This is a single arm screening study. All eligible participants will be subjected to low dose CT (LDCT) screening and biomarker testing.

The primary aim of the study is to determine the feasibility of conducting LDCT screening in at-risk populations for lung cancer in Singapore:

• For the smoker population, LDCT screening for lung cancer will be implemented in accordance to Academy of Medicine, Singapore screening test guidelines with the aim of investigating the feasibility of instituting lung cancer screening clinical service in Singapore.
• For the non-smoker population, LDCT screening for lung cancer will be introduced to systematically collect baseline data to better understand and provide evidence for lung adenocarcinoma in never-smoker phenotype that is unique to East Asia/Singapore. This will help address unmet needs in local population research as reported by Academy of Medicine, Singapore, to validate risk factors and inform future screening guidelines for the at-risk population.

Screening results will be reported based on Lung CT Screening Reporting & Data System (Lung-RADS).

This is a single arm cohort screening study. Briefly, this prospective study will involve screening the general population with risk factors for lung cancers with the aim of investigating the feasibility of implementing LDCT screening in the local context. Both smokers and non-smokers with the known risk factor of family history of lung cancer up to 2nd degree are eligible to participate in the study. Depending on emerging epidemiological data, additional high-risk cohorts may be included in this study. Subject demographics, smoking history, exposure to the aforementioned environmental factors, family history of lung cancer, history of tuberculosis and comorbidity will be captured in detail. The age range for inclusion is 55 to 74 years. Given the higher proportion of never-smoker lung cancer in Singapore, we aim to recruit 650 non-smoking and 350 smoking individuals for our study.

LDCT scan results will be reported based on the Lung-RADS classification. Participants will be stratified into various Lung-RADS groups based on the CT appearance and size of nodules. An alphanumeric Lung-RADS score will be assigned to each subject which will guide the downstream management of screened participants.

Participants with LDCT scan results of Lung-RADS score 2 and above will be referred to the nodule clinic under SingHealth DUKE-NUS Lung Centre for standardized follow-ups and/or diagnostic evaluation. These patients will undergo clinical surveillance (up to maximum of 5 years depending on their nodules) and will be managed as per current clinical practice. Participants with LDCT scan results of Lung-RADS score of 1 will undergo further screening surveillance which will end after 2 years if they have no nodules detected.

Inclusion Criteria:

Smoker:

• Participant is willing and able to give informed consent for participation in the study
• Male or female, aged 50-80 years of age
• No prior history of cancer, or cancer free in the last 5 years and not currently on cancer treatment
• ECOG 0/1
• Current or former smokers with at least 30 pack years of smoking history
• Willing to comply with study follow-up schedule and tests
• Willing to cover the costs of downstream standard of care management and investigations including doctor's fee, CT scan and biopsy etc.
• A Singapore citizen/Permanent Resident of Singapore

Non-Smoker:

• Participant is willing and able to give informed consent for participation in the study
• Male, or female, aged 50-80 years of age
• No prior history of cancer, or cancer free in the last 5 years and not currently on cancer treatment
• ECOG 0/1
• Never smoker, or has smoked less than 10 pack-years and has quit smoking for at least 15 years
• Family history of lung cancer up to 2nd degree relatives
• Willing to comply with study follow-up schedule and tests
• Willing to cover the costs of downstream standard of care management and investigations including doctor's fee, CT scan and biopsy etc.
• A Singapore citizen/Permanent Resident of Singapore

Exclusion Criteria:

• Uncontrolled medical comorbidity on enrolment
• Previous diagnosis of cancer
• Bleeding diathesis that will preclude blood sampling
• Fear of blood draw or needles
• Pregnancy

De-identified and/or anonymized data.