Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And joining me today, we have Dr. Ioannis Papagiannis. He's an Assistant Professor of Medicine in the Division of Endocrinology, Metabolism and Molecular Medicine at Northwestern Medicine. He's here to discuss the most meaningful updates in thyroid cancer care, specifically the changes within the 2025 American Thyroid Association Differentiated Thyroid Cancer Guidelines.

Ioannis Papagiannis, MD: Good morning. And thank you for the invitation.

Melanie Cole, MS: Thank you so much for being with us today. So to begin, can you summarize the most important updates as you see it, that were featured in the 2025 American Thyroid Association Guidelines for Differentiated Thyroid Cancer.

Ioannis Papagiannis, MD: Absolutely. The previous guidelines were combined thyroid cancer and thyroid nodule guidelines. The current 2025 guidelines are specifically only for differentiated thyroid cancer. They separate between the different pathologies of thyroid cancer—papillary, follicular, and oncocytic—whereas previously they were all lumped together.

They have a much more accurate and updated initial risk stratification system. They also are leaning more heavily into deescalation of care, choosing the appropriate initial surgery, choosing the appropriate patients to treat with the radioactive iodine, as well as facilitating easier and simpler followup.

Melanie Cole, MS: And we are going to get into some of those specifics in a minute as we break it down a little bit. So, the updated guidelines place an emphasis on refined risk stratification models. What are some of the biggest shifts, Doctor, that clinicians, that you want them to be aware of, and how should these influence initial management plans?

Ioannis Papagiannis, MD: Thank you for this question. So, the previous guidelines had essentially three broad categories: low, high, and intermediate. And intermediate was kind of a big bucket category that a lot of diseases that didn't really belong together were clumped into. The new guidelines have four categories. They are essentially low, low intermediate, intermediate high and high. And they are different for papillary follicular as well as oncocytic thyroid cancer.

The features that are actually able to describe different diseases incorporate a lot more pathologic features than the previous guidelines. For example, extrathyroidal extension, vascular invasion, multifocality, unilateral or bilateral. And these are a little bit more accurate in predicting recurrence risk. So, they're a little bit better at allowing us to risk stratify patients so we can initially recommend a more appropriate surgery, deescalate it if possible, identify the patients that will or will not benefit from radioactive iodine treatment. And the other thing is that this is a dynamic risk stratification, means that it can change during the course of the disease. It can be updated. We can incorporate new data into it.

Melanie Cole, MS: That's so interesting and important too. So, can you discuss how pathology-driven insights such as tumor genomics or more nuanced histologic criteria are really shaping this treatment selection in this differentiated thyroid cancer?

Ioannis Papagiannis, MD: So for example, tumor multifocality, we can have multiple tumors. And according to the new guidelines, if they're bilateral, that increases the recurrence risk. The new guidelines also incorporate things like extrathyroidal extension, number of lymph nodes, size of lymph nodes. These were present before, but they're a little bit more accurately able to describe a patient and categorize them and risk stratify them.

Also, the new guidelines mentioned a little bit more in depth about genomic changes. They don't discriminately recommend it on everyone, so they're not saying that everybody should get next generation sequencing. But when available, this info is incorporated with a cytological pathological knowledge we may have of the tumor so we can accurately risk stratify the patient. Additionally, and something that was not there before, the new guidelines mentioned the possibility of germline mutation so we can accurately predict tumors that may have a suspected genetic component.

Melanie Cole, MS: It's a pretty exciting time in your field, Doctor. So, there's a growing focus on treatment deescalation within thyroid cancer. So, what scenarios do the new guidelines outline where less aggressive therapy may be appropriate?

Ioannis Papagiannis, MD: This is something that has gradually changed over the last, I would say, 20 to 30 years. And the new guidelines make that a little bit more mainstream, if you will. They bring it out in the open. So traditionally, the treatment for thyroid cancer has been total thyroidectomy with or without radioactive iodine treatment.

The new guidelines explicitly say for the first-time that active surveillance is an option with shared decision-making, so as long as the patient is okay with that, for very small tumors that do not have any suspicious features. For example, a subcentimeter tumor without any cervical lymphadenopathy, active surveillance is an acceptable option. Also, for tumors that may be up to two centimeters or even up to four centimeters, again, with shared decision-making with the patient, lobectomy may be an acceptable option or maybe even be the preferred option other than total thyroidectomy.

Additionally, there is more data that may or may not recommend radioactive iodine, so this way we can avoid overtreating people with radioactive odine and avoiding complications or side effects.

And lastly, the thyroid suppression goals, the TSH goal, for postoperative thyroid hormone replacement are a little bit more inclusive, I would say, a little bit less strict. So, they allow thyroid hormone replacement to be more easily managed, keeping the patient where they need to be, minimizing complications, and side effects from the treatment.

Melanie Cole, MS: So, Doctor, based on these updated guidelines and with all of the new tools in your armamentarium and different therapies available, how important and what's the emphasis on the multidisciplinary care? What role do your colleagues, endocrinologists, surgeon, oncologists play in these developing therapies?

Ioannis Papagiannis, MD: So, the focus has been like that for a while, but it's even more evident now is for, as you mentioned, multidisciplinary care. So, we have input from the surgeon, from the cytopathologist who's looking at the specimen, from the endocrinologist that might have biopsied the nodule or done the initial neck ultrasound or even the primary care doctor that detected the nodule in the first place.

So, the idea is that along the course of the evaluation, we gather data. And that data allows us to tailor the treatment specifically for this particular patient. We don't do blanket treatments. We don't treat everybody the same way. This allows us to offer personalized care for the particular patient, the particular patient's features or characteristics, the particular tumor features or characteristics. This way, we treat the patients appropriately, avoiding overtreatment. And using some of the new guidelines that are associated with the risk factors, we do not undertreat the minority of patients that actually do need more aggressive approaches. And that comes from the initial surgery, choice of initial surgery, if there is any surgery at all. It comes from the selection for radioactive iodine treatment. It allows for TSH suppression goals to be a little bit more, I would say, less aggressive.

And lastly, it allows for the followup to be individually tailored. We don't offer a calendar for everyone to follow. The idea is that we offer surveillance that's tailored to the particular patient that's also dynamic based on the response. So gradually, for the vast majority of people who do very well, we don't need to offer aggressive imaging. We don't need to offer aggressive testing that may offer no benefit and may expose them to risks. So, there is also this deescalation of followup that's outlined in the new guidelines that was not there before.

Melanie Cole, MS: These are such important aspects. And along those lines, do you have some examples, Doctor, of how the guidelines promote that more patient-centered that you just mentioned? The individualized approach for surveillance, surgical decisions, adjuvant therapies. Can you give us some examples where you've seen this really come into practice?

Ioannis Papagiannis, MD: Absolutely. So, we have a number of patients that are a little bit elderly, and they have a very, very small thyroid cancer that has been there for a while. And traditionally, their recommendation is to send everybody to surgery. Active surveillance now is an acceptable option. The guidelines do recommend it is an accepted alternative. So, a lot of people that might have never needed surgery in the first place now are offered the choice to avoid it. And they have the choice to either proceed with surgery or surveillance.

Another example, we do have a lot of patients that have had some very small lymph nodes that may look suspicious. With the previous guidelines, their recommendation was to biopsy everything, and then surgery, if required, if recommended by the physician or the patient. Nowadays, the guidelines give us the option to actually leave any lymph nodes alone as long as they are small, less than eight to ten millimeters in the shorter axis as long as they're not close to critical structures and as long as they're not growing. So for a lot of patients that may have some findings that may appear suspicious, we can deescalate testing, we may avoid unnecessary biopsies or surgeries. That's something that will not affect the patient's health.

Melanie Cole, MS: This is such great information and thank you so much. As we get ready to wrap up, Doctor, for busy clinicians, what are some of the takeaways from the 2025 ATA guideline updates that could be integrated into everyday practice? Take us from bench to bedside and give us your key takeaways.

Ioannis Papagiannis, MD: So, I would say from the start to finish, from the initial identification of the patient and bench to bedside, the incorporation of any genomic knowledge that we have accumulated over the years, I would say the most important thing is to do proper initial risk stratification. Try to identify any risk factors that might put the patient at the higher risk category so we can offer individualized care. Not everybody deserves or needs the same surgery or the same radioactive iodine. So as we mentioned, active surveillance may be an option or even a lobectomy rather than a total thyroidectomy.

The guidelines also recommend, as I mentioned before, radioactive iodie for selected patients. And for the first time, they actually recommend that in order to decrease the amount of discomfort for the patient, that they recommend recombinant TSH stimulation rather than withdrawal, which is a little bit of a shift in the new guidelines. Also, allowing for more individualized and deescalated followup. So, we focus on thyroglobulin measurements, neck ultrasounds, avoiding CAT scans and MRIs and PET scans, and avoiding radiation exposure. That also allows for increased patient satisfaction, decreased stress, okay? And last but not least, I would say that thyroid hormone suppression has been a little bit less aggressive with the new guidelines that may avoid secondary complications from that.

So in summary, I would say that there is a lot more individualization in patient treatment. So, it's not a one-size-fits-all approach. It's a constant risk stratification from the very get-go, from the initial diagnosis all the way up to five or eight years later. That allows us to actually offer de-escalated, non-aggressive, non-harmful care to the majority of patients while, all at the same time, it allows us to identify the minority of patients that harbor more aggressive disease and they don't get undertreated.

Melanie Cole, MS: Wow. It's a lot of great information. Thank you so much, Doctor, for joining us today and sharing your incredible expertise for other providers. And to refer your patient or for more information, you can visit our website at breakthroughsforphysicians.nm.org/endocrinology to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole.