Prognostic Impact of KRAS-TP53 Co-Mutations in Patients with Early-Stage Non-Small Cell Lung Cancer: A Single-Center Retrospective Study.

: The clinical value of mutations in lung adenocarcinoma, alone or in combination with other mutations, has been assessed especially in advanced stages. This study evaluates how and the presence of co-mutations could affect survival in early-stage lung. : We analyzed a real-world cohort including all staged NSCLC patients diagnosed and treated from 2018 to 2022 at our Institute with availability of NGS molecular data. Statistical analyses were made using log-rank test, the two-tailed Fisher's exact test and Kaplan-Meier survival curves. : mutations were observed in 179/464 cases (38.6%). The majority of co-mutations were in (74%) and (14.3%) genes. + co-mutations were more frequent compared to -only tumors in stage IV NSCLC ( = 0.01). In early stage and locally advanced cases (stage I-III), better prognosis was associated to -only mutated NSCLC and to + mutated cases compared to + ( = 0.008). In particular, patients carrying + in stage I and II displayed a shorter survival, similar to patients diagnosed at stage III. : Routine NGS provides important information for potential actionable mutations but also for the prognostic and predictive role of the presence of co-occurring mutations. In particular, the presence of + in stage I and II NSCLC may be considered an unfavorable prognostic marker possibly leading to adapt the perioperative chemo-immunotherapy.