Lung cancer screening guidelines are clear but are they being followed?

Abstract

Lung cancer is the second most common cause of cancer worldwide and the leading cause of cancer death in the USA [1]. The American Cancer Society (NY, USA) estimated a total of 228,150 new cases of lung cancer with 142,670 deaths from lung cancer in the USA for 2019 [1]. Smoking is the main cause of lung cancer and contributes to 80% of lung cancer deaths in women and 90% in men [2]. Lung cancer is typically diagnosed at advanced stages and carries a high mortality rate, with a 5-year survival rate of only 18% [3]. Randomized controlled trials targeted toward lung cancer screening started in the 1970s when the US National Cancer Institute (NCI; MD, USA) sponsored several clinical trials to evaluate the benefit of adding sputum cytology to annual chest radiography (CXR) [4,5]. However, none of the trials showed a reduction in lung cancer mortality (Supplementary Table 1). Decades later, the NCI initiated the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), a large randomized controlled trial that aimed to reduce disease-specific cancer mortality by evaluating the use of CXR for screening [6]. The study found that 2% of participants that had a positive radiographic findings were diagnosed with lung cancer within 12 months of the screen, 44% of whom were diagnosed with stage I disease [6]. Pertinent findings that paved the road for future guidelines included the discovery that high incidences of lung cancer were noted in active smokers or those that had quit within 15 years of randomization [6]. In the 2000s, prospective studies were created throughout the world to evaluate the role of low-dose computed tomography (LDCT) for screening. The Lung Screening Study compared LDCT and CXR as screening modalities and revealed that LDCT was twice as effective as CXR in detecting lung cancer [7]. It also showed that 48% of lung cancers detected by LDCT screening were diagnosed at stage I [7]. Inspired by the Lung Screening Study, a large scale study called the National Lung Screening Trial (NLST), which enrolled 53,456 participants, was created. Participants were randomized to LDCT or CXR at a 1:1 ratio. The study demonstrated a 20% relative reduction in mortality in patients screened with LDCT compared with CXR [8]. Results from this trial were updated in 2013 and confirmed the benefit of LDCT for lung cancer screening in specific patient populations [9]. Similar results were showcased from The Dutch–Belgian Randomized Lung Cancer Screening Trial (NELSON) which began in Europe in 2003 [10]. More than 15,000 participants were enrolled and assigned to either computer tomography (CT) screening or to the control group with no screening [10]. The study reported a 41% positive predictive value with screening and 50% of the cancers diagnosed in the screening arm were found at early stages of the disease [10]. During a 10-year follow-up, there was a 26% mortality rate reduction in men and 39% in women [10]. Updated results published in the New England Journal of Medicine in 2020 confirmed that lung cancer mortality was significantly lower in patients who underwent CT screening compare to those in the control arm [11].