By Dr. Geoffrey Modest
A retrospective cohort analysis of participants in the National Lung Screening Trial (NSLT), the trial that propelled forward low-dose lung CT (LDCT) screening in smokers, found that those with a negative initial LDCT actually had a much lower subsequent incidence of lung cancer and that annual screening may not be necessary (see doi.org/10.1016/ S1470-2045(15)00621-X). See blogs at the end for details and my analysis of the NSLT study, and the perhaps overenthusiastic guidelines than ensued.
Details:
- 26,231 people were screened, according to the criteria: aged 55-74, with at least a 30 pack-year history of cigarette smoking, and, if a former smoker, had quit within the past 15 years. They had 3 annual LDCT screens and were followed for 5 years after the last screen.
- 19,066 (73%) had a negative initial screen
Results:
- Those with a negative initial screen had a lower incidence of:
- Lung cancer than the group as a whole (371.88/100K person-yrs, vs 661.23)
- Lung cancer-related mortality than the group as a whole (185.82/100K person-yrs, vs 277.20)
- The finding of lung cancer at the first annual LDCT screen in those with initially negative initial screen was:
- 34% (62 screen-detected cancers out of 18,121 screens), which was much lower than on the initial screen of all participants, 1.0% (267 of 26,231)
- The mathematical estimate was that if those with negative initial LDCT screens had skipped the first annual screen, at most 28 additional participants would have died from lung cancer (i.e., a rise in mortality from 185.82 to 212.14/100K person-yrs over the course of the trial).
So, this brings up a few points:
- Not so shockingly, if you cull out those with lung cancer on the initial screen from those with normal screens, the pick-up of lung cancer the next year would be lower
- Why might this be true?? Perhaps those smokers with normal looking lungs at the initial screen are actually different from the group who develop lung cancer. Perhaps there are factors beside the quantity of cigarettes smoked which matter… well, it turns out that an old study from 30 years ago, based on the Johns Hopkins Lung Project participants (one of the 3 early clinical trials looking at sputum cytology and CXR as a means to pickup early lung cancer in smokers), found that “among cigarette smokers, the presence of airways obstruction was more of an indicator for the subsequent development of lung cancer than was age or the level of smoking. The risk for lung cancer also increased in proportion to the degree of airways obstruction. These data suggest that smokers with ventilatory obstruction are at greater risk for lung cancer than are smokers without obstruction. ” (see Ann Intern Med 1987; 106: 512). And, in fact, emphysema in NSLT conferred a 96% increase in lung cancer risk in those with an initially negative LDCT
- So, maybe there should be more risk stratification in doing LDCT screening. My real concern here is that radiation is bad for you. There is a potential creation of cancers by excessive radiation (and given the high false-positivity rate of LDCT, 39% in NSLT as mentioned in blogs below, the actual dose of radiation is on average about 4x higher, equivalent to a regular high-dose CT). And, I would imagine, it might well be that lungs that are adversely affected by smoking, perhaps those with COPD from tissue destruction and maybe with important changes in local defenses, may be even more susceptible to radiation-induced lung cancer (i.e., even more than the estimated one cancer death in 2500 screened). Perhaps assessing airway obstruction, as in the old Annals study above, would be useful (and spare lots of people from the potentially harmful effects of radiation)
- And, besides, there is no biological reason to think that annual screening is the correct interval anyway, even if long-term screening were appropriate. It’s just that annual screening was arbitrarily chosen by NSLT (which, again from the perspective of this study, only did 3 screens, yet this was generalized in the recommendations to a whopping potential of 22 screens). And, by the way, as mentioned in prior blogs, though not statistically significant (perhaps from low numbers of cases and short-term followup), the NSLT pick-up rate for positive LDCT screens went from 27.3% in year 1 to 27.9% in year 2, then dropped to 16.8% in year 3. Would that continue to decrease? Are there subgroups where the decrease was more profound? These are really essential questions to answer in order to optimize screening in terms of the risk/benefit ratio.
- But, the wholesale acceptance of annual LDCT by the USPSTF and by Medicare does put us at very significant medico-legal risk if someone develops lung cancer and were not screened (and it is hard to prove on an individual basis that one prevented a cancer by not screening). Just makes things harder for us to figure out what to do for our patients….
https://stg-blogs.bmj.com/bmjebmspotlight/2015/01/24/primary-care-corner-with-geoffrey-modest-md-uspstf-lung-cancer-screening-revisited/ is a critical review of the NSLT and the US Preventative Services Task Force recommendations, including that NSLT actually had decreasing pick-up of lung cancers on year 3 vs year 1 of the 3-year study
https://stg-blogs.bmj.com/bmjebmspotlight/2015/02/18/primary-care-corner-with-geoffrey-modest-md-medicare-and-lung-ct-screening-of-smokers/ which reviews Medicare recommendations and highlights several points, including that screening for just 3 years is projected to create one cancer death per 2500 screened from radiation. And, per Medicare, patients could be subjected to 22 annual screens if they continue to smoke and we follow the letter of the guidelines.