Abstract SS03-01: Follow-up on the National Lung Screening Trial: The next steps
Authors: Field John K. 
Published: June 2012

Abstract
The publication of the NLST randomized controlled trial from the USA has provided evidence that CT screening reduces mortality from lung cancer by more than 20.3 percent and the all cause mortality was 6.9 percent lower in those screened with low-dose CT, relative to those screened with chest radiography1. The NLST is the first randomized controlled trial for lung cancer screening to show a significant mortality benefit. These findings may potentially lead to one of the most important developments in lung cancer care. However there remain important questions about the applicability of the results globally and the clinical effectiveness of this intervention including its feasibility and cost-effectiveness.
A number of randomized trials have recently reported their preliminary findings, which includes the ItaLung and Dante Trials in Italy, the French randomized pilot study, Depiscan, comparing LDCT and chest radiography, and the Danish lung cancer screening trial, however, the largest of the European trials is the DutcheBelgian NELSON (NEderlands-Leuvens longkanker Screenings ONderzoek). Recently the UK have launched the UKLS CT screening trial. One of the major attributes of the European CT trial groups, is their readiness to share data in the coming years, as agreed in the Liverpool Statement 20052.
Many of the European studies have employed conventional methods to analyses the images, but the NELSON trial uses volumetric analysis to classify both the initial characteristics and growth behavior of nodules3. The UKLS trial design team used the data available from NELSON to develop the nodule management protocol which relies heavily on this technology4. The UKLS pilot trial will randomize 4000 individuals with at least a 5% risk of developing lung cancer over 5 years as predicted by the Liverpool Lung Project Risk Prediction Model5. If the pilot shows that a trial is feasible, a further submission will be made to undertake an RCT, randomizing 28 000 individuals from seven centers in the UK with the same 5% 5-year risk of lung cancer. The ‘Wald Single Screen Design’4 has been chosen for the UKLS RCT. The aim of the main UKLS trial is to establish whether CT screening can reduce lung cancer deaths by at least 30% and to determine the cost effectiveness of CT screening in the UK.
The IASLC set up a Task Force6 to respond to the NLST press release in October 2010. The NLST is the first randomized clinical trial to show a significant decline in lung cancer deaths, however, there are a number of opportunities to improve further this approach. There is a need to introduce quality control measures to ensure the quality of the screening management. For example, the follow-up of patients with indeterminate nodules is critically important and should be done by a team experienced in evaluation of such nodules to ensure safe, economical screening care. The Position Statement from the UKLS team supported these recommendations and also indicated that additional research will also define risk profiles of individuals who would benefit most from screening7. Screening can be improved through ongoing research, which is essential, as the resolution of spiral CT imaging continues to improve, and this can drive further progress with a safer and more effective surgical management approach. The advice of the IASLC Task Force at this time is that, it is appropriate for heavy smokers ages 55 to 74 to discuss relevant lung cancer screening information with their physicians to assist them in deciding whether to undergo spiral CT screening. In addition it is very important that smoking cessation is linked with all future CT screening programs.
There remain unresolved issues with respect to CT screening for lung cancer. These include its feasibility, psychosocial and cost-effectiveness, harmonization of CT acquisition techniques, management of suspicious screening findings, the choice of screening frequency and the selection of an appropriate risk group for the intervention.
References:
1. National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, et al. Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening. N Engl J Med. 2011.
2. Field JK, Smith RA, Duffy SW, Berg CD, van Klaveren R, Henschke CI, et al. The Liverpool Statement 2005: priorities for the European Union/United States spiral computed tomography collaborative group. J Thorac Oncol. 2006; 1(5): 497–8.
3. van Klaveren RJ, Oudkerk M, Prokop M, Scholten ET, Nackaerts K, Vernhout R, et al. Management of lung nodules detected by volume CT scanning. N Engl J Med. 2009; 361(23): 2221–9.
4. Baldwin DR, Duffy SW, Wald NJ, Page R, Hansell DM, Field JK. UK Lung Screen (UKLS) nodule management protocol: modelling of a single screen randomised controlled trial of low-dose CT screening for lung cancer. Thorax. 2011; 66(4): 308–13.
5. Cassidy A, Myles JP, van Tongeren M, Page RD, Liloglou T, Duffy SW, et al. The LLP risk model: an individual risk prediction model for lung cancer. Br J Cancer. 2008; 98(2): 270–6.
6. IASLC-CT-Screeing-Task-Force. IASLC'S 2011 Statement on CT Screening for Lung Cancer. http://iaslcorg/policies/statement-on-ct-screening/.
7. Field JK, Baldwin D, Brain K, Devaraj A, Eisen T, Duffy SW, et al. CT screening for lung cancer in the UK: position statement by UKLS investigators following the NLST report. Thorax. 2011.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):SS03-01.