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P037 Surgical management of renal cell carcinoma (RCC) with venous invasion in patients with distant metastases
202
posters / european urology supplements 11 (2012) 191–235
fair for T3 stage (44%) with an overall accuracy of 80% and 20% of understaging. Conclusions: MDCT results are indeterminate investigating venous involvement if there is a badly defined extension of locally advance masses and inferior vena cava tumour thrombus. P035 Non-cutaneous de novo malignancy following kidney and liver transplantation: A comparison in a single centre cohort of 2941 recipients F. Branco1 , V. Cavadas1 , L. Osorio ´ 1 , I. Braga2 , E. Cordeiro3 , 1 4 M. Silva-Ramos , A. Rocha , L. Martins2 , D. Silva5 , J.D. Silva5 , J. Daniel5 , A. Fraga1 . 1 Centro Hospitalar Do Porto, Dept. of Urology, Oporto, Portugal; 2 Centro Hospitalar Do Porto, Dept. of Nephrology, Oporto, Portugal; 3 AMC Hospital, Dept. of Urology, Amsterdam, The Netherlands; 4 Centro Hospitalar do Porto, Dept. of Nephrology, Oporto, Portugal; 5 Centro Hospitalar Do Porto, Dept. of General Surgery, Oporto, Portugal Introduction & Objectives: De novo malignancy after kidney and liver transplantation has become a major concern in recent years, being one of the most important causes of death in these patients. Herein we compare non-cutaneous de novo tumors arising in a single-centre cohort of renal and hepatic transplant recipients. Material & Methods: Renal and hepatic transplantation were initiated in January 1983 and May 1995, respectively, in our hospital. Until August 2011, 2016 kidney and 925 liver transplants were performed. Mean age at transplantation was 44 and 43 years for kidney and liver transplantation, respectively; 61% of kidney and 58% of liver recipients were male. Overall allograft survival at 5 and 10 years was 80 and 66% for kidney and 60 and 48% for liver, respectively. Our prospective database was surveyed to retrieve data for all patients who developed non-cutaneous de novo tumors. Kaplan–Meier survival was calculated for both kidney and liver recipients. Results: Eighty-four and 15 non-cutaneous de novo tumors were detected respectively in 2016 kidney (4.2%) and 925 liver transplant recipients (1.6%). Mean age at diagnosis was 55 years in both groups, after a mean follow-up until diagnosis of 142 and 58 months for renal and hepatic transplanted patients, respectively. The table depicts the type of neoplasms diagnosed in each group. Mean 1 and 5-year cancer-specific survival after diagnosis was 85 and 70% for kidney and 20 and 7% for liver recipients, respectively. Table 1. Non-cutaneous de novo malignancies in kidney and liver recipients. Kidney recipients
Gastrointestinal Gynecological Hematological Miscellaneous Urological Total
Liver recipients
Total
Death
Total
Death
16 21 14 18 15 84
8 3 6 2 4 23
6 1 1 6 1 15
6 1 1 6 1 15
Conclusions: In our cohort, non-cutaneous de novo tumors, despite being less frequent, are more aggressive in liver transplant recipients. Risk factors contributing for hepatic failure and the need of transplantation may be more important than immunosuppression in the development of de novo malignancy in this group of patients, when compared to kidney recipients.
P036 Bisphosphonates (Bis) combined with sunitinib (Su) may improve the response rate (RR), progression free survival (PFS) and overall survival (OS) of patients (pts) with bone metastases (mets) from renal cell carcinoma (RCC) D. Keizman1 , M. Ish-Shalom1 , N. Maimon1 , M. Gottfried1 , A. Peer2 , A. Neumann2 , H. Hayat3 , B. Boursi4 , S. Kovel5 , A. Sella5 , R. Pili6 , H. Hammers7 , V. Sinibaldi7 , M. Eisenberger7 , R. Berger4 , M. Carducci7 . 1 Meir Medical Center, Institute of Oncology, Kfar Saba, Israel; 2 Rambam Medical Center, Department of Oncology, Haifa, Israel; 3 Wolfson Medical Center, Department of Oncology, Holon, Israel; 4 Sheba Medical Center, Department of Oncology, Tel Hashomer, Israel; 5 Asaf Harofe Medical Center, Department of Oncology, Zerifin, Israel; 6 Roswell Park, Cancer Institute, Buffalo, United States of America; 7 Johns Hopkins, Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America Introduction & Objectives: Bis are used to prevent skeletal events of bone mets, and may exhibit anti tumor effects. We aimed to evaluate whether Bis can bring a RR, PFS, and OS benefit to pts with bone mets from RCC that are treated with Su. Material & Methods: We performed an international multicenter retrospective study of pts with bone mets from RCC who were treated with Su. Pts were divided into Bis users (group 1) and nonusers (group 2). The effect of Bis on RR, PFS and OS, was tested with adjustment for known prognostic factors using a chisquare test from contingency table and partial likelihood test from Cox regression model. Results: Between 2004–2011, 244 pts with metastatic RCC were treated with Su. 92 pts had bone mets, 41 group 1 and 51 group 2. The groups were balanced regarding the following known prognostic factors: past nephrectomy, clear cell vs non clear cell histology, initial diagnosis to sunitinib treatment (tx) time, presence of ≥ 2 mets sites, presence of lung/liver mets, ECOG performance status, anemia, calcium level >10 mg/dL, elevated alkaline phosphatase (AP), pre-tx neutrophil to lymphocyte ratio (NLR) >3, sunitinib induced HTN, and the use of angiotensin system inhibitors. They were also balanced with regard to past cytokines/targeted tx, and mean sunitinib dose/cycle. Objective response was partial response/stable disease 85% (n = 35) vs 71% (n = 36), and progressive disease 15% (n = 6) vs 29% (n = 15) (OR 3.287, p = 0.07) in group 1 vs 2 respectively. Median PFS was 15 vs 5 months (HR 0.433, p = 0.035), and median OS not reached with a median folloup time of 43 mos vs 12 months (HR 0.398, p = 0.003), in favor of group 1. In multivariate analysis of the entire pt cohort (n = 92), factors associated with PFS were Bis use (HR = 0.433, p = 0.035), pre-tx NLR ≤3 (HR 0.405, p = 0.016), and elevated AP (HR = 3.63, p = 0.012). Factors associated with OS were Bis use (HR 0.32, p = 0.003), elevated AP (HR 3.18, p = 0.002), and Su induced HTN (HR 0.193, p < 0.001). Conclusions: Bis may improve the outcome of Su tx in RCC with bone mets. This should be investigated prospectively, and if validated applied in clinical practice and clinical trials. P037 Surgical management of renal cell carcinoma (RCC) with venous invasion in patients with distant metastases M.I. Davydov, V.B. Matveev, K.M. Figurin, M.I. Volkova, V.A. Chernyaev, K.A.V. Kimov. N.N. Blokhin Cancer Center, Dept. of Urology, Moscow, Russia Introduction & Objectives: To assess the results of surgical management of RCC with venous invasion in patients with distant metastases. Material & Methods: 127 consecutive patients with RCC T3abN0–2M1 with venous involvement were treated surgically at our institution between 1984 and 2010. Median age was 57±11.2 years, male to female ratio – 1.5. Right kidney was
posters / european urology supplements 11 (2012) 191–235
involved in 60.2%, left – in 36.6%, both – in 3.1% of cases. The tumor thrombus was confined to the renal vein in 48 (37.8%), extended to the perirenal IVC – in 13 (10.2%), subhepatic IVC – in 24 (18.9%), retrohepatic IVC – in 18 (14.2%), intrapericardial IVC – in 10 (7.9%) and the right atrium in 14 (11.0%) of 127 cases. Distant metastasis were present in all patients (solitary – 28.3%, multiple – 71.7%). One metastatic site occurred in 58.4%, >1 – in 41.6% of cases. 67.5% of patients were diagnosed with pulmonary, 14.3% – adrenal gland, 7.8% – bone, 10.4% – other metastases. All patients underwent nephrectomy and thrombectomy, 14 (11.0%) – resection of solitary metastasis [simultaneous – 7 (5.5%)]. Histology showed lymph node metastasis in 54 (42.6%) patients [N1 – 11 (8.7%), N2 – 43 (33.9%)]. The perinephric fat invasion was in 54 (42.6%) cases. 118 (92.9%) patients were considered for conservative treatment postoperatively. Median follow-up was 15 (3–132) months. Results: Complete removal of the kidney and tumor thrombus was performed in 111 (87.4%), radical metastasectomy – in 11 (8.7%) cases. Serious complications and mortality rates were 26.0% and 7.9% respectively. The overall 5- and 10year survival of 127 patients was 34.9% and 13.1%, cancer specific – 40.9% and 15.3% respectively. In the univariate analysis survival was affected by perinephric fat invasion (p = 0.008), pN+ (p < 0.0001), >1 metastatic sites (p = 0.002), complete removal of all lesions (p = 0.080). Category pN+ (p = 0.050) and number of metastatic sites (p = 0.022) were independently associated with cancer-specific survival. The groups of patients with or without adverse factors (pN+ and/or >1 metastatic sites) had distinctly different prognosis (5-year cancer-specific survival – 55.3% vs 0.0% respectively, p < 0.0001). Conclusions: Surgery allows to escape fatal complications of tumor venous invasion in RCC patients. Cytoreductive nephrectomy and thrombectomy is relatively safe and effective in selected cases of metastatic RCC. Surgery is justified in patients without regional metastases. P038 Laparoscopic radical nephrectomy: Techniques, results and oncological outcome in 150 consecutive cases O.B. Halawa Gonzalez, ´ J. Falcon ´ Barroso, J. Rodriguez Talavera, B.F. Amir Nicolau, V. Del Rosario Rodriguez, C. Fumero Gorrin, J. Monllor Gisbert. Hospital Universitario Nuetra Se˜ nora De Candelaria, Dept. of Urology, Santa Cruz De Tenerife, Spain Introduction & Objectives: The laparoscopic technique combines the benefits of minimal invasive approach with established surgical principles. In our institution the laparoscopic transperitoneal approach with intact specimen removal has become the standard technique for radical nephrectomies. We report the indications, techniques and oncological outcome in a single center experience. Material & Methods: Between 2007 and 2011 we performed laparoscopic radical nephrectomies for in 150 patients, 111 oncological and 39 non oncological. Their initial staging, complications and postoperative course were evaluated. Results: 145 procedures out of 150 were successful. In five cases (7.5%) conversion to open surgery was necessary due to bleeding. Intraoperative complications could be managed laparoscopically. In one case (1.5%) postoperative bleeding lead to open revision for hemostasis. The mean surgical time was 220 min. In the oncological group, 88 patients (80%) were renal cell carcinoma and 20 (17%) upper urinary tract urothelial cell carcinoma. The main indication for non oncological laparoscopic radical nephrectomy was benign non-functioning kidney (33 patients). The follow-up was between 3 and 60 months. Conclusions: Laparoscopic radical nephrectomy has clear advantages compared to the traditional surgery, especially about less morbidity, less blood loss, shorter hospitalization, with an
203
oncologic outcome absolutely comparable to the laparotomic procedure. P039 Pulmonary metastases (PM) of renal cell carcinoma (RCC): Results of surgical resection V.B. Matveev1 , M.I. Volkova1 , B.E. Polotskiy2 , I.N. Turkin2 , A. Klimov1 . 1 N.N. Blokhin Cancer Center, Dept. of Urology, Moscow, Russia; 2 N.N. Blokhin Cancer Center, Dept. of Thoracic Surgery, Moscow, Russia Introduction & Objectives: The main purpose of the study was to assess the results of surgical management of pulmonary metastases of RCC. Material & Methods: From 1985 to 2010, 60 consecutive patients underwent surgery for PM of RCC [in view of cure – 55 (91.6%)]. Median age was 55 (31–70) years. PM were diagnosed synchronously with the kidney tumor in 20 (33.3 %), metachronously – in 40 (66.7 %) patients. Unilateral lesions occurred in 53 (88.3%), bilateral in 7 (11.7 %) cases. 41 (68.3%) patients had solitary, 19 (31.7 %) – multiple PM. Lung lesions less than 2 cm were revealed in 69% of cases. All 60 patients underwent surgery for PM. Complete PM removal was performed in 50 (83.3%) of 60 cases. The primary tumor was removed in 56 (93.3%) patients. Median follow-up was 20 (3– 155) months. Results: Major complications and mortality rates were 6.6% and 0% respectively. Histology proved PM of RCC in all cases. Metastases in mediastinal lymph nodes were found in 3 (5%) patients. 5- and 10-year overall, specific and relapsefree survival was 36.3% and 19.1%, 38.9% and 27.2%, 20.4% and 11.7% respectively. In the univariate analysis specific survival was affected by bilaterial pulmonary lesions, metastases in mediastinal lymph nodes and incomplete removal of PM. Radical surgery was the only factor independently associated with cancer-specific survival in multivariate analysis. Conclusions: Surgical resection of PM of RCC is safe and effective procedure. The best candidates for surgical intervention are patients with limited intrathoracic extension of the tumor. P040 Tivozanib pharmacokinetic (PK)/pharmacodynamic (PD) analysis of blood pressure (BP) and soluble vascular endothelial growth factor receptor 2 (sVEGFR2) in patients with advanced renal cell carcinoma (RCC) D.A. Nosov1 , R.J. Motzer2 , J. Loewy3 , L. Hodge3 , B. Esteves4 , A. Berkenblit4 , W. Yin4 , K. Dykstra3 , T.E. Hutson5 , M.M. Cotreau4 . 1 N.N. Blokhin Cancer Research Center, Under The Russian Academy of Medical Sciences, Dept. of Clinical Pharmacology & Chemotherapy, Moscow, Russia; 2 Memorial Sloan-Kettering Cancer Center, Dept. of Oncology, New York, United States of America; 3 QPharmetra, Dept. of Oncology, Andover, United States of America; 4 AVEO Oncology, Dept. of Oncology, Cambridge, United States of America; 5 Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dept. of Oncology, Dallas, United States of America Introduction & Objectives: Tivozanib is a potent, selective, long half-life tyrosine kinase inhibitor of VEGF receptors (VEGFRs) 1, 2, and 3, demonstrating activity against advanced RCC in Phase II–III trials. This analysis explored the relationship between tivozanib PK and BP, as hypertension is a mechanismbased adverse event and a potential surrogate of response. The relationship between exposure and sVEGFR2 also was explored. Material & Methods: PK, BP, and sVEGRF2 data from tivozanibtreated RCC patients from a Phase II (n = 21) and a Phase III (n = 259) study were pooled; patients were treated with tivozanib 1.5 mg daily for 3 weeks followed by a 1 week rest period (4-week treatment cycle) in each study. A population PK
posters / european urology supplements 11 (2012) 191–235
fair for T3 stage (44%) with an overall accuracy of 80% and 20% of understaging. Conclusions: MDCT results are indeterminate investigating venous involvement if there is a badly defined extension of locally advance masses and inferior vena cava tumour thrombus. P035 Non-cutaneous de novo malignancy following kidney and liver transplantation: A comparison in a single centre cohort of 2941 recipients F. Branco1 , V. Cavadas1 , L. Osorio ´ 1 , I. Braga2 , E. Cordeiro3 , 1 4 M. Silva-Ramos , A. Rocha , L. Martins2 , D. Silva5 , J.D. Silva5 , J. Daniel5 , A. Fraga1 . 1 Centro Hospitalar Do Porto, Dept. of Urology, Oporto, Portugal; 2 Centro Hospitalar Do Porto, Dept. of Nephrology, Oporto, Portugal; 3 AMC Hospital, Dept. of Urology, Amsterdam, The Netherlands; 4 Centro Hospitalar do Porto, Dept. of Nephrology, Oporto, Portugal; 5 Centro Hospitalar Do Porto, Dept. of General Surgery, Oporto, Portugal Introduction & Objectives: De novo malignancy after kidney and liver transplantation has become a major concern in recent years, being one of the most important causes of death in these patients. Herein we compare non-cutaneous de novo tumors arising in a single-centre cohort of renal and hepatic transplant recipients. Material & Methods: Renal and hepatic transplantation were initiated in January 1983 and May 1995, respectively, in our hospital. Until August 2011, 2016 kidney and 925 liver transplants were performed. Mean age at transplantation was 44 and 43 years for kidney and liver transplantation, respectively; 61% of kidney and 58% of liver recipients were male. Overall allograft survival at 5 and 10 years was 80 and 66% for kidney and 60 and 48% for liver, respectively. Our prospective database was surveyed to retrieve data for all patients who developed non-cutaneous de novo tumors. Kaplan–Meier survival was calculated for both kidney and liver recipients. Results: Eighty-four and 15 non-cutaneous de novo tumors were detected respectively in 2016 kidney (4.2%) and 925 liver transplant recipients (1.6%). Mean age at diagnosis was 55 years in both groups, after a mean follow-up until diagnosis of 142 and 58 months for renal and hepatic transplanted patients, respectively. The table depicts the type of neoplasms diagnosed in each group. Mean 1 and 5-year cancer-specific survival after diagnosis was 85 and 70% for kidney and 20 and 7% for liver recipients, respectively. Table 1. Non-cutaneous de novo malignancies in kidney and liver recipients. Kidney recipients
Gastrointestinal Gynecological Hematological Miscellaneous Urological Total
Liver recipients
Total
Death
Total
Death
16 21 14 18 15 84
8 3 6 2 4 23
6 1 1 6 1 15
6 1 1 6 1 15
Conclusions: In our cohort, non-cutaneous de novo tumors, despite being less frequent, are more aggressive in liver transplant recipients. Risk factors contributing for hepatic failure and the need of transplantation may be more important than immunosuppression in the development of de novo malignancy in this group of patients, when compared to kidney recipients.
P036 Bisphosphonates (Bis) combined with sunitinib (Su) may improve the response rate (RR), progression free survival (PFS) and overall survival (OS) of patients (pts) with bone metastases (mets) from renal cell carcinoma (RCC) D. Keizman1 , M. Ish-Shalom1 , N. Maimon1 , M. Gottfried1 , A. Peer2 , A. Neumann2 , H. Hayat3 , B. Boursi4 , S. Kovel5 , A. Sella5 , R. Pili6 , H. Hammers7 , V. Sinibaldi7 , M. Eisenberger7 , R. Berger4 , M. Carducci7 . 1 Meir Medical Center, Institute of Oncology, Kfar Saba, Israel; 2 Rambam Medical Center, Department of Oncology, Haifa, Israel; 3 Wolfson Medical Center, Department of Oncology, Holon, Israel; 4 Sheba Medical Center, Department of Oncology, Tel Hashomer, Israel; 5 Asaf Harofe Medical Center, Department of Oncology, Zerifin, Israel; 6 Roswell Park, Cancer Institute, Buffalo, United States of America; 7 Johns Hopkins, Sidney Kimmel Comprehensive Cancer Center, Baltimore, United States of America Introduction & Objectives: Bis are used to prevent skeletal events of bone mets, and may exhibit anti tumor effects. We aimed to evaluate whether Bis can bring a RR, PFS, and OS benefit to pts with bone mets from RCC that are treated with Su. Material & Methods: We performed an international multicenter retrospective study of pts with bone mets from RCC who were treated with Su. Pts were divided into Bis users (group 1) and nonusers (group 2). The effect of Bis on RR, PFS and OS, was tested with adjustment for known prognostic factors using a chisquare test from contingency table and partial likelihood test from Cox regression model. Results: Between 2004–2011, 244 pts with metastatic RCC were treated with Su. 92 pts had bone mets, 41 group 1 and 51 group 2. The groups were balanced regarding the following known prognostic factors: past nephrectomy, clear cell vs non clear cell histology, initial diagnosis to sunitinib treatment (tx) time, presence of ≥ 2 mets sites, presence of lung/liver mets, ECOG performance status, anemia, calcium level >10 mg/dL, elevated alkaline phosphatase (AP), pre-tx neutrophil to lymphocyte ratio (NLR) >3, sunitinib induced HTN, and the use of angiotensin system inhibitors. They were also balanced with regard to past cytokines/targeted tx, and mean sunitinib dose/cycle. Objective response was partial response/stable disease 85% (n = 35) vs 71% (n = 36), and progressive disease 15% (n = 6) vs 29% (n = 15) (OR 3.287, p = 0.07) in group 1 vs 2 respectively. Median PFS was 15 vs 5 months (HR 0.433, p = 0.035), and median OS not reached with a median folloup time of 43 mos vs 12 months (HR 0.398, p = 0.003), in favor of group 1. In multivariate analysis of the entire pt cohort (n = 92), factors associated with PFS were Bis use (HR = 0.433, p = 0.035), pre-tx NLR ≤3 (HR 0.405, p = 0.016), and elevated AP (HR = 3.63, p = 0.012). Factors associated with OS were Bis use (HR 0.32, p = 0.003), elevated AP (HR 3.18, p = 0.002), and Su induced HTN (HR 0.193, p < 0.001). Conclusions: Bis may improve the outcome of Su tx in RCC with bone mets. This should be investigated prospectively, and if validated applied in clinical practice and clinical trials. P037 Surgical management of renal cell carcinoma (RCC) with venous invasion in patients with distant metastases M.I. Davydov, V.B. Matveev, K.M. Figurin, M.I. Volkova, V.A. Chernyaev, K.A.V. Kimov. N.N. Blokhin Cancer Center, Dept. of Urology, Moscow, Russia Introduction & Objectives: To assess the results of surgical management of RCC with venous invasion in patients with distant metastases. Material & Methods: 127 consecutive patients with RCC T3abN0–2M1 with venous involvement were treated surgically at our institution between 1984 and 2010. Median age was 57±11.2 years, male to female ratio – 1.5. Right kidney was
posters / european urology supplements 11 (2012) 191–235
involved in 60.2%, left – in 36.6%, both – in 3.1% of cases. The tumor thrombus was confined to the renal vein in 48 (37.8%), extended to the perirenal IVC – in 13 (10.2%), subhepatic IVC – in 24 (18.9%), retrohepatic IVC – in 18 (14.2%), intrapericardial IVC – in 10 (7.9%) and the right atrium in 14 (11.0%) of 127 cases. Distant metastasis were present in all patients (solitary – 28.3%, multiple – 71.7%). One metastatic site occurred in 58.4%, >1 – in 41.6% of cases. 67.5% of patients were diagnosed with pulmonary, 14.3% – adrenal gland, 7.8% – bone, 10.4% – other metastases. All patients underwent nephrectomy and thrombectomy, 14 (11.0%) – resection of solitary metastasis [simultaneous – 7 (5.5%)]. Histology showed lymph node metastasis in 54 (42.6%) patients [N1 – 11 (8.7%), N2 – 43 (33.9%)]. The perinephric fat invasion was in 54 (42.6%) cases. 118 (92.9%) patients were considered for conservative treatment postoperatively. Median follow-up was 15 (3–132) months. Results: Complete removal of the kidney and tumor thrombus was performed in 111 (87.4%), radical metastasectomy – in 11 (8.7%) cases. Serious complications and mortality rates were 26.0% and 7.9% respectively. The overall 5- and 10year survival of 127 patients was 34.9% and 13.1%, cancer specific – 40.9% and 15.3% respectively. In the univariate analysis survival was affected by perinephric fat invasion (p = 0.008), pN+ (p < 0.0001), >1 metastatic sites (p = 0.002), complete removal of all lesions (p = 0.080). Category pN+ (p = 0.050) and number of metastatic sites (p = 0.022) were independently associated with cancer-specific survival. The groups of patients with or without adverse factors (pN+ and/or >1 metastatic sites) had distinctly different prognosis (5-year cancer-specific survival – 55.3% vs 0.0% respectively, p < 0.0001). Conclusions: Surgery allows to escape fatal complications of tumor venous invasion in RCC patients. Cytoreductive nephrectomy and thrombectomy is relatively safe and effective in selected cases of metastatic RCC. Surgery is justified in patients without regional metastases. P038 Laparoscopic radical nephrectomy: Techniques, results and oncological outcome in 150 consecutive cases O.B. Halawa Gonzalez, ´ J. Falcon ´ Barroso, J. Rodriguez Talavera, B.F. Amir Nicolau, V. Del Rosario Rodriguez, C. Fumero Gorrin, J. Monllor Gisbert. Hospital Universitario Nuetra Se˜ nora De Candelaria, Dept. of Urology, Santa Cruz De Tenerife, Spain Introduction & Objectives: The laparoscopic technique combines the benefits of minimal invasive approach with established surgical principles. In our institution the laparoscopic transperitoneal approach with intact specimen removal has become the standard technique for radical nephrectomies. We report the indications, techniques and oncological outcome in a single center experience. Material & Methods: Between 2007 and 2011 we performed laparoscopic radical nephrectomies for in 150 patients, 111 oncological and 39 non oncological. Their initial staging, complications and postoperative course were evaluated. Results: 145 procedures out of 150 were successful. In five cases (7.5%) conversion to open surgery was necessary due to bleeding. Intraoperative complications could be managed laparoscopically. In one case (1.5%) postoperative bleeding lead to open revision for hemostasis. The mean surgical time was 220 min. In the oncological group, 88 patients (80%) were renal cell carcinoma and 20 (17%) upper urinary tract urothelial cell carcinoma. The main indication for non oncological laparoscopic radical nephrectomy was benign non-functioning kidney (33 patients). The follow-up was between 3 and 60 months. Conclusions: Laparoscopic radical nephrectomy has clear advantages compared to the traditional surgery, especially about less morbidity, less blood loss, shorter hospitalization, with an
203
oncologic outcome absolutely comparable to the laparotomic procedure. P039 Pulmonary metastases (PM) of renal cell carcinoma (RCC): Results of surgical resection V.B. Matveev1 , M.I. Volkova1 , B.E. Polotskiy2 , I.N. Turkin2 , A. Klimov1 . 1 N.N. Blokhin Cancer Center, Dept. of Urology, Moscow, Russia; 2 N.N. Blokhin Cancer Center, Dept. of Thoracic Surgery, Moscow, Russia Introduction & Objectives: The main purpose of the study was to assess the results of surgical management of pulmonary metastases of RCC. Material & Methods: From 1985 to 2010, 60 consecutive patients underwent surgery for PM of RCC [in view of cure – 55 (91.6%)]. Median age was 55 (31–70) years. PM were diagnosed synchronously with the kidney tumor in 20 (33.3 %), metachronously – in 40 (66.7 %) patients. Unilateral lesions occurred in 53 (88.3%), bilateral in 7 (11.7 %) cases. 41 (68.3%) patients had solitary, 19 (31.7 %) – multiple PM. Lung lesions less than 2 cm were revealed in 69% of cases. All 60 patients underwent surgery for PM. Complete PM removal was performed in 50 (83.3%) of 60 cases. The primary tumor was removed in 56 (93.3%) patients. Median follow-up was 20 (3– 155) months. Results: Major complications and mortality rates were 6.6% and 0% respectively. Histology proved PM of RCC in all cases. Metastases in mediastinal lymph nodes were found in 3 (5%) patients. 5- and 10-year overall, specific and relapsefree survival was 36.3% and 19.1%, 38.9% and 27.2%, 20.4% and 11.7% respectively. In the univariate analysis specific survival was affected by bilaterial pulmonary lesions, metastases in mediastinal lymph nodes and incomplete removal of PM. Radical surgery was the only factor independently associated with cancer-specific survival in multivariate analysis. Conclusions: Surgical resection of PM of RCC is safe and effective procedure. The best candidates for surgical intervention are patients with limited intrathoracic extension of the tumor. P040 Tivozanib pharmacokinetic (PK)/pharmacodynamic (PD) analysis of blood pressure (BP) and soluble vascular endothelial growth factor receptor 2 (sVEGFR2) in patients with advanced renal cell carcinoma (RCC) D.A. Nosov1 , R.J. Motzer2 , J. Loewy3 , L. Hodge3 , B. Esteves4 , A. Berkenblit4 , W. Yin4 , K. Dykstra3 , T.E. Hutson5 , M.M. Cotreau4 . 1 N.N. Blokhin Cancer Research Center, Under The Russian Academy of Medical Sciences, Dept. of Clinical Pharmacology & Chemotherapy, Moscow, Russia; 2 Memorial Sloan-Kettering Cancer Center, Dept. of Oncology, New York, United States of America; 3 QPharmetra, Dept. of Oncology, Andover, United States of America; 4 AVEO Oncology, Dept. of Oncology, Cambridge, United States of America; 5 Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dept. of Oncology, Dallas, United States of America Introduction & Objectives: Tivozanib is a potent, selective, long half-life tyrosine kinase inhibitor of VEGF receptors (VEGFRs) 1, 2, and 3, demonstrating activity against advanced RCC in Phase II–III trials. This analysis explored the relationship between tivozanib PK and BP, as hypertension is a mechanismbased adverse event and a potential surrogate of response. The relationship between exposure and sVEGFR2 also was explored. Material & Methods: PK, BP, and sVEGRF2 data from tivozanibtreated RCC patients from a Phase II (n = 21) and a Phase III (n = 259) study were pooled; patients were treated with tivozanib 1.5 mg daily for 3 weeks followed by a 1 week rest period (4-week treatment cycle) in each study. A population PK