The ‘irrefutable evidence’ that Lung cancer CT screening works

Lung cancer

Professor John Field is the Chief Investigator of the UKLS (UK Lung cancer Screening Trial) and is heavily involved in European and international lung cancer screening efforts. He works in the University of Liverpool’s Department of Molecular and Clinical Cancer Medicine.

Stephen W. Duffy is a Professor of Cancer Screening at the Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine and Dentistry, Queen Mary University of London.

“We now have unequivocal evidence as to how to control the impact of Lung cancer in our society. Currently, Lung cancer kills more people than any other cancer in Europe and the five-year outcome is poor for late stage disease.

The recent publication of the NELSON lung cancer screening trial in the New England Journal of Medicine (Dutch-Belgian lung cancer screening trial), which was led by Professors Harry de Koning and Matthijs Oudkerk, has now provided policy makers with irrefutable evidence of the mortality benefit of CT screening for lung cancer. This is likely to add to the drive to implement CT screening in the UK and in Europe.

NELSON is the only adequately powered lung cancer screening trial, other than the National Lung Screening Trial in the USA. NELSON recruited 15,789 subjects, which were randomized to periodic low dose CT screening or to a no-screen arm. The former group showed a significant 24% reduction in mortality from lung cancer in male participants. This translates to around 60 lung cancer deaths prevented as a result of four offered rounds of screening in 7,900 subjects.
We have known for some time if one can identify early stage lung disease in high risk individuals using CT (which are special X rays, called Computed Tomography), and are treated successfully, usually by surgical intervention, these individuals have a very good five-year prognosis.

The UK pilot lung cancer screening trial (UKLS) has demonstrated that a high percentage of early stage disease (67%) were identified, of which over 80% were suitable for surgery. A number of extremely important lessons were learnt from the UKLS, which included: minimal psychological impact on the participants; successful integrated smoking cessation and the intervention was estimated to be cost effective.

The immediate impact of the UKLS trial was taken up by Liverpool CCG, with the Liverpool Healthy Lung Programme, followed by major implementation and evaluation projects in Manchester, Yorkshire and London. Most recently NHS England have made a major investment into the ‘Targeted Screening for Lung Cancer with Low Radiation Dose Computed Tomography’, which provides support for 10 new early detection sites. We could say, therefore, that the UK is leading the implementation of lung cancer screening in Europe, but we have to be aware that these remain local projects and a policy decision is awaited on the issue of a National Lung Cancer Screening Programme. The NELSON results provide valuable information for such a decision. Furthermore, the impact of the NELSON trial will be considered beyond Europe, especially in Asia, where there is already major interest in lung cancer screening.

Even though the NELSON trial mainly focused on men, the trial included a small sample of women (because of costs), which provided a very interesting observation of a greater relative benefit in women than in men. NELSON demonstrated a non-significant 33% reduction in lung cancer mortality in females, at 10 years follow-up bearing out results observed in NLST and elsewhere to a lesser degree. The reason for this finding is currently unclear, however, it may relate to lesser comorbidity in women. There is a need for further examination of the other European trial results, to ascertain if this is a general phenomenon, and more importantly, why it occurs.

In any screening setting, one has to examine the harms and benefits and if patients are undergoing unnecessary extra examinations or treatment. In lung cancer, this relates to the numbers of screened subjects undergoing further investigation. Results in the past have indicated that around 20% of screenees require at least an additional scan to check for growth or regression. In NELSON, this was only observed at the first screen, with proportions of 1.9-6.7% at subsequent screens, and an average over all four screens of less than 10%. This was achieved by using a very effective strategy of classifying the risk posed by abnormalities found on CT screening. This strategy used the volume and rates of growth in volume of the abnormality, rather than older studies which relied only on the diameter.

The success of the NELSON lung nodule management system has resulted in it being advocated in the European Position Statement on Lung Cancer Screening. This will improve the acceptability of CT screening, as the rate of recall for further investigation has been a major concern.

This conversation needs to be taken forward in the UK with the health service policy makers, taking account of the potential number of lives saved through screening and identifying the high-risk individuals with validated prediction tools. There is an urgent need to identify the target risk population in which the screening will be acceptable and cost-effective.”

Further information can be found in the recent New England Journal of Medicine Editorial written by Professor Field and Professor Duffy which can be found here.