Lung Cancer Screening in NLST Eligibles: Tailoring Annual Low-Dose Computed Tomography by Post-Test Risk Stratification

PURPOSE: To calculate the risk of lung cancer (LC) in 1 and 3 years after baseline low-dose computed tomography (LDCT), in screenees selected by National Lung Screening Trial (NLST) criteria. METHOD AND MATERIALS: For the aim of this post-hoc analysis, screenees from a prospective lung cancer screening (LCS) trial were retrospectively selected: age>=55years, pack-years>=30. Pre-test metrics: baseline demographics, medical interview, and pulmonary function test. Post-test metrics: retrospective LDCT reading by FDA-approved workstation for LCS, featuring computer aided diagnosis (CAD) and advanced semi-automatic algorithm for volumetric segmentation of nodule. Solid nodules were classified into 3 categories: 1)no nodule or nodule 1-112mm^3; 2)nodule 113-260mm^3; 3)nodule>260mm^3. Subsolid nodules were assigned either category 2(non-solid or part-solid nodules with solid component>5mm) or category 3(solid component>=5mm). The highest category was used for screenee-wise risk assessment. The primary outcome was LC diagnosis at 1 year or 3 years; the secondary outcome was the stage of LC. The Chi squared test was used to test the association between metrics and the primary outcome at 1 or 3 years. The risk of LC in 1 or 3 years was calculated by univariate and multivariate models. RESULTS: In 1,248 NLST-eligible screenees, LC frequency was 1.2% at 1 year and 2.3% at 3 years. At 1 year, category 3 was the only predictor of LC risk in multivariate model (odds ratio 79.84 p<0.001), confirming that early follow up by LDCT (e.g.3months) is needed for characterisation of such nodules. At 3 years, LC risk was predicted by category 2 (OR5.99 p=0.009) and 3 (OR26.55 p<001), Tiffeneau<70% (OR 2.75 p=0.024). LCS simulation with triennial screening rounds for category 1 and selective annual round for category 2 and 3 (29% in our population) showed 35% reduction of LDCT through 3 years. CONCLUSION: Annual LCS could be selectively offered to 30% of NLST eligible screenees, while longer interval might be safe in those with category 1. Validation of volumetric thresholds is granted through multiple software vendors. CLINICAL RELEVANCE/APPLICATION: LCS strategy can be optimised by tailoring annual LDCT to a minority of subjects at high risk, while longer screening intervals could be a safe strategy for low risk subjects yielding substantial reduction of LDCT burden (radiation and cost). This model is being prospectively tested in a LCS trial with LDCT every 3 years