Just as physicians and patients had finally begun to resolve debates over prostate-specific antigen testing and mammography, a new significant change in screening recommendations has arrived.
On Dec. 31, 2013, the U.S. Preventive Services Task Force (USPSTF) issued a final recommendation calling for annual screening for lung cancer with low-dose CT in adults age 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years.
The recommendation, published in Annals of Internal Medicine along with the modeling study on which it's based, represents a major shift, according to experts in the field. “Starting on lung cancer screening is definitely a big practice change,” said Lisa Schwartz, MD, professor of community and family medicine at the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, N.H.
Because of a high risk of false positives and an evolving evidence base, initiating lung cancer screening is likely to be trickier than following most preventive care guidelines, experts said.
“People look at this like giving a shot for flu. It's a different kind of prevention. It's much, much more complicated,” said Michael Unger, MD, FACP, a professor of medicine and director of prevention and early detection of lung cancer at Fox Chase Cancer Center in Philadelphia, who wrote an editorial accompanying the recommendation. “Screening is not a test; it is a process,” he said.
Before starting their patients on this process, internists have to consider a number of issues, from how to explain lung cancer screening to patients to where to send them to how to deal with the results.
General internists are likely to carry much of the responsibility for implementing the guideline and getting appropriate patients screened, experts said. “The internists are the initial people who see these patients. I think it is the responsibility of primary physicians to inquire and understand who are the people at risk,” said Dr. Unger.
Experts agreed on the importance of physicians and patients understanding the evidence behind the guideline. “We should be critically appraising guidelines to see if the guidelines have made recommendations based on a full understanding about benefits and harms,” said Russell P. Harris, MD, ACP Member, professor of medicine and epidemiology at the University of North Carolina in Chapel Hill.
The USPSTF guideline is largely based on evidence from the National Lung Screening Trial (NLST), results of which were first published in the Aug. 4, 2011, New England Journal of Medicine. The NLST randomized more than 50,000 participants to low-dose CT or chest X-rays and found that lung cancer deaths were reduced by 20% in the CT group, leading to a 6.7% drop in all-cause mortality.
That was a very significant finding, experts agreed. “The benefit of lung cancer screening is much bigger than mammography. And it is the only screening test that has been shown to reduce all-cause mortality. That reflects the fact that lung cancer is a major cause of death for people with a substantial smoking history,” said Dr. Schwartz. “There's good evidence that people who meet the criteria from the study should consider screening.”
Deciding which people are in that category is somewhat more controversial. The NLST enrolled patients between ages 55 and 74 years who had a history of cigarette smoking of at least 30 pack-years and currently smoked or had quit within the previous 15 years. After the study's publication, a number of organizations, including the American College of Chest Physicians, the American Society of Clinical Oncology, the American Thoracic Society and the American Cancer Society, recommended CT screening for precisely this population.
The USPSTF guideline extends the recommended age range up to 80. This decision was based on the modeling study conducted for the Task Force.
“We actually estimated harms and benefits of almost 600 scenarios,” said lead modeling study author Harry J. de Koning, MD, PhD, professor of public health and screening evaluation at Erasmus University Medical Center in the Netherlands. “It appears that stopping at 75 is not on the efficient frontier, looking at lung cancer deaths prevented.”
He also noted that the NLST screened patients for 3 years, so some participants were as old as 77 during the trial. “There are unfortunately simply many lung cancer cases at older ages, which can be addressed effectively with CT screening,” Dr. de Koning said.
“I applaud them for extending the age, because today we see many 80-year-olds who are really in good health,” said Claudia I. Henschke, MD, professor of radiology and head of the Lung and Cardiac Screening Program at Mount Sinai Hospital in New York. “If you expect to reach 100, it makes absolute sense [to screen at 80].”
(It's important to note that the USPSTF recommended discontinuing screening in patients with a health problem that substantially limits life expectancy or without the ability or willingness to have curative lung surgery.)
Not all researchers are so convinced, including Peter Bach, MD, attending physician and researcher at Memorial Sloan-Kettering Cancer Center in New York, who wrote an accompanying editorial criticizing the guideline's reliance on modeling. “The Task Force recommended screening people in ways that have never been studied and in populations that have never been studied, which I raised some concerns about,” he said.
Dr. Bach worries that the benefit of screening will not be as great for this additional population. Even within the studied age range, there will be a lot of variation in the benefit patients see from screening, he said.
“In the NLST study, about 1 in 320 people who were screened had a death from lung cancer prevented .... If they're older and they've smoked a lot, the chance that they'll benefit can be as good as 1 in 100, but if they're on the younger age range and haven't smoked as much, it can be more like 1 in 1,000,” Dr. Bach said.
He and some other experts recommended explaining this uncertainty and variation to patients when offering them screening. The USPSTF guideline also called for shared decision making.
“The most important message about any screening test, and especially this screening test, is to have a discussion about it and not make it an imperative. ‘You need to do this' is not the right message,” said Dr. Schwartz.
“It's not a 1-minute talk. This will require time from committed and educated physicians,” said Dr. Unger.
A major part of the discussion should be the potential harms from screening, which include radiation exposure, incidental findings and overdiagnosis, but much more commonly, false positives. In the NLST, about a quarter of patients screened by CT had positive results, and more than 95% of those did not ultimately receive a diagnosis of cancer.
In some parts of the country, that rate of initial positive CTs could be even higher. “In the Mississippi/Ohio Valley, the rate of false positives will be much, much higher because of previous exposure to possible fungal infections,” said Dr. Unger.
Internists who offer screening need to explain the risks and consequences of false positives to patients before the scan, the experts urged. “[A false-positive result] will increase their anxiety, it will increase the workup, it will increase the cost and their risk for unnecessary procedures and potential complications,” said Dr. Unger. “People who are getting into it should be educated by those physicians who are writing the order.”
To assist with educating patients, the National Cancer Institute (NCI) released a fact sheet. “It's a 1-pager that synthesizes what we think are the important elements to making an informed decision about lung cancer screening. It's an easy way to structure the discussions for doctors. It lays out how big the benefit is, and it tells you that there are tradeoffs,” said Dr. Schwartz.
For more help, Dr. Bach recommended a Web tool from Memorial Sloan-Kettering that allows patients to enter their data (including age and specific smoking history) and get an estimate of their risk of developing lung cancer.
In addition to explaining the risk of false positives, internists should also do what they can to reduce it.
“Doctors can help to minimize that problem by making sure that they're referring to centers that are doing this responsibly,” said Dr. Schwartz. “If it's just some for-profit center and they are not adhering to the guidelines of when things need to be followed up, the false positives will really escalate.”
Profit-seekers jumped on lung cancer screening before any guidelines recommended it, Dr. Unger noted. “The first paper that [showed benefit to CT screening] was published in the New England Journal of Medicine in October 2006,” he said. “By December, there were billboards in many places in the United States: ‘Give your loved one the gift of life. Make them have a CAT scan’ ... That's not the way it should be done.”
Ideally, screening should be done at an NCI-designated cancer center. If that's not available, opt for the best around, often an academic medical center, Dr. Bach said.
“You want to go to a place that's got coordinated care,” he said. “Have patients in a situation where they can go to a place with expertise and experience handling these kinds of abnormalities in a conservative way, because more than 95% of them will not be cancer.”
Specialists in the field are still working out the optimal follow-up for abnormalities, the experts said. “The radiology and chest organizations are discussing changing the threshold of the size of the spot that requires [additional testing],” said Dr. Schwartz.
The response to findings may in some cases need to be individualized based on patient history. “If we know the patient had histoplasmosis or tuberculosis, obviously we can expect certain findings and look at this differently,” said Dr. Unger.
Many of the experts supported greater individualization of screening recommendations, either now or in the future.
Dr. Bach said he wishes that the Task Force guideline had divided the patients into more groups and varied the strength with which it recommended screening based on more individualized calculations of harms and benefits.
Physicians can do this in their own practices, he noted. “There's a spectrum ... The patients I would target for the greatest encouragement would be the ones who are most likely to benefit. Those at the low end, it's very reasonable to say, ‘This is something you could do, but you don't have to,’” Dr. Bach said.
Dr. Henschke, on the other hand, wants more patients screened than the USPSTF suggested. “I hope over time the guidelines will be reviewed and hopefully broadened, because when you save a life of someone that's 50 years old instead of 55, you're creating a lot of benefit,” she said.
She is examining screening patients as young as 40 and also favors screening patients who quit smoking more than 15 years earlier. Recommendations should also be specified by sex, she suggested.
“Women are at more risk for lung cancer than equally smoking, equally aged men. Women are at somewhat of a disadvantage under the current guidelines,” she said.
Overall, the patients who are to be screened under the guideline represent only a fraction of the population who will die of lung cancer, she and other experts noted. “There are about 160,000 deaths from lung cancer each year in this country, but if you look at the people who were in the NLST ... about 20 to 30,000 of those 160,000 deaths come from those people,” said Dr. Harris.
However, screening a broader population, in order to catch more of the cancers, would also increase the number of patients who were harmed by screening, he noted. “This demonstrates the trade-offs inherent in all screening programs,” he said.
The American Academy of Family Physicians (AAFP) recently concluded that those trade-offs were too great to recommend lung cancer screening. Disagreeing with the USPSTF, the AAFP declared that evidence was insufficient to recommend for or against screening high-risk patients. In a statement issued Jan. 13, the organization cited the harms and costs of screening, and the reliance on a single study, the NLST, for evidence of benefit.
Research to come
All of the experts would like to see additional evidence about the effects of lung cancer screening.
Future research may eventually identify additional factors, other than smoking history and age, that could identify patients who have higher risk for lung cancer and more likelihood of benefitting from screening. “Other biomarkers in the future will become very important,” said Dr. Unger.
More data could also be used to refine recommendations about the frequency of screening, suggested Edward F. Patz, Jr., MD, professor of radiology and pathology at Duke University in Durham, N.C. “Maybe we can be more efficient and somebody who has no abnormality at the beginning may not need an annual. They may be able to wait 2 or 3 years, such as with colonoscopy, where you can wait 10 years,” he said.
Researchers are generally looking for more evidence on the appropriate repetition of screening, which is another area where the USPSTF extrapolated from the NLST. The trial included only 3 years of annual scanning, but under the guideline, some patients could be screened for as long as 25 years.
“If you were strictly going by the evidence, you would do it exactly as they did in the trial, because that's what we really know,” said Dr. Schwartz. “If clinicians decide they really want to practice evidence-based medicine and just do 3 screens, I think that's an OK decision.”
Dr. Henschke countered, “The NLST only did 3 rounds of screening because they wanted to conserve money. They didn't want to do additional rounds of screening if they could come up with the results. It was always for the purpose of annual screening.”
The USPSTF called for development of a registry from lung cancer screening programs, which could provide more information on the effects of longer-term screening as well as answer some of experts' other questions and concerns. A large European trial, called NELSON, is also expected to provide more data.
“There will be a plethora of papers, especially as far as the algorithms on what to do with those patients. There will be more money for research,” said Dr. Unger.
While they determine whom and how to screen for lung cancer, internists should remember to strongly encourage smoking cessation with every patient who smokes, the experts agreed. No additional evidence is needed to show the most cost-effective, least-harmful way to reduce lung cancer deaths.
“By far the benefit of stopping smoking is way greater than the benefit of screening, because smoking also increases death from heart disease and many other causes,” Dr. Schwartz said. “Even if you get the scan, it doesn't get you out of stopping smoking.”