Elsevier

Lung Cancer

Volume 59, Issue 3, March 2008, Pages 355-363
Lung Cancer

Lung cancer screening with spiral CT: Baseline results of the randomized DANTE trial

https://doi.org/10.1016/j.lungcan.2007.08.040Get rights and content

Summary

Background

Despite the high survival rates reported for screening-detected cases, the potential of screening of high-risk subjects for reducing lung cancer mortality is still unproven. We herewith present the baseline results of a randomized trial comparing screening for lung cancer with annual spiral computed tomography (CT) versus a yearly clinical review.

Methods

Male subjects, 60–74 years old, and smokers of 20+ pack-years were enrolled. All participants received a baseline medical examination, chest X-rays (CXR) and sputum cytology upon accrual. Subjects randomized in the spiral CT group received a spiral CT scan at baseline, then yearly for the following 4 years. For controls, a yearly clinical examination was scheduled for the following 4 years.

Results

2472 subjects were randomized (1276 spiral CT arm, 1196 controls). Age, smoking exposure and co-morbid conditions were similar in the two groups.

In the spiral CT group, 28 lung cancers were detected, 13 of which were visible in the baseline chest X-rays (overall prevalence 2.2%). Sixteen out of 28 tumours (57%) were stage I, and 19 (68%) were resectable. In the control group, eight cases were detected by the baseline chest X-rays (prevalence rate 0.67%), four (50%) were stage I, and six (75%) were resectable.

Conclusions

Baseline lung cancer detection rate in the spiral CT arm was higher than in most published studies. The stage I detection rate was increased four-fold by spiral CT versus chest X-rays. However, more tumours in an advanced stage were also detected by CT. The high resection rate of screening-detected patients suggests a possible increase in cure rate. However, longer follow-up is required for definitive conclusions.

This trial has been registered at www.Clinicaltrials.gov, registration No. NCT00420862.

Introduction

Lung cancer is the most frequent malignancy in the adult population of the western world, and carries a severe prognosis with 5-year survival rates in the range of 7–15% [1]. In only 16% of the cases is the disease still localized at the time of diagnosis [2].

Given its high incidence and the existence of an easily identifiable high-risk population, e.g. smokers and former smokers [3], lung cancer appears to be an ideal candidate for screening programs. As with any other form of cancer screening, the basic assumption is that the detection of early-stage tumours in asymptomatic subjects should prevent the eventual appearance of advanced incurable disease at a later time, thus reducing mortality.

Unfortunately, the randomized trials on lung cancer screening carried out in the seventies and eighties [4], [5], [6], [7] were unable to demonstrate any mortality reduction in spite of the detection of an increased number of resectable, early-stage cases. However, all of those studies employed chest X-rays (CXR) and sputum cytology for early diagnosis.

With the advent of new technology and the introduction of low-dose spiral computed tomography (LDCT), new hopes have been raised. In Japan, mass screening programs with spiral CT have been active since the mid-nineties [8], [9], [10], and many uncontrolled studies were launched in the following years in western countries [11], [12], [13], [14], [15], [16].

All of these studies demonstrated that screening with spiral CT allows the detection of a high proportion of early-stage lung cancers. Additionally, the I-ELCAP group has reported a 10-year survival rate of 92% for resected stage I patients and of 80% for the whole series [17].

Nonetheless, the potential of screening with spiral CT not only for detecting patients with early-stage disease but especially for reducing mortality has yet to be demonstrated and carefully weighed against its costs and expected screening-related morbidity. Furthermore, the cost-effectiveness of lung cancer screening with spiral CT is controversial, as it depends on a number of conditions [18], [19], [20].

To help answer the question, in March 2001 we launched a randomized study (the DANTE Trial) comparing clinical review versus spiral CT at annual intervals for 4 years. We herewith present the baseline findings of this prospective randomized study on the early diagnosis of lung cancer.

Section snippets

Study design

DANTE is a prospective randomized trial exploring the effects of screening with spiral CT on lung cancer-specific mortality and on the stage distribution and resectability rates in a high-risk population. The prevalence of a set of biomarkers in sputum and blood samples is also being assessed.

The research has been conducted by the Istituto Clinico Humanitas, Milan, Italy, starting in March 2001. In 2005, two more centres of the same hospital network, Humanitas Gavazzeni Hospital, Bergamo, and

Results

Accrual was opened in March 2001 and closed in February 2006. In this period, 2564 subjects underwent the baseline medical assessment, and 92 of them were considered ineligible. The most common causes for non-eligibility were a history of neoplasia, insufficient exposure to cigarette smoking or advanced comorbidity.

As shown in Table 3 and Fig. 1, 2472 subjects (1276 in the spiral CT arm and 1196 controls) were finally randomized: 2033 (83%) at the Istituto Clinico Humanitas Hospital, Milan, 269

Discussion

High resection rates and 5-year survival have been reported for incidental and especially for screening-detected stage I lung cancer patients [17], [21], [22], [23]. These data are in contrast with the low resectability rates and dismal prognosis of symptom-detected cases [2]. Consequently, screening of high-risk subjects has become an attractive option. However, concerns were raised as early as 2000 [24], [25] about the potential biases of uncontrolled screening studies. The overdiagnosis

Conflict of interest statement

None.

Acknowledgements

The Authors wish to thank Mrs. Penelope Ann Taylor for her kind assistance and advice in the preparation of the manuscript.

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    Members of the DANTE Study Group, Gianluigi Ravasi (MD), Maurizio Infante (MD), Umberto Cariboni (MD), Marco Alloisio (MD), Alberto Testori (MD), Matteo Incarbone (MD), Valentina Errico (MD), Edoardo Bottoni (MD), Diego Ruzzante (MD), Francesco Inzirillo (MD), Thoracic Surgery Department, Istituto Clinico Humanitas, Rozzano, Milan, Italy. Fabio Lutman (MD), Giorgio Brambilla (MD), Pasquala Ragucci, Radiology Department, Istituto Clinico Humanitas, Rozzano, Milan, Italy. Arturo Chiti (MD), Gianluigi Ciocia (MD), Nuclear Medicine Department, Istituto Clinico Humanitas, Rozzano, Milan, Italy. Anna Destro (PhD), Paolo Bianchi (PhD), Giovanna Gribaudi (PhD), Massimo Roncalli (MD, PhD), Pathology Deparment, Istituto Clinico Humanitas, Rozzano, Milan, Italy. Silvio Cavuto (DSc, Consultant Statistician), Italian Association for the Fight against Cancer, Milan, Italy. Michele Tedeschi (MD), Emanuela Morenghi (PhD), Clinical Research Department, Istituto Clinico Humanitas, Rozzano, Milan, Italy. Giuseppe Chiesa (MD), Eliseo Passera (MD), Alberto Meroni (MD), Giovanni Guanella (MD), Adriano Rizzi (MD), Thoracic Surgery Department, Humanitas-Gavazzeni, Bergamo, Italy. Enzo Angeli (MD), Bertacchi Giacomo (MD), Radiology Department, Humanitas-Gavazzeni, Bergamo, Italy. Aranzulla Giuseppe (MD), Pane Francesco (MD), Radiology Department, Humanitas–Catania Oncology Centre, Italy. Maurizio Chiarenza (MD), Michele Caruso (MD), Oncology Department, Humanitas–Catania Oncology Centre (Centro Catanese di Oncologia), Italy.

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