Incidence and Prognostic Value of TP53, STK11, and KEAP1 Mutations Between De Novo Versus Recurrent Actionable Mutation-Negative Non-Small Cell Lung Cancer: A Single-Center Retrospective Study.

Abstract

Background: In non-small cell lung cancer (NSCLC), mutations in TP53, STK11, and KEAP1 are common in tumors lacking actionable oncogenic drivers and have been associated with poor outcomes, though their prognostic impact remains context-dependent. We evaluated the incidence and prognostic significance of these mutations in actionable mutation-negative NSCLC, stratified by de novo versus recurrent disease.

Methods: We retrospectively analyzed 119 adult patients with NSCLC and available next-generation sequencing (NGS) results treated at our center through 2024. Cases with actionable mutations were excluded. Patients were classified as de novo (n = 82) or recurrent (n = 37) based on the disease status at the point of analysis. Between-group comparisons were done using Fisher's exact and Wilcoxon Rank-sum test. Overall survival and progression-free survival were assessed. All tests were two-sided and a P value < 0.05 was considered statistically significant.

Results: TP53 mutations were most frequent (61% de novo vs. 54% recurrent; P > 0.05). STK11 and KEAP1 mutations occurred at similar rates between groups (5-15%; P > 0.05). Baseline clinical characteristics were balanced. No significant differences in overall or progression-free survival were observed by mutational status in either cohort.

Conclusion: In this real-world cohort of actionable mutation-negative NSCLC cases, we did not detect significant prognostic associations for TP53, STK11, and KEAP1 mutations, and their incidence was similar between de novo and recurrent disease. These findings underscore the need for larger studies to evaluate the prognostic utility of these mutations in this clinical context.