- Email: [email protected]
UP-01.157 Metastatic Renal Cancer in the Targeted Therapy Era: The Sherbrooke Experience
UNMODERATED POSTER SESSIONS
strated that surveillance for Bosniak IIF cyst is a safe strategy. Furthermore, such cases may not even require routine follow-up. However; longer term study is required before this can be confirmed. Due to the high malignancy rate associated with category III cysts these should be managed surgically where possible.
UP-01.155 Correlation Between B7-H1/H3 Expression, Survival and Pathologic Parameters in Renal Cell Carcinoma Patients Mischinger J, Gutschi T, Pummer K, Zigeuner R Dept. of Urology, Medical University of Graz, Graz, Austria Introduction and Objectives: The aim of this pilot study was to evaluate the impact of B7-H1 and B7-H3 glycoprotein expression by tumor cells in patients with clear cell renal cell carcinoma RCC (ccRCC) on overall survival (OS) and pathologic features defined by the MayoSSIGN-score (Stage, Size, Grade, Necrosis). Complementary, the prognostic value of the SSIGN-score concerning overall survival was validated. Materials and Methods: Nephrectomy specimens of 45 patients with ccRCC who developed metastases in the course of their underlying disease and received interferon therapy for at least 3 months were evaluated for B7-H1 and B7-H3 expression by immunohistochemical staining.The percentage of tumor tissue with glycoprotein-expression was correlated to overall survival and SSIGN-score. Results: Within the scope of the KaplanMeyer analyses no significant correlation between B7-H1 expression and survival or SSIGN-score was observed. However, B7-H3 expression greater than 15% was associated with significantly reduced OS and higher SIGGN scores compared to patients with less than 15% B7-H3 expression by tumor cells (p⫽0,011). Consistently patients with a low SSIGN-score (0-4) showed a 4% lower B7-H3 expression than those with a higher score (513), although no significant difference (p⫽0.097) regarding overall survival was observed between the two SSIGN-Score groups 0-4 and 5-13. Conclusion: In our study the B7-H1 glycoprotein could not establish itself as a prognostic factor. However, augmented B7-H3 glycoprotein expression by tumor cells in ccRCC was associated with reduced overall survival and negative pathologic features (SSIGN-Score). The lack, of
S238
prognostic value of the SSIGN-Score may be attributed to the low number of cases. If confirmed by subsequent studies in larger cohorts, B7-H3 may prove useful to identify high risk patients who require more frequent controls or early adjuvant therapy. Furthermore blockade of B7-H3 could be a potential immunotherapeutic target in patients with ccRCC.
UP-01.156 Reassessing the 2009 AJCC TNM Staging System for Renal Cell Carcinoma with Regard to Lymph Node Metastasis Iizuka J, Kondo T, Hashimoto Y, Kobayashi H, Tomita E, Takagi T, Tanabe K Dept. of Urology, Tokyo Women’s Medical University, Tokyo, Japan Introduction and Objective: According to the 2002 TNM staging system, patients with one affected lymph node (N1) and those with multiple affected nodes (N2) were distinguished. However, the 2009 TNM staging classification for renal cell carcinoma (RCC) has changed the definition of lymph node metastasis to be gathered as one grade and regulated as stage III whatever the number or the region of positive nodes. The prognostic outcome has still remained controversial. So, in this study we reassessed the 2009 TNM staging system with regard to lymph node metastasis. Materials and Methods: Until October 2010, a total of 1900 patients underwent curative surgery for renal tumors at our institution. Of these, 73 patients who were diagnosed as renal cell carcinoma with lymph node metastasis were enrolled in this study. Pathological findings revealed that the nodal status was N1 in 15, and N2 in 58. Of these, 35 patients had distant metastases. We divided these patients into three groups, Group1 as N1M0, Group2 as N2M0 and Group3 as N1N2M1. We analyzed the cancer specific survival among the groups in comparison with that of patients with stage III or IV tumors as regulated in the 2002 TNM staging system. Results: Median age was G1: 62.5(48-73) years old, G2: 55.5(17-77) years old and G3: 61.0(39-78) years old, respectively. Among Group 1 and Group 2, cancer-specific survival at 5 years was 75% and 69.5%, with no significant difference (p⫽0.50). Then, we compared patients with N(⫹)M0 (combined G1⫹G2) to those with stage III or IV tumors with regard to cancer-specific survival. Five-
year cancer-specific survival was 29.7%, 76.7% (p⬍0.01, vs N(⫹)M0), 20.6%(p⫽0.09, vs N(⫹)M0), respectively. Conclusions: Based on the findings of this study, the prognosis of patients with N(⫹)M0 is closer to that of patients with stage IV tumors than that of patients with stage III tumors. So we conclude that it is not appropriate to define patients with node positive as stage III regulated in the 2009 TNM staging system. However, further analysis and longer follow-up is needed.
UP-01.157 Metastatic Renal Cancer in the Targeted Therapy Era: The Sherbrooke Experience Jundi M1, Bettez M1, Richard P1, Abatzoglou A1, Mija F1, Ramsay S1, Girard N1, Carmel M1, Asselah J2, Sabbagh R1 1 Dept. of Urology; 2Dept. of Oncology, Sherbrooke University Hospital Center, Sherbrooke, QC, Canada Introduction and Objective: In the past 5 years, the introduction of targeted therapy has dramatically changed the outcome of patients with metastatic renal cell cancer (mRCC). In particular, drugs that inhibit signaling of vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) have significantly improved the perspectives of patients. The aim of this study is to compare the survival of our population to the literature pertaining patients with mRCC with or without VEGF inhibitors. Materials and Methods: We retrospectively reviewed the charts of 46 mRCC patients treated at our center from January 2004 to November 2010. We estimated the overall survival rate using Kaplan-Meier curves. Results: Of the forty-six patients, 30 patients received VEGF inhibitors. Patients were stratified according to the Memorial Sloan Kettering Cancer Center predictors of short survival. Seven, 15 and 6 patients had good, intermediate and poor prognosis, respectively with a median overall survival rate of 3.5, 1.8 and 2.1 years, respectively. There were no statistically significant difference (p ⫽ 0.3494) in overall survival rate between patients on VEGF inhibitors and those on conservative treatment regardless of the prognosis stratification. Conclusion: We found no significant differences in overall survival rate between patients taking or not VEGF inhibi-
UROLOGY 78 (Supplement 3A), September 2011
UNMODERATED POSTER SESSIONS
UP-01.157, Figure 1.
tors. Compared to the literature, this study has a similar median survival rate.
UP-01.158 Metanephric Adenoma: Unusual Renal Neoplasm, 2 Case Reports Leao R1, Azinhais P, Alves J2, Pereira B1, Borges R1, Grenha V1, Coelho H1, Retroz E1, Sobral F1 1 Dept. of Urology; 2Dept. of Pathology, Centro Hospitalar Coimbra, Coimbra, Portugal Introduction and Objective: Benign lesions of the kidney present a challenging clinical diagnosis. Despite the sensitivity of current imaging techniques, definitive diagnosis is made histologically. The metanephric adenoma of the kidney is a rare, slow-growing tumor with good prognosis (although there are descriptions of cases of metastatic disease). It can present itself (ultrasound and CT scan) as a well circumscribed, solid lesion, sometimes with calcifications and hypovascular on angiography. Usually it is asymptomatic, being in 10% associated with polycythemia. It occurs mostly in young and middle aged people, and is more common in females. Histologically it is composed of epithelial cells, whose origin is related to the development of the fetal kidney proximal tubule. Differential diagnosis with malignant lesions as nephroblastoma or papillary renal cell carcinoma may make this condition over treated. We present two clinical cases of renal metanephric adenoma. Materials and Methods: Two female patients, 59 (A) and 37 (B) years. Incidental finding in routine ultrasound revealed renal lesions well demarcated, rounded, varied content, and suggestive of hemorrhagic cyst. TC (A) showed a solid and
limited right renal mass of 5cm, without contrast uptake, suggestive of a cyst without liquid content: TC (B) “. . . nodule, 18mm, middle third left kidney, hypovascular enhancement effect . . . solid mass hypovascular”. No hematological changes, normal renal and hepatic function (A and B). Results: Patient (A) has undergone renal mass biopsy that revealed renal metanephric adenoma. Performed right partial nephrectomy, with histological diagnosis of metanephric adenoma (6.5 ⫻5, 5⫻4, 5cm). Patient B underwent laparoscopic left partial nephrectomy, converted to radical nephrectomy, revealing a “. . .tumor with 2.2 ⫻2⫻1. 5cm. . .metanephric adenoma of the left kidney”. Conclusion: Metanephric adenoma of the kidney is a rare benign lesion. Like other renal lesions, diagnostic imaging is difficult. The combination of imaging studies revealing a circumscribed solid lesion with calcifications and hypovascular in individual middle-aged female can suggest a metanephric adenoma and can guide the clinician to perform a diagnostic biopsy. Given its low incidence, lack of means of definitive imaging and cytology, surgical therapy is recommended because of the risk of malignancy.
UP-01.159 Prognostic Factors and Survival of Renal Cell Carcinoma in Japanese Patients Miyaji Y1, Kanomata N2, Ohira S1, Tsukimori S1, Fukumoto K1, Hara R1, Fujii T1, Jo Y1, Yokoyama T1, Nagai A1 1 Dept. of Urology; 2Dept. of Pathology, Kawasaki Medical School, Kurashiki, Japan Introduction and Objective: Incidence
UROLOGY 78 (Supplement 3A), September 2011
rate of renal cell carcinoma (RCC) differs among countries.We evaluated the impact of these pathological features on renal cell carcinoma survival and recurrence in Japanese patients. Materials and Methods: We identified 187 consecutive patients who underwent partial or radical nephrectomy at our institution from 1996 to 2009 for RCC. Specimens were re-reviewed by a single pathologist (NK) blinded to clinical outcome data. The data captured were histological type according to the 2004 WHO classification and conventional Fuhrman grade (1 to 4). Furhman grade, stage, subtype, size, gender and age were also analyzed. Results: Median follow-up was 49 months (range 2 to 169). Median age at diagnosis was 65 years. The TNM stage was I in 124 cases, II in 22, III in 24 and iV in 17. A total of 24 partial and 163 radical nephrectomies were performed. The metastasis-free survival rates in stage I, II and III at 5 years were 91.5% ,65.8% and 52.6%, respectively (p⬍0.001). Univariate analysis revealed that there were significant risk factors in T stage, in Furhman grade, in microscopic venous invasion, in capsular invasion and in tumor size more than 4.1cm diameter. On multivariate analysis Furhman grade (grade I and II vs. III, vs. IV) was the only significant risk factor (HR 5.19 (III vs. I and II), HR 3.03 (IV vs. I and II), p⫽0.032). There were 21 cases (11.2%) of cancer death and 14 cases (7.4%) of those who died of another cause. The overall survival rates in stage I, II , III and IV at 5 years were 85.8%, 81.8%, 76.4% and 38.4%, respectively (p⬍0.001). Univariate analysis revealed that there were significant risk factors in T stage, in Furhman grade, in microscopic venous invasion and in capsular invasion. On multivariate analysis Furhman grade (grade I and II vs. III, vs. IV) was the only significant risk factor (HR 6.16 (III vs. I and II), HR 9.89 (IV vs. I and II), p⫽0.003). Conclusions: In Japanese patients with renal cell carcinoma undergoing nephrectomy, Fuhrman grade is the most important prognostic factor for survival and disease-free survival.
UP-01.160 Long-Term Follow-Up Is Necessary for Patients Presenting With pT1 and pT2 Renal Cell Carcinoma Nestler S, Thomas C, Jäger W, Brenner W, Hampel C, Thüroff J, Roos F Dept. of Urology, University of Mainz, Mainz, Germany
S239
strated that surveillance for Bosniak IIF cyst is a safe strategy. Furthermore, such cases may not even require routine follow-up. However; longer term study is required before this can be confirmed. Due to the high malignancy rate associated with category III cysts these should be managed surgically where possible.
UP-01.155 Correlation Between B7-H1/H3 Expression, Survival and Pathologic Parameters in Renal Cell Carcinoma Patients Mischinger J, Gutschi T, Pummer K, Zigeuner R Dept. of Urology, Medical University of Graz, Graz, Austria Introduction and Objectives: The aim of this pilot study was to evaluate the impact of B7-H1 and B7-H3 glycoprotein expression by tumor cells in patients with clear cell renal cell carcinoma RCC (ccRCC) on overall survival (OS) and pathologic features defined by the MayoSSIGN-score (Stage, Size, Grade, Necrosis). Complementary, the prognostic value of the SSIGN-score concerning overall survival was validated. Materials and Methods: Nephrectomy specimens of 45 patients with ccRCC who developed metastases in the course of their underlying disease and received interferon therapy for at least 3 months were evaluated for B7-H1 and B7-H3 expression by immunohistochemical staining.The percentage of tumor tissue with glycoprotein-expression was correlated to overall survival and SSIGN-score. Results: Within the scope of the KaplanMeyer analyses no significant correlation between B7-H1 expression and survival or SSIGN-score was observed. However, B7-H3 expression greater than 15% was associated with significantly reduced OS and higher SIGGN scores compared to patients with less than 15% B7-H3 expression by tumor cells (p⫽0,011). Consistently patients with a low SSIGN-score (0-4) showed a 4% lower B7-H3 expression than those with a higher score (513), although no significant difference (p⫽0.097) regarding overall survival was observed between the two SSIGN-Score groups 0-4 and 5-13. Conclusion: In our study the B7-H1 glycoprotein could not establish itself as a prognostic factor. However, augmented B7-H3 glycoprotein expression by tumor cells in ccRCC was associated with reduced overall survival and negative pathologic features (SSIGN-Score). The lack, of
S238
prognostic value of the SSIGN-Score may be attributed to the low number of cases. If confirmed by subsequent studies in larger cohorts, B7-H3 may prove useful to identify high risk patients who require more frequent controls or early adjuvant therapy. Furthermore blockade of B7-H3 could be a potential immunotherapeutic target in patients with ccRCC.
UP-01.156 Reassessing the 2009 AJCC TNM Staging System for Renal Cell Carcinoma with Regard to Lymph Node Metastasis Iizuka J, Kondo T, Hashimoto Y, Kobayashi H, Tomita E, Takagi T, Tanabe K Dept. of Urology, Tokyo Women’s Medical University, Tokyo, Japan Introduction and Objective: According to the 2002 TNM staging system, patients with one affected lymph node (N1) and those with multiple affected nodes (N2) were distinguished. However, the 2009 TNM staging classification for renal cell carcinoma (RCC) has changed the definition of lymph node metastasis to be gathered as one grade and regulated as stage III whatever the number or the region of positive nodes. The prognostic outcome has still remained controversial. So, in this study we reassessed the 2009 TNM staging system with regard to lymph node metastasis. Materials and Methods: Until October 2010, a total of 1900 patients underwent curative surgery for renal tumors at our institution. Of these, 73 patients who were diagnosed as renal cell carcinoma with lymph node metastasis were enrolled in this study. Pathological findings revealed that the nodal status was N1 in 15, and N2 in 58. Of these, 35 patients had distant metastases. We divided these patients into three groups, Group1 as N1M0, Group2 as N2M0 and Group3 as N1N2M1. We analyzed the cancer specific survival among the groups in comparison with that of patients with stage III or IV tumors as regulated in the 2002 TNM staging system. Results: Median age was G1: 62.5(48-73) years old, G2: 55.5(17-77) years old and G3: 61.0(39-78) years old, respectively. Among Group 1 and Group 2, cancer-specific survival at 5 years was 75% and 69.5%, with no significant difference (p⫽0.50). Then, we compared patients with N(⫹)M0 (combined G1⫹G2) to those with stage III or IV tumors with regard to cancer-specific survival. Five-
year cancer-specific survival was 29.7%, 76.7% (p⬍0.01, vs N(⫹)M0), 20.6%(p⫽0.09, vs N(⫹)M0), respectively. Conclusions: Based on the findings of this study, the prognosis of patients with N(⫹)M0 is closer to that of patients with stage IV tumors than that of patients with stage III tumors. So we conclude that it is not appropriate to define patients with node positive as stage III regulated in the 2009 TNM staging system. However, further analysis and longer follow-up is needed.
UP-01.157 Metastatic Renal Cancer in the Targeted Therapy Era: The Sherbrooke Experience Jundi M1, Bettez M1, Richard P1, Abatzoglou A1, Mija F1, Ramsay S1, Girard N1, Carmel M1, Asselah J2, Sabbagh R1 1 Dept. of Urology; 2Dept. of Oncology, Sherbrooke University Hospital Center, Sherbrooke, QC, Canada Introduction and Objective: In the past 5 years, the introduction of targeted therapy has dramatically changed the outcome of patients with metastatic renal cell cancer (mRCC). In particular, drugs that inhibit signaling of vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) have significantly improved the perspectives of patients. The aim of this study is to compare the survival of our population to the literature pertaining patients with mRCC with or without VEGF inhibitors. Materials and Methods: We retrospectively reviewed the charts of 46 mRCC patients treated at our center from January 2004 to November 2010. We estimated the overall survival rate using Kaplan-Meier curves. Results: Of the forty-six patients, 30 patients received VEGF inhibitors. Patients were stratified according to the Memorial Sloan Kettering Cancer Center predictors of short survival. Seven, 15 and 6 patients had good, intermediate and poor prognosis, respectively with a median overall survival rate of 3.5, 1.8 and 2.1 years, respectively. There were no statistically significant difference (p ⫽ 0.3494) in overall survival rate between patients on VEGF inhibitors and those on conservative treatment regardless of the prognosis stratification. Conclusion: We found no significant differences in overall survival rate between patients taking or not VEGF inhibi-
UROLOGY 78 (Supplement 3A), September 2011
UNMODERATED POSTER SESSIONS
UP-01.157, Figure 1.
tors. Compared to the literature, this study has a similar median survival rate.
UP-01.158 Metanephric Adenoma: Unusual Renal Neoplasm, 2 Case Reports Leao R1, Azinhais P, Alves J2, Pereira B1, Borges R1, Grenha V1, Coelho H1, Retroz E1, Sobral F1 1 Dept. of Urology; 2Dept. of Pathology, Centro Hospitalar Coimbra, Coimbra, Portugal Introduction and Objective: Benign lesions of the kidney present a challenging clinical diagnosis. Despite the sensitivity of current imaging techniques, definitive diagnosis is made histologically. The metanephric adenoma of the kidney is a rare, slow-growing tumor with good prognosis (although there are descriptions of cases of metastatic disease). It can present itself (ultrasound and CT scan) as a well circumscribed, solid lesion, sometimes with calcifications and hypovascular on angiography. Usually it is asymptomatic, being in 10% associated with polycythemia. It occurs mostly in young and middle aged people, and is more common in females. Histologically it is composed of epithelial cells, whose origin is related to the development of the fetal kidney proximal tubule. Differential diagnosis with malignant lesions as nephroblastoma or papillary renal cell carcinoma may make this condition over treated. We present two clinical cases of renal metanephric adenoma. Materials and Methods: Two female patients, 59 (A) and 37 (B) years. Incidental finding in routine ultrasound revealed renal lesions well demarcated, rounded, varied content, and suggestive of hemorrhagic cyst. TC (A) showed a solid and
limited right renal mass of 5cm, without contrast uptake, suggestive of a cyst without liquid content: TC (B) “. . . nodule, 18mm, middle third left kidney, hypovascular enhancement effect . . . solid mass hypovascular”. No hematological changes, normal renal and hepatic function (A and B). Results: Patient (A) has undergone renal mass biopsy that revealed renal metanephric adenoma. Performed right partial nephrectomy, with histological diagnosis of metanephric adenoma (6.5 ⫻5, 5⫻4, 5cm). Patient B underwent laparoscopic left partial nephrectomy, converted to radical nephrectomy, revealing a “. . .tumor with 2.2 ⫻2⫻1. 5cm. . .metanephric adenoma of the left kidney”. Conclusion: Metanephric adenoma of the kidney is a rare benign lesion. Like other renal lesions, diagnostic imaging is difficult. The combination of imaging studies revealing a circumscribed solid lesion with calcifications and hypovascular in individual middle-aged female can suggest a metanephric adenoma and can guide the clinician to perform a diagnostic biopsy. Given its low incidence, lack of means of definitive imaging and cytology, surgical therapy is recommended because of the risk of malignancy.
UP-01.159 Prognostic Factors and Survival of Renal Cell Carcinoma in Japanese Patients Miyaji Y1, Kanomata N2, Ohira S1, Tsukimori S1, Fukumoto K1, Hara R1, Fujii T1, Jo Y1, Yokoyama T1, Nagai A1 1 Dept. of Urology; 2Dept. of Pathology, Kawasaki Medical School, Kurashiki, Japan Introduction and Objective: Incidence
UROLOGY 78 (Supplement 3A), September 2011
rate of renal cell carcinoma (RCC) differs among countries.We evaluated the impact of these pathological features on renal cell carcinoma survival and recurrence in Japanese patients. Materials and Methods: We identified 187 consecutive patients who underwent partial or radical nephrectomy at our institution from 1996 to 2009 for RCC. Specimens were re-reviewed by a single pathologist (NK) blinded to clinical outcome data. The data captured were histological type according to the 2004 WHO classification and conventional Fuhrman grade (1 to 4). Furhman grade, stage, subtype, size, gender and age were also analyzed. Results: Median follow-up was 49 months (range 2 to 169). Median age at diagnosis was 65 years. The TNM stage was I in 124 cases, II in 22, III in 24 and iV in 17. A total of 24 partial and 163 radical nephrectomies were performed. The metastasis-free survival rates in stage I, II and III at 5 years were 91.5% ,65.8% and 52.6%, respectively (p⬍0.001). Univariate analysis revealed that there were significant risk factors in T stage, in Furhman grade, in microscopic venous invasion, in capsular invasion and in tumor size more than 4.1cm diameter. On multivariate analysis Furhman grade (grade I and II vs. III, vs. IV) was the only significant risk factor (HR 5.19 (III vs. I and II), HR 3.03 (IV vs. I and II), p⫽0.032). There were 21 cases (11.2%) of cancer death and 14 cases (7.4%) of those who died of another cause. The overall survival rates in stage I, II , III and IV at 5 years were 85.8%, 81.8%, 76.4% and 38.4%, respectively (p⬍0.001). Univariate analysis revealed that there were significant risk factors in T stage, in Furhman grade, in microscopic venous invasion and in capsular invasion. On multivariate analysis Furhman grade (grade I and II vs. III, vs. IV) was the only significant risk factor (HR 6.16 (III vs. I and II), HR 9.89 (IV vs. I and II), p⫽0.003). Conclusions: In Japanese patients with renal cell carcinoma undergoing nephrectomy, Fuhrman grade is the most important prognostic factor for survival and disease-free survival.
UP-01.160 Long-Term Follow-Up Is Necessary for Patients Presenting With pT1 and pT2 Renal Cell Carcinoma Nestler S, Thomas C, Jäger W, Brenner W, Hampel C, Thüroff J, Roos F Dept. of Urology, University of Mainz, Mainz, Germany
S239