Assessing the Effectiveness of Low-Dose Computed Tomography in Lung Cancer Screening for High-Risk Smokers: A Randomized Controlled Trial in Hong Kong

Background:

Lung cancer is an important public health problem in Hong Kong and worldwide. In Hong Kong, lung cancer always ranked the top in terms of incidence and mortality among common cancers in both sexes. Previous studies has suggested that cancer screening could potentially achieve a stage shift that enables the diagnosis of more cancer cases in early-stages (I or II), thereby enabling earlier treatment of early-stage cancers rather than advanced-stage cancers to achieve higher survival rates and reduction in the overall mortality. In particular, low-dose computed tomography (LDCT) was reported to be effective in screening for lung cancer among smokers in some countries. However, given the vast difference in smoking prevalence, lung cancer incidence and staging pattern at presentation, findings regarding both benefits and harms from one population may not be directly applicable to other populations. This highlights the importance of local evidence on both clinical effectiveness and cost-effectiveness of LDCT lung cancer screening in Hong Kong.

Aim:

To implement LDCT screening for high-risk ever-smokers to generate local data and robust evidence on the clinical effectiveness, cost-effectiveness, and feasibility of LDCT screening.

Study Design and overview:

This study will adopt the design of a randomized controlled trial. A total of 15,000 high-risk Chinese ever-smokers, aged 50-79 years with a smoking history of at least 20 pack-years in Hong Kong will be recruited. We target both current smokers, and former smokers who had quitted within the past 10 years. All participants are targeted to be recruited in the first year of the study, and to be followed-up for a total of 10 years; including regular active follow-up in the initial five years followed by an interim analysis to be conducted by the end of that period, and continuous outcome ascertainment by data matching in the next five years before the final analysis. After the baseline recruitment visit (T0), all enrolled participants will be randomized with a 1:1 ratio into either the screening arm (n = 7,500) with 3 LDCT screening to be done during the study period, or the control arm (n = 7,500) with no screening provided. All participants will be followed-up at 18 ± 3 months (T1), 42 ± 3 months (T2), and at 60 months (T3) from baseline. The three rounds of LDCT screening for participants in the screening arm will be performed at T0, T1, and T2. Participants in both arms will have free blood tests at T0, T1, and T2, with complete blood count (CBC), lipid function, and basic renal and liver function test (RFT/LFT) to be tested at different designated time points. All participants, in both the screening or control arm will be referred to smoking cessation services provided by the participating non-government organizations (NGOs) upon randomization.

Participants' consents for accessing their updated health status data from various sources will be obtained. Data on lung cancer incidence and mortality of participants will be continuously ascertained on follow-up contact. Cancer-related details including stage on diagnosis, laboratory test results, treatments including medication offered and procedures performed will be collected every 6 months through an agreement to be worked out with the Data Sharing Portal services of the Hospital Authority (HA), to be supplemented by clarification through HA's Clinical Management System (CMS) if needed. The survival status of participants will be continuously updated on follow-up contact, and to be checked though the Deaths Registry if needed, for up to 10 years since randomization on a half-yearly basis.

Interventions:

SCREEN arm: 3 LDCT screening services will be provided. CONTROL arm: No LDCT screening service will be provided.

Study Endpoints and outcome measures:

The primary endpoint of this study is lung cancer mortality. Secondary endpoints includes (i) stage distribution of lung cancer cases; (ii) lung cancer incidence; (iii) prevalence of false-positive of screening cases; (iv) percentage of overdiagnosis of lung cancer cases; (v) prevalence of radiation-induced cancers; and (vi) health-related quality of life (HRQoL).

Main analysis:

Intention-to-screen (ITS) approach.

Potential significance:

The findings will help to inform evidence-based recommendations for the consideration of lung cancer screening in Hong Kong's healthcare system.

Inclusion criteria

• Adults aged between 50 and 79 years
• Current smokers or ex-smokers quitted for less than 10 years, with a history of cigarette smoking equivalent to at least 20 pack-years

Exclusion criteria

• Non-Chinese population
• Individuals who are not mentally competent to provide informed consent (e.g., those with a history of dementia)
• Individuals with a known prior diagnosis of lung cancer or detection of lung nodules
• Individuals with a history of other cancers within the last five years or currently under treatment
• Individuals who have undergone a CT scan of the thorax in the previous 12 months
• Individuals who are either unwilling to undergo a chest LDCT scan, or having a condition that prevents them from having a LDCT scan (for example, pregnancy or inability to lie flat on the CT table)