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Molecular Testing for Early Non-Small Cell Lung Cancer


Dr. Martin Dietrich explains the role of molecular testing in early non-small cell lung cancer.

Jessica Donington, MD, MSCR: There’s one more factor that in 2021 plays a huge role in how we determine upfront treatment and treatment plans altogether and that’s something called molecular testing. And that means taking the tumor and looking inside the tumor for what’s going on in the DNA of the tumor. And that’s because now, we have lots of molecularly-targeted medications, medications that were designed just for some of the mutations. And we also have cancer immunotherapies. But we need to know about the DNA of the tumor to appropriately pick those treatments. And that is important, even for early-stage patients, as we design a treatment that’s specific for each patient.

Martin Dietrich, MD, PhD: Going back into how treatment is going to look like and how it’s going to impact the quality of life and treatment options, in general terms, the early detection of lung cancer is often a coincidence. We are aiming at increasing the rate of lung cancer screening similar like we would encourage breast and colorectal cancer screening. We know especially for certain high-risk patients, there is a role for lung cancer screening with an annual low-dose CT [computed tomography]. There are pros and cons that should be discussed. But in general terms, it is a reasonable intervention that helps us catch a cancer early. If we find a cancer early in lung cancer, again, there goes a big deal of discussion and planning, testing ahead of time into finalizing the disease treatment plan. Obviously, surgery is always on the table. Radiation and systemic therapy options that would entail chemotherapy, targeted therapy, and immunotherapy — all of them are now combined. What you’ll ideally find is a table of experts for their respective specialties that are reviewing images, pathology, and the patient’s clinical status at the same time and come up with a joint treatment plan. Early-stage lung cancer doesn’t necessarily mean it’s easier treatment. And oftentimes, the short-term investment is quite significant. We made quite a bit of progress for treating early-stage lung cancer, the surgical techniques have been clearly more refined, and the endobronchial diagnostic approaches have been substantially better. I always tell my patients when you have a smaller robotic surgery, it doesn’t mean that it is a small surgery because you’re operating on a very large organ and you want to be sure that you have a clear understanding of the anatomic extend that certainly guides the treatment options and radiation therapy as part of this consideration. And radiation’s impact on treatment is mainly guided to what organ structures are in the vicinity. The radiation therapists and radiation oncologists have gotten a lot better at delivering radiation in that precise fashion. But when you have spread into areas of lymph nodes, for example, you do want to have a mix of precision by avoiding unnecessary tissues. And when I say dispersion or more broad distribution — because you’re covering not one spot but an entire field. Then the main concern here is typically the irritation and inflammation of the food pipe or the esophagus, and swallowing concerns are an issue. Other than that, it’s very well-tolerated. It’s the localized collateral impact that makes the decision-making process for the surgery and radiation. I have to say that even though most patients have a challenging time at some point for their early-stage treatment, this is typically short-lived and can be recovered from well. And it’s worthwhile to early discovery. That’s a fair statement. When it comes to systemic therapy, as Dr Donington already pointed out, the molecular testing just decides, in 2021, how your treatment is going to look like. At this point, we are basically looking at first a genetic marker called EGFR [epidermal growth factor receptor]. If this is present, we would always consider chemotherapy, especially for high-risk patients. But if a patient is not eligible for chemotherapy and chooses not to pursue chemotherapy for personal reasons, then targeted therapy remains an option. We’ve always known this in breast cancer for estrogen receptor-positive disease that we would give an estrogen blocker for treatment after surgical resection, and we knew that patients would do better, and their cancer would either not come back or at least come back later. For EGFR, we have a similar EGFR blocker or inhibitor that can do similar things. Now, not everybody has EGFR. It’s about 15% to 20%, depending on geography. We have many cancers that respond very well to immunotherapy. This was just approved by the FDA [Food and Drug Administration] last month, options to introduce immunotherapy that was available for now for many years in stage 4 disease in the early stage 1, 2, and 3 disease post-surgery. There is plenty of opportunity for treatment that may be improving outcomes and that’s well-tolerated. It’s a little bit of a mix, where you go from a very high-intensity pace in the beginning where you control all the visible disease to then a more long-term, I call it the sprint and the marathon sequence from our patients, into disease control systemically afterwards. The prognosis for patients with early-stage lung cancer, unfortunately, tells you that the systemic component is always of concern. It doesn’t mean that you don’t want to take out the primary tumor, but you do have to account that even in a stage 2 setting, you’re looking at, depending on the studies, you’re looking at 30%, 40% disease recurrence. And if you go into stage 3 disease, you can certainly see up to 70%, 80% of patients recurring. This is a very high rate of concern for patients that have been treated. And if you have a chance after surgery to experience disease recurrence that high, systemic therapy should be on the table for discussion and obviously should be tailored to your individual needs. We have a lot of interest in immunotherapy but again, not everybody does qualify for it. And those are risk factors. There’s some risk factors on the pathological level that the size and lymph node involvement, and then some more refined histological features of pleural involvement and other microsatellites within the lungs. Those are things that your healthcare provider will discuss with you at the time of decision-making for a follow-up systemic therapy. We have a pretty good handle and understanding how high-risk disease is and what should be offered. In general terms, with the exception of very early-stage disease, and Dr Donington mentioned the 4 cm [centimeter] tumors as kind of the cutoff, unless you have a very small, isolated tumor, systemic therapy is on the table for discussion for virtually all early-stage lung cancers at this point.

Transcript edited for clarity.

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