Lori Wirth, MD: Hello, and welcome to this OncLive® Peer Exchange® titled“The Evolving Landscape of Differentiated Thyroid Cancer Treatment.” I’m Dr Lori Wirth, the medical director of the Center for Head and Neck Cancers at Massachusetts General Hospital [in Boston, Massachusetts]. Joining me in this discussion are my colleagues. I’m going to ask them to introduce themselves. Giuseppe?

Giuseppe Barbesino, MD: Good afternoon. I’m Giuseppe Barbesino, one of the endocrinologists at Mass General Hospital in Boston. I work with Lori very closely on patients with thyroid cancer. Thank you for having me.

Lori Wirth, MD: Marcia, please introduce yourself.

Marcia Brose, MD, PhD, FASCO: Hi, I’m Marcia Brose, and I’m the chief of cancer services at the Sidney Kimmel Cancer Center, Jefferson Northeast Division. I’m also the head of the advanced thyroid cancer program. Thank you for having me.

Lori Wirth, MD: Naifa?

Naifa L. Busaidy, MD, FACP, FACE: Hi, I’m Naifa Busaidy, and I’m an oncologic endocrinologist. I work at [The University of Texas] MD Anderson Cancer Center in Houston, Texas. It’s my pleasure to be here. I do clinical trials in thyroid cancer, and love what I do.

Lori Wirth, MD: Great to have you. Last and certainly not least, Maria.

Maria E. Cabanillas, MD: My name is Maria Cabanillas. I am also an oncologic endocrinologist at MD Anderson. I treat thyroid cancer, both early stage and advanced thyroid cancers. And I’m the faculty director [of clinical research in the department of endocrine neoplasia].

Lori Wirth, MD: Thank you, everyone. We’re going to discuss a number of topics pertaining to the treatment of DTC [differentiated thyroid cancer] from a medical oncology perspective as well the endocrinology perspective. We’ll discuss the latest treatment and the impact of recent clinical trials on treatment selection and patient management. Let’s get started on our first topic. Giuseppe, tell us a little about the basics of thyroid cancer.

Giuseppe Barbesino, MD: Thank you, Lori. When we think about the follicular thyroid cell, which is the most important constituent of the thyroid, there are basically two main lineages of cancer that we see. And they have somewhat different epidemiology and different clinical behavior. The papillary thyroid cancer we’ll start from is the most common type. It’s seen across the ages with mostly nodal metastasis, sometimes lung and occasionally other organs. Then we have the follicular type that tends to metastasize to the bone, but the lungs can also be involved. Of course, other localizations can happen.

Then there’s a series of higher-grade histologies, which include subtypes of papillary thyroid cancer with more aggressive behavior and also more aggressive appearance on histology. We don’t have time to list them all, but there are many. Then there’s Hurthle cell carcinoma, which increasingly occupies a slot of its own previously classified under the follicular thyroid cancer. But it’s clear from molecular studies and from the clinical behavior that that’s a cell with a different origin from the follicular cancer. Then we have the more dangerously, fully differentiated carcinomas. They can derive both from papillary or follicular cancers, ending in the deadly anaplastic, which is 1 of the most aggressive cancers in humans.

That’s as far as the follicular thyroid cell. As you know, there are also other cells within the thyroid. There are C cells [parafollicular cells], completely different neuroendocrine cells, and from those the majority of cancer also with its own subset of different aggressiveness and behaviors are derived. It’s not really the topic today, but it’s important to classify that among the different types of thyroid cancers.

In terms of how we stage them, there have been several staging systems and a difference with many cancers. We do recognize that age is a risk factor for the outcome of thyroid cancer, and that it’s largely independent of other typical adverse risk factors that we see playing a role in other types of tumors. What this means is that given, for example, a thyroid cancer that’s 5 cm at maximum diameter, the risks of an incomplete response after initial treatment are higher in patients who are older than 55 years old. In addition, older patients who experience an incomplete response will have a greater mortality than younger subjects with an incomplete response.

This seems to be particularly clear in the most common type of papillary thyroid cancer: the 1 driven by the BRAF V600E mutation, which is about 50% of cases of papillary. The data suggest that older patients with BRAF V600E have a much greater mortality than younger patients with the same mutation. Instead, people with wild-type BRAF and papillary thyroid cancer will have no clear difference with age. There are a lot of subtleties to this classification based on age. It’s also important to realize that studies have changed our staging. Older studies suggested that age 45 was a suitable turning point for thyroid cancer mortality, with people older than 45 being more likely to die from thyroid cancer. But more recent studies in larger populations with more sophisticated statistics suggested that 55 is a closer or more adequate cutoff. This has resulted in changing in our staging system, the AGCC [American Joint Committee on Cancer] staging system, in which we use 55 as a cutoff for classifying tumors in terms of risk.

It’s clear that age acts as a continuous variable and that these cookie-cutter methods can be optimized. They’re a handful mnemonically, but they reflect only partially a more complex reality, with age being a factor among many others. Indeed, the many others are factors that are clearly known to all oncologists. The size of the tumor is very important, as is the completeness of the resection and the extension of the disease outside the thyroid at the time of diagnosis.

There’s 1 important factor, however. It’s different with other tumors: at least with the well-differentiated thyroid cancer, the presence or absence of nodal metastasis is not associated with an increased mortality in many states. It’s different from many other cancers. It’s something that’s important to stress with patients because when they hear that there’s 1 nodal metastasis, the horse is out of the barn, and in reality that’s not the case. It’s peculiar. Sometimes I tell my patients or I think about it and say, “This thyroid cancer is the only cancer in which lymph nodes do their job,” meaning blocking the cancer before it becomes deadly. This is the way I look at the classification. Of course, there are very important staging systems with detailed tables that I’d refer to and turn to. But this is a story of how I see the staging of thyroid cancer.

Transcript edited for clarity.