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Primary Care Corner with Geoffrey Modest MD: lung cancer screening results at the VA

28 Feb, 17 | by EBM

By Dr. Geoffrey Modest

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 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 x-rays]

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 (e.g. 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 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 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:

 

Primary Care Corner with Geoffrey Modest MD: Lung Cancer Screening for Smokers, an Individual Risk-Based Approach

20 Jul, 16 | by EBM

By Dr. Geoffrey Modest

The USPSTF strongly recommends low-dose chest CT (LDCT) annual screening for ever-smokers with >30 pack-year smoking history aged 55-80 or until they are 15 years after stopping smoking, based on the 3-year National Lung Screening Trial (NLST). JAMA just published an article evaluating the use of risk models/individual risk-based strategies to help focus the LDCT intervention (see  doi:10.1001/jama.2016.6255). By looking at individual lung cancer risk beyond the criteria of NLST, they actually found relatively higher risk in some patients with a low risk by NLST (and therefore no screening done in NLST or offered by USPSTF) but a low risk for many included in the USPSTF guidelines. Of note, there is no currently accepted validated risk tool for lung cancer for population screening.

Details:

  • They looked at 3 databases: the CXR-only wing of the NLST (2002-2009), the ever-smokers control group of the Prostate, Lung, Colorectal, and Ovarian cancer screening trial (PLCO, 1993-2009), and the National Health Interview Survey (NHIS, 1997-2001)
    • PLCO: 155K US men and women 55-74 yo had 4 annual CXRs and found no benefit from screening CXR in smokers
    • NLST randomized 53.5K smokers aged 55-74 with at least 30 pack-years smoking to LDCT vs CXR and found 20% decrease in lung cancer mortality by LDCT
    • NHIS: 87.5K people followed in annual cross-sectional US group from 2004, with linkage to the National Death Index. This database from 1997-2001 was used to validate the lung cancer death model. Then the model was applied to a more contemporary US population (NHIS 2010-2012) looking at all ever-smokers aged 50-80, which included 18,643 people, 52% male, 72% white/15% black/9% Hispanic, 55% post-high school education, 32% with BMI>30, 36% current smoker and 26% <10 pack-yrs, 21% 10-20, 15% 20-30, 14% 30-40, 24% >40; 67% had quit >15 years; 98% no family history, 7% had emphysema.
  • They assessed an array of characteristics from these databases (including age; education; sex; race; smoking intensity, duration, and quit-years; BMI; family history of lung cancer; self-reported symptoms of emphysema) to develop risk-based models for lung cancer incidence and deaths, then applied that to the later NHIS database.

Results:

  • Hazard Ratios for lung cancer incidence (will only mention the really significant ones)
    • Age, very highly correlated with lung cancer incidence (HR 80) and lung cancer death (HR 432)
    • Pack-years smoking:
      • 30-40: HR 1.63 for lung cancer incidence; 1.74 for lung cancer death
    • 90% of the CT-preventable lung cancer deaths are likely preventable by screening only 49% of US ever-smokers aged 50-80
    • One remarkable finding: in the risk-based model to USPSTF, 36% of the USPSTF-eligible smokers would not be screened (5-year lung cancer risk, 1.3%; NNS, 647), and would be replaced by 36% high-risk smokers (5-year lung cancer risk, 3.2%; NNS, 226) who did not meet the USPSTF criteria (mostly because they were African-American, lower BMI, less educated; 22% smoked <30 pack-years but tended to be longer-term smokers (>45 years, but 61% smoked <1/2  pack-per-day), and 14% quit > 15 years ago but were high intensity smokers, almost all having >30 pack-years and 53% >45 pack-years ).e., following the USPSTF recommendations, instead of an individual risk-based approach (incorporating more than just the smoking history), would both over-screen many low-risk people and not screen some of the high risk ones.
  • The lung cancer incidence model was validated by the chest x-ray groups of the NLS and PLCO of ever-smokers; the lung cancer death model was validated in the 1997-2001 NHIS and in the PLCO x-ray group of ever-smokers
  • Lung cancer mortality, by this model, was 24% lower than expected in the NLST x-ray group
  • Based on the NHIS 2010-2012 data, there was an estimated 43.4 million ever-smokers aged 50-80 in the US.
  • Screening the 9 million ever-smokers eligible by the USPSTF criteria for LDCT: the estimate was to prevent 46,488 deaths over 5 years
  • But screening 9 million of the highest risk group by the risk-based population would prevent 55,717 deaths (9229 more)
    • So, in this risk-based model NNS (number-needed-to-screen to prevent a death) was 162 vs 194 with USPSTF, with fewer false-positives (116 vs 133), all with p<0.001
    • And if one used the USPSTF NNS of 194 and applied that to the highest risk of the risk-based group (with risk >1.9%) [i.e., increasing the screening by the risk-based analysis to equal the NNS from USPSTF], then 3.1 million more people would be screened and then 62,382 deaths would be prevented. This increase to 12.1 million would also not have an increase in numbers of false positives.

Commentary:

  • So, this study did a good job developing risk models and validating them through several US cohorts, thereby suggesting that they are pretty robust and transportable. The models seemed to be more efficient than the USPSTF recommendations in terms of identifying higher risk individuals, decreasing lung cancer incidence and mortality, and decreasing the false-positive rates from LDCTs.
  • In the NLST itself, 88% of CT-prevented lung cancer deaths occurred in the 60% of those at highest risk and there were 64% with false positive results; only 1% of the lung cancer deaths occurred in the 20% at the lowest risk (see Kovalchik SA. N Engl J Med 2013; 369: 245). In fact, if one looks at those with normal LDCT in the initial NSLT, there was a dramatically lower risk of lung cancer development or death (see blog at end), to the point that I am strongly considering stopping LDCT after a couple of negative scans.
  • A few limitations of the risk-based study:
    • There is the assumption that the 20% decreased mortality in NSLT-eligible would apply to the NSLT-ineligible that would be included in the risk-based strategy.
    • The NHIS cohort only has data on lung cancer mortality not incidence, so the above risk-based model for mortality was validated only by the 2 research studies (PLCO and NLST x-ray only groups)
    • Confining the LDCTs to the high risk only, by using the risk-model, may be associated with more complications from procedures and surgery (these people are generally at higher surgical risk), so might distort the risk:benefit calculations from NLST
  • The risk-based approach does have some improvement in decreasing lung cancer deaths from 46488/9 million screened to 55717/9 million, which is increasing absolute numbers from 5.2 to 6.1/1000 screened. Still pretty small numbers.
  • So, as per my prior blogs on the USPSTF recommendations, I think they way-over interpreted NLST by extending a 3 year study (with decreasing pickup of incident lung cancers by the 3rd year), to the potential for 25 years of annual screening and the attendant high radiation exposure, to extending the upper age limit from 74 in NLST to 80, and then to codifying a single but good study into routine practice though the absolute risk reduction was relatively small (62 deaths per 100,000 person-years). The current individual risk-based approach suggests that there are many high risk patients who would not be screened by the USPSTF criteria, and many on the USPSTF list who are actually quite low risk and likely do not benefit much from the screening. I hope (and sort of expect) that the current USPSTF guidelines will be reviewed and reconsidered at some point in the next couple of years… And, it is important to remember that, as pointed out in the other blogs, lung cancer is not even close to being the primary killer associated with smoking (heart disease from smoking being much more prevalent, and COPD, etc. rating pretty high as well). And focusing on lung cancer screening may dilute the bigger message (i.e., it would be pretty awful if patients who had a normal LDCT felt that smoking was not really so bad for them, and it was okay to continue smoking…) see older blogs below for more on this.

See: http://blogs.bmj.com/ebm/2016/04/05/primary-care-corner-with-geoffrey-modest-md-need-annual-low-dose-chest-cts/ which analyzes a retrospective study from NLST finding that those with an initial normal LDCT had about 35% lower rates of lung cancer incidence and mortality

http://blogs.bmj.com/ebm/2015/01/24/primary-care-corner-with-geoffrey-modest-md-uspstf-lung-cancer-screening-revisited/ is a critique of NLST, especially its perhaps overenthusiastic acceptance and extensions by USPSTF

Primary Care Corner with Geoffrey Modest MD: Need Annual Low-Dose Chest CTs?

5 Apr, 16 | by EBM

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….

http://blogs.bmj.com/ebm/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

http://blogs.bmj.com/ebm/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.​

Primary Care Corner with Geoffrey Modest MD: Another Downside of Lung Cancer CT Screening

26 Aug, 15 | by EBM

By Dr. Geoffrey Modest

There was a small but I think important study on the perceptions of patients who smoke and had low-dose lung cancer screening –LDCT (see lung cancer CT and continued smoking jamaintmed 2015 in Dropbox, or doi:10.1001/jamainternmed.2015.3558​). This was a VA study of patients who had in-depth semi-structure qualitative interviews about their health beliefs relating to smoking and lung cancer, done in 2014.  Details:

  • 37 patients (89% male, mean age 62, 62% white/27% black or pacific islander, mean 49 pack-years smoking, mean Fagerstrom score of 4.75 — suggesting moderate nicotine dependence) who participated in the VA pilot study on lung cancer screening in one of 151 VA medical centers were interviewed, most after they got their results. There was a detailed pretest description of the risks and benefits of screening.
  • Results:
    • 18 of the participants had abnormal screening results (9 with nodules <1 cm, 12 with nonpulmonary incidental findings)
    • Despite education on the limited benefit of screening, many participants thought that everyone undergoing screening would benefit
    • Many patients thought that screening would give a more precise estimate of their individual risk of cancer, to see “how much damage was done do their lungs” by smoking
    • Many acknowledged the need to quit smoking, but focused on “catching” cancer early
    • Many patients were reassured that by finding a nodule meant that the screening worked for them (and protected them from getting cancer), that finding a cancer meant that it could be cured and was harmless [in fact, >1/3 of the cancers detected by screening in National Lung Screening Trial were > stage 1]. Several thought they were going to get “bad news”, and the lack of an abnormality on CT led to “a lack of urgency for quitting” smoking. “It is more of a relaxing thing that there is a part of my body that I know is working and looks like it is continuing working fine for the rest of the year at least”.
    • Some participants felt that screening would itself cure cancer, that they would not need chemotherapy (and perhaps avoid these treatments that their relatives had gone through)
    • Some people thought they were the “lucky ones”, citing that they knew of people who lived to be 100 and smoked over 50 years without a problem. Some acknowledged that smoking caused cancer but that “like most smokers it’s not going to be me”

For my general critique of the lung cancer screening guidelines, see http://blogs.bmj.com/ebm/2015/02/18/primary-care-corner-with-geoffrey-modest-md-medicare-and-lung-ct-screening-of-smokers/ , which mostly focuses on the limitations of the National Lung Screening Trial and the related development of pretty aggressive national guidelines, and the potential of radiation-induced cancers. This current small qualitative study, done in veterans, brings up another major issue of screening: patients’ understanding and interpretation of both the screening process and the results. My major concerns from this study are:

  • It is often very difficult for patients (including some of us when we are patients…) to think objectively about cancer. It is scary, both in what it is/can do and in its treatment (it is the “crab” that extends itself relentlessly throughout your body, the emperor of all maladies). Many people are willing to take large risks of screening or treatment to decrease their risks from even not-so-aggressive cancer: “just take everything out”. This inability to sort out risks and benefits objectively and not just focus on the word “cancer” more emotionally, I think, leads to misperceptions in this study that screening protected them from cancer, small nodules are not significant but only need followup, that it was okay to continue smoking since they were one of the lucky ones who would not get cancer.
  • ​Although lung cancer is certainly a risk of smoking, many more patients die of cardiovascular disease related to smoking (the single most important correctable cause of heart disease), and almost as many die from COPD (158K lung cancer deaths/year vs 135K with COPD). The focus on CT scans to pick up lung cancer effectively de-emphasizes and diminishes even more important morbidity/mortality issues and provides a false sense of reassurance.
  • Ultimately, there are also ethical and social issues regarding the approach to serious preventable illnesses. Huge amounts of funding and resources are going into early detection of lung cancer, which had very small absolute benefit (decreased mortality by 62 deaths per 100,000 person-years of screening in NLST), instead of inexpensive (and severely underfunded), community-based prevention programs — see prior blog describing a very impressive, low-cost, community-initiated and community-based program in a poor rural Maine community, which achieved impressive cardiovascular risk factor reduction, including for smoking (http://blogs.bmj.com/ebm/2015/01/21/primary-care-corner-with-geoffrey-modest-md-community-wide-rural-cardiac-health-program/​ ). Devoting 1/10 the $$ from lung cancer screening to such initiatives would likely have much more dramatic population benefits.

So, this adds to my concerns about the appropriateness of the LDCT screening. In some circumstances, medicalizing (getting CT scans) a social issue (smoking) can lead to undercutting the real social message (smoking is really bad for you, for a lot of reasons beyond lung cancer). As another example where medicalizing may undercut the important public health message, there was a recent study showing that patients put on statins tend to stop doing the lifestyle changes (diet, exercise, weight loss) since they were taking a medication which was so effective in lowering the cholesterol.​..

Primary Care Corner with Geoffrey Modest MD: Medicare and lung CT screening of smokers

18 Feb, 15 | by EBM

By: Dr. Geoffrey Modest 

Medicare just came out with their formal decision on low dose CT scans (LDCT) for lung cancer screening in smokers (see here)​. These are somewhat between the USPSTF recommendations, recommending screening 55-80 year olds annually, and the actual criteria for the National Lung Screening Trial (NSLT) which was only 3 annual screens for the age range of 55-74 (and was the study upon which USPSTF based their recommendations).

lung

For Medicare, eligibility criteria are:

  • Age 55 – 77 years;
  • Asymptomatic (no signs or symptoms of lung cancer);
  • Tobacco smoking history of at least 30 pack-years (one pack-year = smoking one pack per day for one year; 1 pack = 20 cigarettes);
  • Current smoker or one who has quit smoking within the last 15 years; and
  • Receives a written order for LDCT lung cancer screening that meets the following criteria:
    • For the initial LDCT lung cancer screening service:  a beneficiary must receive a written order for LDCT lung cancer screening during a lung cancer screening counseling and shared decision making visit, furnished by a physician or qualified non-physician practitioner (physician assistant, nurse practitioner, or clinical nurse specialist).  A lung cancer screening counseling and shared decision making visit includes the following elements (and is appropriately documented in the beneficiary’s medical records):
      • Determination of beneficiary eligibility including age, absence of signs or symptoms of lung cancer, a specific calculation of cigarette smoking pack-years; and if a former smoker, the number of years since quitting;
      • Shared decision making, including the use of one or more decision aids, to include benefits and harms of screening, follow-up diagnostic testing, over-diagnosis, false positive rate, and total radiation exposure;
      • Counseling on the importance of adherence to annual lung cancer LDCT screening, impact of comorbidities and ability or willingness to undergo diagnosis and treatment;
      • Counseling on the importance of maintaining cigarette smoking abstinence if former smoker; or the importance of smoking cessation if current smoker and, if appropriate, furnishing of information about tobacco cessation interventions; and
      • If appropriate, the furnishing of a written order for lung cancer screening with LDCT.
    • For subsequent LDCT lung cancer screenings:  the beneficiary must receive a written order for LDCT lung cancer screening, which may be furnished during any appropriate visit with a physician or qualified non-physician practitioner. If a physician or qualified non-physician practitioner elects to provide a lung cancer screening counseling and shared decision making visit for subsequent lung cancer screenings with LDCT, the visit must meet the criteria described above for a counseling and shared decision making visit.
    • Written orders for both initial and subsequent LDCT lung cancer screenings must contain the following information, which must also be appropriately documented in the beneficiary’s medical records:
      • Beneficiary date of birth;
      • Actual pack – year smoking history (number);
      • Current smoking status, and for former smokers, the number of years since quitting smoking;
      • Statement that the beneficiary is asymptomatic (no signs or symptoms of lung cancer); and
      • National Provider Identifier (NPI) of the ordering practitioner.

So, the decision has arrived. As noted in my prior blogs, there are several very important issues. The extent of radiation exposure by doing the LDCT scans is perhaps the most important, and there are a few salient points with the Medicare recommendation:

​–patients could get up to 22 annual LDCTs done, if they continue to smoke or stop after age 62.

–in NSLT, the average individual’s radiation exposure was essentially the same as with the regular (high-dose) CT, when one adds in the additional radiation from follow-up studies from positive LDCTs (the vast majority of which were false positives)

the NSLT was mathematically projected to create one cancer death per 2500 screened in just 3 years!!  Medicare only noted that there is a radiation risk but felt that we needed to study/quantify the effects of the radiation exposure.

See my prior blog for more detailed critique.

Primary Care Corner with Geoffrey Modest MD: USPSTF Lung cancer screening revisited

24 Jan, 15 | by EBM

By: Dr. Geoffrey Modest 

There has been more chatter in the medical literature about the pluses and minuses of routine low-dose CT screening for lung cancer in smokers. Given that the USPSTF endorsed this, I decided to post again an old blog analyzing the study on which the recommendations were based (National Lung Screening Trial, NSLT) and critique of the recommendations, as below. A recent article in the NY Times (I believe) noted that Medicare would not cover until 2015, which is later than expected, suggesting they are rethinking this recommendation??? I added some specific issues with the recommendation:

  1. The USPSTF extended the recommendation from the age range of 55-74 in NSLT​to 55-80 year olds, presumably because of mathematical modeling.
  2. the USPSTF extended the interval of screening from 3 years in NSLT to all who smoked 30 pack-years and currently smoke or quit within the  past 15 years (i.e., with the potential that someone could get 25 annual LDCTs if they continued to smoke, with the attendant high dose follow-up scans in the large number who will have false positives), with the likelihood of creating additional cancers from radiation exposure (the NSLT was projected to create one cancer death per 2500 screened in just 3 years!!).
  3. The basis of the USPSTF extension of screening from 3 to up to 25 years was that in the 3 years of NSLT, they kept picking up new cancers. BUT, if you look at the year-by-year pickup, there was a pretty dramatic drop off by year 3 (goes from positive results of 27.3% in year 1 to 27.9% in year 2, then drops to 16.8% in year 3), which I think makes the potential 25 year annual screening suggestion a tad iffy…

___

This is from the Boston Globe today (December 2013):

Current cigarette smokers ages 55 to 80 who have smoked the equivalent of a pack a day for 30 years, or people who had those same smoking habits within the past 15 years, should be screened, advised the US Preventive Services Task Force, a group created by Congress. Under the federal health law, insurance companies will have to begin covering the $300 to $400 cost of the screening by the end of 2014.

 

Below is a review of the most important trial (National Lung Screening Trial):

Recent recommendations by the Am College of Chest Physicians to perform low-dose CT screening of smokers (see DOI: 10.1378/chest.12-2377). These recommendations parallel the interim recommendations of the American Lung Association.

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 (i.e., possible that these new treatments could change the risk/benefit analysis of screening in the future).  of note, the arena of 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. [And, as an addition to this blog, a fundamental shift by the cigarette companies to focus on developing and advertising e-cigarettes]

Cancer prevention: attempts to prevent cancer in smokers mostly with different antioxidants or anti-inflammatories (e.g. b-carotene, aspirin, selenium, inhaled steroids, vitamin 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: prior studies have not shown clinical benefit with either CXR of sputum cytology screening.

Low-dose CT screening (LDCT) has found lots of nodules identified in 10-50% of smokers. Here is the current LDCT study by the National Lung Screening Trial Research Team (NSLT)—(see DOI: 10.1056/NEJMoa1102873).

Details:

–screened 27K high risk patients with LDCT and 27K with CXR yearly for 3 years and followed another 3.5 yrs

— found 25% with positive screen on LDCT and 7% by CXR,

–lung cancer: 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 LDCT 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 (from NSLT):  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 (e.g., as with the American urology assn and PSA screening).  We may want to wait for a more neutral group (e.g. 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 by screening), 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).

 

 

 

Primary Care Corner with Dr. Geoffrey Modest: Time to screen for lung cancer with CT scanning?

2 Jan, 14 | by EBM

News on New Years Eve Day:

Directly from USPSTF – here is the URL for their formal position: http://www.uspreventiveservicestaskforce.org/uspstf13/lungcan/lungcanfinalrs.htm

and

this is from the Boston Globe:

“Current cigarette smokers ages 55 to 80 who have smoked the equivalent of a pack a day for 30 years, or people who had those same smoking habits within the past 15 years, should be screened, advised the US Preventive Services Task Force, a group created by Congress. Under the federal health law, insurance companies will have to begin covering the $300 to $400 cost of the screening by the end of 2014.”

Here for easy reference is my blog post from 6 months ago on the subject, with review of the most important trial (National Lung Screening Trial):

Recent recommendations by the Am College of Chest Physicians to perform low-dose CT screening of smokers (see DOI: 10.1378/chest.12-2377). these recommendations parallel the interim recommendations of the American Lung Association from 2012

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 (doi 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).

–i spoke with radiology at BMC (in fact, one of the participants involved in designing and analyzing NLST) who said:

–not ready to do screening yet. need to develop protocols. but will be a low dose CT, probably no more than the 2mSv (as point of reference: CXR is 5-10x less than that).   more later….

geoff

Primary Care Corner with Geoffrey Modest: Lung Cancer Screening with low-dose CT–ready for prime time?

16 Jul, 13 | by EBM

Recent recommendations by the Am College of Chest Physicians to perform low-dose CT screening of smokers (see DOI: 10.1378/chest.12-2377).

these recommendations parallel the interim recommendations of the American Lung Association

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 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.

–i spoke with radiology at a local major hospital (in fact, one of the participants involved in designing and analyzing NLST) who said:

–not ready to do screening yet. need to develop protocols. but will be a low dose CT, probably no more than the 2mSv (as point of reference: CXR is 5-10x less than that).

geoff

Universal screening with computed tomography for lung cancer? Finally a randomized trial…but what to do??

11 Jul, 11 | by EBM

Expert opinion and observational studies have favored lung cancer screening but trials (of plain xrays) have not shown benefit, until now. For years, many have been asking for a randomized trial. Now that the results of the (US) National Lung Screening Trial (NSLT) have been published, it reminds me of the admonition to “be careful what you ask for, you just might get it.”

The randomized trial compared three screenings, either low dose CT scans or plain chest radiographs and adherence to the screening protocol was >90%.  How to address a positive test was left to clinicians outside the trial. It enrolled 53 454 participants age 55-74, who smoked at least 30 pack-years currently or who had quit in the past 15 years, and had not had lung cancer or a recent chest CT scan, hemoptysis or unexplained weight loss. The authors estimate only 7% of US current or former smokers would meet these criteria. So the study results do NOT apply to 93% of smokers. One wonders though, to whom they will be applied (paying customers?).

What were the results? Amazingly, despite the publication source (New England Journal of Medicine, http://bit.ly/qKs6Lq) and widely agreed upon reporting guidelines, the main results are presented as relative reductions, making them seem large (a 20% decrease in death from lung cancer). I don’t mean to minimize though, just to be clear—it is important that there was a reduction, and more lung cancers were diagnosed in the (low dose) CT group, which had fewer lung cancer deaths. The absolute reduction was the difference between 356 lung cancer deaths in 144,103 person-years in the CT group and 443/143,368 in the plain x-ray group. The absolute risk of lung cancer death among those screened at least once was 1.3% in the CT group, 1.6% in the x-ray group, an absolute risk reduction of 0.312%, for a number needed to screen with 3 tests of 320 to prevent 1 lung cancer death over 7 years. Overall mortality was also reduced (by 0.5%). Complications of evaluation of a positive test were 1.4% in the CT group, 1.6% in the x-ray group.
The vast majority of positive tests were false positives (96% in the CT group, 95% in the x-ray group).

None of this addresses long term cumulative population harms from radiation exposure or any impact on likelihood of quitting smoking.

What to do? Many may reach different conclusions depending on the presentation of the results. Others will take these results and then add patient values and preferences. Others still may wish to wait to see the cost effectiveness analyses.

What will you do? You now have the evidence…

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