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MP40-02 INCREASED UPTAKE OF RENAL TUMOUR BIOPSIES FOR SMALL RENAL MASSES – RESULTS OF A MULTICENTRE CANADIAN EXPERIENCE
THE JOURNAL OF UROLOGYâ
e434
Vol. 191, No. 4S, Supplement, Sunday, May 18, 2014
Kidney Cancer; Evaluation/Staging IV Moderated Poster Sunday, May 18, 2014
3:30 PM-5:30 PM
MP40-01 HEDGEHOG PATHWAY BIOMARKERS PREDICT ONCOLOGIC OUTCOME IN CLEAR CELL RENAL CELL CARCINOMA €ger*, Vancouver, Canada; Christian Thomas, Mainz, Wolfgang Ja Germany; Claudia Janßen, Vancouver, Canada; Irene Schmidtmann, €roff, Walburgis Brenner, Michael Hainz, Frederik Roos, Joachim Thu Mainz, Germany; Peter Black, Vancouver, Canada INTRODUCTION AND OBJECTIVES: Despite the advent of targeted therapy for renal cell carcinoma (RCC), responses to such therapy are rarely durable and metastatic RCC remains nearly uniformly fatal. The need for additional novel therapies persists. Aberrant hedgehog (HH) signaling has been proven important in the pathogenesis of several solid cancers. Limited in vitro analyses suggest an oncogenic role for HH in RCC and point towards HH signaling as a potential target for therapy. In the current study we sought validation of aberrant HH expression in patients with RCC. We investigated the expression levels of nine signaling markers of the HH pathway and their correlation with patient survival. METHODS: A tissue microarray (TMA) was constructed from 140 tumors taken from patients who underwent radical nephrectomy for clear cell RCC (ccRCC) between 1994 and 2002. Immunohistochemistry for the following HH pathway biomarkers was performed: Patched, CD31, Smoothend (Smo), Sonic Hedgehog (SHH), Indian Hedgehog (IHH) Dessert Hedgehog (DHH), Gli1, Gli2, and Gli3. Staining intensity was measured by automated image processing and was related to tumor stage and grade. Impact of biomarker expression on cancerspecific survival was determined with uni- and multivariate Cox regression analysis. RESULTS: The staining intensity of Gli1 and Smo was significantly higher in pT1 compared to pT2 ccRCC (for each p<0.001). DHH and CD31 showed significantly higher expression in the higher stage tumors (for each p<0.001). Expression of HH biomarkers was not related to tumor grade. In univariate analysis, DHH expression (p<0.05), tumor grade (p<0.01) and stage (p<0.001) correlated with cancer-specific survival. Multivariate analysis revealed DHH (p<0.05), Smo (p<0.05) and tumor stage (p<0.001) as independent predictors for cancer-specific survival (CSS). CONCLUSIONS: We have demonstrated for the first time that biomarkers of the Hedgehog pathway correlate with adverse pathologic features and poor disease outcome in patients with ccRCC. This supports further evaluation of HH signaling as a novel therapeutic paradigm. Source of Funding: German Research Foundation (DFG)
MP40-02 INCREASED UPTAKE OF RENAL TUMOUR BIOPSIES FOR SMALL RENAL MASSES e RESULTS OF A MULTICENTRE CANADIAN EXPERIENCE Jaimin R. Bhatt*, Toronto, Canada; Simon Tanguay, Zhihui Liu, Montreal, Canada; Patrick O. Richard, Toronto, Canada; Anil Kapoor, Hamilton, Canada; Ricardo Rendon, Halifax, Canada; Louis Lacombe, Quebec City, Canada; Peter Black, Vancouver, Canada; Stephen Pautler, London, Canada; Rodney Breau, Ottawa, Canada; Ronald Moore, Edmonton, Canada; Michael Jewett, Antonio Finelli, Toronto, Canada INTRODUCTION AND OBJECTIVES: Renal tumour biopsy (RTB) has become increasingly important in the management of the
small renal mass (SRM) especially over the last decade. We aim to evaluate the uptake of RTB across Canadian centres using the Canadian Kidney Cancer Information System (CKCis) - a centralised database of kidney tumour patients. METHODS: A review of the CKCis database on RTB recorded from 6 provinces across Canada was performed. The database was started in 2011 and preceding data has been entered retrospectively. We analyzed patient demographics, biopsy diagnostic rates, histological subtype, tumour grade specifically in clinical T1a tumours, and determined concordance rates compared with surgical pathology. RESULTS: Of 2927 patients and 882 biopsies recorded on the CKCis database, 616 were RTBs of 552 patients between 1994 and 2013. There was a significant increase in the uptake of renal tumour biopsies (15% in 2010, 22% in 2011 and 42% in 2013) when compared to overall new diagnoses. Left and right renal biopsies were roughly equal. Mean age was 64 years. There was a male preponderance of 65%. Ninety per cent had one biopsy, while 10% had 2 or more. Of 470 patients with a recorded clinical T-stage, 259 or 55% were cT1a tumours, with 45% biopsies performed for lesions > 4cm. For the cT1a sub-group of 259 patients, a diagnosis was available in 236 or 91%. Of these, a malignant diagnosis was made in 80.4% while 19.6% were benign. Histological subtype was available in 88% of diagnostic biopsies (208/236) with 190 malignant (117 conventional clear cell, 44 papillary and 29 chromophobe) and 18 benign (2 angiomyolipoma and 16 oncocytoma). Grade was available in 67% of malignant cases. Of 259 cT1a tumours, 116 underwent surgery with partial nephrectomy in 78% and radical nephrectomy in 22%. Of all lesions recorded with a final surgical pathology, there was a 100% malignancy concordance rate. Histological subtype concordance rates varied between 80-85%. Grade concordance was lower at 65%. CONCLUSIONS: Our findings confirm an increased uptake of RTB in diagnosis of SRMs of <4cm over time with excellent diagnostic rates and overall malignancy concordance rates. There is however need to improve concordance rates for both grade and histological subtype as centres increase their uptake of renal tumour biopsies with the opportunity for enhanced experience and skills transfer. Source of Funding: None
MP40-03 TRENDS IN THE UTILIZATION OF PERCUTANEOUS RENAL MASS BIOPSY TO GUIDE THE MANAGEMENT OF RENAL MASSES: A POPULATION-BASED ANALYSIS Tudor Borza*, Brookline, MA; Ramdev Konijeti, Adam Feldman, Boston, MA; Benjamin Chung, Stanford, CA; Steven Chang, Boston, MA INTRODUCTION AND OBJECTIVES: The traditional paradigm for the management of renal masses involves therapy without a tissue diagnosis. However, there is a growing body of evidence supporting the use of percutaneous renal mass biopsy (RMB) to guide therapy to identify tumors not appropriate for surgery. Therefore, we sought to characterize trends in RMB utilization using a populationbased cohort. METHODS: We captured patients with a renal mass by identifying individuals in the Premier Perspective Database (Premier, Inc, Charlotte, NC) based on ICD9 codes for radical nephrectomy (55.51 who underwent a radical nephrectomy (ICD9 55.51, 55.52, 55.54), partial nephrectomy (55.4), ablation (55.32-55.39) and percutaneous renal biopsy (55.23); all patients had a concomitant diagnosis consistent with a renal mass (189.0-189.1, 196.x, 198.8x, 223.0-223.1, 236.91, 593.2, 594.9, 753.3, V10.52-V10.53). Patients were assumed to have a RMB to guide therapy if it was performed on a date separate from any intervention. We performed trend analysis to assess RMB utilization and multivariable logistic regression adjusting for survey
e434
Vol. 191, No. 4S, Supplement, Sunday, May 18, 2014
Kidney Cancer; Evaluation/Staging IV Moderated Poster Sunday, May 18, 2014
3:30 PM-5:30 PM
MP40-01 HEDGEHOG PATHWAY BIOMARKERS PREDICT ONCOLOGIC OUTCOME IN CLEAR CELL RENAL CELL CARCINOMA €ger*, Vancouver, Canada; Christian Thomas, Mainz, Wolfgang Ja Germany; Claudia Janßen, Vancouver, Canada; Irene Schmidtmann, €roff, Walburgis Brenner, Michael Hainz, Frederik Roos, Joachim Thu Mainz, Germany; Peter Black, Vancouver, Canada INTRODUCTION AND OBJECTIVES: Despite the advent of targeted therapy for renal cell carcinoma (RCC), responses to such therapy are rarely durable and metastatic RCC remains nearly uniformly fatal. The need for additional novel therapies persists. Aberrant hedgehog (HH) signaling has been proven important in the pathogenesis of several solid cancers. Limited in vitro analyses suggest an oncogenic role for HH in RCC and point towards HH signaling as a potential target for therapy. In the current study we sought validation of aberrant HH expression in patients with RCC. We investigated the expression levels of nine signaling markers of the HH pathway and their correlation with patient survival. METHODS: A tissue microarray (TMA) was constructed from 140 tumors taken from patients who underwent radical nephrectomy for clear cell RCC (ccRCC) between 1994 and 2002. Immunohistochemistry for the following HH pathway biomarkers was performed: Patched, CD31, Smoothend (Smo), Sonic Hedgehog (SHH), Indian Hedgehog (IHH) Dessert Hedgehog (DHH), Gli1, Gli2, and Gli3. Staining intensity was measured by automated image processing and was related to tumor stage and grade. Impact of biomarker expression on cancerspecific survival was determined with uni- and multivariate Cox regression analysis. RESULTS: The staining intensity of Gli1 and Smo was significantly higher in pT1 compared to pT2 ccRCC (for each p<0.001). DHH and CD31 showed significantly higher expression in the higher stage tumors (for each p<0.001). Expression of HH biomarkers was not related to tumor grade. In univariate analysis, DHH expression (p<0.05), tumor grade (p<0.01) and stage (p<0.001) correlated with cancer-specific survival. Multivariate analysis revealed DHH (p<0.05), Smo (p<0.05) and tumor stage (p<0.001) as independent predictors for cancer-specific survival (CSS). CONCLUSIONS: We have demonstrated for the first time that biomarkers of the Hedgehog pathway correlate with adverse pathologic features and poor disease outcome in patients with ccRCC. This supports further evaluation of HH signaling as a novel therapeutic paradigm. Source of Funding: German Research Foundation (DFG)
MP40-02 INCREASED UPTAKE OF RENAL TUMOUR BIOPSIES FOR SMALL RENAL MASSES e RESULTS OF A MULTICENTRE CANADIAN EXPERIENCE Jaimin R. Bhatt*, Toronto, Canada; Simon Tanguay, Zhihui Liu, Montreal, Canada; Patrick O. Richard, Toronto, Canada; Anil Kapoor, Hamilton, Canada; Ricardo Rendon, Halifax, Canada; Louis Lacombe, Quebec City, Canada; Peter Black, Vancouver, Canada; Stephen Pautler, London, Canada; Rodney Breau, Ottawa, Canada; Ronald Moore, Edmonton, Canada; Michael Jewett, Antonio Finelli, Toronto, Canada INTRODUCTION AND OBJECTIVES: Renal tumour biopsy (RTB) has become increasingly important in the management of the
small renal mass (SRM) especially over the last decade. We aim to evaluate the uptake of RTB across Canadian centres using the Canadian Kidney Cancer Information System (CKCis) - a centralised database of kidney tumour patients. METHODS: A review of the CKCis database on RTB recorded from 6 provinces across Canada was performed. The database was started in 2011 and preceding data has been entered retrospectively. We analyzed patient demographics, biopsy diagnostic rates, histological subtype, tumour grade specifically in clinical T1a tumours, and determined concordance rates compared with surgical pathology. RESULTS: Of 2927 patients and 882 biopsies recorded on the CKCis database, 616 were RTBs of 552 patients between 1994 and 2013. There was a significant increase in the uptake of renal tumour biopsies (15% in 2010, 22% in 2011 and 42% in 2013) when compared to overall new diagnoses. Left and right renal biopsies were roughly equal. Mean age was 64 years. There was a male preponderance of 65%. Ninety per cent had one biopsy, while 10% had 2 or more. Of 470 patients with a recorded clinical T-stage, 259 or 55% were cT1a tumours, with 45% biopsies performed for lesions > 4cm. For the cT1a sub-group of 259 patients, a diagnosis was available in 236 or 91%. Of these, a malignant diagnosis was made in 80.4% while 19.6% were benign. Histological subtype was available in 88% of diagnostic biopsies (208/236) with 190 malignant (117 conventional clear cell, 44 papillary and 29 chromophobe) and 18 benign (2 angiomyolipoma and 16 oncocytoma). Grade was available in 67% of malignant cases. Of 259 cT1a tumours, 116 underwent surgery with partial nephrectomy in 78% and radical nephrectomy in 22%. Of all lesions recorded with a final surgical pathology, there was a 100% malignancy concordance rate. Histological subtype concordance rates varied between 80-85%. Grade concordance was lower at 65%. CONCLUSIONS: Our findings confirm an increased uptake of RTB in diagnosis of SRMs of <4cm over time with excellent diagnostic rates and overall malignancy concordance rates. There is however need to improve concordance rates for both grade and histological subtype as centres increase their uptake of renal tumour biopsies with the opportunity for enhanced experience and skills transfer. Source of Funding: None
MP40-03 TRENDS IN THE UTILIZATION OF PERCUTANEOUS RENAL MASS BIOPSY TO GUIDE THE MANAGEMENT OF RENAL MASSES: A POPULATION-BASED ANALYSIS Tudor Borza*, Brookline, MA; Ramdev Konijeti, Adam Feldman, Boston, MA; Benjamin Chung, Stanford, CA; Steven Chang, Boston, MA INTRODUCTION AND OBJECTIVES: The traditional paradigm for the management of renal masses involves therapy without a tissue diagnosis. However, there is a growing body of evidence supporting the use of percutaneous renal mass biopsy (RMB) to guide therapy to identify tumors not appropriate for surgery. Therefore, we sought to characterize trends in RMB utilization using a populationbased cohort. METHODS: We captured patients with a renal mass by identifying individuals in the Premier Perspective Database (Premier, Inc, Charlotte, NC) based on ICD9 codes for radical nephrectomy (55.51 who underwent a radical nephrectomy (ICD9 55.51, 55.52, 55.54), partial nephrectomy (55.4), ablation (55.32-55.39) and percutaneous renal biopsy (55.23); all patients had a concomitant diagnosis consistent with a renal mass (189.0-189.1, 196.x, 198.8x, 223.0-223.1, 236.91, 593.2, 594.9, 753.3, V10.52-V10.53). Patients were assumed to have a RMB to guide therapy if it was performed on a date separate from any intervention. We performed trend analysis to assess RMB utilization and multivariable logistic regression adjusting for survey