Presentation Authors: Cedric Lebacle, Le Kremlin Bicetre, France, Aydin Pooli*, Nagesh Rao, Erika L. Wood, Los Angeles, CA, Nils Kroeger, Greifswald, Germany, Grace-Hyun Kim, Izak Faiena, Sandy T. Liu, Karim Chamie, Arie S. Belldegrun, Brian Shuch, Alexandra Drakaki, Allan J. Pantuck, Los Angeles, CA
Introduction: Thirty percent of patients with localized clear-cell renal cell carcinoma (ccRCC) will ultimately develop recurrence (local or metastatic) after nephrectomy. Current risk stratification systems still misclassify patients. We developed a novel classification integrating cytogenetic findings to better stratify the risk of recurrence and overall survival (OS) after surgery for localized ccRCC.
Methods: A total of 646 patients from UCLA with ccRCC and tumor cytogenetic analysis, were included in this study. After a logistic regression analysis to select histologic parameters and a principal component analysis for cytogenetic parameters, a CHAID decision tree and Kaplan Meier analysis were used to build the UCLA Histo-Genetic Risk Classification (U-HGRC). Survival analyses of the model were validated on two random samples of 323 patients. Recurrence was defined as any local recurrence or development of new metastasis after surgery.
Results: The T-stage, tumor size, presence of sarcomatoid features, gain of chromosome 5q, loss 10q, and loss X/Y were used to stratify the risk of recurrence of ccRCC into three U-HGRC groups of low (1), intermediate (2) or high-risk (3). After a mean follow-up of 55 months, risk of recurrence (HR=2.44, p=.001 for U-HGRC 2; HR=9.90, p < .0001 for U-HGRC 3), disease-free survival (DFS) (Log-rank p < .0001), risk of death (HR=1.72, p=.033 for U-HGRC 2; HR=4.74, p < .0001 for U-HGRC 3) and OS (Log-rank p < .0001) were significantly different between groups. These findings were validated on two random samples. For the high-risk group, median DFS and OS were 2.7 and 6.3 years, respectively. The 5-year risks of recurrence for U-HGRC group 1, 2 and 3 were 9%, 25% and 62%, respectively. The AUC of the model was significantly improved comparing to the current UISS system (0.72 for U-HGRC vs 0.65 for UISS, p=.008) with an accuracy of 82.8% for the U-HGRC high-risk group.
Conclusions: The U-HGRC, which integrates genomic alterations with clinical and pathologic features, allowed a better stratification of recurrence risk and overall survival that could help to select appropriate patients for surveillance and adjuvant therapy protocols.
Source of Funding: Grants from French urological association, Philippe Foundation, Groupe Pasteur Mutualite, Servier Foundation, Astellas