Abstract
KEY POINTS
A single radiofrequency ablation (RFA) session can achieve durable volume reduction over up to 8 years of follow-up, with most shrinkage occurring within the first year.
Baseline nodule volume is the strongest independent predictor of regrowth: nodules ≥20 mL carry a nearly fourfold higher risk of recurrence than those <10 mL.
In toxic adenomas, a strategy of single-session RFA followed by low-dose radioiodine or repeat RFA for the minority who relapse achieves euthyroidism in 99% of patients without the need for lifelong thyroid hormone replacement.
SUMMARY
Background
Radiofrequency ablation (RFA) is a minimally invasive, ultrasound-guided thermal technique for treating benign thyroid nodules that cause compressive symptoms, cosmetic concern, or hyperthyroidism. It is increasingly offered as an alternative to thyroidectomy or radioactive iodine therapy, both of which carry well-recognized risks, including a substantial risk of hypothyroidism requiring lifelong replacement therapy. Although short-term efficacy data for RFA are robust, rates of long-term recurrence, defined as nodule regrowth ≥50% from nadir volume or relapse of hyperthyroidism in toxic adenomas, have been less thoroughly characterized. 1 Most published long-term series come from high-volume Asian centers, and often at centers where repeat ablations are standard practice, potentially inflating reported efficacy. The present study 2 aims to address these gaps by describing mid- to long-term outcomes after a single RFA session in an experienced single-center cohort.
Methods
This retrospective analysis examined a prospectively maintained database of patients treated at a single Austrian thyroid clinic between April 2014 and July 2024. Eligible patients had cytologically confirmed benign nodules (Bethesda II), unremarkable cervical nodes, calcitonin levels within the reference range, and nontoxic nodules that must be associated with symptoms of compression or cosmetic concern. Patients with toxic adenomas were identified by thyrotropin (TSH) ≤ 0.4 mU/L or thyrostatic medication use. A total of 896 patients were included: 765 with nontoxic nodules and 131 with toxic adenomas. Monopolar or bipolar RFA was performed under local anesthesia by a single operator using the moving-shot or multiple overlapping technique. Follow-up visits occurred at 3 months, 1 year, and annually thereafter, with thyroid volume assessment and laboratory testing at each visit. Nodule regrowth was defined as a ≥ 50% increase from minimum posttreatment volume 1 ; recurrence in toxic adenomas was defined as TSH ≤ 0.4 mU/L regardless of the change in nodule volume.
Results
Median baseline nodule volume was 10.1 mL (interquartile range, 5.5–20) for nontoxic nodules and 7.2 mL (IQR, 4.2–14.3) for toxic adenomas. The majority of nodules (>80%) were solid or predominantly solid. Follow-up of ≥ 3 years was available for 437 nontoxic nodules and 58 toxic adenoma patients. The median follow-up was 3 years (range, 0.3–8) for both nontoxic and toxic nodules. After 1, 3, and 5 years, average volume reduction rates were 79%, 82%, and 86%, respectively, for nontoxic nodules and 84%, 88%, and 89% for toxic adenomas, with volume reduction rates remaining stable thereafter.
Regrowth occurred in 54 of 765 nontoxic nodule patients (7.1%), with a cumulative incidence of 17.3% over 8 years. Most regrowth was observed between years 2 and 5. A second RFA treatment was administered to 27 of 54 patients (50%) with regrowth of a nontoxic nodule. Recurrence of hyperthyroidism occurred in 15 of 131 toxic adenoma patients (11.5%), with a cumulative incidence of 21.6% over 7 years, predominantly in years 1 through 3. Of the 15 patients with recurrence, 11 underwent radioactive iodine ablation and 3 had a second RFA treatment.
Baseline nodule volume was the primary predictor of regrowth in multivariable analysis. Initial nodule volumes of 10–19 mL and ≥ 20 mL conferred hazard ratios of 2.71 (95% CI, 1.14–6.45) and 3.78 (95% CI, 1.57–9.06), compared to nodules <10 mL. Older age was independently protective (4% risk reduction for growth per year). Euthyroidism was achieved in 14 patients with toxic adenoma relapse with low-dose radioiodine (n = 11) or a second RFA (n = 3). The overall complication rate was 3.7%, including 2.3% moderate and 0.3% severe events; moderate-to-severe complications declined significantly after technical refinements (3.5% vs. 1.2%, p < 0.05).
Conclusions
A single RFA session achieved favorable mid- to long-term outcomes in 83% of patients with nontoxic nodules and 78% of patients with toxic adenomas over up to 8 years of follow-up, with an acceptable complication profile. Smaller nodule size, cystic composition, and older patient age were associated with lower recurrence risk. With appropriate rescue therapy for the minority who experienced a relapse, 99% of toxic adenoma patients ultimately achieved a euthyroid state without requiring thyroid hormone replacement.
COMMENTARY
This study is one of the largest and longest single-center Western experiences with RFA of benign thyroid nodules to date. The 8-year cumulative regrowth rate of 17% for nontoxic nodules is notably consistent with Italian multicenter data reporting 20%–23% recurrence over 5 years, providing external validation that a single ablation can achieve durable disease control for most patients.3,4 Importantly, regrowth rates plateaued after year 5, suggesting that patients who remain recurrence-free at 5 years are unlikely to require reintervention, which is a reassuring finding that can be integrated into patient counseling. This finding suggests that once past this 5-year window, ongoing annual surveillance may be safely de-escalated in appropriately selected patients.
The toxic adenoma data are particularly noteworthy. Although the cumulative hyperthyroidism relapse rate of 21.6% is higher than many clinicians would expect—and higher than what a single course of radioiodine typically achieves 5 —the key result is that reintervention as needed achieved euthyroidism in 99% of patients at final follow-up without thyroid hormone replacement. When accounting for this metric, RFA compares favorably to lobectomy or radioiodine therapy in avoiding the need for lifelong thyroxine replacement.6–8 This thyroid function–sparing property is an underappreciated advantage of RFA that deserves greater emphasis in shared decision-making discussions with patients.
We frequently encounter patients in our own clinical practice with symptomatic thyroid nodules who are motivated to avoid surgery or lifelong medication therapy. For those with nodules in the 5-to-15-mL range, data support RFA as a first-line, durable intervention. This study’s finding that larger nodule volume is the dominant predictor of regrowth is notable and underscores the importance of patient selection. Patients presenting with multinodular goiters or dominant nodules exceeding 20 mL who are offered RFA should be counseled carefully about the real possibility of necessary reintervention. This study also reinforces that the quality and energy delivery of the ablation itself matters. Lower energy per milliliter was associated with both higher regrowth risk and hyperthyroidism relapse, which supports a meticulous, thorough technique rather than a conservative one. The limitation of a single experienced operator performing all procedures is worth emphasizing when extrapolating these outcomes to centers earlier in their learning curves. We look forward to multiinstitutional studies to further validate long-term outcomes for RFA of symptomatic benign thyroid nodules.