but significantly higher compared to LNU (4 vs 2, p<0.01). After controlling for age, distance to treatment facility, type and surgical volume of facility, Charlson comorbidity index and clinical stage and grade; the laparoscopic approach was negatively associated with performance of LND (OR=0.58; P <0.001) and LNY 8 (OR=0.49, p <0.001) compared to ONU. There was no significant difference between ONU and RNU regarding performance of LND or LNY. Minimally invasive NU was an independent predictor of lower 90-day mortality (OR=0.6 for LNU and OR=0.5 for RNU, P-value <0.001). However, overall survival at 5 years (51%) was not different between surgical approaches after controlling for clinical and sociodemographic variables. Conclusions: Patients undergoing LNU are less likely to undergo LND and tend to have lower LNY compared to those undergoing open or robotic surgery. Although minimally invasive NU is associated with improved 90-day mortality, 5- year survival outcomes were not different among patients undergoing open and minimally invasive surgery.

7 UROLOGIC TRAUMA: HOW OFTEN ARE UROLOGISTS INVOLVED? Bernard Morris M.S., Kelly K. Bree M.D., Jill Buckley M.D.: San Diego, CA (Presentation to be made by Dr. Kelly Bree) Introduction and Objective: Injury to the genitourinary (GU) system occurs in approximately 10% of patients presenting with abdominal trauma, often in the setting of polytrauma. GU trauma presents unique reconstructive challenges to the physician, as well as significant psychological and functional challenges to the recovering patient. Therefore, there exists an important need to assess the incidence of GU trauma and evaluate the efficacy of care being delivered. We aim to examine urologic trauma care at a level I academic trauma center looking at operative versus non-operative management, level of care required and level of urologic involvement. Methods: IRB approval was granted to retrospectively analyze prospectively collected data from our institution s level I trauma registry for all patients presenting with GU trauma from using ICD-9 codes and chart review. Data reviewed included demographics, type and mechanism of injury, type of management, and involvement of the urologic team. GU trauma was then further classified by organ specific injury: kidney, ureter, bladder, and external genitalia (penis, testes, or scrotum). Results: 352 patients were identified with urologic trauma at our institution: Kidney 245 (69.6%), Ureter 7 (2%), Bladder 48 (13.6%), Urethra 22 (6.3%), External genitalia 30 (8.5%). Urologic consultation varied with organ specific injury with the urology team being consulted in less than 20% of kidney injuries but greater than 90% of urethral injuries. Across all GU traumatic injuries urology was involved on average in 59% of cases (figure 1). The vast majority of kidney injuries were observed (80%), while 15% required open exploration and 5% underwent stenting or embolization. All ureteral injuries required intervention. 60% of bladder ruptures were explored (100% intraperitoneal). No urethral injuries underwent primary repair. 73% were managed with urethral catheters alone, 32% had suprapubic tubes placed, and primary re-alignment occurred in 14%. Nearly all (>90%) of external genitalia injuries were operatively addressed. Conclusion: Acute urologic trauma often requires a high acuity of care and need for intervention. The urology team at our institution was involved in <50% of cases of GU trauma. Consultation and management should involve a urologist as this would likely optimize patient care and improve outcomes, especially in complex urologic injuries. Funding: None Figure 1