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Annual low-dose CT lung cancer screening got the thumbs-up from the U.S. Preventive Services Task Force (USPSTF) for adults ages 55 through 79 who have a 30 pack-year history of smoking or who have quit in the past 15 years.

That strategy garnered a grade B in draft recommendations released today and is expected to pave the way for reimbursement from Medicare and private insurance.

Other screening modalities, such as chest x-ray and sputum cytology, were not recommended.

"This is a huge step. This is going to save lots of lives. I get choked up because it really will make a tremendous difference, more than anything else for cancer, for all cancers combined," said , PhD, MD, a radiologist at Mount Sinai Medical Center in New York City and a long-time lung CT screening advocate.

The task force had originally recommended against lung cancer screening (grade D) when reviewed in 1996, and then concluded there was .

The National Lung Screening Trial, stopped early in 2010, was the first to show a mortality benefit from lung cancer screening.

"It's been more than 20 years since we started and more than 14 years since we really knew it would give this great benefit," she told 乌鸦传媒. "It took that additional time to get enough convincing evidence from other people."

Her group's earlier International Early Lung Cancer Action Project (I-ELCAP) study had suggested that treating the early stage cancers predominantly picked up by CT improved outcomes but was controversial both for misreporting key data and failure to disclose tobacco company funding and royalties for the imaging technology to Henschke and a co-author.

The , published simultaneously online in the Annals of Internal Medicine, used the evidence from that study only in calculation of CT's predictive value for various sized nodules.

Screening Criteria

Other organizations have also been recommending CT screening for lung cancer, although they have not been unanimous on the criteria for doing so.

Guidelines from the American Cancer Society and the American College of Chest Physicians favored screening patients using the National Lung Screening Trial criteria of smokers ages 55 to 74 with at least a 30 pack-year history of smoking or those who have quit in the prior 15 years.

The National Comprehensive Cancer Network guidelines extended that to individuals as young as 50 or those with a 20 pack-year history of smoking if they had additional risk factors, such as occupational exposure to carcinogens like asbestos.

The USPSTF diverged from all three with its recommendation to stop screening once an individual reaches age 80.

The reason for the change: the National Lung Screening Trial enrolled individuals up to age 74 but then continued to screen them for several years and because the modeling suggested 55 through 79 as offering the best balance of benefit and risk, , MD, MPH, chair of the USPSTF, told 乌鸦传媒.

Henschke predicted that the guidelines would expand to a broader age range with a lower pack-year smoking history threshold for screening as further research develops.

The trial enrollment criteria were picked to maximize the number of cancers found for appropriate statistical power.

"I don't think it was ever envisioned that that would be the only group who benefits from it," she explained, adding that "the person who falls outside of these criteria really has to talk to his physician and discuss the risks and benefits of screening."

However, "caution should be used in recommending screening to patients with significant comorbidity, particularly those who are toward the upper end of the screening age range," the task force wrote.

Expected Benefits

The commissioned by the USPSTF found "adequate evidence" of benefit for otherwise healthy persons.

The National Lung Cancer Screening Trial showed a 20% lung cancer mortality reduction and nearly 7% all-cause mortality reduction with low-dose CT screening, with a number needed to screen to prevent one lung cancer death of 320 and 219 to save one life overall.

The review compared that with numbers needed to screen or to invite to screen for other common screening tests:

• For mammography, one breast cancer death prevented over 11 to 20 years per 1,905 women ages 40 to 49, or 1,339 in those ages 50 to 59, or 377 in women ages 60 to 69
• For flexible sigmoidoscopy, one colon cancer death prevented per 871 screenings

The other three studies included in the review did not supported a significant mortality advantage to lung cancer screening.

But those small European studies "were underpowered and of insufficient duration to evaluate screening effectiveness," Linda L. Humphrey, MD, MPH, of the Pacific Northwest Evidence-based Practice Center at the Oregon Health & Science University in Portland, and colleagues wrote in the review.

In practical terms, the USPSTF recommendations will likely mean a big uptick in actual screening rates.

Primary care physicians largely have not been recommending CT lung cancer screening, which few insurance companies cover, commented Dan Raz, MD, surgical director of lung Cancer and thoracic oncology at City of Hope in Duarte, Calif.

The out-of-pocket cost, ranging from $50 to $400, can be a "huge barrier for people," he told 乌鸦传媒.

Under the Affordable Care Act, insurance companies are required to cover any screening service that is given an A or B rating by the USPSTF without any copay or deductible, , MD, director of the MD Anderson Cancer Prevention Center in Houston, explained in an interview.

That shift should provide more opportunity for cure by catching tumors at an early stage, rather than metastatic at presentation as most patients do now, Raz added.

Risk of Harm

However, the USPSTF warned about the downside of CT's expertise in detecting small nodules: the high rate of recall and biopsy of lung nodules that turn out to be benign.

On their first screening, 9% to 51% of patients had an abnormal scan, which fell to 4% to 42% on subsequent scans.

Most were cleared with further imaging but the 94% false positive rate meant extra radiation exposure and anxiety as well as cost.

Overdiagnosis is a concern, as an estimated 10% to 12% of the screen-detected cancer cases wouldn't have been detected in the patient's lifetime otherwise, based on the modeling studies commissioned by the USPSTF.

Its review also warned about false reassurance due to the false negative rate of up to 20%.

The trialists have been careful in setting up how to manage abnormal scans, and that same care needs to be continued in community practice, Edward Kim, MD, chair of solid tumor oncology at Carolinas HealthCare System in Charlotte, N.C., noted in an interview.

"We really have to be diligent in how we set up these parameters and which we look at; was it a positive or was it a negative?" he told 乌鸦传媒.

"The responsibility lies in the hands of pulmonologists, oncologists, and thoracic surgeons to make prudent decisions on how to investigate these lesions, and make sure not to subject patients with benign entities that are detected on the CT scan to undergo invasive procedures," agreed , MD, a pulmonologist at Cedars-Sinai Medical Center in Los Angeles.

The size threshold for lung nodules used in the National Lung Screening Trial (4 mm) may have been too small, based on more recent research, Raz noted.

"As time goes on, we're going to have more and more research about how to select patients in a smarter way, and how to identify who is a positive and who is a negative in a smarter way so that we can reduce the risk and really maximize the benefit of lung cancer screening," he said. "So I think this is really just the beginning."

Another area of concern is that the trials suggested no impact of screening on encouraging smokers to quit or cut down on tobacco use.

"Screening is absolutely not a substitute for stopping smoking," Moyer emphasized.

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