This systematic review, conducted by a multi-society collaborative effort, evaluates the benefits and harms of low-dose computed tomography (LDCT) screening for lung cancer. The review includes eight randomized controlled trials and 13 cohort studies. Key findings include: - **Benefits**: The National Lung Screening Trial (NLST) demonstrated a 20% relative decrease in lung cancer deaths among participants screened with LDCT compared to those screened with chest radiographs over a median follow-up of 6.5 years. However, two smaller RCTs (DANTE and DLST) found no significant difference in lung cancer mortality between LDCT and usual care. - **Harms**: LDCT screening identified a high percentage of subjects with nodules (average ~20%), most of which were benign. Additional imaging and invasive procedures were triggered by these nodules, increasing radiation exposure and the risk of complications. The rate of major complications among those with benign conditions was low, but the impact on quality of life is unclear. - **Generalizability**: The NLST population is the only one for whom a lung cancer mortality benefit from LDCT has been demonstrated. Other studies are too small, preliminary, or poorly designed to draw meaningful conclusions. The review concludes that LDCT screening may benefit individuals at elevated risk for lung cancer, but there are uncertainties about potential harms and the generalizability of results. Further research is needed to refine selection criteria and address critical areas of uncertainty.This systematic review, conducted by a multi-society collaborative effort, evaluates the benefits and harms of low-dose computed tomography (LDCT) screening for lung cancer. The review includes eight randomized controlled trials and 13 cohort studies. Key findings include: - **Benefits**: The National Lung Screening Trial (NLST) demonstrated a 20% relative decrease in lung cancer deaths among participants screened with LDCT compared to those screened with chest radiographs over a median follow-up of 6.5 years. However, two smaller RCTs (DANTE and DLST) found no significant difference in lung cancer mortality between LDCT and usual care. - **Harms**: LDCT screening identified a high percentage of subjects with nodules (average ~20%), most of which were benign. Additional imaging and invasive procedures were triggered by these nodules, increasing radiation exposure and the risk of complications. The rate of major complications among those with benign conditions was low, but the impact on quality of life is unclear. - **Generalizability**: The NLST population is the only one for whom a lung cancer mortality benefit from LDCT has been demonstrated. Other studies are too small, preliminary, or poorly designed to draw meaningful conclusions. The review concludes that LDCT screening may benefit individuals at elevated risk for lung cancer, but there are uncertainties about potential harms and the generalizability of results. Further research is needed to refine selection criteria and address critical areas of uncertainty.