Impact of TP53 Co-Mutation on Clinicopathological Features, Prognosis, Recurrence Patterns, and the Efficacy of EGFR-TKI Treatment After Recurrence in Resected Early-Stage EGFR-Mutated Lung Adenocarcinoma.

Abstract

Objectives: TP53 is the most frequently mutated gene in non-small-cell lung cancer. Although TP53 co-mutation is associated with poor responses to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in advanced EGFR-mutated adenocarcinoma, its impact in resected early-stage lung adenocarcinoma remains unclear. In this study, we evaluated the effect of TP53 co-mutation on clinicopathological features, prognosis, and recurrence patterns in resected early-stage EGFR-mutated lung adenocarcinoma.

Methods: We analyzed 400 patients with completely resected lung adenocarcinoma across pathological stages I-III, screening for EGFR and TP53 mutations using whole-exome sequencing. Among 121 patients positive for EGFR mutations, we categorized those with TP53 co-mutations and those with wild-type TP53. We then compared clinicopathological features, prognostic outcomes, recurrence patterns, and the efficacy of EGFR-TKI treatment postrecurrence between these groups.

Results: TP53 co-mutations were identified in 22 cases (18.2%). The TP53 co-mutation group had significantly more lymphovascular invasion (P = .037) and a higher tumor mutation burden (P = .007) compared with the TP53 wild-type group. Moreover, the co-mutation group exhibited markedly poorer recurrence-free and overall survival rates [hazard ratio (HR) 2.32, 95% confidence interval (CI) 1.12-4.85, P = .025; HR 2.54, 95% CI 1.01-6.36, P = .047, respectively]. However, progression-free survival in patients treated with EGFR-TKIs postrelapse did not differ significantly between the groups.

Conclusions: TP53 co-mutations may negatively affect the prognosis of patients with resected early-stage EGFR-mutated lung adenocarcinoma. Larger studies are needed to confirm these findings.