Molecular Testing and EGFR-Mutant Non-Small Cell Lung Cancer - Episode 3

Diagnostic Workup in Lung Cancer: A Focus on Pathology

Transcript:Philip C. Mack, PhD: The key elements that are required for a pathological workup include a definition of histology—a diagnosis essentially—as well as any information that the pathologist can provide on staging. In adenocarcinoma of the lung, it also requires a suite of molecular markers that are predictive of therapeutic activity for some of the active tyrosine kinase inhibitors that we have.

From my point of view as a molecular biologist who has focused exclusively on translational medicine in clinical trial development of cancer, a core biopsy is essential compared with a fine-needle aspiration (FNA). The reason is that it gives us sufficient material to do the suite of molecular analyses that is necessary for a full diagnostic workup. In most cases, FNA is going to be insufficient for this. It might be enough material for a diagnosis, but not enough to run all the necessary markers.

The results of a biopsy can very much inform clinical decision making on 2 levels. First, by histology—it’s good to know whether it’s adenocarcinoma, a squamous carcinoma of the lung, large cell, etc. This can impact what types of chemotherapy the patient is most likely going to respond to. But, most importantly for adenocarcinoma and large cell carcinoma of the lung, it’s important to look at EGFR mutations; ALK, RET, and ROS fusions; BRAF mutations; and exon 14 skipping events in MET, just to name a few. You have to perform this entire suite of analyses to have a complete diagnosis. If you’re not, then you’re selling your patients a little short.

It’s important for the pathologist and the treating physician to work as a team in this capacity. The reason is that there’s a lot of information that needs to be communicated back and forth. If it’s falling upon the pathologist to provide all the information on the molecular markers—EGF mutation, for instance—then that needs to be communicated readily to the physician. In other cases, the physician may be asking or requiring a particular test. For instance, a patient might be in consideration for enrollment in a clinical trial. This might require that the pathologist provide some tests and information, or, that they provide tissue in a manner that is useful to be sent out for analysis.

For instance, in the SWOG clinical trials, we often require a pathologist to sign off on the tissue to verify that it has sufficient cellularity and tumor content for analysis. We are really dependent on the pathologist to provide us with high-quality material in order for us to do our job. The demands are getting longer now because we are looking at additional analyses, maybe even next generation sequencing—a lot of multiplexing and complex analyses, maybe a series of immunohistochemistry. There’s a lot of demand on that tissue.

Adequate tissue is the absolute key for getting the sort of information that we need on each patient. Following the IASLC (International Association for the Study of Lung Cancer) guidelines, what we recommend is that pathologists use the minimum number of stains required to make a determination about histology. You should not waste additional tumor material to confirm what you’ve already determined. Instead, that additional material needs to go for molecular marker analysis—or PD-L1 analysis. In the future, there will be additional markers necessary for us to define a patient for immune therapy. I think in the next 2 or 3 years, we’re going to have a lot more markers beyond PD-L1. So, it’s essential to save that tissue.

Transcript Edited for Clarity