DFCI's Jacob Sands Discusses All Things Considered About Lung Cancer Screening

Sands ,a medical oncologist who specializes in lung cancer, says the false discovery has been misconstruted as a false positive rate. He also makes a case for early detection and new USPSTF as working to correct disparities.

The uptake of lung-cancer screening has been low even with the advent of low-dose CT scans and the United States Preventive Services Task Force issuing a recommendation for it in 2013. The studies vary but most suggest that less than 20% of those who are eligible have been screened. In March, the task force revisited that recommendation, lowering the age when screening might get started from 55 to 50 and the number of “pack years” from 30 to 20. A pack year is the equivalent of smoking one pack of cigarettes per day for a year and is a measure of a person’s exposure to smoking.

Managed Healthcare Executive® Senior Editor Peter Wehrwein interview Jacob Sands, M.D., a medical oncologist at the Dana-Farber Cancer Institute who specializes in lung cancer. Sands is a volunteer spokesman for the American Lung Associatoin and a strong advocate for lung cancer screening. He was the lead author of an article published in the Journal of Thoracic Oncology in January titled, “Lung Screening Benefits and Challenges: A Review of the Data and Outline for Implementation,” which includes a one-page shared decision guide that Sands and his co-authors hope physicians will use in their discussions with patinets.

Here are excerpts from the transcript of the interview with Sands. They have been edited for clarity and length.

On why the uptake of lung cancer screening is so low

The brief answer is, we're not offering them screening, we're not really setting up programs throughout the country that are robust and approaching patients and really informing them about the decision. I've seen a storyline saying that patients don't want to be screened, their patients aren't getting screened. And that is a direct reflection of the fact that they're not being advised for this.

It's hard to believe — and we'll go through some of the data I know — but it is hard to believe that there are more people willing to go through a colonoscopy for colon cancer screening than a CAT scan for lung cancer screening.That makes no sense. So if people are willing to go through a colonoscopy, I'm sure they're willing to get a CAT scan.

I'll say that that (what it) really means we're doing a very poor job of offering people lung screening, and we're doing a poor job of conveying to patients their real risk and benefit of doing lung screening. And furthermore, we're doing a bad job conveying to primary care doctors how important this is.

On the false positive rate

For example, a storyline that's been out there for a long time is that the false positive rate is very, very high. And numbers like 95% have been discussed, and that is factually incorrect. And what that comes from is the original publication from NLST (National Lung Screening Trial).

This was the biggest (lung) screening trial that's been done. More than 53,000 patients were enrolled. It was a trial that was stopped early because of a 20% lung-cancer mortality benefit. It did show an all- cause mortality benefit as well in the screening group. But in that trial, in the abstract, it of the people who had a positive scan, it's in the 90s percent, of being a false positive and that has been misunderstood to be the false positive rate, which is a number we talk about a lot. What a false positive rate that high would suggest is that we don't know what to do with the result at all. But, in fact, that's not a false positive rate. That's a false discovery rate. False discovery rate is not something that is typically discussed within lung screening. But that description people completely misunderstood.

In the NLST, at that time, a four-millimeter nodule was considered positive. And so yes, the false positive rate was about 24%. But now with current guidelines [which increased the threshold for positive nodule to tsix millimeters] the first year of screening, so there's no prior screening and you can't say whether a nodule changed in size, the false positive rate is about 13%. And in following years, it's about 5%.

On radiation exposure

It is really minimal. I mean, the amount of radiation exposure in most programs is around or even less than one millisievert, and to put that into context, living in Denver, the exposure is about 12 per year. And no one says, ‘Oh, you shouldn't live at high altitude, you have a higher risk of cancer.’ Now, I will acknowledge that 12 millisieverts delivered over the course of an entire year, as opposed to one delivered within minutes is a different kind of a thing. But radiation oncologists, they wear a little badge that detects how much radiation they've been exposed to. And they can get up to 50 (millisieverts) in a year. People come into the ER and get CAT scans all the time. I acknowledge, it's a different thing, getting a therapeutic test versus screening test. But, essentially, radiation committees have acknowledged that this is really negligible amount of radiation. On top of that, when you're talking about the effects of radiation and causing cancer, that's really about 20 to 30 years later that that develops. So in somebody with a significant smoking history, who's 60 years old, who has a high likelihood of getting a lung cancer now that is life threatening, we're saying well, when they're 80 or 90, they could possibly get a cancer from radiation — it really is a nonissue.

What I'm saying is that the effects of radiation with such small radiation doses that it is negligible to begin with, and second, that even if they were to develop a cancer from it, which is a very small part number of patients, even with with them, that would be a small number of patients. And it's much later within life at a time frame at a time point where it's really much less of a concern, quite frankly. So this is really a nonissue. But I think the term radiation is scary to patients, and even when I'm counseling patients about them getting radiation to treat their cancer, you know, that's something that patients are worried about, because that word radiation is scary to people. So this is something that really requires primary care doctors and other physicians really explaining to patients the risks and benefits of this and false positive rate.

On finding lung cancer at an earlier stage

In a screening population, there's a very high likelihood that that would be an early stage diagnosis at a time when it is where the goal is to cure it versus outside of a lung screening program, the majority end up with stage four disease and then we're using things like immunotherapy and chemotherapy, and to some extent targeted treatments, although in a higher smoking population, there's fewer of those targeted options. But then it's not cure. And then it's palliative treatment.

If we look at just the screening group, so people who got a CAT scan, who then develop lung cancer, those that were screened detected, 70% of them were early-stage diagnosis So early stage diagnosis when it's most curable.

In the screening group when they had a nonscreen detected lung cancer — so these are in the years, by and large, the years where they weren't getting scans anymore — 64% of patients in those follow-up up years that get lung cancer, in the screening group, had a late-stage diagnosis. So if they were fortunate enough to have their lung cancer develop in those three years of screening, 70% of them early stage, in the follow-up years, 64% were late-stage diagnosis.

So the analogy I used is that we say seatbelts save lives — I'm not saying wearing a seatbelt is the same thing as a CAT scan — but if we were say, ‘Hey, we're gonna study seatbelts, and we're gonna say, hey, for three years, this group is going to wear a seatbelt every time they drive. But then for the next seven years, they're not going to wear a seatbelt. And we're going to see what's the effect?’ Well, there are going to be people that die in car accidents in seven years that wouldn't have had they been wearing a seatbelt.

On the variation in screening rates at different centers

There are a handful that are screening more than 70% of patients who qualify are getting scans, and others were nobody's getting scammed. I don't think that this represents patients being resistant, it represents institutions, and systems that are not adequately conveying to patients, the real risk and benefit. And I think, understandably, a lot of that comes from having seen mixed messages about this.

On the Nelson trial, a lung cancer screening trial conducted in Europe

The Nelson trial, which was the big one out of Europe, which has a smaller patient population, but still thousands of patients randomized to getting the CAT scan or not getting CAT scans. So the more realistic what what's happening for general population. In that trial, there were four time points over the 10 years, that patients ended up getting the scan. So they got a scan at baseline, they got a scan at year one. But then there were there were gaps. And in some cases a year and a half or two years from from when they had gotten the prior scan, but over 10 years. In that trial, the lung cancer mortality benefit was 24%. So it was a bit higher (the NLST). And among the women, which really represented a fraction of the patients, it was really dramatically higher, even.

On cost effectiveness

This is a really complex topic. And obviously, there are a lot of moving parts to really adequately get to a specific number on this. But the cost of doing the number of scans within a big screening program is not minimal. I mean, these are real costs. At the same time, the cost of treating stage-four disease has gotten astronomically more expensive than it used to be. You know, there, there was a cost effectiveness analysis done after the NLST and the I.C.E.R. (incremental cost effectiveness ratio) and came to about $50,000. But that is a way over estimation for various factors. One is in that NLST four millimeters, as we've discussed, was considered positive. So there were more follow up scans done for than there are nowadays. And so there's a substantial drop in the number of those. And on top of just nodule size, ground glass opacity, which on a scan looks kind of like a spiderweb, we know to be very low risk. And so when there's not a solid component, now, it takes a really pretty big size, for there to be any follow up. Otherwise, it's a once a year scan. So I was really dropped the number of scans. That has improved the cost effectiveness by the reduced number of scans.

When you look at the cost effectiveness of various treatments that we utilize, and I'm not minimizing them, I'm a medical oncologist, and these treatments are changing people's lives. And I speak to that frequently. But the cost effectiveness for lung screening is is dramatically better than a lot of these others.

On screening increasing quit rates

Within screening programs, people are quitting smoking, having more success, quitting smoking, then then outside of programs. And this seems to be beyond even just the population going through. But I think in large part, this takes an intellectual truth and makes it emotionally true for people as well. They know that by smoking, health problems can happen. But when they're waiting to get the results of a test to find out if they have lung cancer that emotionally links them in. And I think that one, just the support of a screening program that has smoking cessation and such, but to the emotional experience for patients waiting to find out what the result of that scan is, and understanding their real potential implications. So people are more successful at quitting smoking within a lung screening program, which of course has cost impact later on to the reducing their risk of other kinds of health problems as well.

On the stigma of smoking

That's a big problem. I'm very much of the belief that everyone's life is worth saving. Every lung cancer is worth diagnosing, early, as certainly giving people the opportunity for that. A lot of people started smoking. I mean, I take care of a lot of patients who smoke started smoking back when it was considered cool. And, and it is really hard to quit. This is addictive. And it's not just a matter of willpower. It's hard. And people really struggle with that. And so there are people that are really working to do that, that and we should be supporting them. There are people that actually did quit, they did quit, but they're still at high risk for getting lung cancer, and we should diagnose those.

We had a whole campaign where we demonized smoking to try to stop it. And in the process, unfortunately, I think we've demonized smokers. And people feel a lot of guilt. And I think we need to support them through that. Because guilt also doesn't really help people live their lives better, either. So I would love to see the the overall community go back to loving the people, even if we're really trying to reduce smoking.

On the consequences of March 2021 update to the USPSTF recommendations

By dropping the USPSTF guidelines, from age 55 to 50, and pack years from 30 to 20 pack years, we're really capturing a whole bunch more people that have have a very high risk of developing lung cancer. But on top of that, when you look at subgroups — black men, for example, (they) have a higher risk of developing lung cancer at a lower smoking rate. So this now involves a population of people that didn't qualify before, but in some cases had a higher risk of developing lung cancer than some of the people who already did qualify. So it does potentially reduce baked-in disparities that were present within the the screening guidelines. This is a huge win. This is something that is really being celebrated within the lung screening community. It does almost double the population of people who qualify for lung screening based upon those guidelines.