The UCLA Histo-Genetic Risk Classification (U-HGRC) to predict outcomes of localized clear cell renal cell carcinoma.

Abstract

627 Background: 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 have 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 selection of histologic parameters using logistic regression and cytogenetic parameters using principal component analysis 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, or 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 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.