Prognostic Impact of Tumor Size on pT2 Renal Cell Carcinoma: An International Multicenter Experience Tobias Klatte, Jean-Jacques Patard, Rakhee H. Goel, Mark D. Kleid, Francois Guille, Bernard Lobel, Clement-Claude Abbou, Alexandre De La Taille, Jacques Tostain, Luca Cindolo, Vincenzo Altieri, Vincenzo Ficarra, Walter Artibani, Tommaso Prayer-Galetti, Ernst Peter Allhoff, Luigi Schips, Richard Zigeuner, Robert A. Figlin, Fairooz F. Kabbinavar, Allan J. Pantuck, Arie S. Belldegrun and John S. Lam* From the Departments of Urology (TK, RHG, MDK, AJP, ASB, JSL) and Medicine (RAF, FFK), University of California, Los Angeles, Los Angeles, California, and the Department of Urology, Centre Hospitalier Universitaire Pontchaillou, Rennes (JJP, FG, BL), Centre Hospitalier Universitaire Henri Mondor, Créteil (CCA, ADLT), Centre Hospitalier Universitaire of Saint Etienne, Saint Etienne (JT), France, Medical School of University “Federico II,” Naples (LC, VA) and University of Padua, Padua (VF, WA, TPG), Italy, University of Magdeburg, Magdeburg, Germany (EPA), and University Hospital, Medical University of Graz, Graz, Austria (LS, RZ) Purpose: The current tumor classification for renal cell carcinoma classifies pT2 tumors as larger than 7 cm in greatest dimension and limited to the kidney. We examined the current pT2 tumor classification of renal cell carcinoma and determined whether a tumor size cutoff exists that would improve prognostic accuracy. Materials and Methods: We studied 706 patients with pT2 renal cell carcinoma treated with surgical extirpation at 9 international academic centers. Data collected from each patient included age at diagnosis, gender, 2002 TNM (tumor, node, metastasis) stage, tumor size, nuclear grade, performance status, histological subtype and disease specific survival. Disease specific survival was evaluated with univariate and multivariate analysis. Results: Median followup was 52 months. Univariate Cox regression analysis showed a significant association of tumor size with disease specific survival (HR 1.11, p 0.001). An ideal tumor size cutoff of 11 cm was identified, which led to the stratification of 2 groups with respect to disease specific survival (p 0.0001) with 5 and 10-year survival rates of 73% and 65% for pT2 11 cm or less, and 57% and 49% for pT2 larger than 11 cm, respectively. The incidence of metastases was significantly greater in the larger than 11 cm group, while Eastern Cooperative Oncology Group performance status, Fuhrman grade and histological subtype were similar. Multivariate Cox regression analysis retained tumor size as an independent prognostic factor and as the strongest prognostic factor for patients with pT2N0M0 disease. Conclusions: Our data suggest that the current pT2 classification can be improved by subclassification into pT2a and pT2b based on a tumor size cutoff of 11 cm. Patients in the proposed pT2bN0M0 group are at higher risk for death from renal cell carcinoma and should be considered for adjuvant therapies. External validation is warranted before suggesting change to the TNM classification. Key Words: neoplasm staging, prognosis, neoplasm metastasis, classification R enal cell carcinoma accounts for approximately 3% of all adult malignancies. In 2006 approximately 39,000 new cases and 13,000 deaths were to have resulted from RCC in the United States. 1 About 30% of newly diag- nosed patients present with metastatic disease and metas- tases will eventually develop in 20% to 30% of patients undergoing curative nephrectomy for nonmetastatic RCC. 2 The methods to determine prognosis and select patients for postoperative therapy mainly rely on staging, which is performed worldwide according the American Joint Commit- tee on Cancer (AJCC)/Union Internationale Contre le Can- cer (UICC) tumor, node, metastasis (TNM) classification. 3 Accordingly, primary RCC limited to the kidney with a tu- mor size greater than 7 cm is classified as pT2. Unlike pT1 RCC, which is subdivided into pT1a (4 cm or smaller) and pT1b (4 to 7 cm), all pT2 tumors are classified together regardless of size. Although it has been well accepted that tumor size is an important prognostic factor in RCC, 4,5 few efforts have been made to develop a subclassification for pT2 based on tumor size. Recently Frank et al proposed a sub- classification into pT2a and pT2b based on a tumor size cutoff of 10 cm. 6 However, other groups were not able to demonstrate that tumor size was a prognostic indicator among patients with primary tumors limited to the kid- ney. 7,8 To determine the worldwide prognostic impact of tumor size and, consequently, whether a tumor size cutoff exists within pT2 RCC that improves the prognostic accuracy of the current TNM staging system, we collected data from more than 700 patients at 9 international institutions. Submitted for publication November 27, 2006. * Correspondence: Department of Urology, David Geffen School of Medicine at University of California-Los Angeles, 10833 Le Conte Ave., 66-124 CHS, Box 951738, Los Angeles, California 90095-1738 (telephone: 310-794-6584; FAX: 310-206-5343; e-mail: jlam@mednet. ucla.edu). Oncology: Adrenal/Renal/Upper Tract/Bladder 0022-5347/07/1781-0035/0 Vol. 178, 35-40, July 2007 THE JOURNAL OF UROLOGY ® Printed in U.S.A. Copyright © 2007 by AMERICAN UROLOGICAL ASSOCIATION DOI:10.1016/j.juro.2007.03.046 35