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Introduction and Objectives Lung cancer (LC) is the most common cause of cancer death in the UK and worldwide, but screening with low-dose computed tomography (LDCT) has been shown to reduce LC deaths. The UK National Screening Committee has recommended nationwide roll-out of LDCT screening by 2029, but the optimal risk thresholds for eligibility remain uncertain. This study interrogates the cost-effectiveness of competing risk scores and thresholds, informed by the Yorkshire Lung Screening Trial (YLST).Methods We conducted a cost-effectiveness analysis using data from the YLST to compare different risk thresholds (USPSTF 2013, PLCOM2012≥1.51% and LLPv2≥5%). A Markov model was used to estimate the long-term implications of different screening approaches, including a no-screening counterfactual. Payouts per detected LC were calculated using LC mortality and utility estimates from the literature, and cost data from the literature and the YLST. Scenario analyses assessed how increasing thresholds for the PLCOM2012 and LLPv2 affected LC detection, costs, and quality-adjusted life years (QALYs).Results In the YLST, 6,650 participants underwent LDCT screening after meeting at least one of the three eligibility criteria, and 282 invasive LCs were diagnosed over two screening rounds. The incremental cost-effectiveness ratios (ICER) for the three eligibility criteria used in the YLST ( vs. no screening) were £3,949 for USPSTF2013, £3,797 for LLPv2≥5% and £4,013 for PLCOM2012≥1.51%. Of the three criteria, PLCOM2012 resulted in the largest numbers of people screened and LCs detected, the most QALYs gained and highest incremental net monetary benefit (iMNB), and was the optimal choice based on cost-effectiveness. The figure 1 below shows that PLCO M2012 4%, 3%, 2%, 1.51% form the efficiency frontier, delivering more QALYs for lower costs compared to LLP v2 and USPSTF2013 criteria.Abstract P169 Figure 1Conclusion All three screening eligibility criteria used in the YLST are cost-effective according to UK’s willingness to pay threshold of £20,000/QALY, with PLCO M2012 ≥1.51% being the optimal approach. Although it was not possible to robustly test the impact of lowering risk score thresholds further (i.e. below the thresholds used in the YLST), these and other data suggest that this is likely to detect more cases of LC whilst remaining cost-effective.