Differential effects of the KRAS gene on recurrence in right- vs left-sided colorectal liver metastases undergoing radiofrequency ablation.

Abstract

Background: KRAS mutation status and primary tumor location serve as critical prognostic factors for colorectal liver metastases (CLMs). Emerging evidence suggests a potential interaction between these two variables that may influence clinical outcomes.

Aim: To investigate the association of KRAS mutations with recurrence in patients with CLM who underwent radiofrequency ablation (RFA) according to the primary tumor location.

Methods: This retrospective study analyzed 164 patients with KRAS-determined CLM treated with percutaneous RFA between January 2012 and December 2018. The clinicopathological characteristics, recurrence patterns, and survival outcomes were systematically evaluated.

Results: A total of 164 patients (mean age: 58.0 ± 9.8 years, range: 34-83 years) who underwent percutaneous RFA of 325 CLMs (mean size: 2.2 ± 1.0 cm, range: 0.7-5.0 cm) were included in the study. Eighty-nine (54.3%) patients had wild-type KRAS, and 75 (45.7%) patients had mutated KRAS. Compared with wild-type patients, patients with KRAS mutations presented significantly higher local tumor progression rates (30.7% vs 14.6%, P = 0.013). Among 126 patients (76.8%) who experienced post-RFA recurrence, 61.6% developed intrahepatic metastases, and 53.7% developed extrahepatic metastases. Primary tumor location significantly modified KRAS-related outcomes: Compared with wild-type patients, left-sided colorectal cancer (CRC) patients with KRAS mutations presented higher intrahepatic recurrence rates (77.2% vs 52.5%, P = 0.003) and shorter median intrahepatic recurrence-free survival (15 vs 25 months, P = 0.007). No significant differences in KRAS expression were detected in right-sided tumors.

Conclusion: KRAS mutation status predicts differential recurrence patterns after CLM ablation, with significant prognostic implications, specifically in left-sided CRCs. These findings underscore the importance of integrating molecular profiling and primary tumor characteristics in therapeutic decision-making for patients with metastatic CRC.