Elsevier

Lung Cancer

Volume 61, Issue 3, September 2008, Pages 340-349
Lung Cancer

Lung cancer screening with low-dose computed tomography: A non-invasive diagnostic protocol for baseline lung nodules

The data were presented at ASCO Annual Meetings, 2006 and 2007
https://doi.org/10.1016/j.lungcan.2008.01.001Get rights and content

Summary

Background

Indeterminate non-calcified lung nodules are frequent when low-dose spiral computed tomography (LD-CT) is used for lung cancer screening. We assessed the diagnostic utility of a non-invasive work-up protocol for nodules detected at baseline in volunteers enrolled in our single-centre screening trial, and followed for at least 1 year.

Methods

5201 high-risk volunteers, recruited over 1 year from October 2004, underwent baseline LD-CT; 4821 (93%) returned for the first repeat LD-CT. Nodules ≤5 mm underwent repeat LD-CT at 1 year; nodules 5.1–8 mm underwent LD-CT 3 months later; lesions >8 mm received combined CT-positron emission tomography (CT-PET). A subset of nodules >8 mm was studied by CT with contrast. Protocol failures were delayed diagnosis with disease progression beyond stage I, and negative surgical biopsy.

Results

2754 (53%) volunteers presented one or more non-calcified nodules. Ninety-two lung cancers were diagnosed: 55 at baseline and 37 at annual screening (66% stage I). Among the 37 incident cancers, 17 had a baseline nodule that remained stage I, 7 had a baseline nodule that progressed beyond stage I, and 13 presented a new malignant nodule. Baseline and annual cancers were 79 (1.5%) and 13 (0.2%), respectively. In 15 of 104 (14%) invasive diagnostic procedures, the lesion was benign. Sensitivity, and specificity were 91 and 99.7%, respectively, for the entire protocol; 88 and 93% for CT-PET; and 100 and 59% for CT with contrast.

Conclusions

The protocol limits invasive diagnostic procedures while few patients have diagnosis delay, supporting the feasibility of lung cancer screening in high-risk subjects by LD-CT. Nevertheless further optimization of the clinical management of screening-detected nodules is necessary.

Introduction

There were 100 million tobacco-related deaths in the 20th century, 1 billion deaths are expected in the 21st century, one third of which will be due to lung cancer. Lung cancer is the world's leading cause of cancer death [1], mainly because it is usually diagnosed at a regionally advanced or metastatic stage when incurable [2]. In western countries, including Italy, legal restrictions and campaigns against smoking are helping to reduce cardiovascular disease; however, the increased risk of developing lung cancer persists many years after stopping smoking [3]. Furthermore smoking is increasing among young people [4] and women in western countries, and across the board in developing countries [5].

Better detection of early lung cancers, especially in high-risk current or former heavy smokers, is an important part of the public health response to tobacco-related diseases. The most promising technique is screening with low-dose spiral computed tomography (LD-CT) [6], [7], for which pilot observational studies report high detection rates in high-risk populations: the proportion of stage I cases is high and survival is favourable compared to historical controls [8], [9], [10], [11]. However, non-calcified nodules are detected in a high proportion of screened subjects [12], [13]. Most of these are benign but may require invasive investigations, with high costs and attendant risks of complications; such cases may constitute an obstacle to the large-scale implementation of LD-CT screening [14].

In a pilot study with LD-CT at our Institute, 1035 volunteers were screened. The results were encouraging in that many detected lung cancers were at an early and resectable stage [15]. Our subsequent COSMOS (Continuous Observation of Smoking Subjects) study recruited more high-risk volunteers; one of its aims is to test non-invasive procedures to manage indeterminate screening-detected nodules, thereby contributing to the development of a protocol suitable for large-scale implementation.

The aim of the present paper is to evaluate the diagnostic performance of a non-invasive work-up protocol by analysing the results of baseline screening. A secondary objective is to assess the effectiveness of CT with contrast to evaluate solid nodules >8 mm.

Section snippets

Population and study design

In 2004 and 2005 we enrolled asymptomatic volunteers, age 50 years or above, who were current or former heavy (≥20 pack-years) smokers. Ex-smokers had stopped not more than 10 years previously. Those with malignant disease (except treated non-melanoma skin cancer) or a diagnosis of malignant disease within the previous 5 years were excluded.

This single-centre study was approved by the ethics committee of our institute. All recruited volunteers gave written consent to annual LD-CT for five

Results

From October 2004 to October 2005, 5201 eligible participants of mean age 57.7 years, standard deviation 5.6 years, underwent baseline LD-CT; 3437 (66.0%) were men, and 4164 (80.3%) were current smokers. The median number of pack-years smoked was 44 (range 20–255).

Table 1 shows characteristics of the baseline nodules according to age, sex and smoking status. A mean of 2.3 nodules/person was present in the 2754 volunteers with non-calcified nodules. Table 2 shows the characteristics of the

Discussion

The aim of LD-CT screening in high-risk populations is to reduce lung cancer mortality. However, to achieve this a sensitive protocol for detection, work-up and intervention, also characterized by contained costs and minimum morbidity must be developed. In the present study we present 1-year results (two screening scans) obtained using a non-invasive diagnostic protocol for managing lung nodules detected by annual LD-CT.

Our first important finding is that delay of malignancy diagnosis,

Conclusion

In this prospective study, we were able detect almost 70% lung cancers at stage I, using a protocol characterised by minimal subject recall, predominantly non-invasive case work-up, and low frequency of thoracotomy for benign disease. These outcomes support the feasibility of lung cancer screening in high-risk persons particularly in view of the promising finding of the recent I-ELCAP study, that screening-detected lung cancers have good survival [11]. However, further studies are required to

Conflict of interest

None of the authors have any conflict of interest to declare.

Acknowledgements

This study was supported by the Italian Association for Cancer Research (AIRC) and the America-Italia Cancer Foundation. We thank Giovanna Ciambrone for general management of COSMOS volunteers, Nicole Rotmentsz for designing the database, and Don Ward for professional help with the English (paid for by the European Institute of Oncology).

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