In 2011 The National Cancer Institute published results from their study of low dose CT lung cancer screening of individuals identified as at risk for lung cancer. The investigators enrolled those between 55 to 74 years of age who had at least 30 pack years of smoking under their belt (number of packs per day multiplied by number of years smoked). These people were then randomly assigned to either a chest x-ray group or a “low dose” CT scan group, with 3 images over 2 years. There was initial criticism that the authors used chest x-rays as the control rather than “usual care”. However the PLCO trial, which compared chest x-rays to usual care, subsequently showed no difference between the two, a vindication of the investigator’s strategy.
The study also received some well deserved praise, as it was the largest study of its kind, and demonstrated some very impressive findings, as detailed in the article’s abstract. The most striking findings were:
- a 20% reduction in the risk of death from cancer relative to the control group.
- a 6.7% reduction in the risk of death from any cause relative to the control group.
I cannot sum up how to you how astounding these results were/are to the medical community, specifically to those who are involved as patients, or in the treatment, diagnosis, support, research, and fund raising of lung cancer. For years, many who have suffered from lung cancer, and many more who have labored to care for them and to find a cure, have felt like the orphaned stepchildren of the cancer world. We experience greater incidence than most cancers, have the greatest number of deaths, and yet have less treatment options, less fundraising, less media attention, and the general sense that lung cancer is a condition brought on one’s self by irresponsible behavior.
So these results brought a sense of excitement … finally there is something do! Heck with these results, light me up! I don’t even smoke, but what harm could come from a few seconds of exposure to a little itty-bitty dose of radiation, followed by its interpretation by a guy (or gal) in a dimly lit room?
As it turns out, quite a bit of harm. 26,722 people were assigned to the low dose CT arm of the study, a total of 1060 cancers were diagnosed in these people. And while there was the above mentioned mortality benefit in those that truly did have cancer, about 96% of people who had a positive scan did not end up having cancer (false positive). Those people who received a positive scan (of whom we know 96% did not have cancer) endured 2043 invasive diagnostic procedures (of which 503 were an open chest surgery called a thoracotomy). From these procedures, there were 75 complications classified as “major”, while in the control group, only 768 people underwent an invasive procedure.
An analysis of the data shows that overall, 99.5% of high-risk people who underwent this screening received no benefit from it. A total of 217 people needed to be screened to prevent one death (NNT=217). But at a cost of one in four people being screened receiving false positive test results, and one in thirty people screened undergoing unnecessary surgery.
The question now is “Is it Worth It?” This question comes down to how one would define “harm.” In most analyses, a false positive (i.e. cancer scare) is considered a psychological harm, which places unneeded stress on people and families, even if no procedure is then performed. If a procedure is then performed to confirm a lack of cancer, then from a researcher’s standpoint, this is now 2 harms done to a patient who would have not otherwise had any psychological or physical harm done to them. Conversely many people who have undergone such an ordeal might ultimately be relieved and thankful that they had the test done and reassured that they do not have cancer.
Eventually, some of these people will die from complications to confirm that they did not have cancer, whereas others who did have cancer will survive. On balance, the number of people who survived as a result of this intervention is greater than the number of people who died because of the intervention. These are the sorts of analyses that are currently underway. Investigators are attempting to determine both the length and quality of life gained due to the screening intervention and its cost effectiveness to see whether it falls on the right side of the fine line that takes cost, efficacy, and harm into account.
Some have already decided that the available data is sufficient to make recommendations. Currently the American College of Chest Physicians (ACCP; of which I am a member) and the American Society of Clinical Oncology (ASCO) have released a joint clinical practice guideline endorsing the use of low dose CT screening for “smokers and former smokers who are age 55 to 74 and who have smoked for 30 pack years or more and either continue to smoke or have quit within the past 15 years.”
While we are a long way away from nationwide screening, such statements from interested medical societies are often the first step towards a time when this would be offered by insurance companies as a covered procedure. The next step involves the analysis of quality of life and cost effectiveness data, which is currently underway. Finally other societies and organizations such as US Preventive Services Task Force may weigh in on the issue before Medicare makes its decision on whether to offer CT screening as a covered service. And as Medicare leads, many private insurers often follow.
Deep Ramachandran is a pulmonary and critical care physician who blogs at CaduceusBlog.