Comprehensive biomarker testing is the first step for advanced-stage NSCLC patients to secure personalized and specific information about their cancer to guide critical decisions about the treatments that offer the highest potential for long and high-quality lives. Advocating for patient access to timely, high-quality comprehensive biomarker testing at diagnosis and recurrence of a patient’s disease is the mission of LUNGevity’s Take Aim Initiative.
Time is of the essence in lung cancer care and requires healthcare providers to work with a fully-coordinated multi-disciplinary team to overcome the challenges of biomarker testing. A multi-disciplinary team, which includes pulmonologists, interventional radiologists, pathologists, oncologists, nurses, and nurse navigators, works together to ensure that all necessary steps for biomarker testing, including biopsy procedures, specimen preparation and handling, appropriate biomarker testing, and reporting of results to the patient, are done in a timely manner.
Many people may not realize that pathologists play a critical role helping the multi-disciplinary team keep up with and integrate new biomarker test developments to ensure that all patients continue to receive the latest cancer care. The role of the pathologist in the diagnosis and management of cancer will continue to change and become more central to the patient’s care in this new era of precision medicine and rapidly progressing cancer therapies.
Nikki Martin, Director of Precision Medicine Initiatives, spoke with Dr. Dara Aisner, MD, PhD, University of Colorado School of Medicine about the role of the pathologist in lung cancer patient’s care. Dr. Aisner is a lung pathologist whose primary expertise is biomarker testing. Nikki caught up with her on the phone during her spring break in the mountains of Colorado to learn a little more about the essential work pathologists do for lung cancer patients. She discusses the big changes that pathologists have faced since the advent of biomarker testing, and how molecular pathologists help their laboratories keep pace with changes in biomarker testing, thereby offering patients greater access to advancements in precision medicine.
This interview has been condensed from its original version, and in some places redacted or summarized.
Nikki Martin: What are some of the areas you focus on as a lung pathologist?
Dr. Dara Aisner: Pathology is fundamentally the study of disease and at the end of the day we use a lot of different pieces of data to get to decisions that helps us to diagnose and treat disease. There are two main activities that a pathologist does routinely as part of a lung cancer diagnosis. When lung cancer is suspected, we get a sampling of a lesion (tumor tissue) and determine whether or not it’s cancer and also do special studies to determine whether or not we think it originated from the lung. Although a diagnosis might be 99% certain based on radiology or lab tests, it’s still critical to have the pathologist look at the tissue to be 100% sure. The second activity where pathologists play a key role is staging. Every cancer has a unique way that it gets staged, and it’s almost always a combination of the size of the tumor, how far it has spread locally, and whether or not it has spread to the regional lymph nodes.
There’s been a fairly big shift in the role of the pathologist in lung cancer. A new job has been added on, which is basically the manager of the tissue to make sure that the biomarker testing can happen. Before biomarker testing for targeted therapy was prevalent, the pathologist’s job was to get a diagnosis. Now the job is to get a diagnosis but to do it as “tissue efficiently” as possible to preserve tissue for biomarker testing. This is a delicate balance because sometimes we need to do some stains (tests) to make sure the biopsy tissue isn’t metastatic breast or bladder cancer or something else. But every time we do a stain (test), we use up tissue that could be helpful (for biomarker testing) if it turns out to be lung cancer.
NM: Managing the testing with limited tumor tissue sounds like a bit of science and art. What sort of time constraints do you face in the pursuit of this information?
DA: The balance we seek to maintain is not just with managing the amount of tissue, but in also managing the time it takes to review the case and issue a primary diagnosis report to the physician. A lot of people think we get the biopsy sample and can immediately look at that tissue on slides. But there’s a technical piece that’s behind the scenes when the lab handles and processes the tissue and when each piece of tissue is cut on a slide. This technical piece can take one-to-two days from the time we receive it to being able to look at slides.
Then there’s the time it takes for the pathologist to review the case. Because I am at an academic center and can see the patient’s full medical record, I’m focused on medical integration with other pieces of data. When I review the medical records, I look at the case and put a story together. My mental process usually is: Why was this specimen taken? What was going on with the patient? What are they (the healthcare team) thinking before they did the biopsy? Do they have other considerations that they want to rule out? Sometimes you have to look at the slides, then go back and look at them six hours later, and then go back and look at them the next day because there’s a lot of thinking that’s involved in how you want to assemble all of the information into an actionable report. Pathology requires a lot of thinking. This is why getting a pathology report and final results on a lung diagnosis might take up to one week.
NM: What about biomarker testing? How does that fit into your role?
DA: In addition to lung pathology, my other larger role is medical director of the laboratory that does the biomarker testing for EGFR, ALK, ROS1, etc. My role is to steer the lab in the direction where it needs to be to meet patient needs. A good example of that is in 2013, we were fairly early adopters of next generation sequencing (NGS). That was because we knew that it was going to be better for patients if we could get a whole bunch of information at once (from a multi-gene panel). A couple of years ago we adopted an RNA-based test to look for (gene) fusions because we felt that it performed better and had fewer false negatives.
Another big piece of what I do is assay (diagnostic test) development and validation. This is essentially putting a test through its paces to understand its weak points. By understanding its weak points, I can understand how accurate and reliable individual pieces of data related to each patient are. The more accurate a test is, the more confidence we have in using the test for clinical decision-making. This work is very much patient-centered, but it’s behind the scenes. Personalized medicine tests are much more than sample-in, answer-out, and we have to understand the nuances of the testing.
NM: Do you play a more visible patient-centered role too?
DA: The more direct patient-centered role I have is serving as a clinical consultant to providers. I respond to questions like, “What tests should I do?” and “I got this test result back from your lab, can you help me understand what it means?” I work in an academic lab, and in this environment, the oncologists can contact me directly to discuss the intricacies of the results or why the results might be unexpected compared to the patient’s scenario. I can also proactively make suggestions to the treating physician.
NM: Is there any value in having more interaction than what currently takes place between patients and pathologists? We hear a lot that testing results are getting more complex, and it may be outside the scope of what the oncologist understands.
DA: I do go over results with patients, but it’s not very common. That’s because in my practice setting, our oncologists are very well versed in the intricacies of the testing. But I do think that it would be really valuable for patients to have a resource that can bring the level of expertise to the technical questions of the testing that are outside of the scope of an oncologist’s knowledge. I generally only take a call from a patient after clearing it with their physician, and in any patient consult, I need to walk a line between speaking about how a test works or what the results are, without migrating too much into treatment questions.
My number one mantra with testing is “no test is perfect.” Some of the considerations I look at are, “What is this test really good for? What are its potential weak spots? Should we consider additional testing?" Keeping this in mind, I might end up saying to a patient, “Look, I think that this testing that you had was very comprehensive. This is the only other thing that I could think we could do.” Or “You’ve had the standard of care testing, and it was fine, but we can go two or three steps beyond standard of care to look for additional things.” I do think there’s value to having that specialty consult with patients at the molecular level so they can have resources to better understand what their testing shows.
A special thank you to Dr. Aisner for her time sharing her experience as a lung pathologist.
Have you had direct experiences with a lung pathologist? LUNGevity would love to hear from you about any interactions you’ve had with a pathologist or molecular pathologist to learn more about your biomarker testing results. Were these interactions valuable to your understanding of your disease or treatment decisions? Please contact nmartin@lungevity.org. Do you have questions about biomarker testing? Call us at 844-360-5864 or visit our biomarker testing page.
Nicole Martin is LUNGevity's Director of Precision Medicine Initatives 