Understanding the Changing Landscape of NSCLC in the US

Dr. Melinda Hsu, thoracic oncologist and cancer survivorship director at UH Simon Cancer Center, shares insights on the evolving landscape of non–small cell lung cancer—highlighting challenges in early detection, treatment tolerability, and survivorship, while emphasizing the need for equitable access, personalized care, and continued innovation in second-line therapies.

Melinda Hsu, MD: My name is Melinda Hsu. I'm a thoracic medical oncologist at University Hospital (UH) Simon Cancer Center, and an assistant professor of medicine at Case Western Reserve University in Cleveland, Ohio. I'm also the director of cancer survivorship at our Simon Cancer Center.

What are the most pressing clinical and societal burdens associated with non–small cell lung cancer (NSCLC) today, particularly in the advanced/metastatic setting?

Dr Hsu: Patients with non–small cell lung cancer are a very unique patient population. We know from older studies—not necessarily done in the US but done in other countries—that patients with non–small cell lung cancer are less likely to go back to work compared to patients with other types of cancers, particularly in the advanced and metastatic setting. This may be, in part, because in the past patients were diagnosed in the later stages and so treatments may have been harder, or it may also have been associated with the fact that patients with non–small cell lung cancer may have different comorbidities.

Finally, the treatments for earlier-stage non–small cell lung cancer have different morbidities. For example, having part of your lung removed or an entire lung cut out can make it hard for people to go back to work. But, in general, we do need more research and more focus in terms of things like financial toxicity and ability to return to work for our patients with non–small cell lung cancer.

[Additionally, we need] some thoughts around the amount of time that our patients with non–small cell lung cancer are spending both in the clinics with us as well as all of that other time that's involved with having cancer, whether that's driving to their appointments, getting scans and imaging, getting treatments or infusions, that type of thing.

We know that with non–small cell lung cancer, patients who have a lower socioeconomic status or are not employed have poorer outcomes. We don't know why, but I think that there is a real opportunity to understand and improve on that.

What advances have most significantly reshaped how you approach treatment selection—particularly regarding molecular profiling, immunotherapy, or combination regimens?

Dr Hsu: That's a great question. What's really exciting in non–small cell lung cancer is our ability to provide precision medicine to as many of our patients as we can. Over the last couple of decades, there have been amazing advances in terms of molecular profiling of people with non–small cell lung cancer.

Originally, treatment options started only in the advanced or metastatic setting, but now there are more and more data coming out that show that focusing and treating appropriately based on the molecular profile in the earlier stages also improves outcomes long term. It's really important for all of our patients with non–small cell lung cancer to have a full molecular profile done or next-generation sequencing (NGS) of their cancer tumor. [It's also important] to have PD-L1 testing done, which allows us to predict an expected response or not to immunotherapy. Those two types of biomarker testing have completely changed how we approach the proper treatment for our patients with all stages of non–small cell lung cancer at this point.

How do you balance treatment efficacy with tolerability in patients who may have comorbidities or be ineligible for certain therapies?

Dr Hsu: That is maybe one of the most important questions at the end of the day. Obviously, if our patients are diagnosed at an early stage, we are trying to cure their cancer. Unfortunately, for our patients who are found to have non–small cell lung cancer at stage IV or metastatic disease, we can't cure their cancer, but we are always trying to improve their quality of life while also prolonging their life. That's why it's so important to look at tolerability and patient comorbidities.

No patient is exactly the same as anyone else. While we can't yet predict what side effects patients will have, depending on their comorbidities, sometimes we can tailor their treatments to avoid worsening some underlying chronic condition they may already have.

It's important to have these conversations with patients, what side effects may look like, which side effects may actually be permanent even if we stop the treatment, and what that means in terms of their quality of life and their ability to live their life for how they want to. Every patient has their specific goals for treating their cancer. Obviously, we want the treatments to be efficacious, but there is always that balance in terms of what's important to patients and what they value.

Where do you see the most urgent unmet needs in early detection and diagnosis of NSCLC? Are there strategies or technologies you feel are underutilized?

Hsu: With the advent of lung cancer screening, we now have the ability to detect all types of lung cancer on the earlier side for anybody who has had a certain smoking history. Unfortunately, uptake of lung cancer screening has not been as widespread as we've all hoped that it would be.

Here at UH, we've had a pretty good uptake over the years, especially after we had the hiring of a couple of lung cancer screening navigators. We saw an exponential increase in the number of folks who not only got their lung cancer screening scans but also who came back and got their follow-up scans, because it's not just a one-time scan. Something like navigators to help patients navigate not only the system but also understand the results and when or if they need to come back—but it’s really when—is imperative to increase that early detection rate.

We also know that there are plenty of patients who develop non–small cell lung cancer who have never smoked in their lives or don't meet the current criteria based off of the amount of smoking that they've done. There are no guidelines currently for screening in lung cancer in those patients. That is definitely an unmet need, particularly because that population is growing in the younger population. We're finding more and more younger folks in the US who have never smoked and who are developing lung cancer.

Finally, as we have more and more people who are using vaping or e-cigarettes and that type of thing, there are also no guidelines around lung cancer screening [for those individuals]. We all have concerns that these folks are also at risk for developing lung cancer, but we just don't have that evidence yet.

Despite recent therapeutic innovations, where do you see the greatest gaps in treatment—either due to limited options, resistance mechanisms, or lack of long-term benefit?

Dr Hsu: That's a really good question. Obviously, we are nowhere near where we'd like to be in non–small cell lung cancer, but the field has made immense improvement.

My personal research area is survivorship in lung cancer. If you were trying to talk about survivorship in lung cancer 10 or 15 years ago, that just wasn't a thing. Nobody even mentioned it. We are able to talk about it now, not only in patients with early-stage cancers, but even in our patients with metastatic cancers.

That's because of all of these new treatments that we have, whether they're targeted therapies or immunotherapy by itself or in combination with chemotherapy. There are a lot of new drugs that are coming out and down the pipeline, both, again, for the targeted therapies as well as for patients whose cancers do not have any targetable alterations.

All of that data look really great, but we still don't have any extremely promising drugs, I would say, for patients whose cancers either don't respond at all to their first-line therapy—that frontline therapy—or whose cancers come back later and still also need second-line therapy. That area of research is really important. Additionally, for our patients with the targetable alterations, the second-line and third-line therapies for those patients is where we're also lacking great drugs.

How would you characterize the current epidemiological landscape of NSCLC in the US? Have you seen notable shifts in incidence or patient demographics in recent years?

Dr Hsu: We have definitely been seeing some changes to the epidemiological landscape of non–small cell lung cancer in the US. Probably in large part due to the advent of lung cancer screening, we've been seeing a stage shift. We've been seeing more and more patients being diagnosed with earlier stages of lung cancer in general and, course, specifically in non–small cell lung cancer.

With more patients being diagnosed at earlier stages, we've also been seeing improvements in overall survival, which makes sense. We've also been seeing younger patients being diagnosed with non–small cell lung cancer, not only in the US but actually across the world.

We don't have as many answers for why this is the case, but we've also been seeing a rise in the numbers of folks who have never smoked being diagnosed with non–small cell lung cancer, both in the US and around the world, but again, particularly in the US as we see lower rates of smoking.

Finally, we've also been noticing some changes in terms of sex of people who develop non–small cell lung cancer. Particularly in that younger population, we see that there are more women than men that are being diagnosed with lung cancer for those who are under the age of 50.