Screening for early stage lung cancer and its correlation with lung nodule detection

Lung cancer is the leading cause of cancer-related deaths worldwide, accounting for an estimated 1.6 million deaths each year (1). The survival of lung cancer is strongly related to the stage of diagnosis, with 5-year overall survival decreasing from stage IA disease (85%) to stage IV disease (6%) (2). However, in routine clinical practice, many early-stage lung cancer were delayed in diagnosis, due to that most patients are often asymptomatic. Lung cancer screening is designed to reduce lung cancer related mortality through diagnosing the disease at its early stage in high-risk cohorts with relatively limited harm, in order to enable those patients to receive curative operations (3,4). Early screening trials generally assessed the efficacy of chest radiography (CXR) combined with sputum cytology, and showed no influence on lung cancer mortality (5-8). However, in the last decade, technologic advances in computed tomography (CT) re-brought imaging-based screening into the focus. The National Lung Screening Trial (NLST) demonstrated a 20% reduction in lung cancer mortality for low-dose computed tomography (LDCT) compared with CXR screening, as well as a 6.7% all-cause mortality reduction (9). Although the positive results are being issued, it remains to be seen whether the positive results of NLST can be reproduced by other randomized controlled screening trials. Liquid biopsy is a noninvasive approach to screening and early diagnosis of lung cancer (10,11). It may become one of the complementary or alternative approaches to thoracic imagery for the early diagnosis and screening for lung cancer. Also, how to balance the benefits and harms of the screening is still a controversial issue. Great concerns have arose from lung nodules detected from screening, such as false-positive results, overdiagnosis, false-negative results, physical and psychological problems. This paper briefly 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