Containing a Threat: Screening Creates Opportunity to Cure Lung Cancer

CURE, Lung Cancer Special Issue, Volume 1, Issue 1

Screening with low-dose CT creates opportunities to detect lung cancer at earlier stages, when treatment is more likely to cure the disease.

As Karen Rak watched her sister die of lung cancer just three months after being diagnosed, she was scared that she, too, would suffer that fate. After all, the sisters had both been heavy smokers and, although Karen had long since quit the habit and was otherwise in good health, she knew her smoking history put her at high risk of developing the disease.

“I felt like a sitting duck,” says Rak, who is 75 years old.

Back then, about 10 years ago, there was no recommended screening for lung cancer. But there was a clinical trial a few hours from Rak’s home in Belfast, Maine, that was studying whether regular scans with low-dose computed tomography (CT) could detect lung cancer when tumors were still small enough to be curable. Rak didn’t hesitate to enroll.

“Anybody who has quit smoking just wants to make sure. In the back of their minds, they’re always wondering, if they have a cough or are sick, ‘Is this lung cancer?’ It was reassuring to be able to take a closer look,” she says.

As part of the trial, Rak had an annual CT scan beginning in 2006. All were normal until doctors noticed a suspicious nodule in 2012. A biopsy confirmed she had small cell lung cancer. At just 6 millimeters, Rak’s tumor was extremely small — something an X-ray could not have caught — and her cancer was treatable with surgery alone. Today, three years later, she remains cancer-free.

“I got the best outcome you could ask for. I’m a living, breathing example of why these screening programs work,” she says.

This year, an estimated 221,200 people will be diagnosed with lung cancer (either small cell or nonsmall cell) in the United States, more than with any other cancer except prostate and breast. Like Rak, most people diagnosed with lung cancer smoke or have formerly smoked, or had prolonged exposed to secondhand smoke. But few diagnosed with the disease will fare as well as Rak did.

Despite advances in treating the disease, lung cancer remains, by far, the most deadly of all cancers, surpassing the number of deaths among those with cancers of the colon, breast and prostate combined. Heather Wakelee, an oncologist and associate professor of medicine at the Stanford University Medical Center in California, says that’s because “the vast majority of lung cancers are diagnosed once the disease is in its advanced stages, when it’s hard to treat and a cure is very unlikely.”

Lung cancer, like some other cancers, often doesn’t produce symptoms until it has spread. Even when symptoms of lung cancer do appear — such as coughing or wheezing — they are so commonplace that many people may mistake them for other problems, such as allergies or a cold.

For instance, when non-small cell lung cancer is caught in its earliest stage, about half of all patients will survive for five years of more. But once the cancer has spread beyond the lungs to other parts of the body, reaching stage 4, those expected to survive five years plummets to just 1 percent.

Saving Lives Through Earlier Detection

“If we could diagnose a lot of these patients earlier, cure rates would improve tremendously,” Wakelee says.There are colonoscopies to screen for colon cancer. There are mammograms to screen for breast cancer. Now, for patients who meet certain eligibility requirements, there is a screen for lung cancer. The hope associated with low-dose CT scans, says David M. Waterhouse, chair of the Department of Clinical Research at Oncology Hematology Care in Cincinnati, Ohio, is “to reduce the number of lung cancer deaths through the routine screening of those at highest risk of disease.”

As of April 2015, millions of Americans insured by Medicare have been eligible for free annual screening if they are between the ages of 55 to 77 years, have a 30 pack-year smoking history, and either currently smoke or have quit within the past 15 years. (A pack-year is calculated by multiplying the number of packs of cigarettes smoked per day by the number of years a person smoked. So, a 30 pack-year history means smoking a pack a day for 30 years, or two packs a day for 15 years, or three packs a day for 10 years, and so on). The U.S. Preventive Services Task Force recommends screening of this population, a move that has prompted most private insurers to also cover the cost of the scan.

These policy changes were based largely on the results of the National Lung Screening Trial (NLST), the largest randomized study of lung cancer screening in a high-risk population to date and one of the largest cancer screening trials ever mounted. Launched in 2002, the NLST compared two ways of detecting lung cancer: low-dose helical CT — often referred to as spiral CT or low-dose CT — and standard chest X-ray. Helical CT provides a three-dimensional image of the entire chest, while a standard chest X-ray produces a single two-dimensional image in which anatomic structures overlie one another. The three-dimensional image of the lungs generated by the helical CT is more likely than an X-ray to reveal a tumor at its earliest stage. As part of the study, 53,454 current and former smokers were randomized to undergo screening annually for three years with either CT or chest X-rays. Findings showed that those who received low-dose helical CT scans had a 15 to 20 percent lower risk of dying from lung cancer than participants who received standard chest X-rays, and that annual screening with low-dose helical CT scans could prevent three lung cancer deaths for every 1,000 people screened.

Weighing the Risks

The lung cancers detected in their earliest stages by CT scan were most frequently non-small cell lung cancers; small cell lung cancers, which tend to be more aggressive, were infrequently found in early stages this way, according to the National Cancer Institute.Could the benefits of screening extend to those who do not qualify for screening? After all, screening is limited to certain ages and heavy smokers. What about those who are too young or too old? And what about those who were only light or “social” smokers, or who didn’t smoke at all?

“We don’t yet have the data to support routine screening for anyone outside the parameters of the study,” Waterhouse says.

Absent these data, he says it’s key to adhere to the guidelines. That’s because all screenings tests, including those for lung cancer, come with risks.

“It’s important that the benefit of a screening test outweigh the risk and, for now, that is only the case for some patients,” says Waterhouse.

A lung cancer screening test, for example, can suggest that a person has lung cancer when he or she does not. This is called a false positive. False-positive results can trigger unnecessary follow-up tests that are invasive and stressful and could potentially cause harm. Over the three rounds of screening, about one in four people in the NLST who were monitored by CT had positive test results, and about one of every 15 scanned by X-ray tested positive for lesions, but nearly all of those positive results turned out be false. In most cases, this was confirmed by further imaging, rather than via invasive procedures such as biopsy, bronchoscopy or surgery, according to the NCI.

“The CT scan is so powerful that it can pick up nodules that may not be cancerous, sometimes resulting in increased anxieties or complications as a result of further diagnostics,” Waterhouse says.

Specifically, of the nodules found via screening in the study, more than 90 percent were benign. Of the patients who had benign nodules, 1.2 percent underwent an invasive follow-up procedure such as bronchoscopy or needle biopsy, researchers reported in a 2014 paper in the journal Cancer Control. A smaller 0.7 percent of study enrollees who turned out not to have cancer underwent even more invasive follow-ups: thoracoscopy, mediastinoscopy or thoracotomy, reported the authors, Prema Nanavaty and colleagues.

They noted that, although rare, some complications and deaths occurred in the NLST after follow-up imaging or more invasive testing conducted in response to positive screening results. Among patients with lung nodules but no cancer, five of every 10,000 experienced a major complication and four of every 10,000 died — more than the number of people screened by X-ray who experienced the same results.

For any prevention or screening test, the benefit (lives saved) must be balanced against harms (side effects and lives lost) to make sure that the pluses outweigh the minuses. Evaluating bodies including the USPSTF and the American Cancer Society have agreed that CT screening can be beneficial for the identified at-risk population.

Another concern is that radiation from repeated screening tests could cause harm, even though the radiation exposure is relatively low compared to that emitted by a standard X-ray. Furthermore, some people who are screened may end up needing additional CT scans, and thus being exposed to more radiation.

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Still, Waterhouse is quick to point out that, for those who do fit the screening profile, “the test can be lifesaving.”