Bilateral diffuse metastases in advanced lung adenocarcinoma harboring EGFR mutations was associated with a favorable prognosis to EGFR‐TKIs

Bilateral diffuse metastatic lung adenocarcinoma (BLDM‐LUAD) is a special imaging pattern of lung adenocarcinoma (LUAD). We retrospectively assessed survival outcomes and co‐mutation characteristics of BLDM‐LUAD patients harboring epidermal growth factor receptor (EGFR) mutations who were treated with EGFR‐yrosine kinase inhibitors (TKIs). From May 2016 to May 2021, among 458 patients who submitted samples for next generation sequencing (NGS) detection in 1125 patients with non‐small‐cell lung cancer (NSCLC), and 44 patients were diagnosed as BLDM‐LUAD. In order to analyze the survival outcomes of BLDM‐LUAD patients harboring EGFR mutations who were treated with EGFR‐TKIs, the factors age, gender, smoking history, hydrothorax, site of EGFR mutations and EGFR‐TKIs treatment were adjusted using propensity score‐matching (PSM). The Kaplan‐Meier survival curves and log‐rank test were used to analyze progression‐free survival (PFS) and overall survival (OS). The co‐mutation characteristics of BLDM‐LUAD patients harboring EGFR mutations were analyzed by NGS panels. 64 patients with advanced lung adenocarcinoma harboring EGFR mutations and first‐line treatment of EGFR‐TKIs were successfully matched. BLDM‐LUAD (n = 32) have significantly longer median PFS than control group (n = 32) (mPFS: 14 vs 6.2 months; p = .002) and insignificantly longer median OS than control group (mOS: 45 vs 25 months; p = .052). The patients with BLDM‐LUAD have the higher frequency of EGFR mutation than control group (84.1% vs 62.0%) before PSM. The co‐mutation genes kirsten rat sarcoma viral oncogene homolog (KRAS) (9.4%), ataxia telangiectasia‐mutated (ATM) (7.4%) and mesenchymal‐epithelial transition (MET) (3.1%) only appeared in the control group after PSM. The BLDM‐LUAD harboring EGFR mutations was associated with a favorable prognosis to EGFR‐TKI. What's new? Bilateral diffuse metastatic lung adenocarcinoma (BLDM‐LUAD) is a rare disease characterized by the distribution of many small metastatic nodules throughout both lungs. While some BLDM‐LUADs harbor mutations in epidermal growth factor receptor (EGFR), the genetic characteristics of BLDM‐LUAD and the relevance of EGFR alterations to treatment remain unclear. Here, gene alterations and survival outcomes were assessed among BLDM‐LUAD patients treated with EGFR‐tyrosine kinase inhibitors (TKIs). BLDM‐LUAD patients were found to have an increased frequency of EGFR mutation compared to control patients. Moreover, co‐mutant genes ide