Good News to Catch a Bad Disease

Cecil Pharr thinks he was about 16 when he smoked his first cigarette. He’s not sure about that; he could have been a little younger. But what he is sure of is that it didn’t take long to develop a nasty smoking habit. By the time he was an adult, he was up to two packs a day.

The Tucker, Georgia, man smoked heavily for about 50 years, quitting often, but always going back. He stopped for good about 15 years ago.

Even though he had shown no signs of lung cancer during his life, Pharr’s worries about the damage smoking may have done to his lungs persisted. He was being treated for emphysema in 2003 when his pulmonologist suggested he volunteer to be one of the 53,000 Americans who were eventually enrolled in the National Lung Screening Trial (NLST), one of the largest trials for cancer screening ever conducted by the National Cancer Institute (NCI).

Pharr was randomly assigned to get an annual CT scan at Emory University School of Medicine in Atlanta to test whether the three-dimensional screening method was better at detecting hidden lung cancers among smokers over the age of 55 than conventional chest X-rays.

“I’m here now, when I could have been just another statistic.”

On Nov. 4, the NCI released details of the lung screening trial showing, for the first time, that routine CT screening—like the kind Pharr received—reduces the risk of death from lung cancer among current and former heavy smokers by one fifth. After five years of follow-up study, 442 patients who were getting routine chest X-rays had died of lung cancer, compared to 354 cancer deaths among those getting CT scans. Even more startling was the finding that routine CT scans also seemed to reduce the risk of death from cardiovascular and other diseases.

News of the trial continues to produce great enthusiasm among cancer researchers and clinicians, who have long sought a screening tool to test patients at high risk for lung cancer even though they show no signs of it.

At least for people over the age of 55 who have a history of heavy smoking, the trial produced a “statistically convincing answer” that screening with CT “has the potential to spare very significant numbers of people from the ravages of this disease,” says NCI director Harold Varmus, MD.

The NCI is stressing, however, that it is premature to recommend CT scans as a way to screen for lung cancer. “At this time, NCI is not releasing recommendations for the use of lung screening CT for any population. Once the final data have been fully analyzed and published, recommendations will be made by any of several bodies commonly called upon to make medical service recommendations, including the United States Preventive Services Task Force and the American Cancer Society,” says Varmus in a press release.

The trial is also likely to prompt difficult public policy decisions in the months and years to come about who will pay for the tests and how often they should be administered—exactly the same contentious issues connected to other, now routine forms of cancer screening like mammography and PSA testing.

More problematic, the results also showed that about 25 percent of patients who had CT scans indicating a possible cancerous lesion were found on follow-up to be cancer-free after a biopsy or surgery, a false-positive rate that makes many clinicians uneasy.

The study found that, for every 300 people screened, one person lived who would have otherwise died during the study, according to the NCI.

Still, while virtually every researcher interviewed cautions that details of the huge trial need more study before CT screening becomes routine among smokers, they agreed that the findings represent an enormous advance in detecting lung cancer, which claims more lives every year than breast, pancreatic, colorectal and prostate cancers combined.

“Many of us believe that routine CT screens for heavy smokers is a good idea, but this is the first empirical data we have on it,” said Fadlo R. Khuri, MD, deputy director of the Winship Cancer Institute at Emory, which enrolled about 1,400 patients in the NLST.

“This is robust science we have to work with,” Khuri says. “Trying to determine who benefits the most and how routine the screening should be is the next step. But, clearly there is reason for optimism now in screening for this form of cancer that has defied effective screening mechanisms in the past.”

Finding a way to screen for lung cancer when it is in a localized state—before it has spread to other parts of the lung or migrated to other organs—has been a goal for cancer clinicians for decades. Mammography has become standard practice in screening for breast cancer, and colonoscopies are now routinely used to look for colorectal cancer, but there has been no effective screening method for lung cancer in patients without symptoms of the disease.

Over the next few months radiologists and bioinformatics experts will pore over specific details about the cancer patients who lived and died. They’ll be correlating how old patients were when diagnosed, what their pathology reports showed and how fast their cancers progressed. They’ll also be looking at smoking history, gender, ethnicity and dozens of other variables, all in an effort to create a consensus on the cost, risks and benefits of routine CT screening.

This effort is important because of the estimated 46 million Americans who currently smoke and the additional 48 million who have smoked heavily in the past. Potentially, every one of those—with the exception of those who haven’t smoked in 15 years—may benefit from routine CT screening which could detect lung cancer at its earliest stage.

Even though the form of CT used in the trial, known as helical (or spiral) scanning, is relatively inexpensive (about $300 according to most reports) and it exposes the patient to about one-tenth the radiation of a conventional, whole-body scan, routine use of CT for screening is not without controversy.

Medicare and most private insurance carriers do not pay for the scans in patients who show no signs of lung cancer. (CT use is usually covered only as a diagnostic tool.) But as more information on the benefits of the technology as a screening tool are uncovered, this could change.

On a per-patient basis, spending $300 for a yearly CT scan doesn’t seem like much considering the number of lives that may be saved. But because of the enormous size of the at-risk population, routine use of CT scans would significantly increase overall health care spending—and push up the cost of insurance, if they are going to be covered—when doctors are being urged to rein in the high cost of technology by ordering fewer tests.

Then there is the issue of false-positives.

The helical scan offers radiologists three-dimensional looks that slice through the lungs at multiple angles, allowing it to pick up very slight abnormalities in the tissue. This is both the bane and benefit of CT scanning. Even the healthiest of non-smokers are likely to have some abnormalities inside the lungs as they age. The vast majority of them are not cancer.

Finding a suspicious nodule usually prompts another series of scans—and more exposure to radiation—over three to six months to see if there is any discernable growth. It could also lead to a lung biopsy, which carries its own risks.

These findings should in no way distract us from continued efforts to curtail the use of tobacco. No one should come away from this believing it is now safe to continue to smoke.

In the NLST, 25 percent of the abnormalities in patients who needed follow-up scans and other tests turned out to be benign. That’s a rate that causes some concern among radiologists, not to mention anxiety among patients who think they may be facing a cancer diagnosis.

But as more information is gleaned from the study, radiologists hope to develop better protocols that will help determine which patients need to be re-tested and aggressively followed, says Kay Vydareny, MD, associate executive director for diagnostic radiology and subspecialties of the American Board of Radiology, and principal investigator for the Emory portion of the NLST. That will be one of the many challenges awaiting experts over the next months and years, she says.

From a lung cancer prevention standpoint, clinicians and advocates alike worry, too, that if a relatively inexpensive screening tool becomes available to smokers to reduce their risks of dying, they may lose their motivation to quit.

“These findings should in no way distract us from continued efforts to curtail the use of tobacco. No one should come away from this believing it is now safe to continue to smoke,” Varmus emphasized when the study was released. “Tobacco remains the major causative factor for lung cancer and several other diseases.”

And indeed, one of his first scans showed a suspicious nodule in the upper lobe of his left lung. Follow-up scans showed it was not growing, but by February 2005, at the time of his last scheduled screening, a tumor was clearly present. Three months later, it was surgically removed.

Instead of being among the 157,000 Americans who die every year from lung cancer, Cecil Pharr’s life was changed by a $300 screening test that gave his physicians the time they needed to get ahead of the nation’s number one cancer killer.

“No doubt in my mind, that test saved my life,” says Pharr, now 78.