A 16-year evaluation of opportunistic lung cancer screening with low-dose CT in China: comparative findings between non-smokers and smokers

Background: Although low-dose computed tomography (LDCT) screening effectively reduces LC mortality in high-risk individuals with a history of smoking in China, the feasibility and efficacy of lung cancer screening (LCS) in individuals who never smoked versus individuals who smoked remains unclear.

Methods: We conducted a retrospective analysis of prospective cohort studies at the National Cancer Center (NCC) in China from January 2006 to December 2022. A comprehensive LCS initiative was undertaken, involving 30,468 participants (54.5% male). Participants underwent LCS using LDCT. Potential malignancies were managed through joint consensus between patients and their physicians. Epidemiology, screening eligibility criteria, and LC detection rates and survival outcomes were compared between individuals who smoked and individuals who never smoked.

Results: Among 30,468 participants, 339 LCs were pathologically confirmed in 289 patients. The LC detection rate was 0.9% (289/30,468) overall, 0.8% in individuals who smoked (71/9,042), and 1.0% in individuals who never smoked (218/21,426). In individuals who smoked, LC detection rates were 0.5% (21/4516) and 1.1% (50/4526) in the < 20 and ≥ 20 pack-year subgroups, respectively (P = 0.001). Early-stage LC (stage 0 or I) was detected in 73.8% of the individuals who smoked and in 78.8% of individuals who never smoked, while advanced LC (stage III-IV) was found 8.8% of individuals who smoked and 4.2% of individuals who never smoked, respectively. Significant differences in histologic types were found between individuals who smoked and individuals who never smoked (P = 0.01), although adenocarcinoma was the most prevalent in both groups, at 83.0% and 78.8%, respectively. The median nodule size was 9.9 mm (IQR, 8.0-13.8) in individuals who smoked and 9.2 mm (IQR, 6.8-13.6) in individuals who never smoked (P = 0.228). Individuals who never smoked tended to favour surgical treatment alone (88.0%) more than individuals who smoked (81.3%). The 10-year survival rate was higher in individuals who never smoked (92.6%) than in individuals who smoked (88.8%). Only 15.6% (45/289) of patients with LC met the United States Preventive Services Task Force (USPSTF) criteria for LDCT eligibility, while 29.0% (84/289) met the China guideline for the screening and early detection of lung cancer (CGSL) criteria. Median follow-up for those followed was 25.4 (IQR, 13.7-43.3) months.

Conclusions: LDCT screening improves early LC detection and treatment outcomes for both individuals who smoked and individuals who never smoked. Significant differences exist in epidemiology, histologic type, and survival between these groups. The USPSTF and CGSL criteria miss a significant number of LC cases, particularly among individuals who never smoked. Integrating individuals who never smoked into LCS programs is essential, yet it comes with its own challenges, such as managing radiation risks, allocating resources effectively, and considering financial aspects. Consequently, there is an urgent need for LCS programs in China to better identify the "high-risk" non-smoker population susceptible to LC and to ensure that potential risks associated with screening are reduced.