Impact of RAS mutation status on early progression in patients with initially unresectable colorectal liver...

Colorectal cancer liver metastases (CRLM) frequently recur or progress after systemic and local treatment, particularly in patients with initially unresectable disease. RAS mutations are associated with poor outcomes in CRLM, but their relationship with early progression or recurrence after conversion therapy remains unclear. This study evaluated the prognostic impact of RAS mutation status in patients with initially unresectable CRLM (IU-CRLM) undergoing conversion therapy.

This retrospective cohort study included 194 patients with initially unresectable, pMMR CRLM treated at Sun Yat-sen University Cancer Center between December 2012 and January 2020. Early progression/recurrence was defined as disease progression after failed conversion, recurrence after successful conversion, or death within six months. Event-free survival (EFS) and overall survival (OS) were analyzed according to RAS status.

Of 194 patients, 87 (44.8%) achieved successful conversion and 51 (26.3%) harbored RAS mutations. RAS-mutant patients had a higher early progression/recurrence rate than RAS wild-type patients (41.2% vs. 19.6%, P = 0.004). In patients with failed conversion, RAS mutation was associated with a higher early progression rate (36.7% vs. 13.0%, P = 0.012), whereas the early recurrence rate did not differ significantly by RAS status among successfully converted patients (47.6% vs. 27.3%, P = 0.142). In the clinically adjusted logistic model, RAS mutation remained independently associated with early progression/recurrence (OR: 3.546, 95% CI: 1.290-9.752, P = 0.014).

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