Background: Liquid biopsy analysis for EGFR detection in cell-free DNA (cfDNA) from NSCLC patients has become routine. The aim of this study was to explore its applicability in clinical practice. Methods: We collected data of EGFR-mutated NSCLC patients with liquid biopsy analysis. Data included test timing, concomitant tissue re-biopsy, therapy change, histology, stage, smoking habits, gender and age. All analyses were performed via a real-time PCR method to analyze EGFR mutations at exons 18, 19, 20 and 21. Variant allele frequency was performed for patients with available sequential EGFR mutation analysis in cfDNA. Overall survival was analyzed through the Kaplan–Meier method. We designed flow charts to show the real-life application of liquid biopsy. Results: We found that liquid biopsy is used in treatment-naïve patients as an alternative to EGFR detection in tumor tissue, and in patients with positive or negative EGFR from tumor biopsy. The majority of liquid biopsy analyses were performed in NSCLC patients who were disease progressive during TKI therapy. The presence of EGFR mutation in cfDNA was associated with a worse prognosis. In two patients, VAF of EGFR mutations in cfDNA was concordant with tumor volume changes. Conclusion: These findings suggest that liquid biopsy for EGFR detection can continue to be useful.
