While mature data from trials have demonstrated that periodic rounds of low-dose CT scan reduce lung-cancer related mortality, major issues are now implementation of screening on a large-scale and how to engage the target population
Quitting smoking is often a long-term process with many attempts and smoking cessation rates are still low in the population. In occasion of World No Tobacco Day 2021, the World Health Organisation (WHO) stresses the importance to commit to quit today rather than tomorrow due to the long-lasting consequences of smoking on health, including a heightened risk for lung cancer estimated up to 15 years after quitting. “There is still a denial of the danger tobacco smoking poses, especially in people from lower socio-economic groups and low-income countries,” comments Prof. Sebastien Couraud, Lyon Sud Hospital Centre-HCL, France. “They represent today the primary target for prevention initiatives and screening programmes to reducing the burden of lung cancer in the population. However, they are also the most difficult to engage.”
Lung cancer symptoms occur late in the disease, so the majority of patients with lung cancer present with advanced disease and have limited options of being cured (Annals of Oncology 28 (Supplement 4): iv1–iv21, 2017). The use of periodic low-dose CT scans in the at-risk asymptomatic population has been highly debated as a valuable approach to detect early lesions since mid-2000s, but still struggles to be implemented widely. One major limitation is how to identify and then reach people who may benefit from lung cancer screening. In fact, differently from other well-established cancer screening programmes in breast and colorectal cancer based on demographics, eligibility of lung cancer screening is rather based on smoking history besides age. Candidates are current or former heavy smokers (≥ 30 pack-years or ≤ 15 years since smoking cessation) aged 55–74 years, who are well informed about potential benefits and risks. “Smoking status is not recorded in national files, it is information provided via self-assessment reports only, where people often tend to minimise how much they actually smoke,” continues Couraud.
We need to find alternative ways to engage with the target population, for example through media campaigns, patient advocates, social networks or dedicated websites, bearing in mind that the most disadvantaged groups may not be familiar with some tools or interventions.
According to the pneumologist, primary care physicians can be pivotal in reaching these people, but tailored education programmes on lung cancer screening eligibility criteria are needed. “It is still very difficult to identify the right population,” he adds. “Beyond smoking history, operability must also be assessed, meaning that people engaged in screening should be selected among those who are able to undergo surgery if a lesion is detected by CT scans.”
An implementation issue
In recent large randomised trials, low-dose CT screening has shown to significantly reduce mortality in current and former smokers enrolled. In 2011, the American National Cancer Institute-sponsored National Lung Screening Trial (NLST) demonstrated a 20% reduction in lung cancer-related mortality and a 7% reduction in all-cause mortality in high-risk patients after 6.5 years of follow-up. In 2019, the Dutch/Belgian NELSON trial demonstrated a 26% reduction in lung cancer-related mortality in men after 10 years of follow-up. Similar outcomes were also reported in the Italian MILD trial (Eur J Cancer. 2019 Sep;118:142-148) and in the German LUSI trial. “I do not think that the scientific community needs more evidence in favour of screening,” comments Prof. Jan Van Meerbeeck, University Hospital Antwerp, Belgium, in response to those who deny the benefit of screening by using the argument of length time bias and overdiagnosis bias. By changing the nodule handling algorithm, a 10-fold reduction of positive findings were reported in the European trials compared to the rate from the NLST trial, thus showing an increased sensitivity and predictive value of CT scans.
Despite mature results from research have triggered international efforts to implement lung cancer screening, there are still many questions to be addressed.
The current scenario in Europe
Will screening for lung cancer ever become part of standard evidence-based practice? As of today, implementation of lung cancer screening in Europe is sparse, and mostly relies on pilot projects at local and regional levels. Croatia was the first EU country to introduce nationwide screening for early lung cancer detection as part of its National Cancer Control Plan 2020-2030, while population-based initiatives have been initiated in other countries like Germany, UK and Poland (Health Technol Assess. 2016 May;20(40):1-146). Beyond uncertainties about timing, interval, methodology of screening and overall cost-effectiveness of this approach that need to be addressed, some organisational aspects are also hindering a large-scale implementation. “For example, there is an open debate on how to manage incidental findings,” explains Van Meerbeeck, as CT scan is the only screening imaging method in which other organs are seen and not only the target organ. “In 6-10% of cases, during screening other problems can be detected like calcification of the coronary artery, aneurism of aorta, emphysema, thymic tumours or any other disease in the pleura. So, what will the investigator do with them? When should they be reported? Who will take them on? There is an important ethical and legal issue on who is responsible of reporting incidental findings.”
ESMO recommends that screening should not be offered on an ad hoc individual basis, but patients requesting screening should be referred to a dedicated programme which is fully integrated with smoking cessation interventions. Couraud stresses the importance to keep engaging with the target population throughout the duration of lung cancer screening as the recall phase can also be critical to the success of a programme. In fact, a population-based study conducted in France reported that the participation rate decreased after the first round of screening, and only one in three participants attended visits one year after the baseline CT scans (Clin Lung Cancer. 2020 Mar;21(2):145-152). “Little is known about how smokers respond to lung cancer screening and factors associated to participation need to be further investigated,” concludes Couraud highlighting a positive impact of screening on smoking habits. “Participation in screening programmes or being informed of a positive test are main factors associated to smoking cessation.”
