1. Primary endpoint (Time Frame - 5 years): Positive predictive value (PPV) for lung cancer detection with different inclusion methods (NELSON vs. PLCO) after 2 screening rounds.
Secondary outcome:
1. Key secondary endpoint 1 (Time Frame - 1 year): Proportion of individuals selected for screening within the high-risk population.
2. Key secondary endpoint 2 (Time Frame - 5 years): Proportion of lung cancers detected with different inclusion methods (NELSON vs. PLCO) within the overall study population after 5 years.
3. Key secondary endpoint 3 (Time Frame - 5 years): Proportion of lung cancers detected with in the high-risk population after 5 years.
4. Key secondary endpoint 4 (Time Frame - 5 years): Specificity within the overall population after 5-year follow-up.
5. Key secondary endpoint 5 (Time Frame - 5 years): Sensitivity within the overall population after 5-year follow-up.
6. Additional secondary endpoint 1 (Time Frame - 1 year): Rate of initiation of cardiovascular treatments (in particular lipid-lowering) in the calcium score reporting group vs. the non-reporting group after year 1 of study.
7. Additional secondary endpoint 2 (Time Frame - 1 year): Efficiency of nodule management algorithms (LungRads1.1 + PanCan) will be evaluated according to the number of patients sorted in the category (a) "Next surveillance scan" AND the number of patients with lung cancer sorted into category (b) "early recall scan", or (c) "diagnostic evaluation".
8. Additional secondary endpoint 3.1 (Time Frame - 1 year): Success of screening program. Based on all individuals enrolled. Definition of success is calculated using Response rate.
9. Additional secondary endpoint 3.2 (Time Frame - 1 year): Success of screening program. Based on all individuals enrolled. Definition of success is calculated using Reliability of PLCO risk scoring (self-reported vs. on site assessment).
10. Additional secondary endpoint 3.3 (Time Frame - 1 year): Success of screening program. Based on all individuals enrolled. Definition of success is calculated using Percentage of subjects receiving an adequate low-dose CT scan and report according to DRG guidelines (number of diagnostic CTs/number of all CTs).
11. Additional secondary endpoint 3.4 (Time Frame - 1 year): Success of screening program. Based on all individuals enrolled. Definition of success is calculated using Percentage of subjects receiving adequate follow-up procedures.
12. Additional secondary endpoint 4.1 (Time Frame - 1 year): Quality of screening program: CT reading performance (2nd reader vs. CAD vs. AI)
13. Additional secondary endpoint 4.2 (Time Frame - 1 year): Quality of screening program: Quality of lung nodule management
14. Additional secondary endpoint 4.3 (Time Frame - 1 year): Quality of screening program: Frequency of detection and management of incidental findings from low dose chest CT (emphysema, coronary heart disease, etc.)
16. Additional secondary endpoint 5 (Time Frame - 1 year): Smoking cessation: Success of smoking cessation counseling based on number of participants quitting with or without revealing additional health risks (emphysema score, coronary calcium score or both).
17. Additional secondary endpoint 6.1 (Time Frame - 1 year): Identification of blood-based biomarkers for early detection of lung tumors: Blood collection and evaluation of various blood-based epigenetic biomarkers in positive LDCT cases with subsequent biopsy on the positive predictive value of the LDCT test.
18. Additional secondary endpoint 6.2 (Time Frame - 1 year): Identification of exhalation-based biomarkers for early detection of lung tumors: Collection of breath condensate and evaluation of various exhalation-based epigenetic biomarkers in positive LDCT cases with subsequent biopsy on the positive predictive value of the LDCT test.
19. Additional secondary endpoint 7.1 (Time Frame - 1 year): Cost-effectiveness analysis: Main objectives of the modelling study are to investigate the impact of different components of LDCT lung cancer screening on the long-term all-cause mortality and cost-effectiveness. Key components include risk score-based selection criteria, nodule management protocols, threshold values of imaging biomarkers for cardio-vascular diseases and COPD, and inclusion of smoking cessation programs (performed by Center for Health Economics Research Hannover (CHERH).
20. Additional secondary endpoint 7.2 (Time Frame - 1 year): Cost-effectiveness analysis: Comparison of patient recruitment strategies: Cost-effectiveness of register-based mailing campaign vs. GP referrals in terms of recruitment of qualified screening subjects (Center for Health Economics Research Hannover - CHERH).