Molecular Testing in Lung Cancer: Experts Review Progress, Challenges

At the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, an expert panel convened to discuss non–small cell lung cancer (NSCLC), with an emphasis on young-onset lung cancer, psychosocial considerations, and the evolution of molecular testing and targeted therapy in NSCLC.

Moderated by Millie Das, MD, of Stanford University and the Palo Alto VA, the roundtable featured perspectives from Martin Dietrich, MD, PhD, of the US Oncology Network; Stephen Liu, MD, of Georgetown University; and Eric Singhi, MD, of the University of Texas MD Anderson Cancer Center.

In the second segment of this roundtable discussion, the panel discusses the molecular testing landscape in NSCLC, how it has evolved, current challenges, and what might be on the horizon.

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Dr. Das: We’re going to move on to talking about the current landscape of molecular testing in our lung cancer patients. Eric, how do you think that molecular testing has evolved over the years? And what is the standard approach that you’re using at your institution?

Dr. Singhi: I know it’s evolved tremendously. We are now, as lung cancer, the poster child for precision medicine.

It’s so important to make sure that we’re doing biomarker testing, making sure it’s comprehensive. We toss that word around, but making sure that you look at the report, making sure that DNA and RNA have both been done for a patient to really make sure they have an impactful alteration that’s been identified; it goes a long way.

We really want to be able to personalize our treatments for patients, and biomarker testing is essential. For my practice, for a patient that’s newly diagnosed, I am concurrently ordering both liquid biopsy and tissue biopsy.

Hopefully, the liquid biopsy will come back, and it will come back sooner, and we can get started on treatment as soon as possible. Because the hardest thing to do is to meet a patient—they’ve just been diagnosed with the “big C”—and then you say, “Wait, just wait for me until I get these results.”

But we have data from our colleagues that have shown us that the patients that we wait for, they do better from a tolerability standpoint, from an outcome standpoint. And so we have that conversation, and we eagerly wait for those results. If there’s anything we can do to speed that up, we try to do it.

Dr. Das: Yes, I completely agree. It’s really important that we all try to adopt ways in our clinical practices to really try to speed that process up. We have seen that a lot of the platforms that we’re using for sequencing have a turnaround time [that] has shortened.

But I’m curious to know, Stephen, do you have reflexive testing at your institution? And do you see other ways of trying to bring down that time to get the results of the molecular testing to help inform our treatment decisions?

Dr. Liu: Yes. I think that Eric said that we [have] got to wait for those test results, but anything we can do to shorten that wait, we need to. Martin mentioned earlier about the use of liquid biopsy, and I think that using ctDNA in parallel, in conjunction, at the same time, really can shorten those results. Tissue testing is still very important.

The really important part here is [that] you want to make sure you get enough tissue at the beginning. And this is a dialogue we have to have with our radiologists, our pulmonologists, our surgeons—whoever is acquiring the tissue—and our pathologists to conserve that tissue.

We really need to think of tissue stewardship and not running an exhaustive panel of immunohistochemistry when every slice counts in terms of getting more and more tests done. It really is a different way of thinking because if we go back 20 years, we were telling people the opposite: we want to use the smallest needle, the safest approach, so that we can establish a diagnosis of lung cancer. Nothing else really mattered at that point. But now, if we do that same approach, and we see lung cancer, and that’s all we do, we have to get another biopsy.

We’ve now increased the risk many more–fold by doing another procedure, so it really is getting more tissue at front to get the testing right quickly [and] to not have to repeat it. We don’t want to see that quantity insufficient. I think that’s the dreaded result—that all of us see the worst.

Dr. Das: And who’s doing the testing? That is, the NGS [next-generation sequencing] testing. Is this starting with the interventionist who is doing the procedure? Or are you ordering it when the patient comes to see you?

Dr. Liu: At our institution, which is relatively smaller, it is triggered by the oncologist. The treating physician orders it. But once the suspicion is there, we meet those patients right away, sometimes even before the biopsy. As soon as that biopsy is done, we’re telling our pathologist [to] expedite this; let’s cut out some of the IHC [immunohistochemistry] and just sort of save that tissue. We can get that NGS result going quickly and get this person on the treatment they need.

Dr. Das: Great.

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View the first segment of this roundtable series, titled “The Changing Face of Lung Cancer: Experts Discuss the Rising Incidence in Young Adults.”