In the UK in 1999 lung cancer was responsible for 34 240 deaths (22% of all cancer deaths). Proposals for a randomized controlled trial have been developed by the UK Cancer Coordinating Committee for Research — Lung (UKCCCR). The primary research objective of the UK trial is to determine whether lung cancer screening using low-dose Spiral CT reduces mortality from lung cancer. To address this issue a randomized controlled trial of Spiral CT vs. no screening in smokers, 60 years and over, is proposed, with lung cancer mortality as the primary end-point. Smoking cessation will be offered to both the screened and unscreened group. Initially a pilot trial of 2000 individuals is planned, the purpose of which is to determine the feasibility, compliance and costs of a large randomized controlled trial. There will be six participating centres in the pilot.
It is anticipated that approximately 40 000 individuals will be required in the full trial conducted over 5 years to demonstrate a reduction in lung cancer mortality of 25%. In the pilot we propose to perform Spiral CT at baseline and then at 1 year. In the full trial Spiral CT would be performed annually for 5 years (Fig. 1).
The success of the pilot will be based upon the ability to identify eligible individuals for the trial, the number recruited, and their return for a second Spiral CT scan after 1 year. This information will be used to determine the size, duration and costs of the full trial, provided the pilot is considered to be successful. In addition, the pilot will indicate the proportion of subjects who have nodules which require further evaluation and the proportion of these that are cancers including observation of nodule growth. The algorithm for evaluating nodules is shown in Fig. 2.
Definition and classification of nodules
A pulmonary nodule is defined as soft tissue or ground glass opacity of rounded shape.
Category 1
Benign nodules: lesions showing central, rim, uniform or other benign distribution of calcification; fat attenuation within the nodule, clear linear or linear branching densities, or known to be stable size for at least 12 months (for CT, defined as within measurement error of up to ∼20%).
Category 2
Micronodules, i.e. ≤4 mm diameter. The characteristics and locations of all nodules will be documented for purposes of future comparison at annual screening CT.
Category 3
Indeterminate nodules of 5–10 mm diameter whose growth rate is, as yet, undetermined, which do not fall into Category 1.
Category 4
Nodules >10 mm diameter which do not fall into the description for benign nodules, or those <10 mm if known to be enlarging on serial CT studies. Nodule characteristics may include round or spiculated margins, and cavitation. Focal areas of ground glass are also included in this category.
All Category 3 nodules will be measured and observed for tumour growth at 3, 6, 9, 12 and 24 months.
Nodule measurement
Soft tissue nodules are be measured (in mm) on standard lung and soft tissue windows, as defined above, using the maximum short axis (x) and long axis (y) diameters taken at the widest point of the nodule. Tumour volume can be calculated from the 2-dimensional measurements using the prolate eclipse formula (dimension x × dimension y × 0.52).
Recent research using specially designed computer software (Nodview) developed by Dr A Reeves and colleagues[18] at the Weill Medical College of Cornell University, New York, USA, has shown that tumours are frequently irregular in shape and may also grow asymmetrically. This new software, which is currently still under development, promises to be considerably more accurate for assessing tumour growth.