Currently, the most effective way of reducing lung cancer mortality is early diagnosis of lung cancer. The National Lung Screening Trial has proved the efficacy of lung cancer screening using lowdose computed tomography to reduce lung cancer mortality. However, many questions remain surrounding lung cancer screening implementation, among which include how to select the optimal risk population, the personalized screening interval based different levels of risk, methods to improve diagnostic discrimination between malignant and benign disease in detected lung nodules, and the roles of biomolecular markers in stratifying risk and in guiding the management of indeterminate nodules. This review concentrates on the latest developments of lung cancer screening and provides an overview of the main unanswered questions on lung nodule detection. J Thorac Dis 2018;10(Suppl 7):S846-S859 jtd.amegroups.com reviews the latest progress in lung cancer screening and the main unanswered questions on lung nodule detection, to discuss optimal strategies for implementation of lung cancer detection.
How to conduct screening
Screening by thoracic imageryThe NLST enrolled high-risk asymptomatic individuals: age, 55-74 years; current or former smokers who quit within 15 years with at least 30 pack-years of smoking history. From August 2002 through April 2004 individuals were randomly assigned to annual LDCT screening scans versus CXR for three consecutive years. After a median follow-up of 6.5 years, the study showed that screening lead to a significant reduction of 20% and 6.7% in lung cancer and overall mortality, respectively. LDCT showed better performance for the detection of early-stage lung cancer, with 57% of screening-detected lung cancer cases of stages I or II, compared to only 39% in the CXR arm (9). This has led to the American Cancer Society's guidelines now recommending LDCT screening in high risk individuals aged 55 to 80 years who have a 30-year pack smoking history and currently smoke or have quit within the past 15 years (12).The impact of LDCT screening versus usual care or CXR have been also compared by several large-scale European randomized trials: Dutch-Belgian Randomized Lung Cancer Screening (NELSON) trial (13) (19). So far, the three published trials have reported conflicting results against NLST. The DLCST showed higher rate of all-cause mortality in the CT screening arm compared with usual care [relative risk (RR) 1.03; 95% CI: 0.66-1.60] (20,21). In the DANTE trial, CT screening demonstrated no significant effect on reduce of mortality (RR 0.99; 95% CI: 0.69-1.43) (15). The MILD trial found no effect of biennial screening compared with usual care and a negative effect of annual screening with more detected cancers but also higher all-cause mortality (RR 1.99; 95% CI: 0.80-4.96) (16). It has raised questions about whether the much smaller patient sample size and the inclusion of patients at lower risk (less exposure to tobacco) for lung cancer in these trials diluted any potential benefits of LDCT s...