Surgical Insights into Thyroid Cancer

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals exploring the latest innovative research in clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase I and Sarcoma Programs. Today, I'm happy to be joined by Dr. Joyce Shin, an endocrine surgeon and surgical director of the Cleveland Clinic Thyroid Center here at Cleveland Clinic. She is here today to give us a surgical insight on the use of molecular profiling tools for patients with thyroid cancer. Welcome, Joyce.

Joyce Shin, MD: Thank you. Thank you for having me.

Dale Shepard, MD, PhD: Absolutely. Maybe to start out, give us an idea of what your role is here at Cleveland Clinic.

Joyce Shin, MD: I actually came here in 2009 as a clinical fellow for endocrine surgery. Since 2010, I've been on endocrine surgery staff. And then I was appointed to the surgical director of the Thyroid Center I believe about eight or nine years ago. We have the Cleveland Clinic Thyroid Center is known for its excellence and it involves taking care of patients with thyroid diseases, a lot of thyroid cancer, and it allows us to work with many other specialists. It's a multidisciplinary approach in dealing with patients with thyroid cancer. We try to deliver excellent care for patients with thyroid disorders.

Dale Shepard, MD, PhD: Excellent. We've had a couple of previous episodes of our podcast and we've talked about thyroid cancer, but maybe just as a backdrop, give us an idea, thyroid cancer, what is thyroid cancer? How common is it?

Joyce Shin, MD: The thyroid is an organ that is placed in front of the neck, so on top of the trachea or the windpipe. It is one of the four endocrine disorders that I operate on. It's thyroid, parathyroidal, adrenal, and pancreas, but thyroid disorders is the most common. Most of my patients have thyroid disorders, whether it's benign or malignant. Thyroid cancer is now the fastest growing cancer among women. But fortunately though, most of thyroid cancer is very treatable. Now, why is it becoming so rapidly fast growing?

One of the concepts is that we do a lot of imaging further study, so we're starting to find smaller lesions that's not even palpable. It's just instantly found on other imagings like CT or MRI or other ultrasounds of the carotid. But there are other environmental factors, family history, things like that, that will also predispose patients to having thyroid cancer. Although very treatable, it is very fast growing and it is the most common endocrine disorders that we deal with.

Dale Shepard, MD, PhD: When we think about detection, you mentioned we do more pictures and we see more nodules on films. Is that becoming the most common way this is identified, or is it still identifying nodules through annual physicals and things like that?

Joyce Shin, MD: That's a good question. A lot of patients who come to me for thyroid cancer, they say, "Well, I didn't have any symptoms. The only reason it was picked up is because I had some imaging studies." The smaller cancers that are not palpable, less than two centimeters or sometimes even three centimeters, you can't really palpate it unless it's firm or if the patient has a really thin neck. Most of the times now we're seeing a lot of these smaller cancers incidentally, and then they undergo more workup and biopsies, and then they become known as cancer. But a lot of the cancers now are not found on physical exam, unfortunately.

The larger nodules that become cancer have been there for a while. They probably had the cancer for a longer time. It's unfortunate that we're finding more cancers, but we're finding them earlier as well. The early detection, better prognosis. There is a little bit of a mix of, how do we find these cancers? A lot of the time it is just incidentally in imaging, but physical exam is also very important. Because if it's large enough, you could palpate it on physical exam. The unfortunate thing with thyroid cancer is that there are not a lot of symptoms related to it.

A lot of people come and see me and say, "My voice has changed," but that's not the usual symptom of thyroid cancer unless it's very invasive. Unless you feel something where it's a little bit more constricting around your neck, most of the time it's really asymptomatic.

Dale Shepard, MD, PhD: I guess just as a backdrop, we say becoming more common, what's the annual number of cases? How many cases are we really talking about?

Joyce Shin, MD: I can't give you an exact number, but I would say about one out of five women will have a thyroid nodule detected. That means one out of five women will have something in the thyroid and each nodule will have about a 5 to 15 percent getting cancer. Although the percentage is low, the amount of thyroid nodules is high. And also just because you have a thyroid nodule that is not benign at the present moment doesn't mean that it can turn into cancer.

Once a thyroid nodule is detected, it's very important for the patient to be followed up routinely on imaging or something so that we keep an eye on it, because a lot of these cancers will stay indolent or small. And then in a few decades or even a few years, they can become a cancer. Once it's detected, the most important thing is for routine follow up.

Dale Shepard, MD, PhD: And then I guess just to finalize the intro part here, there's some reassurance that we do see patients a lot that come in for imaging for other things and they have a nodule. You mentioned like 5 to 15 percent of the time these are cancers. At least while the workup is being started, we can provide a little bit of reassurance that probably nothing to worry about.

Joyce Shin, MD: Most of the time, I mean, that's a pretty good percentage of not being cancer. There are some risk factors such as family history, radiation exposure as a child or an infant, some environmental factors as well. Those are the things that we always ask our patients when we see them because that would increase their risk of cancer. But most of the time they're not cancer, which is a good thing. Absolutely.

Dale Shepard, MD, PhD: I guess part of the advantage here at the clinic, you mentioned about multidisciplinary care. As a surgeon, certainly we're a high volume place for doing these surgeries. What are some of the advantages of coming here where there's higher volumes and more multidisciplinary care?

Joyce Shin, MD: It is a proven fact that high volume surgeons have better outcome, not just in the field of endocrine surgery, but I would say for all specialties of surgery. Because the more experience that you have, the better the outcome, the more experience. Coming to the Cleveland Clinic, it's the Cleveland Clinic. I mean, we have fabulous surgeons, we have fabulous medical staff. We're known for good care and good outcome. The good thing about this multidisciplinary approach that we have is that sometimes we get very difficult patients, not the bread and butter first-time cancers. We see a lot of recurrent cases, persistent disease.

If patients have had their surgeries initially by someone who was not familiar with doing thyroid surgeries or other surgeries, then they initially don't get the right procedure. Then we are dealing with a re-operative neck. That's kind of a word you don't want to hear because there's going to be scarring. It's a harder surgery, more morbidity. But we're trained to operate. I mean I would say about 20 to 25 percent of the patients that we see are re-operative cases. We do have a lot of experience in operating on patients not only with difficult disease, but also patients who need surgeries second, third, fourth time around.

Those patients usually have very extensive or more aggressive disease, which will require not just a surgeon removing the cancer, but also medical endocrinologists, regular oncologists, radiation oncologists, ENT surgeons who deal with very advanced cancers that may require laryngectomy. We have all these resources, because it just doesn't require one person for cure, but we really work with our other specialists so that the patient get not even just neoadjuvant, but adjuvant care, which is the treatment they need after surgery.

Dale Shepard, MD, PhD: Let's go to the very beginning. Somebody has a nodule. How do we find out if there's a cancer? Walk us through where we've been and where we're going.

Joyce Shin, MD: Sure. Now that we are seeing nodules, whether it was found incidentally or on physical exam or maybe even the patient was feeling the neck and found something, the first thing, they'll most often be seeing their primary care provider and he or she will do some more workup, whether that means an ultrasound of the neck is usually the most appropriate and the most noninvasive test, or they'll just be directly referred to a thyroid specialist. At that time, the Endocrinology and Metabolism Institute, which consists of endocrine surgeons and medical endocrinologists, we are equipped in our offices to do ultrasounds in the office.

The first time we see the patient, we'll perform the ultrasound in the office. All the endocrine surgeons and some of the medical endocrinologists will offer fine needle asp biopsy at the time of the first consult, which is really nice because a lot of our patients, as you know, who come to the clinic come from far away and they don't want to come back for another ultrasound or another biopsy. We do this what we call this one-stop shop. They're very happy that they get everything done at the first consultation. The fine needle aspiration biopsy is the best tool in diagnosing whether a thyroid nodule is cancer or not very good outcome and there is minimal downtime. Really there's no downtime. I mean, you do the procedure while the patient's there and they go back to work. It's like getting a blood draw, but it's in the neck so it's a little bit more uncomfortable, but no downtime at all. Very minimal risk in the hands of a good technician. And that will be the usual step. Of course, the biopsies are great, but unfortunately, it's not always black and white. There's some gray areas in terms of what the results are.

Dale Shepard, MD, PhD: Tell us a little bit about that part. What are the likely outcomes from a staging off of a fine needle aspiration?

Joyce Shin, MD: People who deal with thyroid nodules and other thyroidologists and are cytologists have this common vocabulary that we use. We call this the Bethesda System for thyroid cytology where there's five categories. There is benign, then there's the obvious cancer, and then there is things in between such as what we consider indeterminate nodules. Depending on if it is an indeterminate nodule or not, there is some other things that now that we can do because before molecular testing, which I'll get into, if it was an indeterminate nodule, you automatically got a diagnostic lobectomy or something in the operating room, which nobody wants to have surgery just to figure out what it is.

A non-invasive procedure will be ideal, but that was not always available. If it was benign, we followed it. If it was cancer, this patient had surgery. And if it was this kind of middle gray zone, indeterminate nodules, then we gave the patient a choice. Do you want to a diagnostic surgery, or do you want to follow it? That really became the conversation between the surgeon and the patient. But now we have some other tools that will sway us one way or the other.

Dale Shepard, MD, PhD: That's where we get into the molecular profiling. Tell us how that works.

Joyce Shin, MD: The molecular profiling that we use, called Afirma testing, when we do the biopsy, we take a small specimen and we will send it routinely to a cytologist. We smear the cells on a slide and they will be able to look at it on the microscope and be allowed to tell us if it's one of those categories. But sometimes there are some atypical cells and they can't call it benign, they can't call it cancer. What we do is we save a small fluid from the initial aspirate and we put it into this Afirma tube, which is molecular profiling. That tube gets sent only if it is one of those indeterminate nodules. If it's benign, we don't need Afirma testing.

If it's cancer, we don't need Afirma testing, unless we need it for further treatment like an adjuvant therapy for aggressive cancers. But if it's one of these indeterminate nodules, whether it's a follicular neoplasm, suspicious for follicular neoplasm, or a follicular lesion of undetermined significance, those are the two categories, then we'll send it to Afirma. There's two results. They will look at all the mutations that could possibly be and they'll test it for thousands and they'll be able to let us know if it is benign or if it's cancer or suspicious is the word that they use.

The great thing about the molecular testing that we use is that it has a great negative predictive rate, meaning that if they call it benign, it's about almost 95 percent that it is benign, which is just as good as having a false negative rate of 5 percent. We treat them like a benign nodule and we follow up accordingly with routine ultrasound. But if they call it suspicious, the cancer rate is about 50 percent. I mean, most patients get a little bit anxious at that time of having a 50 percent chance of having cancer.

Then that leads to another conversation of, what do we do at this point? There are only a few patients that would have to say that hear Afirma suspicions and say, "Well, I don't want surgery. I'm just going to live with it." Most patients will like some type of a procedure done, and that procedure is the discussion between the surgeon and the patient.

Dale Shepard, MD, PhD: You get a cancer, no cancer suspicion, but you had mentioned that this also could give you information about treatment options as well. Is that being incorporated as well, things like certain mutations that might have therapies associated with them?

Joyce Shin, MD: Yes. Like I said, we do not routinely send out the Afirma molecular testing unless it's one of these indeterminate nodules. But I recently had a patient who had a very aggressive cancer and the Afirma tube is kept within our facility for a certain amount of time. I ended up operating on this patient. He had a very aggressive tumor where it was not an R0 resection. I know that he has some type of aggressive form.

Then what I would do is I would ask our Afirma company to take that tube, although it was routinely PTC, we don't routinely send it, but then they'll analyze the initial FNA for certain mutations that can be targeted for our oncologist later on if he ever needs to get adjuvant therapy such as targeted therapy for thyroid cancer or even external beam radiation. That becomes really helpful for our oncology colleagues.

Dale Shepard, MD, PhD: If you have an aspiration, not quite clear if it's cancer or not, you send off this test, what kind of lead time? How much time does that add for an answer for the patient?

Joyce Shin, MD: When this Afirma first came into play for us, it took about six weeks. Now it's much faster. I would say an average of three weeks, so about half the time. By the time we get the Afirma result back, it's in time for them to have surgery. It's very helpful, and it doesn't really delay the treatment plan because it's back in a few weeks, which is nice.

Dale Shepard, MD, PhD: Tell us a little bit about the availability of this. Is this something that's becoming standard of practice, or is this something that some centers are more likely to do or not?

Joyce Shin, MD: There are other molecular testing as well, Thyroseq being the competitor. Thyroseq and Afirma both tend to have relatively the same positive and negative predictive value. Not one is better than another, because I have colleagues all over the country who either use Afirma or Thyroseq. The clinic just started utilizing Afirma several years ago, and it started within our institute because I would say we do the most volume of biopsies. It's funny that you mentioned that because we are now having some of our radiology colleagues, like interventional radiology, do some of these biopsies. Now they are being trained to do Afirma testing.

Now we are really training our whole radiology team, not just at main campus, but all the regional centers, including Akron to utilize this. We have a wonderful rep who is now educating them. The great thing is that the procedure is mostly covered by insurance and it's only utilized if it's one of those two categories. About 25 percent of them up to 30 percent will actually need the molecular testing. Not every biopsy needs it.

Dale Shepard, MD, PhD: That's good to hear though, because it seems like this is a commonplace enough problem where a primary care doc may be the one that sees the nodule and may send a radiology. As an endocrine surgeon, you, of course, are doing this, but there's a lot of avenues for people getting biopsies. It's good to hear that it's a little bit more diverse. When we think about that sort of diversity of patients, are there particular patients certainly redo operations and things like that? Are there categories of patients that really do need to see an endocrine specialist rather than starting the process maybe with a biopsy going from there?

Joyce Shin, MD: Within the clinic, the Endocrinology and Metabolism Institute is very available. I think people know that once a patient has a mass in the neck, a lot of them just get sent directly to us. But the ones that need to be seen are the ones that have rapidly growing masses, patients who may have some nerve compromise. Hoarseness would be another one, that just kind of indication of a potential aggressive disorder, thyroid disease, and just really anyone with a rapidly growing mass would be concerning for something.

And then patients obviously with metastatic disease, especially in the neck and distant, although most of the thyroid cancers metastasize locally in the neck to lymph nodes. There are patients who this has been an undiagnosed disorder for a long time, they could have metastatic disease to other parts of the body.

Dale Shepard, MD, PhD: I guess just a final thought, are there particular gaps either from a surgical perspective, surgical techniques? Are there new things being done to address those? Or on a diagnostic, the molecular profiling is certainly helping identify the right patients that need surgery. Are there other things that are coming along that you're excited about?

Joyce Shin, MD: The molecular testing, the companies are always finding new mutations. We are actually working with some of the clinicians who work directly for the molecular testing companies and are representatives for Afirma where new mutations are coming along. I mean, they're testing on most days with new mutations that will help us lead into the surgical decision, whether a partial thyroidectomy will be sufficient or if there are certain mutations that will make us lean towards a total thyroidectomy. That's where our decision making now is, is that once Afirma is done, then the specifics and the details of that will lead us into a partial or a total thyroidectomy. It leads us into our decision tree.

Dale Shepard, MD, PhD: Is there anything from a surgical standpoint, the technique itself that seems particularly exciting?

Joyce Shin, MD: One of my partners had been performing robotic thyroidectomies for a long time. This is a technique that was really started in Korea and it's done robotically through the axilla. The only real advantage of that, and I'm Korean so I know, is to prevent a cervical incision. Because in Korea, the neck was a sign of beauty. It's actually better to have a scar across your face than across the neck. They wanted to preserve that. They will make a bigger incision across axilla and make these flaps to get to the thyroid. The other technique that is being done not here is transorally, which is to make an incision right underneath the inner part of the lip and they would make flaps and go downwards of that.

Now, these are very technically challenging. But like I said, the usual way is to just go through the neck. But some patients are very sheepish is about having an incision on the neck, so they will do these other procedures, although they do require a very talented surgeon and there are some other morbidities associated with that. At the clinic right now, we are using some robotic surgeries, but our standard of care for most of us is still through the neck. Now, it's not like back in the day they used to make an incision from ear to ear. We don't do that anymore. We do where a lot of patients ask about, "Are you going to do my surgery laparoscopically or minimally invasive?"

Those are all fancy terms just to say we're going to make a very small incision, because sometimes our incisions are even smaller than what incision you need to put in a scope. We don't do laparoscopic. It's just that we wear these magnifying loops. We have special lighting in the OR where we're able to see very small things. We're able to do this through a very small incision.

Dale Shepard, MD, PhD: Very good. Well, thank you for all of your insights today.

Joyce Shin, MD: Thank you.

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