From Biopsy to Biomarkers: Panel Shares Insights on NSCLC Diagnostic Process

At the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, a panel of multidisciplinary experts convened to discuss non–small cell lung cancer (NSCLC).

Moderated by Balazs Halmos, MD, of the Montefiore Einstein Comprehensive Cancer Center, the roundtable featured perspectives from Jay Lee, MD, of the University of California, Los Angeles (UCLA), Mary Pasquinelli, DNP, APRN, FNP-BC, of the University of Illinois Chicago (UIC), and Momen Wahidi, MD, MBA, of Northwestern Medicine.

In the second segment of this roundtable discussion, the panel discusses the diagnostic process and biopsy methods, as well as tissue collection considerations surrounding biomarker testing and next-generation sequencing.

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Dr. Halmos: There’s a lot of fear that with CAT scan screening, they’ll find something, and there’s going to be some invasive procedure. They’ll put a needle into the patient’s chest, and consequences will occur.

Did I just notice your name [Dr. Wahidi] on a New England Journal [of Medicine] paper—just a couple of days ago—that might highlight that maybe that risk is not as high? Tell us about it.

Dr. Wahidi: Yes. We conducted a multicenter, randomized clinical trial examining biopsy methods for lung nodules. We compared the percutaneous route from interventional radiology and the bronchoscopic route—from an interventional pulmonologist—navigational bronchoscopy. It has never been done to have a randomized controlled trial comparing those methods.

There are many misconceptions, and we wanted to investigate them. We predicted—that was our hypothesis—that they both are very effective. The diagnostic yield for both was in the mid-80s, but with percutaneous biopsy, the risk of pneumothorax is higher—we kind of knew that—around 28%, while in the bronchoscopic approach, it’s in the single digits.

But again, I think every patient, every lung nodule is different. I think the study shows that you have tools. Choose the one that’s better for your patient. Sometimes, percutaneous biopsy may be a better option, even with a high risk of pneumothorax.  But we’re also showing that bronchoscopic options are valuable and can also have lower risk of pneumothorax.

Dr. Halmos: It seems to me that we’re taking huge steps forward in terms of technology, like these navigational devices and cryobiopsies, etc. It’s just amazing to me. At the tumor board, we look at the tiny, tiny thing, and our bronchoscopists say, “No problem, we’ll do it.” Two weeks later, we see they’ve done it. It’s amazing how much progress has been made.

Dr. Wahidi: Yes, we now have more tools. We have robotic bronchoscopy. We have 3D mobile CT scanners that can be in the bronchoscopy suite and show us where our tools are. All these tools have empowered us to do better. There’s always room for improvement, but I think we are much farther along than 10 years ago or so.

Dr. Halmos: Fantastic. Tell us a little bit about—it’s not enough to diagnose, we need to get enough tissue to guide the treatment, maybe not for the earlier stage, but most of the time—how can we match being able to get to very remote places and taking a tiny sample, but still making it sufficient?

Dr. Wahidi: I want to keep oncologists as my friends, so my goal is to have a 100% success rate in having enough tissue so we can do next-generation sequencing (NGS). As you all know, it’s a standard of care. Now we cannot treat lung cancer without knowing the molecular markers and the driver mutations that led to the growth of that tumor. The challenge is that we’re not performing surgery. Jay does those, but we’re using needles and forceps. We have national guidelines on the number of passes you should do. We educate pulmonologists on [this, we say:] “You need to have enough passes, not just for the diagnosis, but your needle passes have to have enough for NGS.”

Meta-analyses have been done, for instance, on endobronchial ultrasound-guided samples, and the success rate is high, it’s in the upper 80s. Again, we need it to be 100%. Sometimes we sample multiple areas to ensure that we get enough from multiple lymph nodes or the actual nodule or mass. I think it’s standard of care and something we’re always striving to do, to get enough tissue for markers.

Dr. Halmos: Got it. I think this is where the value of the tumor board is: that everybody’s familiar with what needs to be done. Everybody has a path to take, but also, we collaborate and work together to maximize the yield.

Mary, Jay? Anything to comment on from your experience, as to how to maximize the diagnostic yield and biomarker testing in your practices?

Dr. Lee: I just echo the importance of NGS molecular testing as well as immune biomarker testing. There are trials coming out in earlier stages. There are high-risk stage I patients, where we’re rolling out phase 3 trials. I think this is going to be an increasingly important issue. As we start to utilize more than neoadjuvant strategies, it’s all the more reason to know the driver mutation status.

Regardless of whether there are approvals for those targeted therapies in the early-stage setting, you need to know them to know the expected response to neoadjuvant chemo-IO [chemoimmunotherapy]. I think this is going to be an ongoing and increasingly important issue.

Dr. Halmos: Yes, of course. We’ve learned in the metastatic setting that we need to learn the biomarker profile 100%, ten different molecular subsets, and immune biomarkers. But now, we’re learning a lot more, and that for early-stage patients, the same information is helpful; targeted therapy in terms of EGFR-positive patients, and neoadjuvant chemo-IO for others.

Anything from the University of Illinois in terms of how to advise your patient as to this work-up pathway?

Dr. Pasquinelli: When I see patients in lung screening and they have a positive nodule that we biopsy either through EBUS [endobronchial ultrasound], robotic bronchoscopy, or trans-thoracic biopsy, giving those diagnoses can be very challenging sometimes.

Now that you can see the results of pathology electronically, some patients are very concerned right away. Often, when I see a patient and I know that they are going to have a biopsy and they’re going to come back with results, I ask them, “Do you want to get the results in person, or do you want me to call you with them?”

Often, it depends on which way they want to go. However, as soon as we receive the results, we develop a plan with the multidisciplinary team. We have a diagnosis and a plan, and then we walk them through that process.

We use a lot of strong navigation in our practice, and often I have our lung cancer navigator there with me when I give a diagnosis to a patient. Then, we talk about the next steps, everything that needs to be done before we send them to the surgeon, so everything is done in a timely manner. But getting the diagnosis is so important. It’s very difficult when you say, “Well, we went through the procedure, but we don’t have the diagnosis yet.” Knowing the diagnosis and then having enough [information] with the molecular testing is incredibly important.

View the first segment of this roundtable series, titled “Lung Cancer Screening: Multidisciplinary Experts Discuss Barriers, Opportunities.”