Guided by Data: Navigating Biopsies, Biomarkers, and Treatment Strategies in NSCLC

A panel of multidisciplinary experts convened to discuss optimizing perioperative and neoadjuvant immunotherapy strategies and resectable non–small cell lung cancer, with a focus on recent data from the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

Moderated by Ticiana Leal, MD, of the Emory University School of Medicine, the roundtable featured perspectives from Mara Antonoff, MD, FACS, of the University of Texas MD Anderson Cancer Center; Robert E. Merritt, MD, MBA, FACS, of The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center; and Coral Olazagasti, MD, of the Sylvester Comprehensive Cancer Center and University of Miami Miller School of Medicine.

In the second segment of this roundtable series, the panel discusses the importance of safe and adequate sampling in biomarker testing, perioperative versus neoadjuvant strategies, and key challenges and considerations for ensuring adequate tissue yield and conservation for comprehensive biomarker testing.

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Dr. Leal: That takes us to the biopsy and the importance of adequate sampling and the importance of biomarker testing. So Coral, take us through that. In terms of a patient undergoing a biopsy, are you involved at that stage? How do you chaperone the biomarker piece of it, and what are the considerations that you think about?

Dr. Olazagasti: Usually, when patients come to us, they already have biopsy-proven lung cancer, but most of the time that I’m seeing them at this first instance, that’s the only thing that I have. So, it’s starting to try to peel off the layers and get the workup going quickly, but understanding that we really need to know the whole picture. Typically, what I do is send them to interventional pulmonologists. They squeeze the patients in very quickly, within a day or two that I message them, and then they bring them for the bronchoscopy—not only to get a really big sample for the core, but also for mediastinal and hilar staging because that’s something that’s very important. Also, sometimes when the patients come to us for a second opinion, they have been offered surgery or a little bit of premature treatment without having the really complete picture.

This is something that we definitely have the algorithm very well established, and on the moment that they do the bronchoscopy, then our interventional pulmonologists are the ones that oftentimes send for next-generation sequencing [NGS], or we order [it] ourselves. It depends. It’s been a challenge, at least in our institution with physicians other than oncologists, placing the orders. We’ve had barriers because they worry that if someone orders them, and that’s not the physician that’s going to follow the testing, they’re worried that they [the results] might fall through the cracks. Unfortunately, sometimes this can lead to delays, but if not, then we make sure that we work closely with those doing the biopsies. This is the case series, and then we put the order in right away. At that time, while that NGS from the tissue is cooking, we make sure that we also have a blood NGS to at least have both steps running at the same time. Again, it’s very important and completely necessary to have the whole picture before moving along and finalizing the treatment plan with the patients.

Dr. Leal: Yes, you bring up great points. Thinking, though, about early-stage patients whom [you are] are considering for neoadjuvant or perioperative strategies, how does that factor in, for example, if you have a multidisciplinary clinic or if you don’t? Maybe the surgeon is the first person seeing that patient. Tell me about your take on adequate tissue and then biomarker testing when you see that patient for the first time.

Dr. Antonoff: This is something where there’s a huge burden of responsibility on surgeons to do a better job. It’s important for us to recognize that lung cancer resections in the United States are performed by a lot of surgeons who largely do not specialize in thoracic medical oncology. It’s really important to acknowledge that a lot of lung cancer resections are performed by cardiothoracic surgeons who may have a mixed or hybrid practice where they do cardiac and thoracic surgery. There are operations performed by general surgeons, and it’s very easy for those of us who have the privilege and the opportunity to work in a very specialized silo to critique others who may jump to surgery or may not know the importance of multidisciplinary evaluation and complete staging and molecular profiling. But these elements are critically important to our patients having good outcomes.

Honestly, for those of us that really do have the luxury of being super specialized and getting to operate on just a couple of disease processes, the burden is on us, the thoracic surgical oncologists, to ensure that everyone who is participating in the resection of lung cancer really helps drive home the point that in this era, in the current year, it is inappropriate to operate on a patient without a diagnosis and without molecular profiling—or at least an opportunity for molecular profiling—just as it would be inappropriate to operate on someone without staging. This is something that has been in evolution, in as much as we would not have wanted to operate on someone 15 years ago who didn’t have appropriate imaging studies for staging. Then it became why would we ever operate on someone who doesn’t have appropriate invasive mediastinal staging?

It’s very clear that molecular profiling is also part of that, and we are responsible not only for educating our peers, but for educating patients as well, so that patients understand that if they’re not being offered the complete picture beforehand, it’s not okay to be taken to the operating room for someone being on a hunt, having a hunch that they might have cancer. Patients can be their own best advocates as well. Ultimately, surgeons need to be responsible for ensuring that we, as a surgical community, are doing the right thing for our patients.

Dr. Merritt: I agree with you completely. In 2025, getting biomarker testing should be a standard of care, just like mediastinal staging, appropriate imaging studies, preoperative testing for cardiopulmonary fitness. That should be on the checklist of things that should be done prior to any operation or for lung cancer in 2025. And I agree that it’s on the academic thoracic surgeons who work at cancer centers and academic centers to educate our peers that this should be the standard and that we should make every effort to get biomarker testing. It also includes pulmonologists who perform navigation bronchoscopies and radiologists that perform CT-guided biopsies, that the biomarker testing should be top of mind, and they should do additional biopsies to make sure they have enough material to do NGS and PD-L1 testing.

Dr. Leal: Good point. It’s really important, especially thinking about early-stage and resectable non–small cell lung cancer, as we think about the perioperative strategies or neoadjuvant strategies, because in my mind, it would influence the decision of what strategy to use in the preoperative setting. You want to make sure that if a patient has an actionable driver mutation, that perhaps that patient may not be best suited for a perioperative strategy with immunotherapy. One thing that has helped in our institution was to integrate NGS requests within our EMR [electronic medical record]. It made it easier that anybody in our multi-D [multidisciplinary] team could actually order the test. It’s a few additional clicks, and the results come to everyone. It’s in the chart in a specific point, and it has helped us to plan perioperative strategies independent of even clinical trials — just standard-of-care testing that we do. Has that been something that has changed — these factors of not only biomarker profiles, PD-L1 — as you were stating? Would that influence your choice between neoadjuvant and perioperative strategies?

Dr. Merritt: At our institution, if someone has an actionable driver mutation, [such as] EGFR, ALK, and they qualify for adjuvant therapy, we probably would opt for the ADAURA trial or the ALINA trial. If they have high PD-L1 expression, then we may opt for either new adjuvant immunotherapy or perioperative immunotherapy. So, the biomarker testing does really drive our decision-making.