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Pathologists play a key role in lung cancer care, from biomarker testing to tissue triage.
As biomarker-driven treatment expands its role in non–small cell lung cancer (NSCLC), pathologists are playing an increasingly central role in ensuring patients receive timely, appropriate therapy. From initiating reflex molecular testing to guiding test selection based on limited tissue samples, pathology teams are further expanding their role in streamlining the path from diagnosis to treatment, according to Cynthia A. Schandl MD, PhD.
“We’re largely reflexing to our internal testing. One of the challenges with lung cancer testing is that the greater the stage, the less tumor you often get in a biopsy. [Sometimes we only get] a smear or a cytology sample, so we may struggle with reflexing to appropriate testing for the specimen itself,” Schandl said an interview with OncLive®.
“The success of that is improved by inclusion of our molecular genetic pathology team in reviewing those pathology samples that are reflexed to us from the surgical pathology team to assure that every sample gets the most actionable biomarkers [tested] and the most important [markers evaluated] based upon the clinical needs of that patient. That’s where much of the communication is vital,” she added.
In the interview, Schandl, medical director of clinical laboratories and director of the Division of Clinical Pathology in the College of Medicine at the Medical University of South Carolina (MUSC) in Charleston, underscored the importance of aligning pathology workflows with oncology needs to prioritize actionable biomarkers and reduce time to first-line therapy for patients with lung cancer.
Schandl: This varies from institution to institution. At MUSC we’re partnering very closely with our thoracic oncology colleagues, and we’ve also gone to our medical executive committee to assure that we can reflex our molecular biomarkers. There are a couple of groups that we’re working with right now, and that includes the NSCLC group. Our pathologists are reflexing testing.
The pathologist is pivotal. Without the appropriate diagnostic information, the determination as to whether biomarker testing is or isn’t appropriate cannot be made. In addition, they’re the ones who are looking at the tissue and have an opportunity to determine, at least as a first pass before it can move to molecular genetic pathology, whether there may or may not be enough tissue in the specimen for the types of testing that the oncology team is hoping to get. The third pivotal role is to get that testing started, because the goal is to decrease the time from presentation to appropriate first-line therapy. If you don’t have the pathologist involved, that [process] takes longer.
It will depend upon the stage of the disease and your specific oncology teams. They want to get an introduction to biomarker testing [because] they want to have some of that information, regardless of the stage. These are things that you need to discuss with the oncology groups themselves, so that you can get on the same page. Once you have that figured out, and you know what they’re looking for as far as biomarker testing, then you need to determine what modality of testing you need to perform. Whether this falls to the surgical pathologist or falls down stream to a molecular genetic pathologist or other individual is going to be dependent upon the pathology department that you’re in. In our case, it often will come to me as a molecular genetic pathologist.
With lung cancer, not only are there a number of lung cancer–specific molecular biomarkers, but there are also some pan-cancer biomarkers that we need to consider as well. And they’re not all going to be able to be sequenced. Some of them are going to be expression markers, such as immunohistochemical markers, some of them may be identified with fluorescence in situ hybridization [FISH]. There are many different modalities that you have to consider based upon the tumor tissue. Given the stage and the amount of tumor that you have, you can have a conversation with your oncology teams if you have limited tissue or it’s very early stage and you don’t have specific reflex protocols in place for early-stage tumors to determine what the priority is for testing. There are certainly a number of molecular biomarkers, particularly in lung cancer that are appropriate for first-line therapy, and then there are some that are for downstream therapies as well. Understanding those and determining which ones are crucial before first-line [treatment is needed] can also assist in that evaluation.
One is certainly going to be the expected nucleic acid yield or the number of cells that you have in the sample. For example, if you’re going to get a PD-L1 [test with an] in vitro diagnostic vs a laboratory developed test, generally, you’re going to need it to have at least 100 tumor cells. Knowing those numbers and understanding the relative yield of DNA and/or RNA from a specific amount of tumor, whether it’s from a smear or a cell block, or whether it’s from a resection or core biopsy is crucial, because you need to base the test you choose on what you have to work with. If you have very little to work with, it’s very useful to be able to use different methodologies.For example, rather than relying necessarily on RNA, if you have a very low likelihood of having good RNA yield, maybe you need to do some rearrangement FISH probes. Of course, there are other things where you’re going to have to have unstained slides to get your HER2 [assessment], for example. Some folks are doing C-MET [testing] on the adenocarcinomas and PD-L1. I’ve seen [individuals] order next-generation sequencing [NGS] for lung [cancer], and what they may mean is that they want all the actionable biomarkers appropriate for lung cancer [tested]. But NGS isn’t going to do all that. That knowledge base is also very important if we’re expecting the oncologist or the surgical pathologist to choose those specific tests.
It is extremely challenging, even in our situation where we have active collaboration with our oncology teams, [because] we still have many oncology teams who are not working directly with us for reflexive testing. Those end up being outside of the pathologist’s realm to assist with when they’re being sent to outside vendors, and the materials are leaving the facility.
The other thing is with new biomarkers emerging, updating testing, whether it’s an internal or external vendor, can be very challenging. Validating these tests is an extremely expensive and complex process, it takes some time. When there is a biomarker that hasn’t been anticipated, it can take a [while] to get the right tests available for it. You also have to consider that sometimes you need to use a test that isn’t perfect, because that’s the best that you can do for that particular situation, so understanding the different modalities and how to best leverage them based upon what you have in hand and what the patient needs is key.
