In the Heat of the Moment: Thermal Ablation for “All Things Thyroid”

Thermal ablation has entered the mainstream conversation for treatment of “all things thyroid.” It is no longer just an alternative therapy, but a first line option for the appropriately selected patient and has been a game changer for many patients and physicians. The benefits of ablation are that it can be performed in an outpatient setting under local anesthesia with minimal observation time, except in rare instances the procedure will not cause hypothyroidism or other permanent side effects, and there is no surgical scar. However, patients should continue to have regular follow-up, and the results are not as immediate or definitive as surgical resection. Efficacy is also operator dependent, and somewhat based on the volume of the area to be treated, though the later can be overcome with additional treatments.

Despite the ever-increasing number of published articles, society guidelines, and clinical trials that demonstrate the safety, patient satisfaction, cost-effectiveness, and overall success of the procedure, there are still many questions related to thyroid thermal ablation that remain unanswered. This month’s journal features three articles by groups with significant experience in thermal ablation that explore different elements of thyroid radiofrequency ablation.

The first from Park et al. ¹ reports the longest follow-up to date of more than 400 patients treated with radiofrequency ablation (RFA) for benign thyroid nodules. This will be a landmark paper for thermal ablation, similar to the earlier Italian series with five-year follow-up, ² paving the way for even greater adoption as therapy for benign nodules. Their overall results are excellent. After following patients for 10 years, they describe a mean volume reduction ratio (VRR) of 80% at 2 years, 90% at 5 years and 94% at 10 years. There were no long-term complications, all patients had symptom improvement and many, but not all, had disappearance of cosmetic complaints. Nodule regrowth occurred in 12% of patients, with 2/3 opting for retreatment. Those at increased risk for retreatment had an initial nodule volume >20cc, whereas those with the least risk had an initial nodule volume of <10cc. Some patients had more than one treatment, with the value of additional RFA treatments discussed in more detail elsewhere. ³

The authors appropriately discuss the importance of establishing and utilizing a consistent set of definitions when describing treatment efficacy and comparing therapies. They describe three different standards for “regrowth”: >50% increase in volume from minimum recorded volume at any given follow-up time point, >20% increase in volume from one year after ablation, or any volume larger than the initial volume. In practice, any patient meeting one of the three definitions of regrowth should prompt evaluation with repeat biopsy and/or surgical resection. The authors also propose a definition of “cure” as >90% VRR, no change to a residual linear or flat hypoechoic lesion measuring <0.5 cc, no vascularity inside the treated nodule, and no symptoms or cosmetic concerns. Although this definition has little meaning for benign nodules, it will prove important in future series of malignant as well as suspicious nodules where the goal is cure, as opposed to benign nodules where the goal is to shrink the nodule with disappearance of symptoms and cosmetic concerns.

One question that needs to be answered going forward is what is the optimal interval for ultrasound follow-up after ablation that balances cost and patient anxiety with the benefit of catching regrowth early as well as the occasional missed cancer. In this large series, 10 cancers were found in 23 residual nodule specimens. Although this number may seem high, there was no nodule regrowth indicating that the small amount of residual cancer in the ablated nodule was not “active” or “aggressive,” and these results are similar to an earlier published Italian series with five years of follow-up. ² Given the encouraging data being published of thermal ablation for small papillary thyroid carcinomas of the size of the residual tumors, small missed cancers do not seem to adversely affect the overall success of ablation; larger tumors that had no nodule shrinkage or growth would not apply, pointing to the importance of continual monitoring and the need for common ultrasound language to describe nodules post-ablation as discussed in the next article.

The second paper is a timely letter to the editor by Dionisio and Mauri ⁵ on the lack of current terminology and standards for post thermal-ablation ultrasound findings. These two clinicians have significant experience with thermal ablation, making their insight a call to action for international thyroid and radiology societies to establish some general guidelines that can help clinicians better follow patients as ablation becomes even more widespread. Many ultrasound changes with ablation abate over time, but some residual calcification and/or hypoechoic areas remain. For instance, there is a different significance between nodular and scar-like hypoechoic lesions in ablated malignant nodules, as well as peripheral versus central remaining vascularity. ⁴ Most ablated lesions will be reported as “suspicious” at least initially by a general radiologist, which can cause significant patient and clinician anxiety. I agree with the authors’ suggestion that the current classification systems NOT be used in the post-ablation setting unless there is some adaptation and acknowledgement that changes may be normal in the ablated patients and words such as “suspicious” are not used.

In that context I also agree with Dionisio and Mauri’s argument that ultrasound can be somewhat subjective. Ideally, either the operator (person performing the ablation) or someone within their group with expertise in thyroid ultrasound would follow a treated patient over. If a patient travels for an ablation procedure, then a clinician close to home with expertise in thyroid ultrasound should be designated to perform the subsequent follow-ups. As we saw in the large series by Park et al., ¹ some patients do need retreatment, and a plan for follow-up should be established with the patient first. A discussion should include the potential wording that may come in future ultrasound reports if the ablation operator will not be doing the follow-up ultrasound in real-time with the patient, as well as the need to repeat a biopsy and/or proceed to surgery when there is no shrinkage by a certain time point or a significant amount of regrowth.

As clinicians continue to push the envelope and develop alternatives to standard therapy for patient benefit, the last of the articles describe a more novel use of thermal ablation. All of the current treatment options for Graves’ disease have both positives and negatives, and therefore novel therapies have a role in the appropriate patient. Fung et al. ⁶ updated their early results of 30 patients with relapsed Graves’ disease treated with RFA. In this highly selected group of patients with small thyroid glands that did not want thyroid surgery, 60% were in remission after 12 months and 56.7% at 24 months; however, in 9 patients with thyroid volume <20 cc, the success rate was 100%. Permanent hypothyroidism occurred in 7% of the total patient group and of the patients that did relapse after a successful treatment, 70% required a lower dose of anti-thyroid medication.

Although thermal ablation is obviously much less successful than either surgery or radioiodine, RFA appears nearly equivalent in the short-term to sustained remission after discontinuation of medication in this highly selected relapsed group. Not surprisingly, an increased volume of thyroid gland was associated with decreased success rate. Moreover, patients were under some conscious sedation and required post-procedure monitoring similar to post-thyroidectomy patients, so it is not as “outpatient” friendly as ablation for thyroid nodules or RAI/medication treatment for Graves’. It is important to note that surgery after full thyroid RFA was fairly smooth except for adhesions at the isthmus in the hands of experienced endocrine surgeons. As the authors reiterate, it is not better nor meant to replace current more definitive treatment options, but rather is yet another potential use of thermal ablation for select patients.

In summary, thermal ablation appears here to stay as a treatment option for many things thyroid, paving the way for future innovations that focus on decreasing invasiveness and improving patient satisfaction. Moving forward, clinicians should educate patients as to the natural history of ablated nodules and strive to have patients receive consistent follow-up with a single operator/group. Optimal follow-up protocols for various treatment conditions need to be established, including timing of retreatment and when surgery is indicated. Lastly, standards are needed for post-ablation ultrasound reporting and consistent reporting of definitions for success and failure.