Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial

IF 52.5 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature Medicine Pub Date : 2026-09-22 DOI:10.1038/s41591-026-04652-8

Richard D. Neal, Saoirse Dolly, Peter Johnson, Helen Jones, Sir Harpal Kumar, Lennard Y. W. Lee, Yujin Lee, Wei Liang, Thomas Round, Rebecca Smittenaar, Jane Warwick, Peter Sasieni, Charles Swanton

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引用次数: 0

Abstract

The NHS-Galleri trial was a randomized controlled trial evaluating a multi-cancer early detection (MCED) test added to usual care. We reported elsewhere that the primary endpoint of a reduction in the incidence of stage III/IV cancer diagnoses in the intervention arm versus control arm was not met. Here we report prespecified secondary test performance endpoints among evaluable intervention arm participants across three annual screening rounds. These analyses were descriptive; there was no hypothesis testing. Participants aged 50−77 years (N = 142,250) were randomized 1:1 into intervention (MCED) or control arms. Intervention arm participants with positive MCED results were referred to National Health Service (NHS) standard-of-care pathways for diagnostic workup, with referrals informed by the predicted cancer signal origin (CSO). Positive test results were returned for 722 of 70,325 (1.03%), 518 of 64,498 (0.80%) and 561 of 62,323 (0.90%) participants in rounds 1−3, respectively. In aggregate, 937 participants had MCED-detected primary cancers. Respective by-round cancer detection rates were 0.60%, 0.40% and 0.41%; positive predictive values were 58.0% (419/722), 50.4% (261/518) and 45.8% (257/561); and negative predictive values were 98.98% (68,895/69,603), 98.90% (63,278/63,980) and 98.86% (61,058/61,762). Across rounds, specificity ranged from 99.50% to 99.60%; episode sensitivity ranged from 26.7% to 37.2% for all cancers and from 47.6% to 63.4% for 12 prespecified types; and CSO accuracy ranged from 91.1% to 93.6%. These data provide insights on the performance of the MCED test in population screening within the NHS setting. ClinicalTrials.gov: NCT05611632 ; ISRCTN: ISRCTN91431511 . Secondary endpoint analyses in the NHS-Galleri randomized controlled trial, testing a multi-cancer early detection test added to usual care, provide insights on the performance of the blood-based test in more than 142,000 participants without suspicion of cancer.

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在NHS-Galleri随机对照试验中多癌早期检测试验的表现

NHS-Galleri试验是一项随机对照试验，评估在常规护理中增加的多癌早期检测（MCED）。我们在其他地方报道，干预组与对照组相比，未达到降低III/IV期癌症诊断发生率的主要终点。在这里，我们报告了三轮年度筛查中可评估干预组参与者预先指定的次要测试性能终点。这些分析是描述性的；没有假设检验。年龄在50 ~ 77岁之间的参与者（N = 142250）按1:1的比例随机分为干预组（MCED）和对照组。MCED结果阳性的干预组参与者被转介到国家卫生服务（NHS）标准护理途径进行诊断检查，并根据预测的癌症信号起源（CSO）通知转诊。在第1 - 3轮中，70,325名受试者中有722名（1.03%）、64,498名受试者中有518名（0.80%）和62,323名受试者中有561名（0.90%）的检测结果为阳性。总共有937名参与者患有mced检测到的原发性癌症。逐轮肿瘤检出率分别为0.60%、0.40%和0.41%；阳性预测值分别为58.0%（419/722）、50.4%（261/518）和45.8% (257/561)；阴性预测值分别为98.98%（68,895/69,603）、98.90%（63,278/63,980）和98.86%（61,058/61,762）。各轮的特异性从99.50%到99.60%不等；所有癌症的发作敏感性为26.7%至37.2%，12种预先指定类型的发作敏感性为47.6%至63.4%；CSO准确度为91.1% ~ 93.6%。这些数据提供了对MCED测试在NHS设置的人群筛查中的表现的见解。ClinicalTrials.gov: NCT05611632；isrctn91431511。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Medicine 医学-生化与分子生物学

CiteScore

100.90

自引率

0.70%

发文量

525

审稿时长

1 months

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