Huicong Liu,1,* Hui Li,2,* Lisha Xiao,1 Yubiao Guo,1 Gengpeng Lin1 

1Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-sen University, Institute of Pulmonary Diseases, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Gengpeng Lin, Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China, Email lingp6@mail.sysu.edu.cn

Background: ctDNA is a non-invasive and convenient method for detecting EGFR mutations in non-small cell lung cancer (NSCLC). However, its sensitivity is lower than that of tissue-based testing. To enhance ctDNA detection efficiency, we identified the patient population most suitable for ctDNA testing, assessed the relationship between ctDNA and tumor markers, and examined the clinical significance of ctDNA in medical practice.
Methods: A single-center retrospective study was conducted, including 135 patients with NSCLC who underwent histological and liquid Super-ARMS tests. Of these, 92 patients with EGFR mutations detected in both tumor tissue and plasma were classified into the EGFRt+, p+ group, while 43 patients with EGFR mutations detected only in tumor tissue were classified into the EGFRt+, p− group. The clinical features and outcomes between these two groups were compared.
Results: The positivity rate of Super-ARMS test was 68.1% (92/135). The presence of EGFRt+, p+ in the Super-ARMS test was significantly associated with pleural effusion, bone, liver, and multiple organ metastases. Compared to the EGFRt+, p+ group, the EGFRt+, p− group had a significantly better PFS (P < 0.01). Carcinoembryonic antigen (CEA) levels demonstrated a strong predictive value for identifying plasma EGFR-mutated patients (AUC 0.828, sensitivity 68.8%, specificity 84.4%), while Maximum Standardized Uptake Value (SUVmax) also showed diagnostic value for plasma EGFR-mutated patients (AUC 0.78). Additionally, combination of TP53 and EGFR mutations in plasma provided improved risk stratification for PFS (P < 0.001).
Conclusion: Patients exhibiting metastasis, elevated levels of tumor markers and SUVmax are more suitable for plasma EGFR mutation testing in clinical NSCLC management. Moreover, a positive plasma ctDNA test not only guides targeted therapy but also predicts a worse prognosis.

Keywords: NSCLC, EGFR mutation, ctDNA, CEA, prognosis