Background: Cell free DNA (cfDNA) shed by cancer cells into blood and body fluids is a potential substrate for molecular testing. While plasma is approved for EGFR mutation testing in certain clinical settings, mutation testing on urine is not well explored in lung cancer. In this study, we assess the feasibility and diagnostic accuracy of EGFR mutation analysis on plasma and urine samples. Methods: Matched plasma and urine were collected prospectively from TKI-naïve lung adenocarcinoma (ADCA) patients (Group A) with available tumor tissue. Only plasma was collected from TKI-treated, known EGFR mutant ADCA patients developing TKI resistance (Group B). qPCR (tumor tissue) or digital droplet-PCR (urine/plasma) was performed for exon 19 deletions, exon 21 L858R and exon 20 T790M. Results: Eighty-one patients (60 Group A, 21 Group B) were included. In Group A, EGFR mutations were detected in tissue in 34/60 (57%) patients. Mutations were detected in matched plasma in 24 (24/34, 70.5% sensitivity), and in matched urine in 15 (15/25, 60% sensitivity) of the 34 EGFR mutant cases, with no false positives (100% positive predictive value). Plasma and urine mutation results showed moderate agreement (70%) with a combined sensitivity of 88% (22/25). In Group B, new T790M mutations were detected in plasma in 61% (13/21) patients. Conclusion: Liquid biopsies show moderate sensitivity (plasma > urine) with 100% positive predictive rates for EGFR mutations. Testing of more than one type of liquid biopsy sample increases sensitivity. In TKI-resistant settings, liquid biopsies can obviate need for invasive biopsies in >60% patients.

背景：癌细胞脱落到血液和体液中的无细胞 DNA (cfDNA) 是分子检测的潜在底物。虽然血浆在某些临床环境中被批准用于EGFR突变检测，但尿液突变检测在肺癌中的研究还没有得到很好的探索。在本研究中，我们评估了对血浆和尿液样本进行EGFR突变分析的可行性和诊断准确性。方法：从具有可用肿瘤组织的 TKI 初治肺腺癌 (ADCA) 患者（A 组）前瞻性收集匹配的血浆和尿液。仅从 TKI 处理的已知EGFR收集血浆发生 TKI 耐药性的突变 ADCA 患者（B 组）。对外显子 19 缺失、外显子 21 L858R 和外显子 20 T790M 进行 qPCR（肿瘤组织）或数字液滴 PCR（尿液/血浆）。结果：共纳入 81 例患者（A 组 60 例，B 组 21 例）。在 A 组中，34/60 (57%) 患者的组织中检测到EGFR突变。在 34 例EGFR突变病例中， 24 例（24/34，70.5% 敏感性）在匹配的血浆中检测到突变，在匹配的尿液中检测到 15 例（15/25，60% 敏感性），没有假阳性（100% 阳性预测值）。血浆和尿液突变结果显示中等一致性 (70%)，综合敏感性为 88% (22/25)。在 B 组中，61% (13/21) 患者的血浆中检测到新的 T790M 突变。结论：液体活检显示中等敏感性（血浆 > 尿液）， EGFR突变的阳性预测率为 100% 。测试不止一种类型的液体活检样本会增加灵敏度。在 TKI 耐药的情况下，液体活检可以避免 >60% 的患者需要进行侵入性活检。