Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Exact Sciences, Madison, WI, USA.
Lancet. 2023 Oct 7;402(10409):1251-1260. doi: 10.1016/S0140-6736(23)01700-2.
BACKGROUND: Multicancer early detection (MCED) blood tests can detect a cancer signal from circulating cell-free DNA (cfDNA). PATHFINDER was a prospective cohort study investigating the feasibility of MCED testing for cancer screening. METHODS: In this prospective cohort study done in oncology and primary care outpatient clinics at seven US health networks, a convenience sample of adults aged 50 years or older without signs or symptoms of cancer consented to MCED testing. We collected blood, analysed cfDNA, and returned results to participants' doctors. If a methylation signature indicative of cancer was detected, predicted cancer signal origin(s) informed diagnostic assessment. The primary outcome was time to, and extent of, diagnostic testing required to confirm the presence or absence of cancer. This trial is registered at ClinicalTrials.gov, NCT04241796, and is completed. FINDINGS: Between Dec 12, 2019, and Dec 4, 2020, we recruited 6662 participants. 4204 (63·5%) of 6621 participants with analysable results were women, 2417 (36·5%) were men, and 6071 (91·7%) were White. A cancer signal was detected in 92 (1·4%) of 6621 participants with analysable results. 35 (38%) participants were diagnosed with cancer (true positives) and 57 (62%) had no cancer diagnosis (false positives). Excluding two participants whose diagnostic assessments began before MCED test results were reported, median time to diagnostic resolution was 79 days (IQR 37-219): 57 days (33-143) in true-positive and 162 days (44-248) in false-positive participants. Most participants had both laboratory tests (26 [79%] of 33 with true-positive results and 50 [88%] of 57 with false-positive results) and imaging (30 [91%] of 33 with true-positive results and 53 [93%] of 57 with false-positive results). Fewer procedures were done in participants with false-positive results (17 [30%] of 57) than true-positive results (27 [82%] of 33) and few had surgery (one with a false-positive result and three with a true-positive result). INTERPRETATION: This study supports the feasibility of MCED screening for cancer and underscores the need for further research investigating the test's clinical utility. FUNDING: GRAIL.
背景：多癌种早期检测（MCED）血液检测可从循环游离 DNA（cfDNA）中检测到癌症信号。PATHFINDER 是一项前瞻性队列研究，旨在研究 MCED 检测用于癌症筛查的可行性。
方法：在这项在美国七个健康网络的肿瘤学和初级保健门诊进行的前瞻性队列研究中，年龄在 50 岁或以上、无癌症迹象或症状的成年人，通过便利抽样，同意进行 MCED 检测。我们采集血液，分析 cfDNA，并将结果反馈给参与者的医生。如果检测到提示癌症的甲基化特征，则告知预测的癌症信号来源，以进行诊断评估。主要结局是确定需要进行何种诊断检测以确认是否存在癌症，以及完成这些检测所需的时间。本试验在 ClinicalTrials.gov 注册，编号为 NCT04241796，现已完成。
结果：2019 年 12 月 12 日至 2020 年 12 月 4 日期间，我们招募了 6662 名参与者。在可分析的 6621 名参与者中，4204 名（63.5%）为女性，2417 名（36.5%）为男性，6071 名（91.7%）为白人。在可分析的 6621 名参与者中，有 92 名（1.4%）检测到癌症信号。35 名（38%）参与者被诊断患有癌症（真阳性），57 名（62%）无癌症诊断（假阳性）。排除两名参与者的诊断评估在 MCED 检测结果报告之前开始，中位诊断解决时间为 79 天（IQR 37-219）：真阳性参与者为 57 天（33-143），假阳性参与者为 162 天（44-248）。大多数参与者都进行了实验室检查（33 名真阳性结果中有 26 名[79%]，57 名假阳性结果中有 50 名[88%]）和影像学检查（33 名真阳性结果中有 30 名[91%]，57 名假阳性结果中有 53 名[93%]）。假阳性结果参与者的检查程序（17 项[30%]）少于真阳性结果参与者（27 项[82%]），且很少进行手术（1 名假阳性结果参与者，3 名真阳性结果参与者）。
结论：本研究支持 MCED 筛查癌症的可行性，并强调需要进一步研究该检测的临床实用性。
资金来源：GRAIL。
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