During an interview with Targeted Oncology, Geoffrey Young, MD, PhD, discussed the impact of molecular testing, targeted therapies, and new approaches to surgical management of thyroid cancers.
Although many types of thyroid cancer have traditionally been treated with surgical resection, more options have become available in recent years, leading to a more multidisciplinary approach to treatment.
For patients who are refractory to surgery and radioactive iodine therapy, targeted therapies including BRAF, ALK, RET, and NTRK-targeted agents have been established as valuable treatments, particularly when a patient’s disease is symptomatic.1 This makes next-generation sequencing (NGS) essential in the progressive disease setting. Additionally, molecular testing plays a role in determining the likelihood of malignancy based on genomic characteristics more accurately than prior approaches based on cytology.
The ability to identify early whether tumors are aggressive or slow growing is shaping decision-making in terms of whether full thyroidectomy is necessary, or if lobectomy or even active surveillance can be done instead in patients with low-risk tumors.
These new opportunities contribute to the importance of a team of healthcare providers that can evaluate options with the patient and decide on the best approach.
“We do a lot in a multidisciplinary format where our patients with aggressive thyroid cancer are seen by medical oncologists, radiation oncologists, surgeons, and endocrinologists as part of a multidisciplinary team,” says Geoffrey D. Young, MD, PhD, a specialist in head and neck surgical oncology. “That's become more important as these new therapies have come through.”
During an interview with Targeted OncologyTM, Young, the chief of head and neck surgery for Baptist Health Miami Cancer Institute and vice chair of surgery for Herbert Wertheim College of Medicine at Florida International University, discussed the impact of molecular testing, targeted therapies, and new approaches to surgical management of thyroid cancers.
TARGETED ONCOLOGY: Could you give an overview of how the field of thyroid cancer treatment has changed compared with a few years ago?
YOUNG: Thyroid cancer continues to predominantly be managed by surgery and radioactive iodine. Until a few years ago, we had very little we could offer patients whose disease did not respond to either surgery or radioactive iodine. The major change in the past few years is that we have developed FDA-approved therapies that can be given to patients who have refractory disease or metastatic disease, which we didn't have available 5 years ago.
What changes in practice have been most significant for helping patients with thyroid cancer?
I think [we are] understanding that usually, most well-differentiated thyroid cancers are slow growing and tend not to metastasize. Less is more in certain situations; we don't want to start causing harm for a disease that's less likely to harm someone. But the flip side of that is, we've started to recognize when there is potential for the disease to harm someone, [when] it is showing signs of being more aggressive, [or] it is showing that it is not responding to standard therapies, and therefore may need…tyrosine kinase inhibitors, BRAF inhibitors, or NGS to find [actionable mutations]. These are platforms that we now have available that we didn't have before.
How has molecular testing has changed the diagnosis and treatment of thyroid cancer?
There are many companies that now that do analysis of thyroid nodule biopsies. It used to be that [when] you got a biopsy of a thyroid nodule, they looked at the cytology characteristics, and they put it on a Bethesda scale and graded its chance of malignancy. Now we have companies that…are able to do genomic analysis looking at expressed genes and then can tell you a calculated risk of a malignancy. These are very good at letting us know which nodules are most likely benign and can be left alone or monitored.
They're getting better at telling us which [tumors] are malignant. They're still not perfect, but they're guiding our hands as to which ones we should be more concerned about and get to surgery. That's the diagnostic side, and that's become fairly routine now with multiple labs available that do this testing.
From the treatment side, most well-differentiated thyroid cancers, papillary, follicular, or medullary thyroid cancer, are still surgical diseases. There sometimes comes a point in time when the patient has had so many surgeries…the disease has metastasized or the disease is in an area that surgically inaccessible. Therefore we have some ability, mainly in some very aggressive tumors [such as] poorly-differentiated cancers and anaplastic cancers, where NGS and molecular analysis can help to determine if there are targetable mutations to treat these cancers with that weren't available more than 5 years ago.
How does the use of targeted therapies affect your practice from your surgical perspective?
These drugs tend not to affect your ability to do surgery, which is good. But…usually by the time they're given, the patients are no longer being considered for surgery.
With targeted therapies, these drugs all have adverse events. From what I've seen from my oncology colleagues, they're reserving using targeted therapies until there are enough symptoms being produced by the disease to warrant the use of the drugs. Just because you have a few pulmonary metastases of papillary thyroid cancer, if you're asymptomatic, you're more likely to have issues with the drug you're taking than to actually get a benefit from that drug. When the disease starts causing symptoms, then the drugs become effective at controlling the disease burden and controlling the symptoms. There's a hand-in-hand play in figuring out when is the best time to start these drugs. How it affects me surgically, these are usually [where] it's gotten to the point where if patients are being considered for these drugs, they usually are no longer surgical candidates or refusing surgery.
What new trends in surgical treatment of thyroid cancer are important to highlight?
The first one is not doing surgery. It's not new in the last few years…but it's becoming more and more present in the public as well as in the medical community. Great institutions like the Mayo Clinic and Memorial Sloan Kettering Cancer Center, and several institutions in Asia, have been observing thyroid cancers [safely] for a long time. For the majority of these patients with very small thyroid cancers, not all of them need surgery. They can be monitored and [only] operated on if their disease shows signs of aggression or progression.
This is highly new; it's something that should be done in a setting where there is experience doing this. But we have patients who have heard of these studies and will ask if their cancer can be monitored, [as opposed to] being operated on. As a medical community, we have to come to terms on how that should best be done, and what those protocols should be. We’ve been getting closer to consensus on that in recent years.
The other things that have come through are non-standard surgical management of recurrent thyroid disease. These are ablative therapies, such as injecting alcohol into recurrent thyroid cancer in lymph nodes or in the…thyroid bed or using radiofrequency ablation for certain thyroid nodules or lesions. Targeting the lesions with nonsurgical ablative technology has become more prevalent in the past decade or so. We all are trying to come to consensus on which kind of lesions would benefit from this. Those are still ongoing, and some of it is still considered experimental, but it shows a lot of promise as we move towards the future of treating this disease.
What are the benefits and risks of reduced surgical intervention for patients?
Thyroid surgery in the hands of an experienced surgeon is very safe. Injury to one of the recurrent laryngeal nerves can cause hoarseness, and injury to both of these nerves could cause an issue with the airway. Then there are the parathyroid glands that control calcium in the body. All these could potentially be injured during surgery, but the injury rates are very low in an experienced thyroid surgeon's hands.
However, a patient who has an incidentally found 0.8 cm papillary thyroid cancer who is a singer and doesn't want to have a chance to have any potential injury to their voice, might be a patient who might want…this observed. Then you do serial ultrasounds, you assess for growth, you make sure that there are no adverse features of the nodule or lymph nodes. There are a lot of things that go into a patient being a candidate for observation.
You can see particular scenarios where someone may want to avoid surgery for health reasons. A patient might have cardiopulmonary disease [with a risk to using] anesthesia. We've gotten very good at detecting these cancers. We have ultrasound availability at almost every institution around the country and around the world. We're detecting a lot more of these cancers. I'm not advocating that patients don't have surgery for thyroid cancer, but there are instances where it might be acceptable to watch a known thyroid cancer. That conversation should be between the multidisciplinary team and the patient so that everybody is on the same page as to what that entails.
How do you collaborate with medical oncologists and how has this changed over time?
[In the past], medical oncology wasn't involved in thyroid cancer, except for poorly differentiated and anaplastic cancers. The majority of patients with papillary, follicular, or medullary thyroid cancer were usually handled between the surgeons, occasionally the radiation oncologist for patients who required radioactive iodine, and an endocrinologist. Those were the physicians who managed it, but now that we're seeing the development of these new drugs…there has become a role for [medical] oncologists in progressive or refractory thyroid cancers. When we start to see these patients progressing down that road, we are luckily able to involve our oncologists very quickly. We also do a lot in a multidisciplinary format where our patients with aggressive thyroid cancer are seen by medical oncologists, radiation oncologists, surgeons, and endocrinologists as part of a multidisciplinary team. That's become more important as these new therapies have come through.
What advice would you give to physicians treating patients with thyroid cancer in the community setting?
Nobody is an island; these patients should be handled by a multidisciplinary team. I don't think every patient with thyroid cancer needs an oncologist; if the patient has papillary thyroid cancer that is treated surgically, they have no aggressive features, [then] that patient can probably be monitored by their surgeon and endocrinologist and the oncologist doesn't need to be involved. But there are more aggressive types of thyroid cancer...progressive thyroid cancer, metastatic thyroid cancer, etc, that the oncologist should be involved with, and they should make sure that the other parts of the team handling the patient—the surgeons and the endocrinologist—are all involved in the conversations, because starting some of these therapies may not be necessary until the patient has symptoms. Just because they have disease doesn't necessarily mean they need the therapy. These decisions should all be part of a multidisciplinary evaluation of the patient.
1. NCCN. Clinical Practice Guidelines in Oncology. Thyroid carcinoma, version 4.2023. Accessed August 28, 2023. https://tinyurl.com/3dwzw3v2