Protocol and Rationale for the International Lung Screening Trial.

Rationale: The NLST (National Lung Screening Trial) reported a 20% reduction in lung cancer mortality with low-dose computed tomography screening; however, important questions on how to optimize screening remain, including which selection criteria are most accurate at detecting lung cancers and what nodule management protocol is most efficient. The PLCOm2012 (Prostate, Lung, Colorectal and Ovarian) Cancer Screening Trial 6-year and PanCan (Pan-Canadian Early Detection of Lung Cancer) nodule malignancy risk models are two of the better validated risk prediction models for screenee selection and nodule management, respectively. Combined use of these models for participant selection and nodule management could significantly improve screening efficiency.Objectives: The ILST (International Lung Screening Trial) is a prospective cohort study with two primary aims: 1) Compare the accuracy of the PLCOm2012 model against U.S. Preventive Services Task Force (USPSTF) criteria for detecting lung cancers and 2) evaluate nodule management efficiency using the PanCan nodule probability calculator-based protocol versus Lung-RADS.Methods: ILST will recruit 4,500 participants who meet USPSTF and/or PLCOm2012 risk ≥1.51%/6-year selection criteria. Participants will undergo baseline and 2-year low-dose computed tomography screening. Baseline nodules are managed according to PanCan probability score. Participants will be followed up for a minimum of 5 years. Primary outcomes for aim 1 are the proportion of individuals selected for screening, proportion of lung cancers detected, and positive predictive values of either selection criteria, and outcomes for aim 2 include comparing distributions of individuals and the proportion of lung cancers in each of three management groups: next surveillance scan, early recall scan, or diagnostic evaluation recommended. Statistical powers to detect differences in the four components of primary study aims were ≥82%.Conclusions: ILST will prospectively evaluate the comparative accuracy and effectiveness of two promising multivariable risk models for screenee selection and nodule management in lung cancer screening.Clinical trial registered with www.clinicaltrials.gov (NCT02871856).