Early Detection Impacts Treatment Decisions in Thyroid Cancers

Catherine Sinclair, MD

Catherine Sinclair, MD

According to the American Cancer Society, the incidence of thyroid cancer is on the rise in the United States; however, Catherine Sinclair, MD, believes this is due to an increase in the diagnosis of thyroid cancer rather than an increase in the disease itself. Either way, the role of early detection of thyroid cancer is of utmost important today.

Patients with a family history of 2 or more people who have been diagnosed with thyroid cancer are at higher risk of developing thyroid cancer and should consider testing so that the disease can be caught early on. Additionally, women are more susceptible than men to develop thyroid cancer, as well as those who have previously been exposed to radiation or nuclear fallout.

When detected, well-differentiated thyroid cancers, including papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) tend to behave more indolently, and in some cases, patients diagnosed with a well-differentiated thyroid cancer may be observed for a period of time under active surveillance rather than being treated immediately. Surgery is the primary treatment for patients with thyroid cancer and is a particularly important strategy in patients with more aggressive diseases, such as medullary thyroid cancer (MTC), differentiated thyroid cancer (DTC), and anaplastic thyroid cancer (ATC).

For patients at higher risk for recurrence or for those with a more aggressive thyroid cancer, surgery may be followed by radioactive iodine (RAI) therapy. Molecular testing can identify genetic markers in patients as well that may put them at higher risk for recurrence and at greater need for RAI. By gaining a very clear picture of the patient’s risk factors and the disease early on, surgeons and oncologists can make the right treatment decisions for each individual patient.

In an interview withTargeted Oncology, Sinclair, associate professor at the Icahn School of Medicine and director of the Division of Head and Neck Surgery at Mount Sinai, discussed the importance of early detection in patients with thyroid cancer. She also highlighted surgical decisions for these patients and how she makes these choices for each patient.

TARGETED ONCOLOGY: Could you discuss the increase in thyroid cancer cases, and how frequently you are seeing thyroid cancer in your own practice?

Sinclair:There has been an increase in the incidence of thyroid cancer over the last few years. We think this is predominantly due to an increase in the diagnosis of thyroid cancer, perhaps not due to a true increase of the disease itself. When you look at that increase and you break it down by cancer size, what we see is that basically all of the increase has been in the small PTCs, in the order of 1-cm tumor size. This category is where the increase has really happened. The rest of the thyroid cancers of larger sizes and different histologic complications has remained relatively constant.

We do see in our practice testing increasing to predict which thyroid nodules that are found on scans, that’s the other reason. Particularly, PET/CT scans find patients with other forms of malignancies, and people have neck CT scans and MRIs for a variety of reasons, including neck pain, swallowing difficulty, and potentially spine abnormalities. We frequently see people come in with thyroid nodules that they themselves have not felt or no one has noticed upon examination, but they noticed on radiologic examinations and scans. We think the increased use of these scans has led to this increase in incidence of thyroid cancer.

TARGETED ONCOLOGY: What groups are more susceptible to developing thyroid cancer?

Sinclair:The known risk factors for thyroid cancer include radiation exposure, and that may be radiation of the malignancy, throat, or breast, as well as being near a nuclear fallout during childhood or adolescence. In addition, family history is important in thyroid cancer. Particularly, people with 2 or more relatives with a history of thyroid cancer are at increased risk of any given thyroid nodule being a cancerous nodule. Those are the main established risk factors for thyroid cancer.

There are other various unusual syndromes that can predispose a patient for thyroid cancer, but they are very rare and in the clinical practice, we rarely see those. The majority of people with thyroid cancer have what we call sporadic thyroid cancer, so they don’t have risk factors for thyroid cancer. They just develop thyroid cancer out of the blue, maybe within a pre-existing nodule or maybe it just comes into detection for another reason.

The population of people that we see are more commonly female than male. It’s common in all age groups; it’s less common in childhood, but it is common in younger adults, especially females. It’s also common in older individuals as well, so we really do see thyroid cancer in a span of age groups.

TARGETED ONCOLOGY: Why do you believe it is important to detect thyroid cancer earlier on?

Sinclair:Thyroid cancer, in general, has a very good survival rate. The most common type of thyroid cancer is well-differentiated thyroid cancer, which encompasses PTC and FTC. Then there are other forms of thyroid cancers, such as MTC, poorly differentiated thyroid cancer, and ATC, which all are different from the well-differentiated thyroid cancers, much less common, and are often more resistant to treatment. [These could also] have worse survival than the well-differentiated. However, the vast majority of thyroid cancers that we see in clinical practice are the well-differentiated types.

For those well-differentiated thyroid cancers, early detection is important. However, what we know about these well-differentiated thyroid cancers is that they are often fairly indolent in the way that they behave, and that small thyroid cancers that are well-differentiated with low-risk features could potentially be observed with active surveillance instead of being operated on. The reason being for that is because over 90% of those will not grow with time. These can be safely observed, and they may not need any treatment.

Early detection is important in thyroid cancer because it has the ability to spread to lymph nodes and elsewhere throughout the body, but it is generally a disease that is very survivable, at least for the well-differentiated subtypes, and it’s a disease that may even be amenable to observation for very small cancers. Knowing of this cancer early is important because it allows us to determine an appropriate observation or treatment strategy. People, if they get thyroid cancer in general, don’t need to panic because the overall survival (OS) rates are excellent for the well-differentiated subtype.

TARGETED ONCOLOGY: What do you look for in a patient with thyroid cancer in terms of genetic testing? How can this impact treatment options for patients?

Sinclair:When we see a patient who has been diagnosed with thyroid cancer, often times they will get genetic studies done on the biopsy of the thyroid nodule that was performed to diagnose the cancer. Genetic testing is a relatively new field over the last decade, and most of us do use it to guide our management to some degree. It is particularly useful when a nodule comes back atypical, not definitely thyroid cancer but atypical with a Bethesda grade of 3 or 4. If the gene mutations are negative where the patient has no gene mutations, it would push us towards perhaps recommending observation rather than surgery, whereas if mutations are positive, we would probably recommend surgery.

The extent of surgery with a gene mutation is an ongoing topic of debate because I don’t think we have had strong literature to date to support just using genetic markers to guide the extent of surgery. What we do know is that certain genetic markers such asBRAF,TERT,and a few others, are markers that are associated with increased risk of recurrent disease and increased risk of aggressive disease. Those particular markers have a higher recurrence rate. OS is probably similar, at least in the well-differentiated subtypes of thyroid cancer, but there is a higher risk of recurrence.

This is part of the discussion I have with a patient who has 1 of those markers, particularlyBRAF, in a thyroid nodule or cancer. I discuss to what extent of surgery should be performed. Now, if it is a big thyroid cancer, we would probably take the whole thyroid out. [In this case] the genetic marker doesn’t make a difference. If it’s a small thyroid cancer, it can be recommended for observation alone, but if it hasBRAFor TERT, you are less likely to recommend observation for that. You are more likely to recommend surgery. Should you do partial surgery or total thyroid surgery, that is a discussion that I have with the patient. I don’t think we have strong evidence 1 way or the other for these slightly more aggressive genetic mutations. It’s a discussion I have with the patient, and the patient needs to understand that there is an increased risk of recurrence if they have a small thyroid cancer and we only take out part of the thyroid with 1 of these mutations. Then again, there is a risk of complications with surgery.

There are pros and cons to every individual case. It’s not a clear-cut answer, but overall genetic markers are useful in determining which patient may be amenable for observation for an atypical nodule, and for a cancer, it may be useful in selecting which patients should be observed or have surgery. Perhaps determining the extent of surgery is a discussion that needs to happen with every individual patient.

TARGETED ONCOLOGY: What are some of the current systemic treatment options for patients with thyroid cancer?

Sinclair:The treatment for thyroid cancer is surgery, unless it is a small well-differentiated thyroid cancer that is amenable for active surveillance. The systemic treatment for well-differentiated thyroid cancer post-operatively is RAI, and the need for this would be determined by the pathology of the thyroid cancer. There are a number of factors that can determine whether a patient needs post-operative RAI therapy, including the size of the tumor, whether there were risk factors involved, the type of histology of the tumor, and whether it has very aggressive features. There are a number of factors that go into that decision, and that decision is usually made between a nuclear radiation specialist, endocrinologist, and a medical oncologist. For well-differentiated thyroid cancer that tends to be the main treatment.

Metastatic disease is a whole different scenario, and that is not something I am heavily involved in because it’s more in the realm of the oncologist. However, there are systemic treatments for people with metastatic disease, particularly for patients with certain gene mutations including theBRAFmutation. There are systemic therapies that are now available for patients with specific genetic mutations, and for patients with well-differentiated thyroid cancer that is metastatic, those are options now for treatment that do tend to prolong OS, although there are adverse effects associated with them.

There are also systemic treatments available for the more aggressive types of thyroid cancer, such as ATC, particularly if it has certain mutations associated with it, such as theBRAFmutation. Again, that’s more in the realm of medical oncology. The systemic treatment decisions are made more by the medical oncologist rather than the surgeon, so once it gets to that stage, the patient will make these decisions with an oncologist.

TARGETED ONCOLOGY: What should community oncologists be aware of in terms of diagnosing and treating patients with thyroid cancer?

Sinclair:The main thing is determining the full extent of the thyroid cancer at initial diagnosis because the best time to get rid of the disease is the first time. We want to be sure that the thyroid cancer is contained within the thyroid gland or not contained in the thyroid gland if it is on the side of the lymph nodes. That is very important information to know before the surgery because it does alter the procedure that we would perform to get rid of that disease. It does potentially affect the outcome of the patient and whether they need RAI treatment or something else.