1840 CAN WE IDENTIFY PATIENTS WHO PROBABLY WILL BENEFIT FROM CYTOREDUCTIVE NEPHRECTOMY IN TARGETED THERAPY ERA?

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undergoing CN. As such, surgical resection should continue to be considered as part of the multimodal approach to treatment in this setting. Source of Funding: None

1838 WHEN TO PERFORM LYMPH NODE DISSECTION IN RENAL CELL CARCINOMA PATIENTS: A NOVEL APPROACH TO PREOPERATIVELY ASSESS THE RISK OF LYMPH NODE INVASION AT SURGERY AND NODAL PROGRESSION DURING FOLLOW UP Umberto Capitanio*, Firas Abdollah, Rayan Matloob, Nazareno Suardi, Andrea Gallina, Paolo Capogrosso, Marco Moschini, Paolo Dell’Oglio, Cristina Carenzi, Alberto Briganti, Francesco Montorsi, Roberto Bertini, Milan, Italy INTRODUCTION AND OBJECTIVES: Whether to perform lymph node dissection (LND) in renal cell carcinoma (RCC) is still debated. We aimed to preoperatively identify patients who might benefit from a LND. METHODS: In 1983 RCC patients treated with partial or radical nephrectomy, we considered as a mutual endpoint the presence of lymph node invasion (LNI) at final pathology and lymph node (LN) progression during the follow-up period. Nodal progression was defined as the onset of a new clinically detected lymphadenopathy (⬎10 mm) in the retroperitoneal lymphatic area. Moreover, all the variables available before surgery were tested as potential predictors of LNI and/or LN progression. Regression analyses were used to assess the effect of each clinical predictor (age, body mass index, tumor side, symptoms, performance status, clinical tumor size, clinical TNM stage, albumin, calcium, creatinine, haemoglobin, and platelets levels) on the outcome of interest. The most parsimonious multivariable predictive model was developed. Discrimination, calibration and net benefit were calculated. RESULTS: The prevalence of nodal invasion was 6.1% (n⫽120/1983). During the follow-up period, 82 patients (4.1%) experienced nodal progression. Of those, 17 (20.7%), 38 (46.3%) and 27 (32.9%) were pNx, pN0 and pN1 cases at surgery, respectively. Therefore, the rate of patients who experienced lymph node progression resulted 1.5 vs. 5.0 vs. 22.5% in pNx vs. pN0 vs. pN1, respectively. At multivariable analyses, the most informative independent predictors resulted T stage [cT3-4 vs. cT1-2, odds ratio (OR) 1.52, p⫽0.05], clinical nodal status [cN1 vs. cN0, OR 7.09, p⬍0.001], metastases at diagnosis (OR 3.04, p⬍0.001) and clinical tumor size (OR 1.14, p⬍0.001). The accuracy of the multivariable model resulted 86.9% with excellent calibration and net benefit. The use of a nomogram cutoff of 3% would allow the avoid of roughly 50% of the procedures with a very low false negative rate (7.4%). CONCLUSIONS: By relying on an unique approach combining the risk of harbouring LNI and/or LN progression during follow-up period, we provided the first clinical pre-surgery model predicting the need for LND. The model showed excellent accuracy and calibration, with a significant benefit in decision curve analyses.

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are monitored by TDM. In this study, we evaluated the pharmacokinetics of sunitinib (SU) in patients who were treated for advanced renal cell carcinoma (aRCC) along with the occurrence of adverse events (AEs) and the treatment outcomes. METHODS: The pharmacokinetics of SU was examined in 20 patients with advanced RCC who were treated with the drug. We enrolled 17 males and 3 females in the study. The trough levels of SU and its metabolite N-desethyl sunitinib (DES) were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays performed on days 1, 3, 5, 7, 14, 21, and 28 in cycle 1 with a pharmacokinetic study performed on day 7. Subsequently, the association of trough levels of SU and DES as measured on day 7 in cycle 1, with patient demographics, existing drug-related polymorphisms, the occurrence of AEs, and treatment outcomes were investigated. RESULTS: The area under the concentration–time curve (AUC) for both SU and DES on day 7 revealed significant correlation with the trough levels (R ⫽ 0.958 and 0.958, respectively). We observed that the trough levels increased in a dose-dependent manner reaching a plateau on day 10 –14. A four-fold difference was observed in the trough levels among patients at the same dose and a negative association was observed between the trough levels and body weight (R ⫽ 0.516).However, no association was observed between the trough levels and patients’ age (Figure 1). Moreover, no significant differences were observed in the trough levels between the haplotypes of CYP3A5, but there was a tendency toward higher trough levels in patients who had the A allele of ABCG2 421C ⬎ A polymorphism (P ⫽ 0.085). Furthermore, in cycle 1, trough levels were significantly associated with an occurrence of grade 2 or higher hypothyroidism and fatigue (P ⫽ 0.044 and 0.032, respectively; Figure 2) In addition, patients who discontinued sunitinib therapy within 3 weeks had significantly higher trough levels compared with those who continued for 3 weeks or longer (116.8 ⫾ 36.5 vs. 80.4 ⫾ 57.3, P ⫽ 0.009; Figure 3). CONCLUSIONS: This study suggests the usefulness of TDM during sunitinib therapy in patients with RCC to determine the adequate dose in each patient and thus, prevent severe AEs. However, further studies are necessary to determine the usefulness of TDM in long-term clinical efficacy of sunitinib in aRCC patients.

Source of Funding: None Source of Funding: None

1839 EVALUATING THE ASSOCIATION AMONG THE PHARMACOKINETICS OF SUNITINIB, ITS ADVERSE EVENTS AND THE TREATMENT OUTCOMES IN ADVANCED RENAL CELL CARCINOMA Norihiko Tsuchiya*, Nobuhiro Fujiyama, Shintaro Narita, Takamitsu Inoue, Kazuyuki Numakura, Aktia, Japan; Susumu Akihama, Mitsuru Saito, Shigeru Satoh, Masatomo Miura, Tomonori Habuchi, Akita, Japan INTRODUCTION AND OBJECTIVES: Even though the dose adjustments during therapy are determined using therapeutic drug monitoring (TDM) in many drugs, only a few molecular targeted agents

1840 CAN WE IDENTIFY PATIENTS WHO PROBABLY WILL BENEFIT FROM CYTOREDUCTIVE NEPHRECTOMY IN TARGETED THERAPY ERA? Dalsan You*, In Gab Jeong, Seoul, Korea, Republic of; Kyung Hyun Moon, Ulsan, Korea, Republic of; Jae Young Joung, New Brunswick, NJ; Jun Hyuk Hong, Hanjong Ahn, Choung-Soo Kim, Seoul, Korea, Republic of INTRODUCTION AND OBJECTIVES: Before the inception of targeted therapy cytokine-based immunotherapy was the most effec-

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tive systemic treatment for patients with metastatic renal cell carcinoma (mRCC), with upfront cytoreductive nephrectomy (CN) indicated for patients suitable for surgery and with good performance status. However, the role of CN for patient with mRCC is still controversial and conflicting in the era of targeted therapy, without selection criteria for CN. The aim of study was to identify preoperative factors that might be used to better identify patients who probably will benefit from CN. METHODS: We reviewed the medical records of 119 patients who presented with synchronous clear cell type mRCC at the Asan Medical Center from November 2006 to December 2010 and had received no systemic therapy before enrollment. Of the 119 study patients 71 underwent CN followed by targeted therapy (CN group) and 48 received targeted therapy alone (nonCN group). Kaplan-Meier curve and Cox proportional hazards model were used for overall survival (OS) analysis. Potential prognostic factors included age at treatment, sex, Karnofsky score, duration from diagnosis to treatment, CN or nonCN, sarcomatoid feature, numbers of metastatic sites, metastatic site (bone, liver, central nervous system), hemoglobin, lactate dehydrogenase, corrected calcium. RESULTS: Mean OS for CN vs. nonCN groups was 29.0 and 14.6 months, respectively (p⬍0.001). On multivariate analysis to predict the probability of death Karnofsky score (ⱕ70%, hazard ratio [HR]⫽4.3, p⬍0.001), numbers of metastatic sites (ⱖ2, HR⫽2.4, p⫽0.001), and any sarcomatoid feature (HR⫽2.0, p⫽0,040) were independent predictors of death. CN did not affect the probability of overall mortality on multivariate analysis (HR⫽0.64, p⫽0.111). Even in analysis according to each prognostic factors, CN was not an independent predictor. In 38 patients with Karnofsky score⬎70%, single metastatic site, and no sarcomatoid feature, mean OS for CN vs. nonCN groups was 42.2 and 20.9 months, respectively (p⫽0.032). On multivariate analysis to predict the probability of death only CN (HR⫽0.28, p⫽0.044) was an independent predictor of death. CONCLUSIONS: The 3 preoperative factors (Karnofsky score⬎70%, single metastatic site, and no sarcomatoid feature) identified from present study results can be used to help identify patients with mRCC who will benefit from CN. Therefore, the treatment of those unable to meet selection criteria can be directed toward targeted therapy alone, helping them to avoid the unnecessary morbidity of CN. Source of Funding: None

1841 LONG TERM MANAGEMENT AND OUTCOMES OF RECURRENCES FOLLOWING RADIO FREQUENCY ABLATION OF RENAL TUMORS Gideon Lorber*, Arturo Castro, Mehul Doshi, Vladislav Gorbatiy, Reymond Leveillee, Miami, FL INTRODUCTION AND OBJECTIVES: We present the long term management and oncological outcomes of patients diagnosed with recurrent renal tumors following primary radiofrequency ablation (RFA) of renal cell carcinoma (RCC). METHODS: We reviewed our prospectively collected database of patients with renal masses treated between November 2001 and October 2012 with laparoscopic (LRFA) or computed tomography (CT) guided percutaneous RFA (CTRFA). All treatments were performed with real-time temperature monitoring to ensure target ablation temperature was adequately obtained. Inclusion criteria consisted of patients with a follow-up (FU) longer than 48 months who developed a recurrence following RFA of a biopsy confirmed RCC. FU consisted of physical examination, serum creatinine and contrast enhanced radiographic imaging (CT or MRI). Recurrence was defined as enhancement of ⬎20 Hounsfield units post contrast confirmed as RCC by biopsy or documented to exhibit persistent growth on serial imaging. We reviewed the management approaches of these patients as well as complication rate and overall survival.

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RESULTS: Out of 434 RFA cases, a total of 77 treatments in 67 patients had a FU longer than 48 months. In this group 6 cases, in 5 patients, met the inclusion criteria of recurrent RCC following primary treatment for RCC. Five were biopsy confirmed recurrent RCC tumor. The mean disease free interval was 27 months (5 to 42 months), the mean FU was 71 months (54 to 96 months) and the mean renal mass size was 2.8 cm (1 to 4 cm). The management of the recurrences consisted of repeat CTRFA in 3 cases, repeat LRFA in 2 cases and nephrectomy in 1 case. Complication rate was 17% (1 out of 6) which consisted of Clavien grade 1 complication. One patient died in the course of the study bringing our survival rate to 83%. CONCLUSIONS: The low recurrence rate of 8% and adequate secondary treatment with no significant morbidities point to the oncologic efficacy and safety of RFA. Source of Funding: None

Urodynamics/Incontinence/Female Urology: Female Urology (II) Podium Session 32 Tuesday, May 7, 2013

1:00 PM-3:00 PM

1842 MINIMALLY INVASIVE LAPAROSCOPIC MANAGEMENT OF URETERAL ENDOMETRIOSIS. PROSPECTVE ANALYSIS OF 54 CASES WITH A MEAN FOLLOW UP OF 36 MONTHS Oskar Kaufmann*, Heloisa Ferreira Brudniewski, Winston Chen, Rosa Maria Neme, Sao Paulo, Brazil INTRODUCTION AND OBJECTIVES: Endometriosis of the urinary tract is rare, compromising 1% to 2% of all endometriosis cases. Most cases are localized in the bladder (84%) or in the lower third of the ureter (10%). The aim of the study was to evaluate prospectively the efficacy of laparoscopic management of ureteral endometriosis. METHODS: We have prospectively followed 54 patients presenting with ureteral endometriosis from October 2008 to October 2012. RESULTS: From 635 endometriosis cases operated from October 2008 to October 2012 in a private clinic, we have found an incidence of 8.5% (54 cases) with preoperative evidence of moderatesevere ureter dilatation. Dysmenorrhea (91%) and dyspareunia (68%) were the symptoms more frequently reported; but only 29.6% (16 patients) had urinary symptoms and one patient had renal exclusion. In 51 cases, laparoscopic ureterolysis and resection of endometriosis was done, in two laparotomic ureterocystoneostomy, and in 1 laparoscopic nephrectomy was performed. In 23 cases we had associated bladder lesions simply treated by laparoscopic resection. No major complications were found. The left ureter was affected in 83 % (n⫽45) of cases and disease was bilateral in just 2 cases. Median follow-up time was 36 months. CONCLUSIONS: Laparoscopic diagnosis and management of ureteral endometriosis is safe and efficient. Preoperative planning should be rigorous, and complete surgical excision of ureteral endometriosis should be ensured by a team of experts familiar with endometriosis, and its management.All patients who undergo laparoscopy for endometriosis should be evaluated for possible ureteral involvement regardless the presence or absence of urinary symptoms or prior radiological evaluation. Source of Funding: None