Earlier diagnosis of lung cancer in a randomised trial of an autoantibody blood test followed by imaging

Abstract

The EarlyCDT-Lung test is a high specificity blood-based autoantibody biomarker that could contribute to predicting lung cancer risk. Here we report on the results of a phase IV biomarker evaluation of whether using the EarlyCDT-Lung test and any subsequent CT scanning to identify those at high risk of lung cancer reduces the incidence of patients with stage III/IV/Unspecified lung cancer at diagnosis, compared with the standard clinical practice at the time the study began.ECLS was a randomised controlled trial of 12 208 participants at risk of developing lung cancer in Scotland. The intervention arm received the EarlyCDT-Lung test and, if test positive, low-dose CT scanning six-monthly for up to 2 years. EarlyCDT-Lung test negative and control arm participants received standard clinical care. Outcomes were assessed at 2 years post-randomisation using validated data on cancer occurrence, cancer staging, mortality and comorbidities.At 2 years, 127 lung cancers were detected in the study population (1.0%).In the intervention arm, 33/56 (58.9%) lung cancers were diagnosed at stage III/IV compared to 52/71 (73.2%) in the control arm. The hazard ratio for stage III/IV presentation was 0.64 (95% confidence interval 0.41, 0.99). There were non-significant differences in lung cancer and all-cause mortality after 2 years.ECLS compared EarlyCDT-Lung plus CT screening to standard clinical care (symptomatic presentation), and was not designed to assess the incremental contribution of the EarlyCDT-Lung test. The observation of a stage-shift towards earlier-stage lung cancer diagnosis merits further investigations to evaluate whether the EarlyCDT-Lung test adds anything to the emerging standard of LDCT.

Personalising lung cancer screening: An overview of risk‐stratification opportunities and challenges

“…To our knowledge, the only biomarker that has been prospectively evaluated in a randomised controlled trial for selecting individuals for lung cancer screening is the EarlyCDT-Lung autoantibody test, which was applied in the Early Diagnosis of Lung Cancer Scotland (ECLS) trial. 127 However, only 32.1% of the individuals who developed lung cancer in the intervention arm had a positive EarlyCDT-Lung test result, suggesting poor sensitivity compared to current risk-prediction models. Furthermore, analyses from the German Lung Tumour Screening and Intervention study (LUSI), showed that the EarlyCDT-Lung test had a low sensitivity (13%) for early stage, small tumours as detected by CT screening.…”

“…Although some promising candidates have been suggested, none are currently applied in routine screening practice. To our knowledge, the only biomarker that has been prospectively evaluated in a randomised controlled trial for selecting individuals for lung cancer screening is the EarlyCDT‐Lung autoantibody test, which was applied in the Early Diagnosis of Lung Cancer Scotland (ECLS) trial 127 . However, only 32.1% of the individuals who developed lung cancer in the intervention arm had a positive EarlyCDT‐Lung test result, suggesting poor sensitivity compared to current risk‐prediction models.…”

A Panel of Tumor-associated Autoantibodies for the Detection of Early-stage Breast Cancer

“…What is encouraging is that autoantibodies are now developing as promising biomarkers for detecting cancers at an early stage. The EarlyCDT-Lung test that measures seven cancer autoantibodies has been proved to contribute to predicting lung cancer risk, and has been clinically used in the risk evaluation for malignancy in vague pulmonary nodules 30 , 31 . For breast cancer, numerous serum autoantibodies have been reported with potential early diagnostic value, whereas only few have been investigated in detail to evaluate the diagnostic utility.…”

Biomarkers for Lung Cancer Screening and Detection

“…Interestingly, mathematical modeling of a high-and low-specificity version of EarlyCDT-Lung has shown the ability to both reclassify nodules into a higher-and a lower-risk group (26). Recently, a double-blinded randomized trial was published describing the use of EarlyCDT-Lung followed by CT scan in a population at higher risk for lung cancer (27). Participants were randomized into an intervention arm that began with the Ear-lyCDT-Lung test then CT scan if the biomarker test was positive versus control, or standard of care that did not include CT scans and relied on symptomatic presentation.…”