Black et al1 reviewed 12 studies of CT screening for lung cancer published up to 2004 and concluded that there is insufficient evidence that CT screening might be clinically effective in reducing mortality from lung cancer.

This study was published immediately after two discordant studies by Henschke et al2 and Bach et al.3 The first study, in spite of the lack of total or disease-specific mortality rates for the screened population, concluded that low-dose CT screening could lead to a therapeutic strategy that resulted in a 10-year survival of 88% for patients with stage I disease.2 The second, in line with Black et al,1 concluded that there is no evidence that CT screening reduces deaths from lung cancer.3 In this study, despite annual screening, most of the individuals who died from lung cancer did not have their cancer detected at an early stage when cure was possible. However, the survival of patients with stage I disease was equivalent to the survival in the study by Henschke et al,2 but the proportion of patients with stage I disease fell dramatically after the second year and the cumulative mortality from lung cancer at 5 years was very close to that expected without screening.

A reasonable explanation is that radiological screening can detect early stage, slow growing or indolent disease, but is unable to prevent more aggressive and early metastatic lung cancer. Indeed, autopsy studies recognise inconsequential lung cancers.4 As a possible consequence, some individuals—even those enrolled in screening trials—will live and die with their lung cancer.

The major finding of these studies is that the natural history of lung cancers detected by CT scanning is unknown. According to the current view on the carcinogenesis of non-small cell lung cancer, it cannot be assumed that the biological behaviour of cancer parallels the anatomical size of the tumour or that small lesions are equivalent to early stage disease. No data are available to confirm that a primary lung tumour of 5 mm has a significantly better prognosis than tumours of 10 mm or even 30 mm.5 In different studies, approximately 60% of patients with clinical (radiographically detected) stage I disease (<3 cm) died from lung cancer within 5 years despite appropriate treatment.6 This suggests that a high percentage of patients have disseminated occult disease at the time of presentation.

With newer and more sensitive methods of detection, sites of isolated tumour cells and micrometastases may now become apparent. Indeed, clinical studies have confirmed that patients with small tumours can harbour malignant cells in lymph nodes of normal appearance detectable only by PCR assay.7 Other investigations have found tumour cells or circulating endothelial progenitor cells in the peripheral blood and bone marrow of patients with lung cancers of all sizes and stages.8

As the debate on lung cancer screening continues, it appears that we must learn more about the biology of this disease and integrate this knowledge with early diagnostic strategies including genomics and/or proteomics.