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The epidermal growth factor receptor ( EGFR ) gene mutation has changed the clinical practice of stage IV non-small cell lung cancer (NSCLC) (1). Many well designed randomized trials have shown that EGFR-tyrosine kinase inhibitors (TKIs) are better treatment than conventional chemotherapy in patients who had sensitizing EGFR mutations (2,3). Therefore, identification of EGFR -sensitizing mutations in tumor tissue is the current standard biomarker to identify candidates who will benefit from first-line EGFR-TKI targeted therapy (4). However, multiple factors make it difficult to obtain enough tumor tissue for EGFR genetic analysis (5,6). When only a small tumor specimen is available, it is more feasible to assess tumor genomics via a blood sample or other body fluid, termed a ‘liquid biopsy’ (7).

Can liquid biopsy-guided EGFR-targeted therapy be a surrogate for the tissue-based standard approach?