Limited Prognostic Value of KRAS in Patients Undergoing Hepatectomy for Colorectal Liver Metastases

Background: RAS mutation status is considered a powerful prognostic factor in patients undergoing hepatectomy for colorectal liver metastases (CLM). However, whether its prognostic power is robust regardless of administration of preoperative chemotherapy or tumor burden remains unclear.

Methods: Consecutive patients who underwent initial hepatectomy for CLM from April 2010 through March 2017 in two hospitals were included. The prognostic value of KRAS was compared based on whether patients received preoperative chemotherapy and their tumor burden score (TBS).

Results: We included 409 patients (median follow-up 38 months). In the preoperative chemotherapy group, patients with mutant KRAS (mt-KRAS) CLM had poorer overall survival (OS) than those with wild KRAS (wt-KRAS; 5-year OS: 37.7% vs 53.8%, p = 0.024), although their OS was not different from patients undergoing upfront surgery. Similarly, patients with mt-KRAS had poorer OS than those with wt-KRAS in TBS of 3-9 (5-year OS: 33.1% vs 63.2%, p = 0.001), although their OS was not different from patients with TBS < 3 or ≥ 9. In multivariate analysis, mt-KRAS was an independent prognostic factor of OS among patients receiving preoperative chemotherapy (hazard ratio [HR] 1.61, 95% confidence interval [CI]: 1.034-2.491; p = 0.035) and patients with TBS of 3-9 (HR 1.836, 95% CI 1.176-2.866; p = 0.008). However, it was not a prognostic factor in patients who underwent upfront surgery or with TBS > 3 or ≥ 9.

Conclusions: In patients undergoing hepatectomy for CLM, the prognostic value of KRAS depends on their history of preoperative chemotherapy or tumor burden.