Prognostic value of the combination of primary tumor location and RAS mutational status on patients with colorectal liver metastasis undergoing hepatectomy

Abstract

Objective To assess prognostic influences of RAS mutational status and primary tumor site on cases with colorectal liver metastasis (CRLM) who underwent hepatectomy. Methods Clinicopathological data of 762 patients with CRLM who underwent hepatectomy between January 2000 and November 2018 were retrospectively analyzed. The left‐sided tumors (LST) included tumors located in the splenic flexure, descending colon, sigmoid colon, and rectum; while right‐sided tumors (RST) included those located in the cecum, ascending colon, and transverse colon. RAS mutational status was determined using Sanger sequencing or next‐generation sequencing, including KRAS (Codons 12, 13, and 61) and NRAS (Codons 12, 13, and 61), which were defined as wild‐type (RASwt) and mutant‐type (RASmut), respectively. Survival curves were plotted using the Kaplan–Meier plotter and compared by the log rank test. The clinicopathological data were analyzed using univariate and multivariate analyses. Results The 5‐year overall survival (OS) in the LST group was longer than that in the RST group (OS: 47.1% vs. 31.0%, p = 0.000, respectively), and the OS in the RASwt group was longer compared with that in the RASmut group (OS: 53.6% vs. 24.0%, p = 0.000). Besides, overall survival of the patients after hepatectomy was alternative, which was stratified by primary tumor site, with the 1‐, 3‐, and 5‐year survival rates of 93.1%, 62.1%, and 47.1% for patients with LST, and 91.1%, 42.8%, and 31.0% for patients with RST, respectively. OS and disease‐free survival (DFS) were significantly different stratified by RAS mutational status, with the 1‐, 3‐, and 5‐year rates of 96.9%, 67.9%, and 53.6% for patients with RASwt tumors, and 85.7%, 41.5%, and 24.0% for patients with RASmut tumors, respectively. The 1‐, 3‐, and 5‐year DFS rates were 51.9%, 30.0%, and 26.7% for patients with RASwt tumors, and 35.8%, 18.2%, and 14.9% for patients with RASmut tumors, respectively. The results of multivariate analysis showed that RAS mutational status and primary tumor site were both independent influencing factors of OS. Conclusion RAS mutational status and primary tumor site affect OS independently in CRLM patients undergoing hepatectomy. The worse prognosis of RST cannot be simply attributed to the imbalance of RAS mutational status in different primary tumor sites.

RAS mutation nomograms to predict prognosis after radiofrequency ablation of recurrent colorectal liver metastases

“…RAS mutations occur in approximately 40-50% of patients undergoing CLM resection 18 and have been associated with lower effectiveness of preoperative chemotherapy 19 and poor OS in patients with resectable CLMs. 20 Many studies have reported that patients with RAS-mutated tumours have a higher risk of intrahepatic recurrence after local treatment. 14,[21][22][23] In this study, RAS mutation was a predictor of a higher rIHR rate and worse OS after RFA for recurrent CLMs, probably because the tumour biology is more migratory and in ltrative.…”

Impact of Age of Onset on Survival after Hepatectomy for Patients with Colorectal Cancer Liver Metastasis: A Real-World Single-Center Experience

“…Numerous studies have shown that RAS mutation is associated with poorer survival following curative resection of CRLM [ 14 , 29 , 30 ]. However, some studies have recently suggested that RAS mutations have different roles when predicting prognosis in CRLM with distinct clinical characteristics [ 20 , 31 ].…”

“…Comprehensive treatment based mainly on surgery is generally recognized as the best treatment option for patients with colorectal liver metastasis (CRLM). Several factors, including KRAS/BRAF mutation, the size of the largest tumor, the number of hepatic nodules, elevated serum tumor markers (CEA and CA 19-9), the interval between the primary tumor and the diagnosis of metastasis, the location, and the positive lymph node of the primary tumor have been found to be associated with oncological outcome after hepatectomy [ 12 , 13 , 14 , 15 , 16 ]. However, the effect of age on the long-term outcome of CRLM remains unclear.…”