Lung cancer screening with low-dose CT
Introduction
The aim of this review is to describe the background for lung cancer screening with low-dose computed tomography (CT), give an overview about recent CT screening studies, analyse their results and describe concepts for future research in this field.
Section snippets
Epidemiology of lung cancer
Lung cancer is the most lethal malignant tumour worldwide with 1.3 million estimated deaths per year [1]. It currently affects 3–4 times more men than women. The probability to develop lung cancer is strongly related to certain risk factors. The most important one is cigarette smoking which is estimated to cause >85% of lung cancer cases [2]. Exposure to asbestos is another important risk factor and—although the industrial use of asbestos has been abandoned in many industrialized countries
Histologic types of lung cancer
For clinical purposes, lung cancer is classified as small-cell-lung cancer (SCLC) and non-small cell lung cancer (NSCLC: squamous cell carcinoma, adenocarcinoma, large cell carcinoma) due to the different biologic behaviour of these entities. SCLC represents approximately 20% of all lung cancer cases and is characterised by rapid growth and usually early hematogenous metastases. The different types of NSCLC represent approximately 80% of lung cancer cases and typically exhibit slower growth and
Prognosis in lung cancer
The prognosis of lung cancer patients is strongly related to tumour stage at diagnosis particularly in NSCLC.
When the tumour is diagnosed at stage IA (tumour<3 cm, surrounded by lung, no lymphatic or hematogenous metastases) prognosis is favourable with a 5-year survival of >60% [4].
However, when diagnosed at more advanced stages 5-year survival drops markedly with almost no cure at stage IV (distant metastases) [5] (Table 1).
Unfortunately, if diagnosed because of symptoms only 20–25% of NSCLC
Symptoms of lung cancer
Lung cancer confined to the pulmonary parenchyma usually does not cause symptoms. Rarely hemoptysis may be an early sign in localised tumours. In most cases symptoms are due to invasion of adjacent structures (stages III or IV), e.g. oesophagus, spine, superior sulcus, superior vena cava, other mediastinal vessels or distant metastases (stage IV), e.g. seizures due to brain metastases or pathologic fractures due to skeletal metastases. Therefore, almost all symptomatic patients present at
Localisation of early lung cancer
Lung cancer may either present as a soft-tissue or ground-glass attenuation pulmonary nodule surrounded by aerated lung or as an endobronchial lesion with or without extrabronchial component. At chest radiography the proportion of cancers presenting as pulmonary nodules and hilar masses, respectively, has been reported as equal. It is believed that in small cancers, which may only be detected at CT, pulmonary nodules surrounded by lung parenchyma are far more common than purely endobronchial
Lung cancer screening with chest radiography and sputum cytology
Considerations to use diagnostic tests for early diagnosis of lung cancer are not new as the tumour is common, prognosis is markedly better at early than at advanced stages, and there are usually no early symptoms to allow the diagnosis.
In the 1970s sputum cytology with or without chest radiography has been used in two large studies for early detection of lung cancer [7], [8], [9], [10]. They demonstrated more asymptomatic, early, resectable tumours in the screened subjects than in a control
Detection of lung cancer with computed tomography
Since its introduction into clinical routine in the early 1980s chest CT has been shown to have a much higher sensitivity for small pulmonary nodules, which are likely to be the most common presentation of early lung cancer, than chest radiography [17], [18], [19], [20].
Compared to an operative and histologic gold standard single-slice spiral CT reached a sensitivity of 95% for nodules larger than 5 mm [21].
Furthermore, significant dose reduction has been shown not to decrease sensitivity of
Lung cancer screening with CT
Several feasibility studies of low-dose CT in heavy smokers have been performed. In summary, using similar diagnostic algorithms, they all demonstrated that non-invasive classification of detected nodules based on density, size and detection of growth is possible resulting in a small proportion of invasive procedures for benign lesions [25], [26], [27], [28], [29], [30], [31], [32]. Briefly, in these studies only non-calcified pulmonary nodules were regarded as potentially malignant and biopsy
Prevalence results
The first publications on results of low-dose CT screening for lung cancer in heavy smokers described findings at baseline (prevalence) CT studies [25], [27], [29], [31], [32].
It was shown that a high proportion of asymptomatic lung cancers was found in populations at risk ranging from 0.43 and 0.48%, respectively, in two Japanese studies [25], [27] up to 2.7% in a study performed in the USA [29]. The proportion of stage I NSCLC of all detected cancers ranged from 63% [31] to 93% [25] and was
Incidence results
These results from baseline CT studies (prevalence results) were also confirmed in preliminary results at repeat CT studies (incidence results) which more likely reflect the true potential of low-dose CT screening as findings at the initial (baseline) CT are influenced by chance (study design can not control whether the first CT scan in a lung cancer patient is performed only days or rather years before symptoms occur).
Classification of nodules at follow-up CT studies was easier than at
Possible biases
The results of the studies published in the literature have shown that lung cancer screening with low-dose CT using the diagnostic algorithms described is feasible in that a high number of asymptomatic tumours was detected with a low proportion of unnecessary invasive procedures. However, they are not appropriate to conclude that low-dose CT screening can, in fact, reduce mortality from lung cancer.
Different biases could explain a high proportion of asymptomatic, small early stage lung cancers
Prospective controlled randomized trials
Although it is likely that low-dose CT screening will actually decrease mortality from lung cancer most researchers feel that unequivocal proof of lung cancer mortality reduction through screening is required before general recommendations can be made to apply this technique to the general population at risk [37]. This is particularly important in view of the enormous cost general CT screening recommendations would cause for health systems.
Also, if low-dose CT screening would not reduce lung
Conclusion
Screening for lung cancer promises reduction in mortality from this common malignancy. Low-dose CT in combination with appropriate diagnostic algorithms has been shown to detect many asymptomatic, small, early stage, resectable NSCLC with a low proportion of invasive procedures for benign lesions. Because of the huge implications of general screening recommendations definite proof of the benefit of screening by controlled randomised trials should be awaited.
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