Liquid biopsy and tissue biopsy for the detection of EGFR mutations in patients with stage III non-small-cell lung cancer: an observational real-world study

Background: In metastatic non-small-cell lung cancer (NSCLC), tissue and plasma (liquid biopsy) testing are recommended complementary approaches to identify actionable gene mutations. In non-metastatic disease, the utility of liquid biopsy is less clear. This retrospective observational study assessed the effectiveness of liquid biopsy to detect epidermal growth factor receptor (EGFR) mutations in stage IIIA/IIIB/IIIC NSCLC against tissue biopsy. Patients and methods: Data from a US nationwide electronic health record-derived deidentified database of patients with NSCLC and liquid and tissue biopsy test results for EGFR mutations were analyzed from time of stage III NSCLC diagnosis (1 January 2017 to 31 August, 2023) until the data cut-off or date of metastasis (if the tumor metastasized). Objectives were to assess concordance and performance of liquid and tissue biopsy tests for the detection of EGFR mutations. Results: Data were analyzed from 425 patients. Some 43%, 41%, and 9% of patients had stage IIIA, IIIB, and IIIC NSCLC, respectively; 27% had unresectable NSCLC. For all EGFR mutation testing methods, median time between specimen collection and test result availability was 8 days for liquid biopsy (n = 494) and 32 days for tissue biopsy (n = 499); 25 (5%) and 41 (8%) samples, respectively, detected EGFR mutations. The concordance rate was 93% overall and was greater for tests conducted in 2020-2023 (96%) than 2017-2019 (87%). Specificity and sensitivity of liquid biopsy were 98% and 45%, respectively. Next-generation sequencing (NGS) was the most common biopsy testing method (liquid, 74%; tissue, 67%). For NGS tests only, concordance was 94% (2020-2023, 96%; 2017-2019, 85%), with a specificity and sensitivity of 99% and 53%, respectively. Conclusions: Liquid biopsy may complement tissue biopsy in detection of EGFR mutations in stage III NSCLC. Using current NGS technology, EGFR mutation status was identified with high specificity. Further research is warranted to confirm the utility of liquid biopsy for these patients.