Lung Cancer Screening with Low-Dose CT: What We Have Learned in Two Decades of ITALUNG and What Is Yet to Be Addressed

The ITALUNG trial started in 2004 and compared lung cancer (LC) and other-causes mortality in 55-69 years-aged smokers and ex-smokers who were randomized to four annual chest low-dose CT (LDCT) or usual care. ITALUNG showed a lower LC and cardiovascular mortality in the screened subjects after 13 years of follow-up, especially in women, and produced many ancillary studies. They included recruitment results of a population-based mimicking approach, development of software for computer-aided diagnosis (CAD) and lung nodules volumetry, LDCT assessment of pulmonary emphysema and coronary artery calcifications (CAC) and their relevance to long-term mortality, results of a smoking-cessation intervention, assessment of the radiations dose associated with screening LDCT, and the results of biomarkers assays. Moreover, ITALUNG data indicated that screen-detected LCs are mostly already present at baseline LDCT, can present as lung cancer associated with cystic airspaces, and can be multiple. However, several issues of LC screening are still unaddressed. They include the annual vs. biennial pace of LDCT, choice between opportunistic or population-based recruitment. and between uni or multi-centre screening, implementation of CAD-assisted reading, containment of false positive and negative LDCT results, incorporation of emphysema. and CAC quantification in models of personalized LC and mortality risk, validation of ultra-LDCT acquisitions, optimization of the smoking-cessation intervention. and prospective validation of the biomarkers.

Automated summary

The ITALUNG trial, conducted from 2004, compared the mortality rates of lung cancer and other causes in smokers and ex-smokers aged 55-69 who were randomly assigned to receive low-dose CT (LDCT) or usual care. After 13 years of follow-up, the ITALUNG trial demonstrated a lower mortality rate for lung cancer and cardiovascular diseases in the screened subjects, particularly in women. In addition, the trial generated multiple ancillary studies on various aspects of lung cancer screening, including software development, assessment of lung nodules and calcifications, and biomarker assays.