Dana-Farber’s Sands: More Lung Screening Would Have Greatest Impact on Cancer Mortality

Thoracic medical oncologist Jacob Sands, MD, leads the small cell lung cancer research program at Dana-Farber Cancer Institute, where he joined the Lowe Center for Thoracic Oncology in 2017. Sands is also an instructor of medicine at Harvard Medical School and a member of the guidelines committees for small cell lung cancer and lung screening for the National Comprehensive Cancer Network (NCCN), which makes recommendations that guide treatment decisions and payer coverage. Sands speaks frequently on aspects of lung cancer with both the public and with patient advocacy organizations. Here, The American Journal of Managed Care (AJMC®) spoke with Sands about the need for more patients who meet the criteria for lung screening to take advantage of this opportunity to catch cancer before it reaches an advanced stage.

AJMC®: It’s widely considered that there's no effective screening test for early stage small cell lung cancer. Can you talk about why screening for small cell lung cancer is so challenging?

Sands: Well, the first thing to point out is that lung screening is really our opportunity to have the biggest impact on any cancer mortality. That is, all cancer mortality can be most impacted by lung screening, and that's because lung cancer is responsible for so many the cancer deaths in the United States and abroad. But in the US, about 25% of all cancer deaths are lung cancer deaths.

Now, small cell lung cancer is generally much more rapidly progressive than non-small cell lung cancer. So, lung screening is particularly effective for diagnosing non-small cell lung cancer at very early stages. But because small cell lung cancer grows so quickly, it does tend to be [diagnosed] at a later stage. Now, that being said, in the numbers that exist it's still around 50% that end up being [at a] limited stage at time of diagnosis with small cell lung cancer. That’s still a meaningful shift. But non-small cell lung cancer is really where lung screening has the greatest impact. So, lung screening is still overwhelmingly important. Those that end up with small cell lung cancer almost across the board qualify for lung screening. And so hopefully, these individuals are getting lung screening; [however], this is still something we're not doing at a level that it should be done. The numbers of people getting screened [compared with] those who qualify are still probably in the range of less than 10%. And so, this is some of the most important work going on in in cancer care.

AJMC®: What sort of innovations would you like to see to help improve screening, whether it’s simply increasing the number of people being screened, improving the accuracy, or being able to detect something like small cell lung cancer in a timely fashion to help prevent significant morbidity in a particular patient?

Sands: Right now, the most important thing that can be done is just doing lung screening for all people who qualify. This is approved, it's covered, and there's really no reason that lung screening shouldn't be happening. As I said, that would shift the diagnosis to more limited stage than what we're seeing currently. If we're looking into the research [area], small cell lung cancer does have more shed than then other diagnoses; so, maybe a blood-based test would have more efficacy within small cell lung cancer. … This is looking forward and imagining what other innovations might happen. But I just can't stress enough how important lung screening is—it’s already approved; it’s already covered. And this is really our greatest opportunity to impact mortality from small cell lung cancer along with non-small cell lung cancer.

AJMC®: Are there any existing datasets that might be useful to help identify people who should be screened and let them know that they should be screened for lung cancer?

Sands: This is some interesting work now—looking at risk modeling. And of course, significant smoking history is the greatest risk factor, particularly for small cell lung cancer. When we [extend] this to all of lung cancer, there are other factors; there are some groups of individuals that have a higher risk of dying from lung cancer even at a lower smoking history. And so, risk modeling is part of the next step in defining who should be screened. There are data that exist more in retrospective than in prospective studies, but they are quite compelling. And then we look at studies, mostly studies from Asia—or if it's in the US, looking at people that self-identify as Asian—and there are some studies to suggest that there may be benefit in groups of people that never smoked, particularly in Asian subsets. But there’s still a lot to look at.

AJMC®: Can you discuss the impact that the COVID pandemic has had on the screening, diagnosis, and treatment of small cell lung cancer?

Sands: It’s had a huge impact, and most likely, it will be seen as affecting different regions in different ways. Here in Boston, we were in the first wave of COIVD; I don't think the public realizes how much happened within hospitals to be able to handle the initial wave that happened here in Massachusetts. We drastically increased our ICU capacity to handle the number of people that required an ICU-level of care. And with that initial wave, we still didn't know enough about how this was transmitted. We didn't have the full appreciation, I think for the respiratory transmission, I remember very early on masks were not in widespread use. And given that we didn't really know, there was a real shutdown to a lot of other services on top of just the strain within the health care system.

As we've gotten further along, and other waves have come, even though there's been a strain in taking care of patients [we’ve gained] a greater understanding of how this has transmitted. I think we've been able to keep certain services open that were stopped at one point due to concerns of how it is transmitted. So, within the [cancer] screening community, we recognized from the very beginning how important it was to continue to do screening. And outside of that initial pause, I think for the most part, as screening programs were reinitiated, they have continued through some of these other [COVID] surges that have followed.

Now I saw a patient in clinic recently who had had missed screening last year because of the pandemic and now has a stage IV diagnosis, with non-small cell, when there was a much higher likelihood of it being an early stage and curable diagnosis had screening happen. So, there absolutely are individuals that have ended up with metastatic disease that could have been caught earlier. The extent of this, I don't think will be known for a couple years. But on top of this, as I've said, the number of patients that are getting lung screening, that qualify is still quite low to begin with. So, we've had our own pandemic of sorts, in the lack of screening, despite the technology existing the proof being there of the benefits, and the coverage that frankly allows for all patients to get that screening. So, there's a lot of work we need to do. And this pandemic did really make that harder in that short term time frame of people not getting screened. But I think the bigger thing is that it may have delayed the building of programs and the infrastructure development to allow for increased lung screening to happen nationally.

AJMC®: I'd like to ask you about staging of small cell lung cancer. Can you go into some depth about how this disease is staged? I understand there are different methodologies for how staging might be described. Can you go into some detail about that, and the prognosis for different types of staged disease?

Sands: Non-small cell lung cancer along with many other cancers are classified as stage I, II, III, IV, and small cell lung cancer does have that staging; certainly, within research studies and an academic data evaluation, the staging is utilized. Clinically limited stage and extensive stage are widely used, because it really comes down to how you treat patients. In non-small cell lung cancer, the stage I, II, III, and IV has implications in in how you treat patients. It’s a bit more complex thansmall cell lung cancer. In most cases staging for small cell lung cancer determine whether treatment with combination chemo and radiation with curative intent is indicated or if systemic therapy as palliative treatment is indicated. I guess I should add, though, that small cell lung cancer patients may undergo surgical resection patients if it's very early stage, but this is fairly uncommon. And to that point when we talk about those patients, we don't just say someone with limited stage disease, but we point out that it was just a lung nodule or give an indicator as to being such early stage. Due to this, limited stage and extensive stage are more commonly used in clinical practice as far as clinical decision making. Now, [with] limited stage the goal is cure. [These are] essentially patients who have disease that fits within a radiation field. As I mentioned, there are some patients with very early stage that end up with surgical resection So limited stage treatment is curative intent. But there is still a high risk for recurrence in these individuals. I think the big cut off in staging is essentially whether you're treating with a goal of cure, and so the intention of the treatment itself is the indicator.

AJMC®: Can you comment on the typical patient presentation of someone who might have extensive stage cancer and perhaps discuss the aggressive nature of this cancer—and the need to rapidly treat it?

Sands: So, almost everyone with small cell lung cancer has an extensive smoking history, and many patients have COPD due to smoking as well. There are rare instances of individuals with a small cell cancer diagnosis without a smoking history—I’ll just highlight that it's very important for those individuals to get genomic testing, because there are people where the diagnosis can look like small cell, but it's more of a neuroendocrine, non-small cell lung cancer. And just the biopsy itself looks like small cell. So, without a smoking history, it’s important to get genomic testing. And I suppose I've started out answering your question about what commonly looks like by saying the rare exception, because it's just so important to highlight.

Most patients do have a have an extensive smoking history and have COPD. As to the aggressive nature of it, that's true. small cell lung cancer tends to grow rapidly, which is why even in a screening program, many patients still have extensive stage disease at the time of diagnosis. Now, some people come in with significant symptoms. In fact, this is a diagnosis where patients will be admitted to the hospital with shortness of breath or pain. That’s what leads to the diagnosis of small cell. Often, we end up treating patients in the hospital with their initial therapy. Now, it does tend to grow rapidly, but at the same time, it tends to respond to treatment rapidly. So fortunately, even if patients are admitted to the hospital with severe shortness of breath, when they get their treatment, that shortness of breath may drastically improve. And so, it's not uncommon to see someone come in with a new oxygen requirement that then when initiating their treatment improves to where they're then able to leave the hospital off oxygen, it can be that rapid.

AJMC®: As you are a member of the small cell lung cancer NCCN guideline committee, what is your process for staying up to date on new information that becomes available in this disease area? How do you keep up with all the manuscripts and posters and presentations for this disease?

Sands: It's a lot of fun being a part of that group; these are very proactive individuals—as we see data become available, we have discussions as a group as to how that might impact the guideline recommendations. We also meet frequently to go over data, and we have opportunities to submit any considerations for adjustment to the guidelines, with the input of everybody at our institutions. So as a representative, it's my duty to make sure that my colleagues across the multidisciplinary spectrum have an opportunity to voice any thoughts they have, and then to bring that forward to the committee. Each of us on the committee does that. And we discuss each of those points. With the guidelines, I think one of the challenges is that we're making broad kind of a broad statement. I wanted to say recommendations, but it's not necessarily recommendations. It's a broad list of what would be reasonable standard of care treatment. And there may be exceptions, or there may be unusual circumstances that are something outside of those guidelines. But we want to make sure we're capturing what is reasonable treatment for each of these individuals to provide some structure, as well as a framework for insurance companies, for other panels for people outside of even beyond the physician teams to essentially say, what would be reasonable for physicians to do in these general circumstances.

AJMC®: In the release of new drugs coming out, we often see randomized clinical trials, but there are some flaws to randomized clinical trials. They perhaps don't include every population that you might see in a clinic. And so those trials might not necessarily be applicable to every patient. How do you and perhaps the guideline committee evaluate things like real-world evidence, where we might see whether it be a retrospective or prospective trial, looking at, outcomes that matter, things like overall survival or progression free survival? Are you taking studies like this into account when you're making decisions?

Sands: Well, we take all data into account. It certainly is something to consider—it obviously doesn't carry the same weight as a randomized controlled trial. And I think this gets back to what I was saying about the guidelines being generally applicable to the broad population without diving into making guidelines for particularly rare or outside the box circumstances. And so, the guidelines are just that they're guidelines, but the treating physician must consider: what is the true risk and benefit to any individual patients in each individual circumstance?

AJMC®: What are the most promising developments that you see on the horizon? You know, maybe in the next two to three years for small cell lung cancer,

Sands: The most exciting thing, to me, is how much research is happening in small cell and how many different novel therapies are in trials. We're seeing such an explosion of new options being tested within small cell lung cancer, and I find that very exciting. That is an incredible trend that's going on—the subtyping of small cell lung cancer that has been proposed, both out of [Dr] Charlie Rudin’s lab at Memorial Sloan Kettering, and [Dr] Lauren Byers’ lab out of MD Anderson. These are 2 very similar models for subtyping. This may provide a new framework upon which we further evaluate these different novel therapies. And it may be that there are subgroups that benefit a lot more from each of these drugs than others. If that does results in more prospective work, that would be an exciting new paradigm.

AJMC®: Are there any closing thoughts that you'd like to provide to your colleagues or to our audience, in small cell lung cancer?

Sands: Well, I just want to underline where we started: for all lung cancer, lung screening really has the most dramatic impact on cancer mortality. We generally talk about that for non-small cell lung cancer. But small cell lung cancer absolutely benefits from that. And the patients that end up with small cell lung cancer are individuals that generally qualify for screening, which includes people that are at high risk of getting non-small cell lung cancer as well. One of the important parts of my work is advancing lung screening as a way of really impacting cancer mortality, and as somebody who treats patients with small cell lung cancer and non-small cell lung cancer in clinic, it's always distressing when I meet somebody who qualified for lung screening with cancer who wasn’t screened—and now I am trying to control metastatic disease. So, anything we can do to advance lung screening is really going to have the biggest impact on lung cancer mortality.