Five year mortality of patients diagnosed with lung cancer within two years of a positive autoantibody blood test in a Randomized Controlled Trial.

Problem

Lung cancer is commonly diagnosed at a late stage, when five-year mortality rates remaining at over 90% are unacceptably high. 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 required. Following the landmark National Lung Screening Trial, low-dose CT screening has been shown to detect cancers earlier and reduce lung cancer mortality by 20-25%. In 2022 the UK National Screening Committee recommended targeted lung cancer screening in people aged 55 to 74 years with a history of smoking. However, uptake by the public can be suboptimal because of lack of health insurance or low income, difficulties getting time off work, and low perceived risk . Moreover, the widespread adoption of low-dose CT screening is limited in many health systems by resource constraints, high false positive rates and concerns about overdiagnosis

Approach

ECLS (Early Diagnosis of Lung Cancer Scotland) was a pragmatic randomized trial involving 12 208 high-risk participants recruited through general practice and community-based recruitment strategies in Scotland. Recruitment occurred between April 2013 and July 2016 with follow up undertaken 60 months after randomization for each participant: adults aged 50–75 considered at increased risk of developing lung cancer compared to the general population. Our earlier publication from this trial reported outcomes after two years showing a significant reduction in late stage presentation, with a hazard ratio for stage III/IV presentation of 0.64 (95% CI 0.41–0.99), but no significant difference in lung cancer or all-cause mortality at 2 years follow-up. This presentation will present five year follow up per protocol analysis on lung cancer and all-cause mortality.

Findings

77 077 invitation letters were sent to people fulfilling the record search criteria from 166 general practices and 16 268 responded (21.1%). 12 241 were invited to an in-person screening appointment, and 12 208 were randomised and followed up. The recruitment rate of people identified as potential study participants from family practice records was 13.4%; and the recruitment rate from self-referral was 79.1%. Participant characteristics were balanced between the intervention and control groups . 28.5% of participants lived in the most deprived quintile in Scotland, the mean age at recruitment was 60.5 years (S.D. 6.58), and the mean pack years smoked was 38.2 (S.D. 18.58). The main findings are undergoing peer review by a major journal at present but will be available outside their embargo in time for the conference

Consequences

Blood tests or other biomarkers could substantially reduce the number of people requiring imaging investigations depending upon where the cut-off for sensitivity and specificity is set. This may have globally significant implications for case finding and screening for lung cancer in people at high risk of the disease. Whether blood based biomarkers should be used as one method to reduce lung cancer mortality requires further elucidation