Efficacy of Ethanol Ablation in Long-Term Local Control of Neck Nodal Metastases in Adult Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the commonest endocrine malignancy (1). Neck nodal metastases (NNM) may be found in 20% to 50% of adult PTC (APTC) patients at the time of initial surgical resection (1) and, despite potentially curative primary operative intervention, a significant number of APTC patients are also later found to have NNM, typically discovered at months to many years after the date of initial operation (2, 3). What to do with these “persistent or recurrent” NNM is a dilemma increasingly faced by thyroidologists seeing APTC patients in clinical practice (2).

The 2015 American Thyroid Association (ATA) Management Guidelines (1) recommended surgery as the optimal directed approach for differentiated thyroid cancer (DTC) patients with “biopsy-proven persistent or recurrent disease”, particularly for central NNM of > 7 mm or lateral nodes of > 9 mm. They advised that in this setting “planned compartmental dissection” results in a “high clearance rate of structural disease in over 80%” but emphasized the importance of employing a surgeon with expertise in the performance of revision thyroid cancer nodal surgery (1). They noted that radiofrequency ablation for recurrent NNM has resulted in mean volume reduction rates of 55% to 95% and complete disappearance of metastatic foci in 40% to 60% of cases but they did note complications including “changes in the voice” and their advice was to consider radiofrequency ablation in “high-risk surgical patients or in patients refusing additional surgery” (1). Their consensus on ethanol ablation (EA) for NNM in DTC was that it “may be beneficial in patients with a single or a few metastases”, should be considered in patients who are poor surgical candidates, and may require more than one treatment session (1). They considered that published reports of EA for NNM (3) were limited by small numbers and included many patients whose NNM diameters were < 9 mm and who had relatively short follow-up after EA (longest 65 months).

A recently published study from the Oslo University Hospital (4) has managed to address many of the limitations identified by the ATA (1) in earlier studies. Frich and colleagues (4) managed to re-examine 44 APTC patients who had previously received EA for selected NNM and had been included in an earlier published study (5). The median follow-up time from last performed EA was 124 months (range, 90-160). Of the 67 initially treated NNM, 97% had fulfilled one or more of the defined response criteria at the end of the earlier study (5), and on later follow-up exam 54/67 (81%) had a “durable response”, of which the majority (91%) were nondetectable (4). Recurrence within a previously ablated node was registered in 13/67 NNM (19%) in 10/44 patients (23%); 7 “residual lesions” detected during years 6-12 (median 9), and 6 at time of follow-up study. Of the 13 recurrent lesions, 7 were treated with EA, 4 with surgery, and 2 underwent active surveillance.

In addition to the lesions considered to be recurrences in previously EA-treated NNM, Frich and colleagues also mapped 22 new NNM in locations outside of previous EA treatment. Most of these new lesions (14/22) were found in 7 of the 10 patients who also had experienced recurrence at the previously ablated site; the other 8 were found in 6 stage I patients who had durable response in their EA-treated lesions in the earlier study (5) and again had a durable response to EA. By contrast, in the patient group experiencing regrowth at the ablation site, a durable response after EA was achieved in only 43% of the newly detected lesions. The authors, after a median follow-up of 11.3 years, found no sign of recurrent disease in the neck in 35 (80%) of the 44 APTC patients at the time of their latest follow-up (4). They concluded (4) that EA is safe, efficient and can provide long-term local control for recurrent NNM in patients with APTC previously treated by thyroidectomy and postoperative radioiodine.

EA for “persistent or recurrent” NNM in APTC had its origins at the Mayo Clinic in 1991 and during 1991-2000 > 50% of EA procedures were performed on DTC patients with distant spread and the procedure considered palliative (3). However, since 2001, EA at Mayo has largely been performed in APTC patients with disease localized to the neck, especially patients with TNM stage I disease (3). Such has been the acceptability of EA to our patients and providers that only a decade ago we were at the Mayo Clinic in Rochester doing about 100 EA procedures annually, while during 2021 the number of EA procedures approached 300. EA has proved for our APTC patients to be a predictably safe, minimally invasive, and cheaper alternative to surgery for those of our patients who are unwilling or unfit to undergo surgery and cannot tolerate a policy of active surveillance.

Unfortunately, as in many areas of DTC management, there are, to our knowledge, no currently published prospective randomized controlled studies of EA compared with surgery in the management of persistent or recurrent NNM in PTC and few papers (6-8) directly comparing EA and surgery. Recurrence rates at the previously ablated sites of 12% to 24% (mean 18%) represents a distressing new feature of papers published since 2011 (4, 6-8) and warrants further analysis. The discovery of new NNM outside the ablated sites is perhaps a predictable consequence of following node-positive PTC under very intense scrutiny with extremely sensitive Doppler flow monitoring and increasing resolution of more recent sonographic probes (3).

How best to reduce the rates of regrowth in ablated NNM certainly requires further study, and more long-term results to compare with Frich and colleagues (4) are needed before we can better establish EA as an acceptable part of recurrent APTC management. While we await the publication of such studies, we will continue to encourage the use of EA as an acceptable alternative to revision surgery for our patients, particularly those with TNM stage I disease, and we applaud our Norwegian colleagues (4, 5) for their patience and hard work in performing their excellent long-term outcome analyses of EA for the management of recurrent NNM in selected APTC patients.