RAS-Beppu Classification: A New Recurrence Risk Classification System Incorporating the Beppu Score and RAS Status...

Background: Preoperative recurrence risk stratification for colorectal liver metastases (CRLM) undergoing hepatectomy is essential when designing a treatment strategy. We developed a Beppu classification system consisting of three risk groups and found that the RAS mutation increased risk in low- and moderate-risk patients. Methods: A total of 173 patients undergoing initial hepatectomy for CRLM between 2004 and 2020 were analyzed. Disease-free survival (DFS) and overall survival (OS) were assessed. Patients in the low- and moderate-risk groups of the Beppu classification with RAS mutations were moved into the moderate- and high-risk groups, respectively, in the RAS-Beppu classification. Results: The DFS curves of the three risk groups in the Beppu and RAS-Beppu classification were significantly different. Five-year DFS rates were 57%, 31%, and 16% in the RAS-Beppu classification of low-, moderate-, and high-risk groups, respectively. With multivariate analysis, Beppu classifications (p = 0.0017) and RAS-Beppu classifications (p = 0.0002) were independent prognostic factors for DFS. The RAS-Beppu classification showed higher hazard ratios than the Beppu classification, as well as the genetic and morphological evaluation score and the modified clinical risk score, which include the RAS status. The hazard ratios in the RAS-Beppu classification were significant in all two-group comparisons (2.22 for moderate vs. low, 3.48 for high vs. low, and 1.70 for high vs. moderate). The multivariate analysis of OS showed benefits of the RAS-Beppu classification in the high- vs. low-risk and high- vs. moderate-risk comparisons. Conclusions: The RAS-Beppu classification using standard parameters is a novel suitable tool for predicting recurrence risk before liver resection.