Prospective analysis of the effects of RAS mutation on local tumor progression and overall survival after radiofrequency ablation for colorectal liver metastases

Objectives: To investigate the effects of RAS mutation on local tumor progression (LTP) and overall survival (OS) after radiofrequency ablation (RFA) for colorectal liver metastases (CRLMs).

Methods: This prospective study consecutively enrolled patients with CRLM who underwent ultrasound-guided RFA between June 2020 and July 2022. RAS mutation status was analyzed via the amplification refractory mutation system PCR method. The safety margin was measured via an anatomic landmark-based manual assessment method. Factors associated with time-to-LTP and OS were assessed via univariate and multivariate analyses.

Results: A total of 163 patients with 284 ablated tumors were included. Sixty-nine patients (42.3%) had RAS mutations. Compared with the RAS-wild-type group, the RAS-mutant group had a higher 2-year cumulative LTP rate (20.0% vs. 9.8%, p = 0.016) and a worse 2-year OS rate (55.7% vs. 79.8%, p < 0.001). Compared with RAS-wild-type tumors, RAS-mutant tumors had a significantly greater 2-year cumulative LTP rate in the subgroups with safety margins <5 mm (47.6% vs. 24.9%, p = 0.034) and ≥5 mm (8.6% vs. 1.9%, p = 0.045). In the multivariate Fine-Gray analysis, RAS mutation (SHR, 2.42; p = 0.007) and a safety margin <5 mm (SHR, 7.94; p < 0.001) were found to be independent predictors of the time-to-LTP. According to the multivariate Cox analysis, RAS mutation (HR, 2.13; p = 0.010), CEA >5 ng/mL (HR, 2.29; p = 0.017), and extrahepatic metastases (HR, 2.04; p = 0.016) were independent predictors of shorter OS.

Conclusions: RAS mutation was an independent predictor of LTP and OS after RFA for patients with CRLM. RAS-mutant tumors require wider safety margins.