Objective:

To evaluate the prognostic impact of RAS mutation status in patients with initially unresectable colorectal cancer liver metastases (IU-CRLM) undergoing conversion therapy.

Approach:

• Study Design: A retrospective cohort study including 194 patients with IU-CRLM treated at Sun Yat-sen University Cancer Center from December 2012 to January 2020.
• Patient Selection: Inclusion criteria included histologically confirmed colorectal adenocarcinoma with proficient mismatch repair, confirmed liver metastasis, and availability of RAS mutation status.
• Outcome Measures: Early progression/recurrence was defined as disease progression after failed conversion, recurrence after successful conversion, or death within six months.

Key Findings:

• 44.8% of patients achieved successful conversion.
• 26.3% of patients harbored RAS mutations.
• RAS-mutant patients had a higher early progression/recurrence rate (41.2% vs. 19.6%, P = 0.004).
• In failed conversion cases, RAS mutation was associated with a higher early progression rate (36.7% vs. 13.0%, P = 0.012).
• In successfully converted patients, early recurrence rates did not differ significantly by RAS status (47.6% vs. 27.3%, P = 0.142).

Interpretation:

RAS mutation is associated with a higher risk of early progression/recurrence in patients with IU-CRLM undergoing conversion therapy, particularly among those who fail to achieve successful conversion.

Limitations:

• Retrospective design may introduce selection bias.
• Single-center study limits generalizability.
• Limited follow-up duration may affect long-term outcome assessment.

Conclusion:

These findings may support individualized surveillance and treatment strategies for RAS-mutant IU-CRLM.