KRAS Mutation Status Predicts Site-Specific Recurrence and Survival After Resection of Colorectal Liver Metastases Irrespective of Location of the Primary Lesion

Junichi Shindoh, Yujiro Nishioka, Ryuji Yoshioka, Toshitaka Sugawara, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Masaji Hashimoto, Norihiro Kokudo

The KRAS mutation status is reportedly correlated with poor survival outcome in patients with colorectal liver metastases (CLM); however, its true prognostic impact and the reason for the poor prognosis remain unclear. Data on 163 patients with a known KRAS mutation status who underwent curative resection for CLM were retrospectively reviewed. The long-term survival and site-specific incidence of recurrence were then compared between patients with a KRAS mutation (mtKRAS) and those without a mutation (wtKRAS). The mtKRAS group had a poorer 3-year disease-specific survival (DSS) rate (59.8 vs. 83.6 %, p = 0.016), 3-year recurrence-free survival (RFS) rate (0 vs. 20.2 %, p = 0.069), and median time to surgical failure (TSF) [18.8 vs. 39.7 months, p = 0.001] than the wtKRAS group. The cumulative incidences of liver recurrence and lung recurrence at 3 years were also higher in the mtKRAS group (76.2 vs. 54.7 %, p = 0.060; and 71.9 vs. 37.3 %, p < 0.001, respectively). A multivariate analysis confirmed that an mtKRAS status had a significant effect on the DSS rate (hazard ratio [HR] 2.9, p = 0.006), RFS (HR 2.0, p = 0.004), TSF (HR 2.4, p < 0.001), liver recurrence (HR 1.7, p < 0.001), and lung recurrence (HR 2.6, p < 0.001). Lung-related unresectable recurrences were more frequent (41 vs. 18 %, p = 0.048) and were associated with an earlier TSF (9.6 vs. 14.0 months, p = 0.14) in the mtKRAS group, regardless of the location of the primary lesions. mtKRAS is associated with poor survival outcome after CLM resection because of a relatively high incidence of lung recurrence and a relatively short TSF.