Microvascular Tumor Invasion, Tumor Size and Fuhrman Grade: A Pathological Triad for Prognostic Evaluation of Renal Cell Carcinoma Marcos F. Dall’Oglio, Leopoldo Alves Ribeiro Filho, Alberto A. Antunes, Alexandre Crippa, Luciano Nesrallah, Pierre D. Gonçalves, Kátia R. M. Leite and Miguel Srougi* From the Division of Urology, Medical School, University of Sao Paulo, Sao Paulo, Brazil Purpose: The biological behavior and clinical outcome of renal cell carcinoma are difficult to predict. We investigated the prognostic impact of clinicopathological variables to establish a risk stratification model to predict recurrence and survival rates. Materials and Methods: We studied 230 patients with renal cell carcinoma (stages T 1–4 N x M 0 ) who underwent radical nephrectomy and/or nephron sparing surgery, and were followed for a median of 48 months (range 3 to 140). Univariate and multivariate analyses were performed, and the influence of clinical presentation, histological tumor size, tumor grade, lymph node involvement and microvascular tumor invasion on disease-free and cancer specific survival curves was determined. A composition model based on independent prognostic variables was then created to stratify tumors into low, intermediate and high risk of progression. Results: The tumor recurrence rate was 17% (39 of 230) and the cancer specific mortality rate was 13% (31 of 230). Multivariate analyses determined that microvascular tumor invasion, tumor grade and tumor size were the only independent prognostic factors. Disease-free survival rates for low, intermediate and high risk tumors were 94.7%, 56.8% and 13.1%, respectively. Cancer specific survival rates were 94.7%, 61.7% and 32.0%, respectively. Conclusions: Tumor size, Fuhrman grade and microvascular tumor invasion are strong and independent predictors of survival of patients with renal cell carcinoma. Risk assessment and stratification based on this triad of pathological features may allow better individualization of followup schedules and trials of adjuvant treatment for patients with renal cell carcinoma. Key Words: carcinoma, renal cell; prognosis; survival; neovascularization, pathologic; microcirculation T he incidence of RCC is increasing, in part due to the more frequent use of abdominal imaging. 1 Although 61% of renal tumors are now incidentally detected as small masses in asymptomatic patients, 2 a significant num- ber of patients undergoing curative surgical treatment can be expected to experience relapse at distant sites. 3 Several anatomical, histological, clinical and immunohis- tochemical features have been described as prognostic fac- tors for disease progression and survival. In addition to well established prognostic factors such as TNM stage, tumor size and Fuhrman grade, 4 the presence of microvascular tumor invasion in RCC is considered an important predictor of disease progression and recurrence. 5–9 Nevertheless, pathological reports of MVI in renal cancer are still rare in the literature. Because RCC is a singular disease with a highly variable natural history, the identification of a reliable set of prog- nostic factors may improve the treatment of patients with this disease. For instance, patients with RCC with indolent biological behavior could benefit from a more flexible fol- lowup schedule. On the other hand, high risk tumors may demand aggressive postoperative surveillance and perhaps some new available adjuvant systemic therapy. In the present study we analyzed the role of pathological prognostic data obtained from the surgical specimen exam- ination, identified independent variables by multivariate analysis, and established groups of patients at higher risk for disease recurrence and disease related death. PATIENTS AND METHODS The records of 230 consecutive patients surgically treated for RCC at our institution between 1988 and 2003 were retrospectively reviewed. The present study included pa- tients who underwent open radical nephrectomy and/or re- nal conservative surgery (partial nephrectomy or tumor enu- cleation). The exclusion criteria consisted of the presence of metastatic disease at the time of diagnosis or incomplete pathological data. The demographic data are described in table 1. Clinical staging (T 1 –T 4 N x M 0 ) was preoperatively deter- mined by imaging studies (computerized tomography, mag- Submitted for publication December 26, 2006. Nothing to disclose. * Correspondence: Rua Barata Ribeiro, n. 414, 7°. Andar, 01308 - 000 - São Paulo – SP, Brazil (telephone: 55 11 32578002; FAX: 55 11 32579006; e-mail: srougi@terra.com.br). Editor’s Note: This article is the first of 5 published in this issue for which category 1 CME credits can be earned. Instructions for obtaining credits are given with the questions on pages 732 and 733. 0022-5347/07/1782-0425/0 Vol. 178, 425-428, August 2007 THE JOURNAL OF UROLOGY ® Printed in U.S.A. Copyright © 2007 by AMERICAN UROLOGICAL ASSOCIATION DOI:10.1016/j.juro.2007.03.128 425