Transcript: John R. Gosney, MD, FRCPath: In Liverpool we are essentially a reference center for lung cancer profiling. So we receive specimens rather than send them out. And we routinely receive specimens from 5 other trusts in the area of Greater Merseyside, which is a population of approximately 3 million, and they are sent into the Royal Liverpool University Hospital, where I work, and we profile all those specimens in-house. And this carries great advantages because all the tests are carried out in a suite of rooms on 2 floors of the same building, and it keeps the whole process very tight. There’s very good communication, and that brings very good efficiency, so we are able to turn around a full range of profiling tests within 5 or 6 days. So we receive specimens rather than send them out. We are a referral center.

Reflex testing essentially means that the pathologist organizes testing profiling of the specimen at the time of diagnosis. In other words, as soon as the pathologist knows that there is non—small cell carcinoma in the biopsy, he or she can then start the ball rolling with the profiling. And that has huge advantages, of course. It means that the testing is done very quickly. It means the inflammation is integrated. It means it’s ready for the oncologist usually by the time of the first meeting of the tumor board or the multidisciplinary team, and it permits forward planning. You have a full profile of the tumor very early on. So there are considerable advantages. It’s also a lot easier for a busy laboratory to perform an array of tests at the same time on the same specimen, rather than to do things sequentially. That causes inefficiencies in the laboratory, and that’s a point which is often forgotten.

There are disadvantages. For example, we often end up testing early-stage disease, and we’re not aware of the fact that it’s early-stage disease because clinicians are not always terribly good at giving the necessary information to the pathologist. And they might not know that. We might not know when we make our diagnosis that this is stage I, or stage II, or stage III, or stage IV. So our default is to test it anyway. Clearly we might test from patients in whom that information might not be of immediate relevance.

A second disadvantage is that it costs more to do all these tests in everybody rather than to pick and choose. But these are not expensive tests in the broader context of how much it costs to manage a patient with lung cancer. I think that’s a rather spurious argument. In fact, I think the only cogent argument against reflex testing is that, as we now know, non—small cell lung cancer evolves all the time, and it evolves particularly when you treat it. It does not like being challenged. And patients on TKIs [tyrosine kinase inhibitors] will relapse usually after 10 months or a year, often with a new mutation. And when the disease comes back, it is a very different beast from where it started. But I think that is less an argument against reflex testing than an argument for rebiopsy on recurrence when the disease might have evolved. I am a great proponent of reflex testing, and this is the way we approach all our profiling in Liverpool.

The most significant change in the methods of biopsy of non—small cell lung cancer over the past 10 years has been the enormous expansion of endoscopic bronchial ultrasound-guided aspiration of thoracic lymph nodes, and this has really revolutionized the diagnosis and the staging of lung cancer. In addition, of course, we now have very sophisticated, very small endoscopic ultrasound-guided radial-guided bronchoscopy, which allows the endoscopist to move right out into the periphery of the lung and to sample tumors that would formerly have been biopsy-able only by transthoracic needle biopsy.

Now, the down side of these major advances is that generally speaking, specimens are smaller. And this is a big problem because, of course, we as pathologists are entirely dependent on the quality of the specimen that we are given. And if that’s not adequate, we can’t do anything. And we’ve rather compromised our own position, I think, over the years by getting so very good at getting a lot of information from such small amounts of tissue. But there is a limit to what we can do, and I think that needs to be borne in mind. And although it sounds quite facetious in a way, I often say to my clinical colleagues that there is no such thing as a biopsy that’s too big. We as pathologists will always want more.

Transcript Edited for Clarity