Clinicopathological Profiles and Prognosis of Postoperative HER2-Mutant Non-Small Cell Lung Cancer: A Real-World Analysis

Background/Introduction: Patients with non-small cell lung cancer (NSCLC) harboring HER2 mutations remain at high risk of recurrence, even following radical resec-tion for early-stage disease. Currently, there is a paucity of research investigating the clini-copathological characteristics and disease-free survival (DFS) outcomes of this specific postoperative population. Methods: This retrospective study investigated the clinicopathological and molecular char-acteristics of 77 patients with surgically resected HER2-mutant NSCLC. HER2 mutation status was identified via next-generation sequencing (NGS). Results: HER2 exon 20 insertions were the most prevalent variant in this cohort. Overall, 76.6% of patients exhibited invasive adenocarcinoma phenotypes. Histopathological exam-ination revealed highly invasive papillary and micropapillary components in 51.9% and 45.5% of patients, respectively. The median DFS was 17.0 months (95% CI, 11.4–22.5), with significant variation across disease stages (P = 0.004). The cumulative number of high-risk recurrence factors (0, 1–3, >3) was significantly associated with DFS (median, 29.3 vs. 14.2 vs. 7.1 months; P = 0.045). However, PD-L1 expression status, TP53 alterations, and histological phenotypes demonstrated no significant impact on DFS. Among the entire co-hort, 80.5% of patients experienced postoperative recurrence, with the lung being the most frequent site of metastasis. Conclusion: HER2-mutant NSCLC constitutes a distinct subtype characterized by unique clinicopathological and molecular features. For postoperative patients presenting with ad-vanced disease or an increased burden of high-risk recurrence factors, more aggressive ther-apeutic strategies should be considered.