Wednesday, March 07, 2007

Study Finds No Benefit to Use of CT Scans to Screen Current and Former Smokers for Lung Cancer

A study published in this week's issue of the Journal of the American Medical Association (JAMA) concludes that CT scan screening of asymptomatic current and ex-smokers in an effort to detect lung cancer earlier has no benefit in terms of reducing mortality. In fact, using such an approach on a population basis could produce more harm than benefit (see: Bach PB, Jett JR, Pastorino U, Tockman MS, Swensen SJ, Begg CB. Computed tomography screening and lung cancer outcomes. JAMA 2007; 297:953-961).

The conclusions were based on a longitudinal study of over 3,000 current and ex-smokers screened for lung cancer using chest CT scans at 3 different academic medical centers. The average follow-up time was 4 years. Subjects underwent baseline and annual low-dose CT scans. There was no difference in lung cancer mortality: the number of lung cancer deaths was nearly the same as predicted (relative risk = 1.0).

The authors conclude: "Screening for lung cancer with low-dose CT may increase the rate of lung cancer diagnosis and treatment, but may not meaningfully reduce the risk of advanced lung cancer or death from lung cancer. Until more conclusive data are available, asymptomatic individuals should not be screened outside of clinical research studies that have a reasonable likelihood of further clarifying the potential benefits and risks."

Not only did the authors fail to find any benefit of CT screening for lung cancer, but they also identified substantial potential harm - the invasive diagnostic procedures required by the finding of what turn out to be benign lung nodules carry with them their own morbidity and mortality risks. They conclude that: "If the majority of excess early cancers found through screening are unlikely to progress rapidly to a point where they cause clinically significant disease or death, then the thoracic surgeries performed to remove them may be insufficiently beneficial to justify the resulting morbidities. Despite some studies that have demonstrated excellent outcomes when lung cancer resections are performed in high-volume hospitals by thoracic surgeons, excellent outcomes are not uniform. Rather, the postoperative mortality rate following resection of lung cancer in the United States averages 5%, and the frequency of serious complications ranges from 20% to 44%. ... biopsies and the other diagnostic procedures that are performed in response to findings on a screening CT constitute another potential downstream harm that could result from widespread CT screening."

The Rest of the Story

While we need to await the results of a large clinical trial of low-dose CT screening for lung cancer before drawing any definitive conclusions, what is clear is that at the present time, there insufficient evidence that the use of CT screening for lung cancer produces any benefit in terms of reducing mortality.

On the other hand, it is clear that the use of CT screening on a large population of smokers and ex-smokers would produce substantial harms. There is a significant risk of morbidity and mortality from the invasive diagnostic procedures required to investigate the large number of lung nodules that will inevitably be detected on CT scan, most of which will end up being benign.
While it is not entirely clear why no mortality benefit was observed even though the screening procedure did result in a large increase in the number of lung cancers detected, the authors postulate that what is happening is that the CT scans are picking up lung cancer nodules that are so small that they would never have progressed to the point that they caused death anyway. This is known as "overdiagnosis" bias and it is a common limitation of this type of screening approach.

Despite the lack of sufficient evidence that there is any benefit to the use of CT screening for lung cancer among current and ex-smokers, the Lung Cancer Alliance - a lung cancer advocacy group - issued a press release in which it stood by its position that people at risk of lung cancer (e.g., smokers and former smokers) should be encouraged to undergo CT scan screening for lung cancer:

"Today, Lung Cancer Alliance President, Laurie Fenton, responded to the most recent criticism of CT screening, calling it 'another delaying tactic to deny people at high risk for lung cancer the chance to have it detected at an early, treatable stage.' ... An article published in the March 7 issue of the Journal of the American Medical Association concludes that high risk individuals should not be screened for lung cancer until more studies have been conducted, as the authors claim CT scans may cause more harm than good. 'This is not productive,' declared Fenton. “We have heard these same statistical arguments used for years... ."

While I admire the Lung Cancer Alliance and the important work they are doing on behalf of lung cancer victims and their families, as well as the work they are doing to try to prevent and more effectively treat lung cancer, I think that advocacy needs to remain science-based. The science simply does not support a recommendation that lung cancer screening be conducted on a population basis at this point in time.

While it is possible that results from the large clinical trial that is now underway could produce very different results, we simply don't have that information yet. In the absence of evidence that screening actually will save lives, I do not believe that the risks of screening outweigh the benefits.

I do not believe this is a delaying tactic. I believe it is wise and responsible public health practice based on the best available science at the time. I also think it is very productive, because it could save people a tremendous amount of unnecessary morbidity and even mortality.

The rest of the story is that while our emotions tell us that we would love to have a way to prevent the devastating effects of lung cancer, the science tells us that CT screening is not yet documented to represent that way. There is no clear mortality benefit that has been demonstrated, yet the harm done by causing unnecesary anxiety among smokers and ex-smokers, and by causing unnecessary morbidity from invasive diagnostic tests, could be substantial.

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