1Division of Pulmonary and Critical Care, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA USA

2Division of Pulmonary, Critical Care, Care New England Kent Hospital, Warwick, RI USA

Lung cancer screening with low-dose CT (LDCT) scans has been widely accepted within the last decade. Our knowledge and ability to implement screening has greatly increased because of significant research efforts and guidelines from multiple professional societies. The purpose of this review is to summarize some of the significant findings pertaining to lung cancer screening.

Screening with LDCT decreases lung cancer mortality in multiple studies. Use of validated risk prediction calculators can improve patient selection and screening efficiency. Shared decision making and smoking cessation counseling are essential screening components. Multidisciplinary involvement is required for the success of a screening program.

Lung cancer screening is complex, and implementation of a successful program requires multidisciplinary expertise. Further prospective studies are required to determine optimal patient selection, screening intervals, and strategies to maximize benefit while further decreasing harms.’

Lung cancer (LC) is the number one cause of cancer-related deaths in the United States and the world in both men and women [1, 2]. Worldwide, there are approximately 1.8 million new cases and 1.6 million deaths every year [3], and in the US alone, LC accounts for approximately 23% of cancer related mortality [1]. The overall 5-year survival rate for LC remains poor at approximately 19% [1]. The mortality rate for LCs is predictably much lower in early compared to late stages [4], when it is potentially curable by surgical resection. There has been a longstanding intense focus on the development of effective LC screening strategies, designed for early identification and intervention in patients who are well enough to benefit. However, unlike in breast, prostate, and colon cancers, there was no widely recommended and effective screening method for LC until this past decade.

The goal of this paper is to briefly review the background of LC screening, recent updates in guidelines and clinical practice, discuss recent challenges, and consider future directions.

LC is strongly linked to tobacco smoking [4]. In fact, the rise in LC parallels the increase in tobacco smoking during the late 1800s and 1900s [5]. However, this association was only proved epidemiologically in 1950, and smoking cessation and abstinence was promoted as a public health effort by the US Surgeon General in 1964 [5]. Through widespread efforts, the rates of smoking cigarettes have been steadily decreasing [4].

Earlier studies in the 1980s [6–9] evaluating the role of chest X-rays (CXRs) and sputum cytology as screening tools suggested an overall survival advantage attributed to length or lead time bias and overdiagnosis [10], but failed to show a LC-specific mortality difference. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was a randomized-controlled trial (RCT) evaluating 154,901 participants aged 55 to 74 years from 1993 to 2001 [11]. Annual screening with CXR for 4 years in the intervention group was compared to usual care without intervention in the control group, and follow-up was continued for up to 13 years. There was no significant LC mortality benefit detected with CXR screening (mortality RR, 0.99; 95% CI, 0.87–1.22).

Studies in the 2000s [12–15] evaluated low-dose computed tomography (LDCT) scans for LC screening, and while CT scans were able to detect more early stage cancers, there was no conclusive proof of a mortality benefit. Some of these studies had design flaws and either lacked controls, adequate power, or sufficient enrollment. The National Lung Screening Trial (NLST) was a landmark study published in 2011, showing for the first time that dedicated annual screening for LC in a high-risk population was effective in decreasing mortality by as much as 20%, when using LDCT compared to CXRs [16••]. The study showed that for every 320 patients screened with CT, one death was prevented. This finally provided the evidence required for wider acceptance of LC screening with LDCT, and set into motion the gradual implementation process of dedicated screening programs.

In 2013, various organizations started recommending LC screening in selected high-risk populations. The US Preventive Services Task Force (USPSTF) recommended it for high-risk smokers age 55–80 [17]. Compared to the NLST criteria, the age limit had been increased to 80 based on modeling results from the National Cancer Institute’s Cancer Intervention and Surveillance Modeling Network (CISNET) for the Agency for Healthcare Research and Quality [18].

In 2015, the Centers for Medicare and Medicaid Services (CMS) announced their decision to approve LDCT for screening in high-risk individuals. However, CMS mandated that counseling with a shared decision-making (SDM) visit also be performed, in addition to ensuring eligibility criteria for the interpreting radiologist and imaging facility were met [19].

In the last 5 years, there were several RCT results published, including long-term follow-up of earlier trials [16••, 20–26, 27••]. These RCTs are summarized in Table ​Table1,1, with NLST baseline data also included as a reference point.

Summary of randomized-controlled trials on LDCT screening with extended follow-up and lung cancer-specific mortality results published within last 5 years

▪ 55–74 years of age

▪ ≥ 30 pack years smoking

▪ Current smoker or quit