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Are Most Lung Cancer Deaths Among Long-Term Smokers Preventable with Affordable Screening?

By UCSF Science Cafe | December 5, 2006

Lung tumors are the leading cancer killer, striking down more than 160,000 Americans each year. A large majority of lung cancer deaths might be prevented by screening exams. At least that's what the principal investigator of a recent, controversial study says. Interim results of the ongoing study - the International Early Lung Cancer Action Program (I-ELCAP) -- were reported on Oct. 26 in the New England Journal of Medicine.

Claudia Henschke, MD, PhD, at Weill Medical College of Cornell University and her I-ELCAP colleagues suggest that periodic screening of smokers and ex-smokers with an imaging technique called spiral CT -- a high-tech kind of X-ray -- may be as cost-effective in saving lives of those with lung cancer as current mammography screening is in detecting early breast cancer.

Lung cancer is usually deadly by the time it is diagnosed. But I-ELCAP researchers estimate that 88 percent of I-ELCAP study participants diagnosed with and treated for early-stage lung cancer will survive the disease for 10 years or more. Already, the eight patients diagnosed with early-stage lung cancer during I-ELCAP who were not treated have died.

Robert A. Hiatt, MD, PhD, is director of population sciences for the UCSF Comprehensive Cancer Center. Hiatt served as deputy director of the Division of Cancer Control and Population Sciences at the National Cancer Institute (NCI) during the time when Henschke made waves with her first major study results on CT screening in 1999, and while the NCI deliberated about whether to expand efforts to evaluate spiral CT for lung cancer screening. The NCI eventually launched a separate randomized, controlled trial, for which patients have been recruited.

Q. Screening by X-ray imaging already has been thoroughly evaluated and adopted for breast cancer screening. Why are these techniques still being evaluated for lung cancer?

A. All cancers are different in terms of their imaging characteristics, and in the sensitivity and specificity of the imaging exam. What we have learned from mammography doesn't translate directly into other types of screening.

The biological characteristics of the tumors are different. A lung cancer, when imaged at the same size as a breast cancer, may be at a more advanced stage. The breast is an external body organ, and can be looked at more carefully and biopsied more easily than the lung. With conventional X-ray imaging, when you can see lung cancer, it may be too late.

Q. Do the I-ELCAP survival estimates seem valid?

A. As far as they go, yes. The model they used to make estimates seems valid. I'm sure that the amount of time between the identification of the tumor by screening and the survival was accurately calculated in I-ELCAP. It's a well-performed study. But what does it mean? Someone with a persistent cough might be diagnosed with a tumor and die five years later. Alternatively, the same person might have been diagnosed via a screening spiral CT exam two years earlier.

Even if whatever treatment was given following the earlier diagnosis made no difference -- and the person were to die on the same calendar date in either scenario -- diagnosing the cancer early would add two years to the measure of survival. It would seem like the survival had gone from five years to seven years, but there was no real difference to the patient. This is called lead time bias. It's why a randomized trial is needed, in which a control, or comparison, group does not receive the same intervention.

Q. Similarly, is it valid to conclude that spiral CT screening for lung cancer is as cost-effective as mammography?

A. I think it's premature to say that. In order to assess cost-effectiveness, you have to first assess the effectiveness in preventing death from lung cancer. That cannot be done on the basis of this recently published study. The only way you can do that in an unbiased way is with a randomized, controlled trial.

Furthermore, they do not account for the fairly large number of people who had benign lesions detected that would have needed biopsies -- and maybe lobectomies -- to really get at the diagnosis. They didn't really go into the morbidity associated with the workup -- and that it is a real cost.

(Note that in November 2007 the UCSF Comprehensive Cancer Center was renamed the UCSF Helen Diller Family Comprehensive Cancer Center.)

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