Personalized Approaches in Thyroid Cancer Surgery

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals exploring the latest innovative research and clinical advances in the field of oncology.

Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepherd, a Medical Oncologist, Director of International Programs for the Cancer Institute and Co-Director of the Sarcoma Program at Cleveland Clinic. Today I'm happy to be joined by Dr. Sam Trosman, a Head and Neck Surgeon at Cleveland Clinic in Weston, Florida. He's here to talk about personalized approaches to thyroid cancer surgery. So welcome, Sam.

Samuel Trosman, MD: Thank you. Thanks for having me.

Dale Shepard, MD, PhD: So give us a little bit of an idea of what you do as a head and neck surgeon there in Florida?

Samuel Trosman, MD: Basically, my background training is in ENT, which is otolaryngology head and neck surgery, which essentially covers all medical and surgical treatments of the head and neck area. And then my fellowship was specifically in head and neck cancer, which is a pretty heterogeneous field involving throat cancer and adjusted tract, tongue, a lot of smoking related cancers traditionally, as well as skin and skull base. And a big part of my practice is thyroid disease. So thyroid cancer is one that has rapidly risen as far as incident goes, over the past 20, 30 years. So something that has come across incredibly common, especially ones that are found incidentally that we're seeing more and more as people get scans and things like that. That's sort of the gist of it.

Dale Shepard, MD, PhD: Okay, so we're going to be talking about thyroid cancer. About how many cases of thyroid cancer do we see a year?

Samuel Trosman, MD: The last kind of big study that I'm aware of cancer trends that came out, it was about 10 years ago. There've been probably updates since then, but for example, incidence wise, 1995 was about six per 100,000 people. By 2010 that had risen to about 14. And the rates separates between women and men. In 1995, about eight women per 100,000, that had risen up to about 21. Men, same thing, much lower incidence, about three, it had risen to about six. So pretty significant rises there.

Dale Shepard, MD, PhD: Pretty significant rise. I guess we're going to end up talking here about personalized approaches to managing thyroid cancer. Some of those increases, do we think there's actually more cancer? Is there more awareness? Is there more imaging and we find it? How much do you think is real and how much do you think of it is our fault, if you will, for looking?

Samuel Trosman, MD: Out of that study, and again, this is several years ago, but kind of eye-opening but also controversial at the same time. The key quote that I always remember is they describe it... because the mortality rate did not really change. It was not zero, but was very, very low despite the increase in incidence. The theory is that we're finding it more and more by getting ultrasounds and CTs, any trauma CTs, CT chest, ultrasound of the carotids, a lot of these are scans that people get that I get referred for incidental finding of nodules.

So yeah, the key statement from these investigators was that the epidemiology of the increased incidence suggests that it is not an epidemic of disease, but rather an epidemic of diagnosis. So essentially definitely over-diagnosing, but I think the key to remember is while thyroid cancer mortality is low, it is not zero. And there is patients that are at moderately high risk and there are patients that are at very high risk depending on their pathology. And the reason we're still treating these patients is we don't know who's going to fall into which category.

Dale Shepard, MD, PhD: And that sort of takes us directly into sort of individualizing care for patients. When we think about something what's referred to as personalized surgery approaches, what exactly does that mean?

Samuel Trosman, MD: Yeah, so I think with thyroid cancer over the years, it was years ago, it would be well, suspicious nodule or suspicious for cancer, total thyroid activate, everybody. But that's a larger surgery. It has a risk of low calcium afterwards, you need to be on thyroid medication the rest of your life, it has the risk of the recurrent laryngeal nerve, basically the voice nerves that sit behind the thyroid, having damage.

So what we found is in a lot of cancers, especially those less than four centimeters and nearly all of them, less than one centimeter, removing just the side of the thyroid where the cancer is located is sufficient. So it's essentially the degree of surgery, number one, which is removing half or near half or the whole thing. It's lymph node removal and the extent of that. And in some cases, especially in small tumors, in older patients or patients who have medical comorbidities, it's, do surgery at all? Is it an active monitoring protocol?

Dale Shepard, MD, PhD: What are some of the factors that currently play into those decisions? Is it patient factors, tumor factors, some sort of markers that you're looking at?

Samuel Trosman, MD: Yeah, I think it's a little bit of everything. Patient factors definitely, in comorbidities, age, risk factors, family history and radiation exposure, prior neck surgeries. And in my practice it's a lot of getting to know the patients, what they do. You treat a patient who's a voice major or a professional singer, very different than you would somebody who's retired and not really using their voice frequently. As far as tumor factors and know molecular genetic testing, molecular sequencing, we're using it for what's called indeterminate nodules. Nodules that we're not sure have cancer or not, frequently. It's not quite to a stage where we're using it on an every nodule as far as creating a molecular signature of their tumor. But I think that's definitely going to be in the future as hopefully the costs come down and those techniques become more sophisticated. Right now, getting covered by insurance is a little challenging and frankly we don't know exactly how it would change our management as far as long-term data on that, but I do think that's coming down the line as it probably is for all tumors.

Dale Shepard, MD, PhD: When you think about thyroid tumors in general, thyroid nodules, how does the multidisciplinary nature of care take place? So want to imagine that primary care finds a thyroid nodule. Does that end up being seen initially by endocrinologist or an endocrine surgeon or someone like yourself who's an otolaryngologist? How does sort of the path go for a patient?

Samuel Trosman, MD: At Cleveland Clinic, we're actively working on sort of streamlining that. The answer right now is all of the above, and it really just depends on the referral patterns and who sees it and where it's referred to. I think what we're trying to do is standardize that sort of algorithm and that approach. That's still going to be kind of fine-tuned over the next year or two. But where we're at right now with thyroid nodules is if one is discovered, the initial workup involves getting a TSH level to make sure that it's non-functional and it's not over producing hormone because that workup is very different. And assuming that it's not, it would be the number one imaging modality is an ultrasound, which is very sensitive at picking out high-risk features. And the ATA has guidelines based on size and ultrasound characteristics as to when they recommend doing biopsies and what's suspicious and what's not. Obviously with clinical concern being mixed in as well.

And then, yeah, I think that the algorithm that we're working on tentatively, anything that's over a centimeter and or has suspicious ultrasound features, the recommendation would be to refer to an endocrinologist that specializes in thyroid disease, with the exception once it gets over four centimeters or if there are significant concerns amongst voice issues, compression, things like that, then there's certainly a benefit to referred directly to a surgeon, either endocrine surgeon, otolaryngologist general surgeon, somebody who has experience with thyroid surgery. Those details are still, we're trying to parse out.

Dale Shepard, MD, PhD: If you think about overall management of thyroid cancers, do you think that the greatest opportunities are in making sure that people with nodules that are really cancers and serious are getting adequate treatment or decrease your de-escalating treatment in people who have known cancer? So are we over treating or under treating?

Samuel Trosman, MD: Yeah, it's a good question. I would say just from a cancer doctor's perspective, my fear is always under treating. If you have a small papillary cancer that ends up being low risk and you do a lobectomy that ends up going well, you don't know whether or not that would've ever impacted the patient long-term. Could they have passed away from other factors and never had to undergo that surgery? It's certainly possible, there's no way to answer that question, but generally the surgery is relatively low risk in the right hands and in the right patient. I think the fear is always doing surveillance or monitoring or doing too little of surgery where you have cancer that actually becomes more aggressive than you think, or even turns into something like a poorly differentiated or anaplastic cancers, which are, so when we talk about thyroid cancers, 90 plus percent are what's called differentiated.

The papillary and follicular, that by and large have excellent survival rates. They invented the staging system, the AJCC, years ago to make these essentially in younger patients, they're all stage one unless they're metastatic. Well, on the other end of the spectrum is something like anaplastic or undifferentiated, where the cancers don't retain the thyroid architecture. The theory is that those arise over years from papillary cancers and those are all stage four essentially. So opposite end of the spectrum used to be highly lethal. Now with immunotherapy, we have a little bit more tools to treat those, but that's what you don't want to miss is something that's actually going to cause significant morbidity and mortality.

Dale Shepard, MD, PhD: When you think about active surveillance or all the way through sort of the personalized approach and maybe not doing a node dissection in certain patients or things like that, are these things that are pretty commonly being practiced in community as well, or is this something that where someone has seen matters much?

Samuel Trosman, MD: I think it certainly matters to a degree. I think there is good evidence about limiting complications and overall success rates of surgery based on multiple metrics for high volume surgeons, and there I think they're looking at something like 50 plus cases a year. And those results have been shown over and over again. I do think that there is benefit in going to high volume surgeons at academic centers, but that's not to say that somebody who has experience, who feels comfortable, who has good outcomes doing less than that is not safer or is not doing adequate surgery. I think it's just a matter of staying up to date with the guidelines of multidisciplinary care, which in mine and probably your practice, traditionally we think of multidisciplinary care and cancer with radiation and medical oncology, and thyroid is a little bit different.

It's multidisciplinary care really with the endocrinologist for the differentiated cancers, and the degree of treatment and then degree in what you do for surveillance. Because the other kind of aspect to this is because a lot of these cancers are not aggressive enough towards things like chemotherapy, like radiation, external beam radium radiation therapy. The one tool we have to treat is radioactive iodine, which is basically a pill to kill off any thyroid cancer cells that may be present and it works quite well. The kicker to that is you really have to have a total thyroidectomy in order to use that. So I think in any time where we consider deescalating degree of surgery or escalating degree of surgery, depending on the patient, it's important to have that communication because if your endocrinologist thinks that the patient warrants radioactive iodine, that shouldn't impact your degree of surgery, because otherwise if you do a lobectomy, they're not going to be able to use it and you just going to have to do another surgery. So I think all those factor in as far as patient discussion.

Dale Shepard, MD, PhD: So I guess sort of this personalized approach and ability to perhaps deescalate therapy from a surgical standpoint has to do with risk assessment. You briefly talked about maybe availability of markers or things like that. What's being looked at currently in terms of maybe modifying risk assessments and really optimizing that part in order to know who we should be treating in what way?

Samuel Trosman, MD: Yeah, I think the molecular markers are definitely important. Right now there is an overall risk calculator that we use, endocrinologists use standardly as far as risk of recurrence. There's different ones based on survival risk, which are more AJCC based, and then the risk of recurrence from the cancer, which is going to be a little bit higher and more tumor-based. And the calculators are pretty good. The kicker or the caveat to that is, with a small recurrence, we sometimes don't know what the significance of that is because there's some studies that show that the actual survival of the patient is not necessarily affected, although CAD called morbidity based on location.

As far as the molecular testing goes, yeah, we certainly will get it for our indeterminate nodules, meaning those where we have atypical cells but are not certain whether they need surgery, what the aggressive nature is, and more and more people are using it for frankly cancerous nodules, where you send it off for genetic testing. And then there's certain mutations that are associated with an increased risk of not only cancer, but also of spread to lymph nodes. So in those, even if it is a small nodule, we would recommend total thyroidectomy for example, even if there's not something like that on the other side, because of a higher risk of lymph node spread, that at least warrants a consideration of radioactive iodine.

And in those cases, you could suddenly make an argument for removing the central neck lymph nodes at least on the side of the tumor, depending on what you see. So again, the exact degree of surgery, it varies a little bit as to how aggressive some people are. I think some of that is going to change based on the upcoming guidelines, hopefully later this year. But yeah, I think it's still... Because a central neck dissection is not overly morbid, but it still has potential to make you hypocalcemic, depending on what the status of the parathyroid gland is. I think it can't be taken as do it on everybody. I think that's going to be overkill.

Dale Shepard, MD, PhD: Just the focus on the surgical technique itself. Is there anything that you see currently as something that you'd like to see change from the technique? Is there anything new coming around in terms of how these surgeries are performed?

Samuel Trosman, MD: I think there's always little nuances. A lot of the technical details are really surgeon preference, and I don't think there's a right or wrong way to use anything. I think that right now, I would say nearly standard of care is to use the nerve monitoring tubes, which help us delineate the integrity of the recurrent laryngeal nerves, which I think have pluses and minuses to them. But I think are especially helpful when doing a total thyroidectomy because the one thing you really want to avoid is a severe complication would be bilateral vocal fold paralysis, which is rare, but obviously it can lead to significant shortness of breath, quality of life issues. So I think the nerve is helpful from that regard, and I think there's advances in that technology.

I think that right now there are services, I've not used them personally but I've at least considered it, for certain cases to have active EMG monitoring of the recurrent laryngeal nerve, because there is a lot of retraction in the nerve and displacement to have that somebody in the room saying when they're seeing some weakness develop, that you can give it time to relax and assess the integrity again, especially in cases where you're doing a total. So that will probably become more and more use depending on resources and overall cost.

There are pretty good techniques nowadays for detection of parathyroid glands that really is more used for parathyroid surgery. But for central neck dissections, especially the inferior gland, almost always gets either taken with the dissection or debascularized. So in cases of re-implantation for identifying those, I always check it pathologically because the last thing you ever want to do is re-implant a lymph node with cancer. But as adjuncts, those techniques are useful for detection of glands. I think those are kind of the big ones.

Dale Shepard, MD, PhD: Well, it certainly looks like a lot of things going on in terms of thyroid cancers and how we manage them, and appreciate you being with us today to share your insights.

Samuel Trosman, MD: Anytime. We'll see what the guidelines show when they come out again, the last ones were 2015, so it's been quite a while and I expect a lot of things to stay the same, but some things could change as well.

Dale Shepard, MD, PhD: Yeah, well look forward to hearing about it.

Samuel Trosman, MD: All right, sounds good.

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