Pathologic Upstaging after Laparoscopic Radical Nephrectomy

Vol. 179, No. 4, Supplement, Monday, May 19, 2008

604 SURGICAL MORBIDITY ASSOCIATED WITH ADMINISTRATION OF TARGETED MOLECULAR THERAPIES PRIOR TO CYTOREDUCTIVE NEPHRECTOMY FOR METASTATIC RENAL CELL CARCINOMA Vitaly Margulis*, Surena F Matin, Pheroze Tamboli, David A Swanson, Christopher G Wood. Houston, TX. INTRODUCTION AND OBJECTIVE: The use of targeted PROHFXODU WKHUDSLHV 707  VXFK DV EHYDFL]XPDE VXQLWLQLE DQG sorafenib prior to cytoreductive nephrectomy (CN) holds promise as a rational treatment paradigm for patients with metastatic renal cell FDUFLQRPD P5&&  7R DQDO\]H WKHLU VDIHW\ LQ SUHVXUJLFDO VHWWLQJ we evaluated surgical parameters and perioperative complications in patients treated with TMTs prior to CN and compared them to a matched patient cohort who underwent initial CN. METHODS: urgical parameters and perioperative FRPSOLFDWLRQVZHUHLGHQWL¿HGLQSDWLHQWVWUHDWHGZLWK707VSULRUWR CN and in a matched cohort of 58 patients who underwent initial CN. RESULTS: Pre-surgical TMT and initial CN patient cohorts were matched in terms of their clinical characteristics, burden of metastatic disease, and number of adverse prognostic factors. A total of 44 complications occurred in 22 (40.0%) patients treated with presurgical TMT and in 16 (37.9%) patients who underwent initial CN. 7KHUHZHUHQRVWDWLVWLFDOO\VLJQL¿FDQWGLIIHUHQFHVLQVXUJLFDOSDUDPHWHUV incidence of perioperative mortality, re-exploration, re-admission, thromboembolic, cardiovascular, pulmonary, gastrointestinal, infectious, or incision related complications between patients treated with presurgical TMT and patients who underwent initial CN. Duration, type and interval from TMT to CN were not associated with the risk of developing perioperative morbidity. CONCLUSIONS: Pre-surgical administration of TMTs is safe, and does not increase surgical morbidity or perioperative complications associated with CN for mRCC. Association of pre-surgical targeted molecular therapy with perioperative complications after CN. Complication Type Odds Ratio 95% CI p All complications 0.667 0.260 - 1.258 0.165 Perioperative mortality 1.113 0.460 - 1.345 0.997 Re-exploration 1.445 0.232 - 8.998 0.693 Re-admission 0.943 0.258 - 3.456 0.930 Thromboembolic 0.224 0.024 - 2.067 0.187 Cardiovascular 0.619 0.099 - 3.854 0.607 Pulmonary 0.811 0.244 - 4.724 0.345 Gastrointestinal 1.154 0.331 - 4.022 0.822 Infectious 1.315 0.361 - 1.447 0.895 Incision related 0.835 0.123 - 1.538 0.196

Source of Funding: American Foundation for Urologic Disease (AFUD).

605 MOLECULAR PROGNOSTIC TUMOR PROFILING OF TYPE 1 AND TYPE 2 PAPILLARY RENAL CELL CARCINOMA: RELEVANCE TO THE DEVELOPMENT OF TUMOR-SPECIFIC TARGETED THERAPIES Tobias Klatte*, Jonathan W Said, David B Seligson, Jeffrey LaRochelle, Brian Shuch, Fairooz F Kabbinavar, Amnon Zisman, $OODQ-3DQWXFN$ULH6%HOOGHJUXQ/RV$QJHOHV&$DQG=HUL¿Q Israel.. INTRODUCTION AND OBJECTIVE: Papillary renal cell carcinoma (PRCC) is the second most common histological subtype among patients undergoing surgery for kidney cancer, but the molecular SUR¿OHRIWKLVHQWLW\LVQRWZHOOFKDUDFWHUL]HG7KHJRDOVRIWKLVVWXG\ZHUH (1) to evaluate differences in expression between type 1 and 2 PRCC, DQG WRDQDO\]HWKHSURJQRVWLFLPSDFWRIPROHFXODUPDUNHUV METHODS: We examined clinicopathological features and molecular markers in 40 patients treated by nephrectomy with the ¿QDO SDWKRORJ\ EHLQJ 35&& 6OLGHV ZHUH DOO UHUHYLHZHG E\ RQH *8 pathologist (JWS). A tissue microarray consisting of the tumor specimens was constructed. Immunohistochemical staining was performed with antibodies directed against 29 tumor markers. Expression was evaluated as the percentage of the entire tumor sample that stained positive. MannWhitney’s U-test was used to compare marker expressions between

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W\SHQ  DQGQ  (QGSRLQWRIWKLVVWXG\ZDVGLVHDVHVSHFL¿F survival (DSS). Median follow-up was 6.9 years. RESULTS: Type 2 expressed VEGF-R2 in the tumor epithelium (mean: 57% vs. 30%, p=0.007), and VEGF-R3 in both tumor epithelium (19% vs. 6%, p=0.028) and endothelium of associated vessels (11% vs. 0.2%, p=0.009) to a greater degree than type 1. All other 26 evaluated markers showed no differences. In univariate Cox regression analysis, lower PTEN (p=0.027), lower gelsolin (p