Risk factors for refractory malignant pleural effusion and the impact on prognosis in non-small cell lung cancer patients with advanced EGFR mutations: a retrospective cohort study using propensity score matching.

BACKGROUND: Malignant pleural effusion (MPE), which arises from pleural metastasis, frequently occurs in advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations (EGFR+) and is often associated with a worse prognosis. Observations in clinical settings have indicated that a subset of patients undergoing first-line therapy with EGFR tyrosine kinase inhibitors (EGFR-TKIs) may continue to experience persistent pleural effusion. This occurs even when other systemic lesions are controlled, leading to respiratory distress due to pleural effusion compression, a condition known as refractory MPE. The factors contributing to the emergence of refractory MPE and their effect on patient prognosis are not yet fully understood. This clinical study aimed to evaluate the risk factors for refractory MPE in individuals diagnosed with EGFR+ non-small cell lung cancer (NSCLC) and their impact on prognosis.

METHODS: We retrospectively screened 157 patients with advanced EGFR-positive NSCLC and MPE who were initially diagnosed at the General Hospital of Western Theater Command between January 2019 and June 2022. According to the inclusion and exclusion criteria, a total of 98 cases were included. Among them, 18 had refractory MPE. Using a 1:2 propensity score-matching method, we matched these patients with 32 patients with non-refractory MPE who also had EGFR+ NSCLC. We monitored clinical characteristics, progression-free survival (PFS), overall survival (OS), and incidence of adverse events between the two groups. Univariate and multivariate analyses were conducted to identify the factors associated with prognosis.

RESULTS: Compared to patients with non-refractory MPE, those with refractory MPE exhibited a higher proportion of EGFR 21 L858R mutations (P=0.03) and co-occurring TP53 mutations (P=0.03). Additionally, a greater number of patients with refractory MPE had larger volumes of pleural effusion at first drainage (P<0.001), higher levels of lactate dehydrogenase (LDH) in the pleural fluid at initial diagnosis (P=0.01), and elevated serum carcinoembryonic antigen (CEA) levels (P=0.002). These patients were also less likely to receive intrapleural treatment (P=0.001) and had shorter PFS (P=0.04) and OS (P=0.01). Multivariate analysis revealed that the Eastern Cooperative Oncology Group performance status (ECOG PS) score, first-line treatment options, and liver metastases were independent risk factors for PFS. The independent risk factors for OS included ECOG PS, histology, EGFR mutation type, combination systemic therapy, liver metastases, and pre-treatment serum CEA levels.

CONCLUSIONS: Patients with advanced NSCLC and refractory MPE have a poorer prognosis after first-line targeted therapy than those with non-refractory MPE. More aggressive systemic and local treatment approaches may offer better survival benefits in these patients.