Efficacy Endpoints: Mortality
Harm Endpoints: False positive, surgery, surgical complication
Narrative: Lung cancer remains the most common cause of cancer death in the US, and smoking remains the most powerful risk factor for lung cancer.1 Early detection offers the potential of treating cancers at an earlier stage and may help to reduce deaths from the disease. The National Lung Screening Trial (NLST) was undertaken to determine whether yearly screening with computed tomography would save lives compared to screening with plain chest radiography. Participants were at very high risk of lung cancer: 55-74 years old with a history of at least 30 pack-years of smoking.
NLST randomized 53,454 to receive annual chest x-rays or CT scans. After 6.5 years the investigators reported a mortality reduction of 0.46% in the group that received CT scans. This number suggests that one life was saved for every 217 people undergoing annual CT when compared to those undergoing annual x-ray.
There were also harms associated with CT lung screening. Compared to x-rays one in 4 people experienced an additional false positive result, one in 29 underwent an unnecessary surgical procedure, and one in 161 had a surgical complication.
Caveats: Early detection has been successful in reducing deaths from cervical cancer, but unsuccessful in reducing deaths from prostate and breast cancers. These failures of early detection may be due in part to ‘overdiagnosis’, in which cancers that would never have posed a threat are unnecessarily treated, with serious consequences.2 As an editorialist points out3 this problem is clearly present in the NLST trial, where CT scanning led to more cancer diagnoses than plain x-ray. In other words, if all detected cancers were aggressive and dangerous then after 6.5 years the major difference between groups should be how cancers were found—not how many there are.
Moreover, in this study CT scans were compared to annual chest x-ray, a screening tool for which studies of a quarter million smokers have already shown no benefit.4,5 In fact, in these studies more chest x-ray screening led to more deaths from lung cancer.5 Comparing a group that undergoes no screening to a group that undergoes CT screening would therefore be a more appropriate, and more realistic, indicator of the many impacts of CT screening. Finally, the surgeries, procedures, surgical complications, and the overwhelming number of false positives caused by CT screening are major down sides and would have to be as carefully communicated as any potential benefits to anyone considering using this modality.
Despite these caveats the significant and surprisingly large reduction in mortality using CT screening in this trial is promising. Because this is the first high quality randomized trial of CT screening it will take multiple further trials to confirm the benefit, and it will be critical to apply these data only to people at very high risk unless future trials expand to include others.
Author: David H. Newman, MD
Published/Updated: August 7, 2011
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