CT Lung Cancer Screening Leaves a Trail of False Positives

ORLANDO, Fla., May 30, 2009— -- A high-tech scanning technique that doctors hoped to use for fast, reliable lung cancer screening has turned out to do its job too well.

Low-dose computed tomography, or CT for short, discovers all sorts of abnormalities in patients' lungs, but produces false positive results for cancer a third of the time, according to a new study.

That's more than twice the false positive rate for standard chest x-rays, and it's not good news for patients, Dr. Jennifer Croswell of the National Institutes of Health said at the annual meeting of the American Society of Clinical Oncology.

"False positive results may create increased psychological stress in patients and an increased burden on the healthcare system," she said.

A false positive may also result in more invasive -- and potentially dangerous -- follow-up tests, she said.

The findings are based on the Lung Screening Study, a randomized trial involving 3,000 patients that examined the feasibility of a large-scale trial of different screening methods, in particular, a head-to-head comparison of CT scans versus regular X-rays.

That larger study, the National Lung Screening Trial, is currently under way and involves 50,000 patients. A similar large study in Europe -- dubbed NELSON -- reported some positive preliminary results earlier this year.

In this study, Croswell reported, 1,610 participants were offered a baseline CT and 1,580 were offered a baseline chest x-ray, with one repeat annual screening. They were followed for a year after their final screen.

A false positive was defined as either a positive screen for lung cancer that was proved false by a complete workup, or by at least 12 months of follow-up with no cancer diagnosis.

By the end of the second screening, CTs had turned up false positives in 33 percent of the patients, compared to 15 percent for standard chest x-rays, the researchers reported.

Of those with false CT positives, 6.6 percent had a more invasive diagnostic test and 1.6 percent had major surgery.

Early Lung Cancer Detection Critical

The studies are critical because more than 219,000 Americans will be diagnosed with lung cancer this year -- about 15 percent of new cancer cases. More than 159,000 will die from the disease, according to the American Cancer Society.

Although lung cancer accounts for 15 percent of cancer cases in the United States, it accounts for 28 percent of cancer deaths. One reason it is so deadly is that lung cancer typically isn't diagnosed till it's too late.

The five-year survival rate for localized lung cancer is only 49.5 percent, about half the rate of breast cancer. But the lung cancer survival rate falls to a dismal 20.6 percent once the disease has spread immediately outside the lung and 2.8 percent if it has traveled farther.

Doctors have been hoping that the CT scan -- an advanced x-ray that produces detailed cross-sections of the lung -- would be able to catch lung cancer early enough to treat it more effectively.

The problem is that CT scans turns up too many things that look like they might be cancerous abnormalities.

"Only very rarely is that thing a lung cancer," said Dr. Peter B. Bach of Memorial Sloan-Kettering Cancer Center in New York.

This study was the first in which the CT scan was pitted head-to-head against the standard x-ray. But even though the CT produced a much higher false positive rate, Bach said real-world physicians don't operate on a "yes-no" basis.

For many physicians, the results of a CT scan that showed a minor abnormality might merely lead a doctor to follow a patient more closely.

"All the way through the follow-up scan, the 3-D rendering, even the biopsy, they're all done based on probability, not based on this preconceived notion that the test is positive or negative," he said.

As a result, he was somewhat critical of the study. "The way the authors analyze it -- calling them all positive -- rigs the study toward finding an extremely high false-positive rate," Bach said.

In the end, others say, the future of CT scanning for lung cancer will involve a risk-benefit analysis.

Experts Debate Usefulness of CT Scans for Lung Cancer Detection

"There is no question that CT screening will detect many lung cancers," said Dr. Martin Edelman of the University of Maryland's Greenebaum Cancer Center in Baltimore and a member of an independent committee verifying results of the NLST.

But so far, there is still a "complete absence of evidence that this approach decreases mortality or morbidity due to lung cancer," he said.

Advocates for screening "have long claimed that there is little or no risk of harm," Edelman added, but Croswell and her colleagues "demonstrate that there is a small, but real potential for harm from screening."

What's more, he said, "the potential for false positivity is highest in those at greatest risk for lung cancer."

The Lung Screening Study was supported by the National Cancer Institute. Croswell did not report any conflicts. Bach has reported financial links with Genentech, Wyeth, Abraxis, Biogen-Idec, and Johnson and Johnson. Edelman has reported financial links with Bristol-Myers Squibb, Cyclacel, Eli Lilly, Genentech, Tragara Pharmaceuticals, Endocyte, Geron, Human Genome Sciences and Schering-Plough.