Transcript:Marcia S. Brose, MD, PhD: When a patient is initially getting diagnosed, and maybe even on the fine needle aspiration, whether or not to send a sample for molecular testing is often considered. At this time, it still is somewhat controversial as to whether or not this should really be done on every patient or not and also if it is appropriate at the time of surgery. Usually, a pathologist looks for the presence of a BRAF mutation, which often indicates thyroid cancer. The pathologist will often tell you that molecular testing doesn’t add to their diagnosis. They either know that it’s cancer or that it’s not. Some endocrinologists will say, “Well, it helps confirm it.” If the patient definitely has a BRAF mutation and they’re not quite sure, if it seems like a borderline case, the results might actually help them determine that it is cancer.

The interesting thing is, regardless of what the molecular testing result is, the therapy is the same for everybody. They will all get referred for surgery. At that time, we’ll learn more about it. The therapy is actually the same. Patients will then get radioactive iodine afterwards, if it’s indicated or is in accordance to the ATA [American Thyroid Association] guidelines. Then they will be worked up appropriately. And so, the molecular answer doesn’t necessarily factor in on the initial therapeutic approach. But as I said, if you have a question regarding whether or not your pathologist can really interpret the results accurately, and you do know that the patient has a BRAF mutation, this gives you a bit more confidence in knowing that the case is thyroid cancer and that you should proceed accordingly.

Johannes (Jan) Smit, MD, PhD: Molecular testing in the diagnosis of thyroid cancer is still a difficult subject because this field is rapidly evolving. There are many new tests available and others are being introduced. Thyroid cancer experts have not concluded definitely on the exact place of molecular testing in the diagnosis of thyroid cancer. Therefore, I believe that molecular testing in thyroid cancer really should be reserved for centers that have much experience in diagnosing thyroid cancer. This may differ between countries. In the United States, there is already a lot of experience with molecular testing, and I know that this is being used extensively. So this could differ between countries. But in general, I think it’s very difficult for doctors who are not treating thyroid cancer patients frequently to really get a good picture on the exact position of molecular testing in the diagnosis of thyroid cancer patients.

We have to think about the risks and benefits of molecular testing. As with all tests, the performance of a test is related to the pretest likelihood of thyroid cancer. If we do a test in subjects with a very low likelihood of thyroid cancer, we might end up with false-positive results. On the other hand, if the pretest likelihood of thyroid cancer is very high, if we do a test, we have the problem of false-negative results. So the selection of subjects for whom we are going to subject to a molecular test is very important. Of course, the performance of a test is also very important. All tests should be validated in relevant populations. We know that this is a difficult point in molecular tests that, nowadays, are available. Some tests are validated in relevant populations, but not all of them have been validated. So the performance of a test is also very important. Subjects who are suspected of thyroid cancer should undergo surgery to confirm or exclude a diagnosis. If we can prevent this surgery by means of a molecular test, this will, of course, be of great benefit.

Transcript Edited for Clarity