Survival advantage of postoperative recurrence compared to de novo stage IV disease in EGFR-mutant lung adenocarcinoma treated with osimertinib: a multicenter retrospective study

The prognostic difference between postoperative recurrence and de novo stage IV disease in epidermal growth factor receptor ( EGFR )-mutant lung adenocarcinoma (LUAD) remains unclear. Additionally, the clinical relevance of the tumor–node–metastasis (TNM) 9th edition M1c1/M1c2 subclassification in this population has not been well established. We retrospectively analyzed 275 patients with EGFR -mutant LUAD who received first-line osimertinib across six institutions between 2018 and 2023. Patients were categorized as either having de novo stage IV disease or postoperative recurrence. Clinical outcomes were compared between groups and further stratified by EGFR mutation subtype and M1 subclassification. Of the 275 patients, 183 had de novo stage IV disease and 92 had postoperative recurrence. Patients with recurrence demonstrated significantly longer progression-free survival (31.6 vs. 17.9 months; P < 0.0001) and overall survival (53.4 vs. 35.2 months; P = 0.0030) than those with de novo disease. The survival advantage was consistent across both exon 19 deletion and L858R subtypes and remained statistically significant after adjustment for age, sex, Eastern Cooperative Oncology Group performance status, and EGFR mutation subtype. In exploratory subgroup analyses, patients with M1c2 disease had numerically shorter survival than those in the other M categories. Postoperative recurrence is associated with significantly better survival outcomes than de novo stage IV disease in patients with EGFR-mutant LUAD treated with osimertinib. Patients with M1c2 disease, representing a high multi-organ metastatic burden, showed less favorable survival outcomes; however, further validation is required.