High-Risk-Pattern Lung Adenocarcinoma With Epidermal Growth Factor Receptor Mutation Is Associated With Distant Metastasis Risk And May Benefit From Adjuvant Targeted Therapy

OBJECTIVES: This study aimed to evaluate the value of the high-risk-pattern histology (micropapillary and solid components) for predicting distant metastasis in lung adenocarcinoma and to determine the survival benefit with adjuvant targeted therapy for resected non-small cell lung cancer with high-risk-pattern histology.METHODS: Patients receiving surgery for non-small cell lung cancer were included in this retrospective study. Histological classification was performed according to 2015 World Health Organization classification. Tumours with micropapillary and solid components were defined as high-risk-pattern tumours. Univariable and multivariable Cox regression analyses were used for survival analysis. Adjuvant targeted therapy was alternative for patients with epidermal growth factor receptor (EGFR)-mutation and refusing adjuvant chemotherapy, and outcome was evaluated between 2 groups.RESULTS: The 514 patients (78 in high-risk group and 436 in low-risk group) were followed up for a median of 64 months. High-risk-pattern adenocarcinoma was significantly more common in male patients (P< 0.001) and in smokers (P< 0.001). Among patients with EGFR mutation (n = 164), the high-risk pattern was significantly associated with distant metastasis (P= 0.028) including brain metastasis (P = 0.022). In the 42 patients with high-risk pattern plus EGFR mutation, survival was significantly better after treatment with adjuvant targeted therapy than with chemotherapy (5-year overall survival: 56.4 +/- 2.6 vs 44.7 +/- 3.7 months, P = 0.011; 5-year disease-free survival: 54.0 +/- 3.3 vs 41.9 +/- 4.5 months, P = 0.006).CONCLUSIONS: High-risk pattern is associated with distant metastasis in non-small cell lung cancer after surgery. Adjuvant targeted therapy may be superior to chemotherapy for treatment of patients with high-risk pattern and EGFR mutation.