Additionally, progressive disease (OR, 3.746; 95% CI, 2.213–6.341; p < 0.001), an M stage above M1a at the time of ctDNA analysis (OR, 2.015; 95% CI, 1.015–3.999; p = 0.045), pleural seeding (OR, 2.088; 95% CI, 1.208–3.607; p = 0.008), bone metastasis (OR, 1.968; 95% CI, 1.142–3.393; p = 0.015), and a testable amount of tumor tissue obtained from distant metastasis sites (OR, 1.674; 95% CI, 1.049–2.673; p = 0.031) were identified as independent factors that significantly increased EGFR mutation detection in ctDNA analysis. The gene discussed is EGFR; the disease is bone metastasis.