lung cancer screening results at the VA

A recent real-world study reported on the results of the implementation of the low-dose CT (LDCT) lung cancer screening in smokers at 8 VA hospitals (see lung cancer CT at VA jamaintmed2017 in dropbox, or doi:10.1001/jamainternmed.2016.9022​).

Details:

--93,033 primary care patients assessed: 4246 met criteria for screening, 2452 [57.7%, a pretty low number…] agreed to be screened: 96% men, mean age 65,

--of note, there was a large variation in the number of positive LDCT screens by site, varying from 31% to 85%. [this raises the issue of lack of consistency in radiologist interpretation of LDCTs, which is also found in mammography evaluation and for several other xrays]

Results:

--1257 (60%) had lung nodules, of whom 1184 (56%) required tracking (solid nodules <8mm without suspicious features (irregular or speculated borders) and not known to be new or growing based on prior imaging, ground glass nodules >5mm, or mixed solid and round glass nodules of any size)

--42 (2%) required further evaluation but did not have cancer

--31 (1.5%) had lung cancer within 330 days of follow-up

--false-positive rate of 97.5% !!!

--857 (41%) had incidental findings (eg emphysema, other pulmonary abnormalities, coronary artery calcification)

--they calculated that 880,899 patients in the VA system would meet criteria for lung cancer screening

Commentary:

--the recommendation for LDCT screening of smokers was largely based on the National Lung Screening Trial (NLST), but

   --there were significant differences in the demographics of these VA patients vs the NLST participants: more men, older group (53% were 65 or older), more current smokers (57% vs 48%)

   --the rate of positive screens was more than twice as high in this study (60%, vs 27% in NLST)

   --I have sent out many blogs on LDCT screening in the past (see below), but my concerns are several: the large number of false positives, the amount of radiation, the fact that one good trial (NLST) which lasted only 3 years generated a massive screening initiative (which can last up to 22 years, or 25 years if you go by the USPSTF guidelines!!), had very few lung cancers actually detected (despite their extrapolation which projected saving 3 deaths/1000 high-risk individuals screened), did not include some high risk patients and did include some low risk ones, and reinforced the false perception that the main problem with smoking is lung cancer.

--the editorialists wrote a very powerful response (see lung cancer CT editorial jamaintmed2017 in dropbox, or doi:10.1001/jamainternmed.2016.9446), noting:

   --for every 1000 people screened:

       --10 would be diagnosed with early-stage lung cancer (potentially curable)

       --5 diagnosed with incurable advanced-stage lung cancer

       --20 would undergo unnecessary invasive procedures (bronchoscopy and thoracotomy) because of the screening

       --550 will have unnecessary alarm and repeated CT scanning, with its attendant radiation [which, as noted in my prior blogs, actually increases the average radiation exposure from the low-dose from the initial screen by 4-fold to that of a regular chest CT, given the follow-up requisite high-dose regular CTs, PET scans etc]

   --they also point out that many of the anticipated problems from LDCT screening were articulated by the CMS advisory body MEDCAC (Medicare Evidence Development and Coverage Advisory Committee), noting that they had "low confidence" that LDCT benefits would exceed the risks, and "high confidence" that evidence gaps remained after the initial studies (NLST did find benefit, though 3 European trials found no benefit)

so, to me, this VA study suggested several things:

--I think it reinforces that there really should be multiple studies done in different patient populations (include some “real-world” sites, where the recommendations will actually be implemented)

--that it is a bit crazy to generalize from a 3-year study to guidelines which could potentially expose millions of people to 22+ years of radiation.

--that all of this is especially true before we embark on a screening test which is so resource-intensive. Not just the cost (which is a lot, and could be used for many other social or medical issues which are underfunded), but also the intensity of resources (developing systems to track these patients, carving out time from the already time-limited primary care encounter to deal with shared decision-making, being sure that the patient qualifies for the study, doing the referral for the screenings over the years, devoting the time and resources of other office staff to dealing with all of this as well, and then doing all of the above for following up on the very common incidental findings (41% in this study), false positives (97.5%) etc ....

--and, by the way, another article in the same journal (see lung cancer CT screen in nonsmokers, low risk jamaintmed2017 in dropbox, or doi:10.1001/jamainternmed.2016.9016 ) found that from 2010 to 2015 (NSLT was published in 2011), there were large % increases in LDCT done in never-smokers and low-risk smokers, such that many more of these who actually do not qualify per the guidelines are getting LDCTs than those who do qualify, suggesting that this very low-risk group is pretty undoubtedly getting risk with almost no benefit, and that there is some collateral damage to having guidelines: either confusion on the part of the clinicians, or insistence on the part of patients who do not want to be denied this (???) potentially life-saving intervention......

--and, speaking of collateral damage, one of the big concerns in primary care is that we are working in a quite litigious society, and we may be medico-legally responsible if a smoker who meets criteria for LDCT does not get one, even if logic is on our side…

prior related blogs:

-- see http://gmodestmedblogs.blogspot.com/2015/08/another-downside-of-lung-cancer-ct.html  which looked at a small number of VA patients, revealing their misperceptions about the screening, with some thinking that since the CT was okay, they could continue smoking (one concern is that LDCT focuses on lung cancer in smokers, but the highest mortality/morbidity is actually from smoking-related atherosclerotic disease)

-- see http://gmodestmedblogs.blogspot.com/2016/07/lung-cancer-screening-for-smokers.html  which questions the criteria for LDCT screening, noting that many very high risk patients do not actually qualify and many low risk ones do

here is one of the original blogs on low-dose screening, which reviews the NLST, from 12/31/2013, including comment that one would create one lung cancer for every 2500 screened

Recent recommendations by the Am College of Chest Physicians to perform low-dose CT screening of smokers (see lung cancer CT screening guidelines chest 2013 in dropbox, or DOI: 10.1378/chest.12-2377). these recommendations parallel the interim recommendations of the American Lung Association (see lung cancer CT screening guidelines ALA 2012 in dropbox)

Baseline: lung cancer is common and has generally poor prognosis (esp with lesions greater than stage 1), causing as many deaths as the combo of the next four cancers. one thing to keep in mind is that there are newer therapies that work better than the old ones -- targeted to the specific tumor-associated genetic mutations engendered by the cancer (ie, possible that these treatments could change the risk/benefit analysis of screening in the future).  of note, the arena smoking-related morbidity is changing: tobacco companies have seen shrinking local markets (showing that sometimes after decades of obvious connection with lung cancer/persistent denial by the corporations, public health initiatives may work....); as a result,  there has been huge-scale exporting ("dumping") of cigarettes to developing nations, with likely huge increases in tobacco-related morbidity and mortality in the near future.

Cancer prevention: attempts to prevent cancer in smokers mostly with different antioxidants or anti-inflammatories (eg b-carotene, aspirin, selenium, inhaled steroids, vitamine E, retinoids) have not panned out and are not recommended. preventing smoking initiation is the clearest prevention (though 15% of lung cancers are not smoking related. we do know, however,  from many epidemiologic studies over the decades that cancer risk geometrically increases with multiple insults, including air pollution/environmental exposures and occupational exposures in addition to smoking). for those who smoke,  smoking cessation clearly helps!, with about a 15 year lag to reducing the lung cancer risk to near non-smoker levels (unlike the heart disease risk, which decreases dramatically within 6 months of smoking cessation).

screening methods: old studies have not shown clinical benefit with either CXR of sputum cytology screening.

                --low-dose CT screening (LDCT). lots of nodules identified (in 10-50% of smokers -- for example, the National Lung Screening Trial Research Team (NSLT)—(see lung cancer CT screen nejm 2011 in dropbox, or (10.1056/NEJMoa1102873) --screened 27K high risk patients with LDCT and 27K with CXR yearly for 3 years and followed another 3.5 yrs, and found 25% with positive screen on LDCT and 7% with CXR, finding 645 cases/100K person-yrs with LDCT and 572/100K person-yrs with CXR --13% more. most notably, there were 247 lung cancer deaths/100K person-yrs with LDCT and 309 lung cancer deaths/100K person-yrs with CXR, a significant 20% decrease (though not very large absolute numbers – difference of only 62 deaths/100K person-yrs...), and all-cause mortality decreased 7%. the LDCT pickup of cancer was similar each of the 3 years (suggesting that it would be useful to continue screening annually). but, very large number of false positives (>95% of positives were false ones). the vast majority of those with abnormal screens had follow-up radiologic procedures, a small  minority with invasive testing (1.2% of pts not found to have cancer had a biopsy or bronchoscopy).  BUT, given the high number of abnormal screens, the "low-dose" radiation did not remain so low. the CT delivered 1.5 mSv of radiation (vs 8 mSv for regular chest CT). because of the large number of positive LDCT who then received follow up chest CT or PET CT,  the average dose overall for the LDCT cohort was actually 8mSv. the rough calculation is that this degree of radiation exposure (mostly based on atomic bomb and some medical imaging studies) would create one cancer death per 2500 people screened.

                --the recommendation:  for smokers and former smokers aged 55-74 who have smoked >30 pack-yrs and either continue smoking or have stopped within the past 15 years should be offered annual LDCT, if comprehensive care can be provided as in the NLST trial.

so, this recommendation, at this point, is by pulmonary specialist organizations, which may have some self-interest (organizationally, or by the individuals involved in crafting the recommendations) to be aggressive (eg, as with the american urology assn and PSA screening).  we may want to wait for a more neutral group (eg USPSTF, though i suspect they will follow suit, given that the NLST is a well-done study). my fundamental concern is that at the same time we are getting recommendations about expensive, intensive, high-tech screening for a largely preventable cancer (and with a significant but low difference in absolute death rates), we in the trenches are getting less and less support for programs to prevent or stop smoking (cutbacks in health educators, varying and variable insurance-based support for smoking cessation devices).  In addition, i am very concerned about the additional radiation exposure (will also resend some of my previous emails about risks of radiation exposure).