Combating colorectal lung metastases via systemic therapy and thermal ablation: RAS mutation impact

To investigate the prognostic value of RAS mutation status and subtypes in colorectal lung metastases (CRLM) patients undergoing image-guided thermal ablation (IGTA), and to evaluate survival outcomes under different systemic therapy regimens.

In this multicenter retrospective-prospective cohort study, 387 patients with CRLM who received percutaneous IGTA between March 2014 and December 2022 were included. Patients were stratified by RAS genotype (KRAS/NRAS wild-type vs mutant). Survival outcomes including local tumor progression-free survival (LTPFS), progression-free survival (PFS), and overall survival (OS) were analyzed using Cox regression. Subgroup analyses were conducted based on chemotherapy regimens and targeted agents.

The 3-year LTP rate was significantly higher in KRAS-mutant patients (25.0%) than wild-type (15.0%). KRAS mutation, lesion diameter ≥20 mm, and elevated CEA were independent risk factors for LTP. Median PFS was 16.0 months; KRAS mutations predicted inferior PFS (13.3% vs 32.8% at 3 years). Median OS was significantly reduced in both KRAS (17.9 vs 56.8 months) and NRAS-mutant patients (22.1 vs 53.8 months). Among KRAS-mutant patients, FOLFOX plus bevacizumab yielded better OS than cetuximab.

RAS mutations are independent predictors of poor local control and survival after IGTA in CRLM. Evaluate interactions between RAS genotype and commonly used targeted agents in the peri-ablative setting. These integrated, real-world insights support the development of genotype-guided ablation planning and peri-ablative systemic therapy strategies.