Lung cancer is the most common cause of cancer-related deaths in the UK ¹ causing more than 95 deaths per day. Unfortunately, a high proportion of patients are still diagnosed at a late and incurable stage, with 43.1% presenting with metastatic disease. ² Notably, lung cancer is increased in areas of social deprivation, with disproportionate incidence rates in the most deprived socioeconomic quintiles for both men and women. More than three-quarters of lung cancer diagnoses in the UK are predicted to be preventable, and two of the major risk factors are age and smoking, with 72% of cases occurring in patients with a history of smoking.

Earlier diagnosis of cancer improves the chance of cure by identifying the disease at a more localised stage where treatment options are more effective, and prognosis is improved. In 2007, the Cancer Reform Strategy ³ put earlier diagnosis of cancer at the forefront of national plans to improve cancer outcomes and support a coordinated effort to accelerate progress. The NHS England Lung Cancer Screening Programme (LCS), formerly the Targeted Lung Health Check, was started in 2019, initially targeting areas of high deprivation and higher rates of lung cancer diagnosis. It is a national programme which is part of the NHS Long-Term Plan ⁴ and The National Cancer Plan for England ⁵ to improve early cancer diagnosis and survival. As part of the programme, individuals aged 55–74 years with a smoking history are invited to have a clinical lung health check with a healthcare professional (via telephone, video, or in-person consultation), and if deemed to be at high risk, they are offered a low-dose CT scan (LDCT) of their lungs. ⁶ LDCT scanners are situated in specialist vehicles located in the community at multiple sites, in addition to those situated in local hospitals. Patients with suspected lung cancer will be notified and referred to their local rapid-access lung clinic. Those participants with no significant findings will be offered a repeat scan in 2 years’ time, while indeterminate findings may require earlier interval imaging according to the LCS protocol. ⁶

At the time of writing, approximately 2 million people have been invited to participate in the LCS ⁷ in England; however, only 49% of those invited attended an LCS risk assessment appointment. The success of screening programmes is dependent on engagement and participation; therefore, further research into methods to enhance engagement is required.

Studies investigating participation in LCS programmes have identified several multilevel barriers, including those related to LDCT, such as concern about unnecessary radiation exposure, cancer-related fear, and practical barriers, such as taking time off work, costs, and travel burden. ^{8 – 11} Individuals from certain demographics, such as those who are disabled, morbidly obese, or imprisoned, may also be unable to partake in the current LCS programme as currently structured. In the UK, factors associated with non-uptake included older age (OR = 0.73, p < 0.001) and current smoking (OR = 0.70, p < 0.01). ¹⁰ Among non-responders who provided a reason, two main themes emerged, with 46.8% reporting practical barriers such as travel and comorbidities and 18.4% reporting emotional barriers such as fear and avoidance of lung cancer information. ¹⁰ One potential approach to overcoming practical and LDCT-related barriers and improving engagement and equity in LCS uptake is to offer self-administered, home-based tests as a pre-LDCT risk assessment. These approaches may be more convenient and acceptable for invitees, particularly given the acceleration of patient collected sampling methods during the COVID-19 pandemic. ¹²

Urine home collection has been shown to be an acceptable sampling method for both women and men across different racial and ethnic groups in both the US and Europe. ^{13 – 15} However, there are very limited data on the uptake rate in non-responding cancer-screening cohorts. In France, urine self-collection for human papillomavirus (HPV)-based testing, offered as part of cervical cancer screening, has been reported to increase participation in non-responding women by 3–5%. ^{16 , 17}

Urine collection for biomarker evaluation was recently cited in the NHS Cancer Plan ⁵ as a target for biomarker development to assess the risk of cancer. Glycosaminoglycans (GAGs) are a family of polysaccharides found abundantly in the extracellular matrix of tissues and are an important component of the tumour microenvironment. ^{18 , 19} Alterations in GAG structure and abundance have been shown to contribute to a range of different processes in cancer development, including metabolic reprogramming, persistent growth signals, immunosuppression, angiogenesis, and tumour invasion. The profiles of GAGs (termed GAGome) have been identified as a promising potential biomarker to improve the early detection of many different cancer types and several commercially available liquid biopsy assays will be made available to assess this, including one under development by Elypta AB to support the earlier detection of multiple cancers, ²⁰ an updated version of this assay will be used for the sample viability assessment in UH-CAN Lung.

UH-CAN Lung is a feasibility study to understand whether individuals who fail to respond to an LCS invitation (LCS non-responders) will complete and return a self-administered urine collection with an analysable sample for GAGome profile testing. The sampling kits will be sent to 1000 LCS non-responders, who may be at a higher risk of developing lung cancer. The sampling kits will also include a short participant questionnaire to evaluate participant ease and acceptability of using a urine home collection kit, participant trust in a urine-based test result, and reasons for non-engagement with the LCS programme.

The ultimate goal of the UH-CAN Lung study is to improve engagement in the LCS programme for individuals who have not responded to LCS invitations by offering them an alternative initial method of engagement. The aim is to try to overcome some of the potential barriers posed by the existing programme structure. The National Cancer Plan for England ⁵ published in February 2026, sets out ambitions to improve and modernise the early detection pathway for cancer and cites the use of urine as a biomarker target. Optimising LCS engagement is an important component of the national initiative to improve early cancer diagnoses with approximately 1.28 million invitees failing to respond since the program commenced. ⁷ Conceivably, alternative testing methods may help to improve engagement. Existing evidence ^{9 – 11} supports the principle that home urine collection is acceptable as a sampling method. UH-CAN Lung represents a step towards identifying feasible options to increase engagement with LCS in people at increased risk of developing lung cancer. The results will inform the required sample size of a follow-up study aimed at evaluating the clinical utility of the test in identifying individuals at a high risk of cancer, including lung cancer, and will contribute to health economic calculations. The data obtained from the participant questionnaires will also help us assess key barriers to LCS engagement within this defined population and will inform future work to overcome such barriers.

Risks associated with this study are minimal, as participants will be utilising a non-invasive urine sampling device; therefore, adverse events are not anticipated. In the absence of receiving the UH-CAN Lung Home Testing Kit, the individuals involved have already opted not to respond to an LCS invitation; therefore, involvement with the study will not increase this risk. It will be clearly explained to all individuals who receive a home testing kit that they will not receive a result from this test and that it does not provide a substitute for their attendance at an LCS appointment. In addition, participant-facing documentation will advocate for engagement with the LCS program and may encourage the uptake of an appointment that could benefit the individual. This documentation was developed with Patient and Public Involvement (PPI) representatives from the study to ensure that all participant-facing documents are in clear, plain English that is felt to be accessible and acceptable. PPI representatives also attended regular Trial Management Group meetings as the patient voice in this study, which is particularly poignant given the nature of our aims. All the risks associated with the study were assessed and documented in the Trial Risk Assessment.

UH-CAN Lung is an observational feasibility study that will investigate whether home urine collection could be an alternative mechanism of engagement in Lung Cancer Screening in non-responders.

The study was designed with the primary aim of understanding how many participants from the 1000 who were selected and posted a home urine collection kit will return a sample. This information will allow us to evaluate whether the return rate is sufficiently high to develop a larger study to evaluate a urine-based biomarker for lung cancer in this population.

Additionally, this study will enable an understanding of non-responders’ perceptions of acceptability and motivation to engage in a home urine test. This will include a 5-point questionnaire with multiple choice answers (Appendix 2 ²² ) assessing whether participants find the home urine collection kit acceptable and easy to use, whether they would trust the results, whether a home urine test would encourage engagement with the LCS, and reasons for non-response to their LCS invitation.

Participants are advised that they could return a urine sample, questionnaire, or both to ensure that we were able to gather as much information as possible. We also ask for permission to collect information from the LCS program about whether participants go on to book an appointment, as our PIS encourages them to do so. If participants do go on to engage with the LCS program, this has the potential to identify additional patients at high risk of lung cancer who would otherwise have not been assessed through this initiative.

If the results of this study are promising, there are two main directions for future research. The first is to inform the design of a larger study evaluating home urine collection in this cohort, while also assessing emerging urine-based biomarkers, such as those developed by Elypta, which uses changes in GAG profiles as cancer signals. Second, while this study focuses on urine-based testing to improve engagement with lung cancer screening, the same methods can be applied to other sample-based tests and other cancer types to evaluate whether it can improve engagement with current screening programs or be utilised as an initial community-based triage test, as cited in the recent National Cancer Plan for England. ⁵

UH-CAN Lung was registered on the ISRCTN website on 24 July 2025, with a unique identifying number ISRCTN10344340.

This study was sponsored by the University Hospitals Southampton NHS Foundation Trust and was approved by the Confidentiality Advisory Group, Health Research Authority, and Health and Care Research Oxford A Research Ethics Committee (25/SC/0182).