ArticlesLung cancer probability in patients with CT-detected pulmonary nodules: a prespecified analysis of data from the NELSON trial of low-dose CT screening
Introduction
Several prominent medical associations have recommended regular low-dose CT screening for asymptomatic smokers and ex-smokers at high risk of developing lung cancer.1, 2 The main challenge faced by clinicians doing CT screening for lung cancer is that about half of people screened have one or more pulmonary nodules, but only a small percent of these people have lung cancer.3, 4 Validated guidelines to determine optimum patient management strategies based on characteristics of detected nodules are urgently needed.
When CT screening for lung cancer first began, the accepted standard of practice was to regard all non-calcified pulmonary nodules as potentially malignant lesions requiring follow-up screening until proven stable for a period of 2 years.5, 6, 7 Later, the Fleischner Society recommended that nodules of 4 mm in diameter or smaller in high-risk individuals (ie, history of smoking or other known risk factors) required no further follow-up if the nodule was unchanged at a 12-month follow-up examination, because the risk of the nodule being malignant was less than 1%.8 However, people with nodules 4–8 mm in size were still recommended to undergo two to three follow-up examinations over a period of 2 years. Individuals with nodules larger than 8 mm were recommended to undergo diagnostic work-up, which consisted of more invasive diagnostic procedures.8 Recently, the results of the Early Lung Cancer Action Project (ELCAP)9—which suggested raising of the threshold for initiation of follow-up CT examinations to nodules of 8 mm or larger—were supported by data from the National Lung Screening Trial (NLST).10 However, the ELCAP analyses were limited to screen detected lung cancers, and only false-positive values and time to diagnosis were taken into account when assessing new thresholds for nodule diameter. Increasing the protocol-screening thresholds for nodule diameter to determine which patients should undergo diagnostic follow-up reduces the potential harms of diagnostic procedures, exposure to ionising radiation, and costs.11, 12 However, it might also decrease the sensitivity for cancerous nodules, thus, in turn, increasing lung cancer mortality, and so it is important to balance these potential benefits and harms.4 Therefore, thresholds for negative, indeterminate, and positive screening results should be based on individual participants' probability of developing lung cancer, and should be assessed in terms of sensitivity, specificity, number of required CT examinations, and number of required invasive diagnostic procedures.
Recommendations of the latest American College of Chest Physicians (ACCP) guidelines for management of individuals with pulmonary nodules with a volume of 8 mm or larger were based on the consensus statement of the Fleischner Society.8 This statement has not been formally validated, and alternative management strategies might yield an improved performance in terms of sensitivity, specificity, and the number of required follow-up scans.
The NELSON trial is a randomised trial to assess whether low-dose CT screening with an increasing length of screening interval (1, 2, and 2·5 years) compared with no screening reduces lung cancer mortality.13 We used data from NELSON to quantify the probability of developing lung cancer within 2 years of CT screening, based on measurements of lung nodule diameters, volumes, and volume doubling times. We used lung cancer probabilities to assess the nodule management protocol recommended by the ACCP, and to propose improved management protocols.8, 14
Section snippets
Study design and participants
Details about the design and conduct of the NELSON trial have been reported previously.13, 15 Briefly, participants from four centres in the Netherlands and Belgium were enrolled and randomly assigned to receive low-dose CT screening or no screening. Eligible participants were adults aged 50–75 years, who had smoked 15 or more cigarettes per day for more than 25 years or ten or more cigarettes per day for more than 30 years, and were still smoking or had stopped smoking less than 10 years
Results
A total of 15 822 participants were enrolled in the NELSON trial between Dec 23, 2003, and July 6, 2006. Screening round one was conducted from January, 2004, to December, 2006, and screening round two from January, 2005, to September, 2008. For this study, we excluded 7907 participants randomly assigned to the no screening group, 477 participants from Belgium (no data were yet available from the Belgian cancer registry), and 283 participants who did not attend their screening examinations (no
Discussion
In this analysis, we used NELSON trial data to calculate the probability of developing lung cancer within 2 years for asymptomatic past or present smokers after a low-dose CT scan, and stratified this risk by nodule volume, diameter, and volume doubling time (panel). We used lung cancer probability to design and assess nodule management protocols. Our findings show that screened participants with nodules with volumes of 100 mm3 or smaller, or diameters of 5 mm or smaller, have a lung cancer
References (34)
- et al.
Screening for lung cancer: diagnosis and management of lung cancer, 3rd edN: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines
Chest
(2013) - et al.
Early Lung Cancer Action Project: overall design and findings from baseline screening
Lancet
(1999) - et al.
Nodule management protocol of the NELSON randomised lung cancer screening trial
Lung Cancer
(2006) - et al.
Blinded and uniform cause of death verification in a lung cancer screening trial
Lung Cancer
(2012) - et al.
“What do you mean, a spot?”: A qualitative analysis of patients' reactions to discussions with their doctors about pulmonary nodules
Chest
(2013) - et al.
Baseline findings of a randomized feasibility trial of lung cancer screening with spiral CT scan vs chest radiograph: the Lung Screening Study of the National Cancer Institute
Chest
(2004) - et al.
The Lung Image Database Consortium (LIDC): a comparison of different size metrics for pulmonary nodule measurements
Acad Radiol
(2007) - et al.
American Cancer Society lung cancer screening guidelines
CA Cancer J Clin
(2013) - et al.
Management of lung nodules detected by volume CT scanning
N Engl J Med
(2009) - et al.
Reduced lung-cancer mortality with low-dose computed tomographic screening
N Engl J Med
(2011)
Clinical practice. The solitary pulmonary nodule
N Engl J Med
The solitary pulmonary nodule
Chest
Guidelines for management of small pulmonary nodules detected on CT scans: axent from the Fleischner Society
Radiology
Definition of a positive test result in computed tomography screening for lung cancer: a cohort study
Ann Intern Med
CT screening for lung cancer: alternative definitions of positive test result based on the National Lung Screening Trial and International Early Lung Cancer Action Program databases
Radiology
Cancer risks associated with external radiation from diagnostic imaging procedures
CA Cancer J Clin
Complications following lung surgery in the Dutch-Belgian randomized lung cancer screening trial
Eur J Cardiothorac Surg
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