Treating Advanced RAI-Refractory DTC: A Two-Way Street: Medical Oncology and Endocrinology - Episode 3

Role of Radioiodine Treatment in DTC

December 21, 2020
Lori J. Wirth, MD, Massachusetts General Hospital

,
Jennifer Sipos, MD, Ohio State University

,
Frank Worden, MD

Lori J. Wirth, MD: What about those patients who do have surgery? What’s happening these days with the use of radioiodine treatment in patients following a standard thyroidectomy, plus or minus central neck dissection, for a fairly typical, garden-variety differentiated thyroid cancer?

Jennifer Sipos, MD: We’re using a lot less radioactive iodine [RAI] than even in the recent past. When I first started treating patients with thyroid cancer about 15 years ago, we used radioactive iodine in just about every patient, except for a small portion of low-risk tumors that were less than 1 cm. Some of that was my own training, where I trained, and with whom I trained. There are certainly regional differences in the use of radioiodine, but we’re all moving along that spectrum toward using a lot less radioiodine. That largely stems from the observation of a number of studies that radioiodine is not necessarily associated with improved survival in low-risk patients. We can probably be more selective in the population of patients for whom we use it.

We are utilizing radioiodine therapy with 3 intentions. The first intention is to ablate residual normal thyroid tissue. We call that remnant ablation. The second indication for radioiodine therapy is adjuvant therapy, or when trying to treat subclinical micrometastatic disease we think may be there. It may or may not be there, so we call that adjuvant therapy. The third indication is to provide treatment of clinically apparent residual or metastatic cancer. 

We are coming into this equation with the intent that we want to reduce the likelihood of this disease coming back. Those 3 indications I just mentioned are the idea of going forward and how we’re going to treat these patients. With that in mind, we think about our patients in 3 general categories: low, high, and intermediate risk of recurrence. In patients with low likelihood of recurrent disease, radioiodine is not routinely recommended. That would include patients who have tumors that measure less than 1 cm, but have no other high-risk features. It may even include patients who have a small volume of regional lymph node involvement. That means a tumor and less than 5 lymph nodes with metastatic deposits that measure less than 2 mm. So even those patients now, we don’t routinely need to treat with radioiodine therapy.

On the other end of the spectrum, for those patients with high-risk disease, radioiodine is recommended. This includes patients with distant metastatic disease, patients who have macroscopic tumor invasion grossly involving the surrounding thyroid tissue or incomplete tumor resection, and patients who have grossly residual disease. In those folks, it’s clear-cut that radioactive iodine is beneficial. It’s recommended for most patients with that disease, absent some other significant medical illness that would prohibit them from getting RAI.

Then, there are all the patients in between, we would call those intermediate-risk patients. In that group of patients, it’s more selective for whom we use RAI. That’s probably the most controversial group in which it’s debated who should get RAI and who shouldn’t. The data don’t bear out very well, from an evidence-based practice perspective, who should get RAI in that group. In those situations, I have a long conversation with my patient and say, “You’re in the gray zone. We can use it or we can choose not to, or we can reserve the right to change our minds later, if we decided at first we’re not going to give it.” I’ll utilize all the tools in my arsenal to make that decision with the patient. That will include the post-operative ultrasound, serum thyroglobulin, and evaluating all their other comorbid conditions, as well as their social situation, to help decide whether to proceed with RAI.

Lori J. Wirth, MD: In general, poorly differentiated thyroid cancers and Hurthle cell thyroid cancers are not thought to concentrate iodine. Do you consider giving radioactive iodine in patients who have resected disease? Let’s say it’s a high-risk patient. They don’t have any known metastatic disease, but they have Hurthle cell thyroid cancer that is poorly differentiated. Do you give radioactive iodine because you have to, with the feeling in your heart of hearts that it’s not really going to help the patient?

Jennifer Sipos, MD: Yes, those are really tough cases. I always labor over those decisions about whether I put the patient through this procedure. That’s particularly the case in patients with Hurthle cell tumors in whom I have a good idea that they’re going to ultimately need the services of one of our oncologists. But I feel like I need to do that. The reason I do end up usually treating these patients is because, at present, the majority of our clinical trials and a lot of our decision-making regarding the use of systemic therapy is concentrated around the idea of establishing that the patient is iodine refractory. I always tell patients when we’re talking about statistics that statistics only mean something on a population basis. They don’t mean anything to the individual. If you tell me that there’s a 5% likelihood of dying from thyroid cancer, if you’re one of those 5%, then it’s a 100%. I try not to apply statistics too much here. I give the patient the benefit of the doubt, but I try to do it in a responsible way. 

If I have a patient with Hurthle cell thyroid cancer, and I have a good idea that their tumor is probably not going to be RAI-avid, but I want to give them a chance, I may try to hedge my bet a bit by going with a slightly lower administered activity. I do that rather than trying to fully blast them and ensuring that I’m going to kill their salivary glands and potentially cause some bone marrow suppression. I try to be responsible about that, but I do like to give them the opportunity to prove to me that the iodine is not going to work.

Lori J. Wirth, MD: Yes, that makes sense to me. You can always circle back and give them another dose if they do….

Jennifer Sipos, MD: Right. If we went low and it worked, and it gave me 12 months of progression-free management, then if it starts to progress again, I may try to give another dose.

Transcript edited for clarity.