Clinical impact of TP53 mutation status on survival outcomes in metastatic colorectal cancer

The prognostic value of TP53 mutations in metastatic colorectal cancer remains unclear owing to inconsistent findings in the literature. Given its central role in tumor biology, clarifying the impact of TP53 status on survival outcomes is clinically relevant.

This retrospective cohort study included 115 patients with metastatic colorectal cancer who underwent TP53 mutational analysis using next-generation sequencing (KAPA HyperPETE Pan Cancer Panel). Eligible patients were aged ≥18 years, had histologically confirmed metastatic colorectal cancer, and received first-line systemic therapy. Patients with incomplete clinical or molecular data were excluded. Based on mutation profiles, those with RAS or BRAF mutations received anti-VEGF therapy, whereas patients with wild-type tumors received anti-EGFR treatment. Patients were stratified according to TP53 mutation status to evaluate differences in clinical outcomes.

Among the 115 patients included, 78 (67.8%) harbored TP53 mutations and 37 (32.2%) had wild-type TP53. The median progression-free survival was significantly longer in the TP53-mutant group (18.6 vs. 10.0 months; p=0.002). The median overall survival was also numerically longer in the TP53-mutant group (32.9 vs. 30.3 months), although this difference was not statistically significant (p=0.114). In the univariate analysis, TP53 mutation was associated with improved progression-free survival (HR 0.479; 95%CI 0.294-0.779; p=0.003). This association remained independently significant in the multivariate analysis (HR 0.477; 95%CI 0.289-0.787; p=0.004). None of the other variables consistently predicted survival.

TP53 mutations appear to be an independent prognostic marker for prolonged progression-free survival in patients with metastatic colorectal cancer. Although the difference in overall survival was not statistically significant, these findings warrant further validation in prospective studies to confirm the prognostic utility of TP53 in therapeutic stratification.