BY JAMES R. JETT, MD
In early November, the NCI announced the closure of the National Lung Screening Trial. This randomized controlled trial (RCT) enrolled current or former smokers with 30 pack-years, age 55-75 years, and randomized participants to three years of screening with low-dose CT chest or chest radiograph.
We were informed that the trial reached its primary endpoint and demonstrated a 20.3% reduction in lung cancer mortality in the CT-screening arm versus the chest-radiograph arm. Total deaths from lung cancer were 354 vs 442 in the two arms, respectively. There was also a 6.9% reduction in all-cause mortality in the CT-screening arm (www.cancer.gov/nlst/updates).
My take is that this certainly is good news for high-risk individuals like those enrolled in the RCT. It is estimated that 80% of the 200,000 new lung cancers and 160,000 deaths per year in the United States occur in current or former smokers (high risk). A 20% reduction in deaths from lung cancer is huge.
This is arguably the single greatest advance in decreasing lung cancer deaths in our lifetime -- Smoking cessation being the other very important contribution.
Obviously, we need more information about the results from the trial, and that is promised for the near future.
To adequately advise our patients we need to know more about costs and risks. Cost-effectiveness studies are part of the NLST, and publication of that data is anticipated.
We also need to know how many participants underwent invasive diagnostic procedures including video-assisted thoracic surgery (VATS) and/or thoracotomy for benign disease.
How do we advise our current and former smokers at this time?
First, we must explain the limitations or risks of screening. These individuals are likely to already know about the benefit from the news media. Over 50% of CT-screened individuals will have a non-calcified nodule that will necessitate follow-up CT scans, at the very least. Most of these nodules are benign lesions. In the NLST, only 3.6% of the positive screens in the CT arm turned out to be a lung cancer.
Additionally not all lung cancers were detected by screening CT scans. Some were interim cancers and occurred between the yearly scans or developed after the three years of active screening.
The NLST showed a 20% decrease in mortality based on just three yearly CT scans. It does not inform us as to how long high-risk individuals need to be scanned on a yearly basis.
Patients with larger size nodules (8-10 mm or larger) will likely be advised to undergo further testing including potential invasive diagnostic tests such as needle biopsy, bronchoscopy, or even VATS and/or thoracotomy with resection in some cases.
Multiple single-arm CT screening trials in the published literature have reported that 15 to 25 percent of the thoracic operations performed were for benign lesions.
All of this needs to be shared with our patients, who may understand potential benefits better that they understand the risks of screening.
Additionally, at this time, the CT screening test will be paid for by the individual, at least until third-party payers and Medicare decide that they will cover CT screening. That may very well happen in the next year or so.
The NLST study did not include never- or light-smokers, nor individuals with a family history of lung cancer in first-degree relatives, unless they met the smoking and age criteria for eligibility.
So at this time we still do not have evidence to recommend screening in these individuals outside the setting of a clinical trial. Some of these individually may elect to be screened anyway, but that is a personal choice. They should be informed of the risks/benefits before proceeding.
At this time I believe the best chance of reducing lung cancer deaths would be to combine CT screening with smoking cessation in these high-risk individuals.
Screening has been reported to be a “teachable moment” for smoking cessation. Smokers inquiring about CT screening should also be referred for a nicotine-cessation consultation.
Patients need to clearly understand that a normal CT scan does not prevent them from developing lung cancer in the future, and is absolutely not a justification to continue smoking.
Before I start actively screening all of my high-risk current or former smokers, age 55 or older, I would like to see the details of the NLST trial that are due out soon. After that, I anticipate discussing CT screening, risks versus benefits, with these individuals.
I also anticipate that these discussions will be initiated by individuals who did not fit the eligibility criteria of the NLST but who perceive themselves to be at increased risk for lung cancer. Without proof of benefit from screening, these decisions will need to be made on an individual basis.
Research is needed to help identify biomarkers or genomic tests that predict increased risk in never smokers, light smokers, or those with a family history of lung cancer.
More trials in screening and early detection of our number one cancer killer are needed and welcomed.
--National Jewish Health
Also in OT: our news article about the NLST by Peggy Eastman