Early Diagnosis of Lung Cancer in Scotland: A Randomised Controlled Trial of an Autoantibody Blood Test

Problem

Five-year lung cancer (LC) mortality rates remain unacceptably high, and the UK’s survival rate is poor by international comparisons. To improve the poor prognosis, methods that detect lung cancer at an earlier stage, when it is more likely to be treated with curative intent, are needed. Several clinical trials have reported that low-dose CT (LDCT) screening can detect lung cancer earlier and reduce lung cancer mortality by around 20%. Most recently, the NELSON trial reported a 24% reduction in lung cancer mortality from screening after 10-years of follow-up of 13,131 men. These findings provide impetus to consider National screening programmes for the early detection of lung cancer. However, the widespread adoption of LDCT screening will likely remain limited by resource constraints, high false positive rates and concerns about overdiagnosis. Less resource-intensive investigations, such as a biomarker test, continue to provide a feasible alternative as a first-line screening test by contributing to more precise, risk-based targeting strategies for LDCT screening.

Approach

ECLS was a pragmatic randomised controlled trial involving 12,208 high-risk participants recruited through General Practices and community-based recruitment strategies in Scotland. The trial addressed whether the EarlyCDT-Lung test and subsequent imaging can reduce the incidence of patients with late-stage lung cancer at diagnosis compared to standard clinical practice. The EarlyCDT-Lung blood test is a biomarker panel that measures seven autoantibodies that can be found in patients with lung cancer up to four years before symptomatic presentation. The intervention arm received the EarlyCDT-Lung blood test and, if test-positive, LDCT scanning 6-monthly for up to two years. The control arm received standard clinical care.

Findings

The trial met its primary endpoint by demonstrating a significant reduction in late-stage lung cancer presentation in the intervention arm compared to the control arm at two years. The trial also demonstrated a reduction in lung cancer and all-cause mortality between arms, albeit not yet statistically significant at two years.

Consequences

ECLS demonstrates that blood-based biomarker panels, such as the EarlyCDT-Lung test, may have an important role in the early diagnosis of lung cancer: whether in clinical care or screening. This trial provides proof of concept and clinical utility that blood testing in combination with optimal selection of high-risk people and imaging can find cancers at the earliest stages when they are most amenable to cure. Further investigation in large, community-based phase V studies are needed to determine the long-term impact of performing the EarlyCDT-Lung test on mortality, cost-effectiveness, the level of risk that should be targeted, the time interval between tests, and how to improve the engagement of people at the highest risk.