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METASTATIC PROGRESSION OF ENHANCING RENAL MASSES UNDER ACTIVE SURVEILLANCE IS ASSOCIATED WITH RAPID INTERVAL GROWTH OF THE PRIMARY TUMOR
Vol. 179, No. 4, Supplement, Monday, May 19, 2008
1089 METASTATIC PROGRESSION OF ENHANCING RENAL MASSES UNDER ACTIVE SURVEILLANCE IS ASSOCIATED WITH RAPID INTERVAL GROWTH OF THE PRIMARY TUMOR David A Kunkle*, David Y T Chen, Richard E Greenberg, Rosalia Viterbo, Robert G Uzzo. Philadelphia, PA. INTRODUCTION AND OBJECTIVE: Although surgical extirpation remains the standard of care for small renal masses (SRMs), HPHUJLQJ GDWD H[LVW UHJDUGLQJ DFWLYH VXUYHLOODQFH RI ORFDOL]HG UHQDO masses. While published series report variability in growth rates of REVHUYHGOHVLRQVQRJXLGHOLQHVH[LVWVIRUVL]HJURZWKWKUHVKROGVDWZKLFK the risk of progression to metastatic RCC (mRCC) warrants intervention. +HUHZHHYDOXDWHWKHJURZWKSDWWHUQVRIORFDOL]HGUHQDOWXPRUVXQGHU active surveillance that progress to mRCC in order to gain insight into the natural history of SRMs. METHODS: We evaluated the published literature in addition to the largest series to date, from our institution, regarding clinically ORFDOL]HG VSRUDGLF UHQDO PDVVHV PDQDJHG E\ DFWLYH VXUYLHOODQFH Clinical and growth rate data pertaining to lesions undergoing metastatic SURJUHVVLRQZKLOHXQGHUREVHUYDWLRQZHUHWKHQDQDO\]HG RESULTS: 470 renal tumors managed by active surveillance DW LQVWLWXLRQV ZHUH DQDO\]HG 0HDQ SDWLHQW DJH ZDV \HDUV 0HDQWXPRUVL]HIRUDOOREVHUYHGOHVLRQVZDVFP0HDQGXUDWLRQ of surveillance was 33.7 months (study range: 26.9-47.6). Metastatic disease was detected in 7/470 (1.5%) lesions under active surveillance. )RUOHVLRQVZKLFKGLGQRWPHWDVWDVL]HWKHPHDQQHWLQFUHDVHLQWXPRU diameter during observation was 0.77 cm (study range: 0.19-1.86) while the mean growth rate was 0.29 cm/year (study range: 0.06-1.02). For those lesions which progressed to mRCC, mean net increase in maximal tumor diameter was 3.15 cm (range 1.8-6) while mean growth rate was 0.74 cm/year (range 0.20-1.33) from the time of diagnosis to detection of mRCC. No lesions progressed to mRCC in the absence of interval radiographic growth. Mean time from tumor diagnosis to clinical metastases was 65.4 months (range 20-132). CONCLUSIONS: Metastatic progression of renal masses managed by active surveillance is an infrequent event. All reported primary lesions which progressed to mRCC during a period of surveillance demonstrated rapid interval radiographic growth prior to clinical detection of metastasis, which was a delayed event (mean 65.4 months). Metastasic progression has not been reported in the absence of interval growth. These data suggest that an initial period of close radiographic surveillance may identify lesions at higher risk for progression. Active surveillance with delayed intervention may be DYLDEOHVWUDWHJ\IRUVHOHFWHGSDWLHQWVXQ¿WRUXQZLOOLQJWRDFFHSWULVNV associated with immediate intervention. Source of Funding: None
1090 INVESTIGATION OF PREOPERATIVE SERUM C-REACTIVE PROTEIN ELEVATION IN RECURRENCE FOR PATIENTS WITH LOCALIZED RENAL CELL CARCINOMA Soichi Mugiya*, Seiichiro Ozono, Masao Nagata, Tatsuya Takayama, Tomomi Ushiyama. Hamamatsu, Japan. INTRODUCTION AND OBJECTIVE: Serum level of C-reactive protein (CRP) is frequently increased in patients with cancer, and was found to be associated with the prognosis in patients with advanced renal cell carcinoma (RCC). However, there are few studies that have H[DPLQHGWKHSURJQRVWLFYDOXHRI&53LQSDWLHQWVZLWKORFDOL]HG5&& We attempted to evaluate the importance of the preoperative serum &53HOHYDWLRQLQUHFXUUHQFHIRUSDWLHQWVZLWKORFDOL]HG5&& METHODS: We studied retrospectively the records of 448 SDWLHQWVZLWK5&&ZKRXQGHUZHQWFXUDWLYHUHVHFWLRQXQGHUFODVVL¿FDWLRQ as T1-3aN0M0. Disease-free and overall survival rates were estimated using the Kaplan-Meier method, and its associations with the CRP and other clinical and pathologic features were evaluated using Cox SURSRUWLRQDOKD]DUGPRGHO:HDOVRH[DPLQHGWKHSUHGLFWLYHYDOXHRI CRP as a predictor for recurrence, using receiver-operator characteristic (ROC) analysis. 5(68/76 7 FODVVL¿FDWLRQ LQFOXGHG 7D LQ SDWLHQWV T1b in 160, T2 in 67, and T3a in 52. Of the 448 patients, 49 patients presented recurrence of RCC during a median follow-up of 54 months.
THE JOURNAL OF UROLOGY®
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Disease-free survival rates at 5 and 10 years accounted for 91 and 84%, UHVSHFWLYHO\3DWLHQWVZLWKHOHYDWHG&53OHYHOVKDGVLJQL¿FDQWO\KLJKHU pathological T stage and histological grade. The preoperative serum CRP OHYHOVLQSDWLHQWVZLWKUHFXUUHQFH ZHUHVLJQL¿FDQWO\KLJKHU than those in patients with non-recurrence (0.867±3.003) (p=0.0132). Using ROC analysis, CRP threshold value of 0.25 mg/dL gave a high VHQVLWLYLW\DQGVSHFL¿FLW\IRUUHFXUUHQFH$QDO\VLVRIGLVHDVHIUHHDQG RYHUDOO VXUYLYDO UDWHV UHYHDOHG WKDW WKHUH ZDV VLJQL¿FDQW GLIIHUHQFH between CRP levels less than 0.25 mg/dL and over 0.25 mg/dL. The IROORZLQJSURJQRVWLFIDFWRUVZHUHIRXQGVLJQL¿FDQWIRUUHFXUUHQFHE\ XQLYDULDWH DQDO\VLV LQFOXGHG 7 FODVVL¿FDWLRQ 77 SUHVHQWDWLRQ (incidental/symptomatic), serum IAP (over 460/under 460), serum CRP (over 0.25/under 0.25) and histological grade (G1/G2-3). Multivariate analysis showed that CRP elevation was only one prognostic factor for recurrence (p=0.0073). CONCLUSIONS: The preoperative CRP elevation in patients ZLWKORFDOL]HG5&&ZDVDQLQGHSHQGHQWSUHGLFWRUIRUUHFXUUHQFH7KH appropriate threshold value of CRP for recurrence was 0.25 mg/dL. Source of Funding: None
1091 MATRIX METALLOPROTEINASES AND ITS RELATED PROTEINS ARE PROGNOSTIC FACTORS OF LOW GRADE RENAL CELL CARCINOMA WITHOUT METASTASIS Kenya Yamaguchi*, Nozomu Kawata, Yusuke Nagane, Takumi Igarashi, Taketo Ichinose, Hitoshi Hirakata, Yukie Takimoto, Satoru Takahashi. Tokyo, Japan. INTRODUCTION AND OBJECTIVE: To determine whether matrix metalloproteinases (MMPs) and its related proteins are prognostic factors of low grade renal cell carcinoma without metastasis. METHODS: From 1988 to 2003, 252 cases with renal cell carcinoma underwent operation at our institution. 187 cases out of 252 had Fuhrman’s grade 1 or grade 2 without metastasis. The group consisted of 144 male and 43 female with an average age of 59.6 years old. The average observation period of them was 55.5 month. According to the AJCC cancer staging manual (the 6th edition), StageIwere in 124 cases, stageII 26 cases and stageIII 37 cases. The histologic FODVVL¿FDWLRQVRIWKHPZHUHFDVHVRIFOHDUFHOODQGRIJUDQXODU cell. The evaluated parameters for uni- and multivariate analysis included positive immunoreactivities for MMP-2, MMP-9, TIMP-1, TIMP-2, MT-1MMP, presence of symptom, tumor diameter>40mm, stage and vascular invasion. For the determination of type of MMP, we combined positive reactivity for MT-1-MMP with MMP-2 or MMP-9 and describe like MTMMP2 or MT-MMP9. RESULTS: Presence of symptoms, tumor diameter, MMP-2, MMP-9, MT-MMP-2 were meaningful prognostic factors by the XQLYDULDWHDQDO\VLVZLWKHDFKKD]DUGUDWLRRI respectively (Fig.1). MMP-9, MT-MMP-2, MT-MMP-9 were independent SURJQRVWLFIDFWRUVE\WKHPXOWLYDULDWHDQDO\VLVDQGHDFKKD]DUGUDWLR was 7.57, 7.51, 17.73 (Fig.2).
1089 METASTATIC PROGRESSION OF ENHANCING RENAL MASSES UNDER ACTIVE SURVEILLANCE IS ASSOCIATED WITH RAPID INTERVAL GROWTH OF THE PRIMARY TUMOR David A Kunkle*, David Y T Chen, Richard E Greenberg, Rosalia Viterbo, Robert G Uzzo. Philadelphia, PA. INTRODUCTION AND OBJECTIVE: Although surgical extirpation remains the standard of care for small renal masses (SRMs), HPHUJLQJ GDWD H[LVW UHJDUGLQJ DFWLYH VXUYHLOODQFH RI ORFDOL]HG UHQDO masses. While published series report variability in growth rates of REVHUYHGOHVLRQVQRJXLGHOLQHVH[LVWVIRUVL]HJURZWKWKUHVKROGVDWZKLFK the risk of progression to metastatic RCC (mRCC) warrants intervention. +HUHZHHYDOXDWHWKHJURZWKSDWWHUQVRIORFDOL]HGUHQDOWXPRUVXQGHU active surveillance that progress to mRCC in order to gain insight into the natural history of SRMs. METHODS: We evaluated the published literature in addition to the largest series to date, from our institution, regarding clinically ORFDOL]HG VSRUDGLF UHQDO PDVVHV PDQDJHG E\ DFWLYH VXUYLHOODQFH Clinical and growth rate data pertaining to lesions undergoing metastatic SURJUHVVLRQZKLOHXQGHUREVHUYDWLRQZHUHWKHQDQDO\]HG RESULTS: 470 renal tumors managed by active surveillance DW LQVWLWXLRQV ZHUH DQDO\]HG 0HDQ SDWLHQW DJH ZDV \HDUV 0HDQWXPRUVL]HIRUDOOREVHUYHGOHVLRQVZDVFP0HDQGXUDWLRQ of surveillance was 33.7 months (study range: 26.9-47.6). Metastatic disease was detected in 7/470 (1.5%) lesions under active surveillance. )RUOHVLRQVZKLFKGLGQRWPHWDVWDVL]HWKHPHDQQHWLQFUHDVHLQWXPRU diameter during observation was 0.77 cm (study range: 0.19-1.86) while the mean growth rate was 0.29 cm/year (study range: 0.06-1.02). For those lesions which progressed to mRCC, mean net increase in maximal tumor diameter was 3.15 cm (range 1.8-6) while mean growth rate was 0.74 cm/year (range 0.20-1.33) from the time of diagnosis to detection of mRCC. No lesions progressed to mRCC in the absence of interval radiographic growth. Mean time from tumor diagnosis to clinical metastases was 65.4 months (range 20-132). CONCLUSIONS: Metastatic progression of renal masses managed by active surveillance is an infrequent event. All reported primary lesions which progressed to mRCC during a period of surveillance demonstrated rapid interval radiographic growth prior to clinical detection of metastasis, which was a delayed event (mean 65.4 months). Metastasic progression has not been reported in the absence of interval growth. These data suggest that an initial period of close radiographic surveillance may identify lesions at higher risk for progression. Active surveillance with delayed intervention may be DYLDEOHVWUDWHJ\IRUVHOHFWHGSDWLHQWVXQ¿WRUXQZLOOLQJWRDFFHSWULVNV associated with immediate intervention. Source of Funding: None
1090 INVESTIGATION OF PREOPERATIVE SERUM C-REACTIVE PROTEIN ELEVATION IN RECURRENCE FOR PATIENTS WITH LOCALIZED RENAL CELL CARCINOMA Soichi Mugiya*, Seiichiro Ozono, Masao Nagata, Tatsuya Takayama, Tomomi Ushiyama. Hamamatsu, Japan. INTRODUCTION AND OBJECTIVE: Serum level of C-reactive protein (CRP) is frequently increased in patients with cancer, and was found to be associated with the prognosis in patients with advanced renal cell carcinoma (RCC). However, there are few studies that have H[DPLQHGWKHSURJQRVWLFYDOXHRI&53LQSDWLHQWVZLWKORFDOL]HG5&& We attempted to evaluate the importance of the preoperative serum &53HOHYDWLRQLQUHFXUUHQFHIRUSDWLHQWVZLWKORFDOL]HG5&& METHODS: We studied retrospectively the records of 448 SDWLHQWVZLWK5&&ZKRXQGHUZHQWFXUDWLYHUHVHFWLRQXQGHUFODVVL¿FDWLRQ as T1-3aN0M0. Disease-free and overall survival rates were estimated using the Kaplan-Meier method, and its associations with the CRP and other clinical and pathologic features were evaluated using Cox SURSRUWLRQDOKD]DUGPRGHO:HDOVRH[DPLQHGWKHSUHGLFWLYHYDOXHRI CRP as a predictor for recurrence, using receiver-operator characteristic (ROC) analysis. 5(68/76 7 FODVVL¿FDWLRQ LQFOXGHG 7D LQ SDWLHQWV T1b in 160, T2 in 67, and T3a in 52. Of the 448 patients, 49 patients presented recurrence of RCC during a median follow-up of 54 months.
THE JOURNAL OF UROLOGY®
375
Disease-free survival rates at 5 and 10 years accounted for 91 and 84%, UHVSHFWLYHO\3DWLHQWVZLWKHOHYDWHG&53OHYHOVKDGVLJQL¿FDQWO\KLJKHU pathological T stage and histological grade. The preoperative serum CRP OHYHOVLQSDWLHQWVZLWKUHFXUUHQFH ZHUHVLJQL¿FDQWO\KLJKHU than those in patients with non-recurrence (0.867±3.003) (p=0.0132). Using ROC analysis, CRP threshold value of 0.25 mg/dL gave a high VHQVLWLYLW\DQGVSHFL¿FLW\IRUUHFXUUHQFH$QDO\VLVRIGLVHDVHIUHHDQG RYHUDOO VXUYLYDO UDWHV UHYHDOHG WKDW WKHUH ZDV VLJQL¿FDQW GLIIHUHQFH between CRP levels less than 0.25 mg/dL and over 0.25 mg/dL. The IROORZLQJSURJQRVWLFIDFWRUVZHUHIRXQGVLJQL¿FDQWIRUUHFXUUHQFHE\ XQLYDULDWH DQDO\VLV LQFOXGHG 7 FODVVL¿FDWLRQ 77 SUHVHQWDWLRQ (incidental/symptomatic), serum IAP (over 460/under 460), serum CRP (over 0.25/under 0.25) and histological grade (G1/G2-3). Multivariate analysis showed that CRP elevation was only one prognostic factor for recurrence (p=0.0073). CONCLUSIONS: The preoperative CRP elevation in patients ZLWKORFDOL]HG5&&ZDVDQLQGHSHQGHQWSUHGLFWRUIRUUHFXUUHQFH7KH appropriate threshold value of CRP for recurrence was 0.25 mg/dL. Source of Funding: None
1091 MATRIX METALLOPROTEINASES AND ITS RELATED PROTEINS ARE PROGNOSTIC FACTORS OF LOW GRADE RENAL CELL CARCINOMA WITHOUT METASTASIS Kenya Yamaguchi*, Nozomu Kawata, Yusuke Nagane, Takumi Igarashi, Taketo Ichinose, Hitoshi Hirakata, Yukie Takimoto, Satoru Takahashi. Tokyo, Japan. INTRODUCTION AND OBJECTIVE: To determine whether matrix metalloproteinases (MMPs) and its related proteins are prognostic factors of low grade renal cell carcinoma without metastasis. METHODS: From 1988 to 2003, 252 cases with renal cell carcinoma underwent operation at our institution. 187 cases out of 252 had Fuhrman’s grade 1 or grade 2 without metastasis. The group consisted of 144 male and 43 female with an average age of 59.6 years old. The average observation period of them was 55.5 month. According to the AJCC cancer staging manual (the 6th edition), StageIwere in 124 cases, stageII 26 cases and stageIII 37 cases. The histologic FODVVL¿FDWLRQVRIWKHPZHUHFDVHVRIFOHDUFHOODQGRIJUDQXODU cell. The evaluated parameters for uni- and multivariate analysis included positive immunoreactivities for MMP-2, MMP-9, TIMP-1, TIMP-2, MT-1MMP, presence of symptom, tumor diameter>40mm, stage and vascular invasion. For the determination of type of MMP, we combined positive reactivity for MT-1-MMP with MMP-2 or MMP-9 and describe like MTMMP2 or MT-MMP9. RESULTS: Presence of symptoms, tumor diameter, MMP-2, MMP-9, MT-MMP-2 were meaningful prognostic factors by the XQLYDULDWHDQDO\VLVZLWKHDFKKD]DUGUDWLRRI respectively (Fig.1). MMP-9, MT-MMP-2, MT-MMP-9 were independent SURJQRVWLFIDFWRUVE\WKHPXOWLYDULDWHDQDO\VLVDQGHDFKKD]DUGUDWLR was 7.57, 7.51, 17.73 (Fig.2).