Low-Dose CT Screening May Result in Overdiagnosis of Lung Cancer
In a study reported in JAMA Internal Medicine, Patz et al of the NLST Overdiagnosis Manuscript Writing Team estimated the magnitude of overdiagnosis using low-dose computed tomography (CT) screening for lung cancer in the National Lung Screening Trial (NLST). They estimated that more than 18% of lung cancers detected by low-dose CT screening in the trial were likely to be indolent and that 1.38 cases of overdiagnosis occurred per one life saved with CT screening.
As stated by the authors, “Screening for lung cancer has the potential to reduce mortality, but in addition to detecting aggressive tumors, screening will also detect indolent tumors that otherwise may not cause clinical symptoms. These overdiagnosis cases represent an important potential harm of screening because they incur additional cost, anxiety, and morbidity associated with cancer treatment.”
Study Details
In the NLST, screening with low-dose CT vs chest radiography among 53,452 persons at high risk for lung cancer observed for 6.4 years resulted in a significant reduction in lung cancer-related mortality. However, the trial also found more cases of lung cancer in the CT group than in the radiography group, a finding that has also occurred in the screening groups of studies comparing radiographic screening with observation. The excess number of early-stage lung cancers observed in the original screening group even after extended periods of follow-up is usually attributed to overdiagnosis—ie, detection of a cancer that would not otherwise have become clinically apparent.
The current study estimated the excess number of lung cancers in the low-dose CT group of the NLST compared with the radiography group. Overdiagnosis was assessed as: the probability that a lung cancer detected by screening with low-dose CT is an overdiagnosis, defined as the excess lung cancers detected by CT divided by all lung cancers detected by screening in the CT group; and as the number of cases that were considered overdiagnosis relative to the number of persons needed to screen to prevent one death from lung cancer.
Overdiagnosis Rates
During follow-up in the NLST, 1,089 lung cancers were reported in the CT group and 969 in the radiography group, including non–small cell lung cancer (NSCLC) including bronchioloalveolar cell carcinoma and not otherwise specified in 926 vs 793, bronchioloalveolar cell carcinoma only in 111 vs 36, small cell cancer in 143 vs 163, carcinoid cancer in 6 vs 3, and unknown in 14 vs 10. The probability that cancer detected by CT was an overdiagnosis was 18.5% (95% confidence interval [CI] = 5.4%–30.6%) for any lung cancer, 22.5% (95% CI = 9.7%–34.3%) for NSCLC including bronchioloalveolar cell carcinoma and not otherwise specified, and 78.9% (95% CI = 62.2%–93.5%) for bronchioloalveolar lung cancer only.
Cases of Overdiagnosis per Life Saved
In the original NLST report, the number of persons needed to screen with CT to prevent one lung cancer death was 320. There were 443 and 356 lung cancer deaths in the radiography and CT groups, a difference of 87. Since there was an excess of 120 lung cancer cases in the CT group vs the radiography group, the number of cases of overdiagnosis in the 320 participants needed to screen to prevent one death from lung cancer was 1.38 (120/87).
The authors concluded, “More than 18% of all lung cancers detected by [low-dose] CT in the NLST seem to be indolent, and overdiagnosis should be considered when describing the risks of [low-dose] CT screening for lung cancer.”
They further noted: “Whereas the NLST demonstrated a relative mortality reduction with [low-dose CT], the limitations of the screening process, including the magnitude of overdiagnosis, should be considered when guidelines for mass screening programs are constructed. In the future, once there are better biomarkers and imaging techniques to predict which individuals with a diagnosis of lung cancer will have more or less aggressive disease, treatment options can be optimized, and a mass screening program can become more valuable.”
Edward F. Patz Jr, MD, of Duke University Medical Center, is the corresponding author for the JAMA Internal Medicine article.
The study was supported by the National Institutes of Health. The study authors reported no potential conflicts of interest.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
