In 2008 in the UK, >33 500 patients died from lung cancer and there were >38 500 new diagnoses.1 2
Five-year survival was only 6.5%, improved since 2005 but still among the lowest in Europe. There are many hypotheses about the reasons for this poor outcome. The delivery of treatment with curative intent is known to vary in the UK. The surgical resection rate may be as low as 4% in some centres and, in others, >25%.3
It is argued that by ensuring a universally high standard of care the overall outcomes will be improved. The stage and fitness of the patient are other factors that are linked by the timeliness of presentation. There are initiatives to increase public awareness of lung cancer symptoms which aim to encourage earlier presentation. However, data suggest that in most patients, these symptoms commence only a few months prior to the first contact with secondary care and therefore there is only a narrow time frame in which to make a difference.4
Lung cancer screening is therefore an important area for study since this offers the potential to detect presymptomatic cancer at a much earlier stage when it is more likely to be curable and when it has not had a chance to take its toll on the patient's fitness.
Early screening studies conducted in the 1950s to 1970s employed chest radiographs and sputum cytology as screening tools and, although survival was improved in some studies in the screened group, there was no overall improvement in mortality from lung cancer.5 6
A number of important lessons were learnt about the influence of bias in this type of study and the importance of using mortality as the principal outcome measure. The lung component of the National Cancer Institute (NCI) PLCO (Prostate, Lung Colorectal and Ovarian) screening trial recruited patients in the USA between 1993 and 2001. In this trial, a total of 77 464 subjects aged 55–74 years were randomly assigned to the active arm of the trial that included a baseline followed by three repeat chest radiographs. A total of 564 lung cancers (0.72%) were detected. The initial results show that for non-small cell lung cancer (NSCLC), 59.6% of screen-detected and 33.3% of interval cancers were stage I–II.7
The study is due to report on mortality in 2015.
CT is a much more sensitive method of detecting lung cancer at an early stage,8
but for this reason is potentially more susceptible to lead time and overdiagnosis bias than chest radiography.9
Thus apparent differences in survival are not enough to ensure efficacy as a screening test, and studies must measure mortality. Benefit in terms of mortality must outweigh the harms that may result from screening. Screening studies in other cancers have shown the importance of taking into account the harms that may result from a screen. This includes not just the physical harm of multiple exposures to radiation, but the less easily measured psychological harm that may result from screening, especially in the vulnerable.10 11
Screening must also be cost-effective, and this consideration strongly influences the design of a screening programme.12
There are now a number of CT-based screening studies that have been published and several randomised trials underway. The first major lung cancer randomised controlled trial (RCT) screening trial utilising low-dose CT (LDCT) was the National Lung Cancer Screening Trial (NLST), which is a combination of two trials, one set up by the US NCI and the other by the American College of Radiology Imaging Network (ACRIN).13 14
Between 2002 and 2004, 53 456 former and current smokers were randomised to either LDCT or chest radiograph annually for 3 years. The major objective was to determine whether LDCT reduces lung cancer mortality compared with chest radiography. This trial has recently been stopped as it has reached the primary end point of a 20% reduction in mortality in the LDCT arm.15 16
The full report is to be published in the next few months. A number of smaller randomised trials have recently reported their preliminary findings. These include the ItaLung and Dante Trials in Italy,17 18
the French randomised pilot study, Depiscan, comparing LDCT and chest radiography,19
and the Danish lung cancer screening trial.20
These studies employ conventional methods to analyse the images, but the Dutch–Belgian NELSON (NEderlands-Leuvens longkanker Screenings ONderzoek) uses volumetric analysis to classify both the initial characteristics and growth behaviour of nodules.21
The UKLS trial design team used the data available from NELSON to develop the nodule management protocol described below.