The UK Lung cancer Screening (UKLS) trial (ODR1819_074)

The Data will be used for the purpose of a clinical trial: The UK Lung cancer Screening (UKLS) trial.

A lung cancer risk prediction model (LLP) was developed based on a questionnaire completed by 75,000 individuals. Of these, 4,050 individuals with a 5% or greater predicted risk of developing lung cancer within the next 5 years consented to participate in the UKLS trial.

The Data will be used to:

• identify the outcomes of the individuals who were not recruited into the clinical part of the trial, including those who subsequently developed lung cancer or died from any cause.

• confirm the long-term outcomes for those who were recruited into the clinical part of the trial.

• ascertain whether the predicted risk of lung cancer agrees with actual incidence of lung cancer.

Where individuals have opted out of disease registration by the National Disease Registration Service (NDRS), their data has been permanently removed from the registry and therefore will not be disseminated under this Data Sharing Agreement (DSA). https://digital.nhs.uk/ndrs/patients/opting-out

RADAR (questionnaire system used by the NHS and research teams) sent 75,000 UKLS participants who responded to the first questionnaire, to PHE (Now NHS England) The data consisted of identifying details (specifically NHS Number, Date of Birth, names and UKLS ID) for the cohort to be linked with NHS England data. This linkage had section 251 support to occur.

PHE (now NHS England) provided the relevant records from the NDRS cancer registrations and LUCADA datasets to University of Liverpool. The Data contained no direct identifying data items but contained a unique UKLS person ID which can be used to link the Data with other record level data already held by the recipient (the questionnaires which only contain the UKLS study ID and no participant identifiers).

The Data will not be transferred to any other location.

The Data will be stored on servers at University of Liverpool.

The Data will not be backed up at another location.

The Data will be accessed by substantive employees of University of Liverpool onsite at the premises of University of Liverpool only.

The Data will be linked with data held by University of Liverpool via a UKLS ID – this data comprises questionnaire data provided by participants, and outcome data of the clinical trial cohort.

The expected outputs of the processing will be:

• A report of findings to The National Institute of Health Research (published)

• Submissions to peer reviewed journals, including an update to the lung cancer risk prediction model (published) and subsequent papers exploring risk factors for lung cancer

• Presentations at appropriate conferences, e.g. World Conference on Lung Cancer

The outputs will not contain NHS England Data and will only contain aggregated information with small numbers suppressed as appropriate in line with the relevant disclosure rules for the dataset(s) from which the information was derived.

The outputs will be communicated to relevant recipients through the following dissemination channels:

• Journals

• Webinars open to scientists and medical professionals

• Social media

• Posters displayed at conferences and public events promoting lung cancer awareness

• Participant Information webpages

• Press/media engagement (usually associated with publication or presentation at conferences)

• Public promotion of the research via the university and study websites

The findings of this research study are expected to contribute to evidence-based decision-making for policymakers, local decision-makers such as doctors, and patients to inform best practice to improve the care, treatment and experience of health care users relevant to the subject matter of the study.

The use of the data could

• help the system to better understand the health and care needs of populations.

• lead to the identification or improvement of interventions to improve health and care outcomes or experience.

• support knowledge creation or exploratory research (and the innovations and developments that might result from that exploratory work).

The UKLS statistician has developed a risk model to predict lung cancer utilising nodule data from the UKLS study. This has now been published in Thorax (Probability of cancer in lung nodules using sequential volumetric screening up to 12 months: the UKLS trial. Michael W Marcus, Stephen W Duffy, Anand Devaraj, Beverley A Green, Matthijs Oudkerk, David Baldwin, John Field. doi: 10.1136/thoraxjnl-2018-212263).

The LLPv2 lung cancer risk model used in UKLS has been validated and update of the LLP lung cancer risk model (to LLPv3) with a more accurate estimation of absolute risk, as published in Thorax (Field JK, Vulkan D, Davies MPA, Duffy SW, Gabe R. Liverpool Lung Project lung cancer risk stratification model: calibration and prospective validation. THORAX. 2021;76(2):161-8). This will allow more efficient selection of at risk groups in future LDCT screening and other early-detection scenarios.

UoL have published lung cancer incidence data and mortality data in relation to the UKLS lung cancer screening trial (including as part of a meta-analysis of all related randomised control trials) in The Lancet Regional Health - Europe (Field JK, Vulkan D, Davies MPA, Baldwin DR, Brain KE, Devaraj A, et al. Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international metaanalysis. The Lancet Regional Health - Europe. 2021;10(100179):100179-). This data completes the world-wide randomised control trial assessment of LD-CT screening and provides evidence for the benefits of LDCT early lung cancer detection.

The UKLS data is particularly informative for UK implementation of LD-CT, supporting the NHS Targeted Lung Health Check programme (which has now been expanded in the NHS Lung Cancer Screening programme). Lives have already been saved as part of UKLS and more lives will be saved by the further implementation of LD-CT that is supported by the UKLS results, with efficiency savings from the demonstrated utility and validation of the LLP lung cancer risk score.

The UKLS data continues to be used for analysis in major international research project (e.g. the NIH-funded INTEGRAL project looking to improve risk-based early detection and lung nodule management, which has been extended by 5 years) and for publications (e.g. Moez, E., et al.2023 Circulating Proteome for Pulmonary Nodule Malignancy. Journal of the National Cancer Institute, doi:10.1093/jnci/djad122; Davies et al. 2024 Impact of single round of low dose CT lung cancer screening on cause of mortality in different socio-economic groups: a post-hoc analysis of long-term follow-up of the UKLS trial. Lancet Regional Health Europe doi: 10.1016/j.lanepe.2024.100936). As an invaluable resource for early detection biomarker studies, being the UK’s oldest establish repository of biosamples taken at the time of low-dose CT screening, with the longest follow-up, the UKLS study will continue to yield significant benefits going forward.

Of emerging benefit is the risk data collected from over 45% of UKLS questionnaire responders who have never smoked. There is a growing awareness that despite being excluded from lung cancer screening, a significant proportion of lung cancers occur in this population (10-15% of lung cancers in the UK). Initial results of risk factor analysis for these UKLS participants has been presented at the 2025 World Conference on Lung Cancer (P3.01.20 Lung Cancer Risk Factors in 35,530 People From the UKLS Trial Who Have Never Smoked. Shire, L. et al. Journal of Thoracic Oncology, Volume 20, Issue 10, S410).