The Treatment of Thyroid Cancer with Radiofrequency Ablation
For decades, the standard of care for treating thyroid cancer has been surgical removal of the gland. This is occasionally followed by post-operative radioactive iodine (RAI) for differentiated thyroid cancer and thyroid replacement hormone at suppressive levels. Over time, the American Thyroid Association (ATA) guidelines have evolved to reflect emerging evidence that well-differentiated thyroid cancer has a spectrum of disease with most small papillary thyroid cancers being indolent.1
The ATA guidelines suggest that not all well-differentiated thyroid cancers require a total thyroidectomy. In certain situations, cancers smaller than 4 cm may be considered eligible for treatment with only a thyroid lobectomy. For smaller tumors, low risk papillary thyroid microcarcinoma (PTMC) can be managed by active surveillance (AS).2 However, not all patients are candidates for AS due to limited access to regular medical follow up. Some patients may even find this approach too anxiety provoking. Within this evolving paradigm, thermal ablation has become an option for patients wishing to actively treat their cancer in a minimally invasive way. Thermal ablative techniques (TAT) are well established in European and Asian countries, and include radiofrequency ablation, laser ablation, microwave ablation, and high intensity focused ultrasound.3, 4, 5, 6, 7, 8, 9 Given that radiofrequency ablation (RFA) is the best studied TAT worldwide, we review the role of RFA for the treatment of small differentiated primary thyroid cancer, recurrent thyroid cancer, and lymph node metastases.
Clinical evaluation of the patient
Ultrasound is the procedure of choice for delineating the size and extent of nodules in the thyroid, determining the proximity of the nodules to important neurovascular structures, and evaluating the lateral neck compartments for metastatic lymph nodes.1 If there is clinical concern that a nodule extends below the clavicles or is locally invasive of the viscera, axial imaging such as a contrast enchanced CT scan can be performed.
If the cytopathology from a fine needle aspiration (FNA) reveals a new diagnosis of papillary thyroid cancer, or other forms of well-differentiated thyroid cancer, surgical referral is generally recommended unless the patient has a low-risk PTMC.1 However, if a biopsy proven recurrent papillary thyroid cancer is present, the patient should first undergo multidisciplinary review to discuss treatment options.9
An important consideration for determining whether a patient is a candidate for thermal ablation include the absence of a family history of thyroid cancer. Certain histopathological variants of thyroid cancer are associated with familial tumor syndromes and are likelly better served by surgery. For example, the cribiform-morular variant of papillary carcinoma is seen in patients with familial adenomatous polyposis (FAP).10 Others, such as PTEN hamartoma tumor syndrome is associated with papillary or follicular thyroid cancer as well as benign and malignant tumors of the breast, endometrium, and colon hamartomas.11 Furthermore, patients who have had prior radiation to their head and neck or environmental exposure (e.g. Chernobyl) would likely benefit from surgical resection instead of RFA given their increased risk of developing additional tumors.
Active Surveillance for low risk pimary thyroid cancer
Over the last few decades, there has been a push towards active surveillance of papillary thyroid microcarcinoma (PTMC) in select patients.12,13 The World Health Organization (WHO) defines PTMC as a small papillary thyroid cancer (≤ 10 mm in greatest dimension).14 The American Joint Committee on Cancer (AJCC) TNM system classifies T1 category (T1: ≤ 2 cm) into T1a: ≤ 1 cm and T1b: ≤ 2 cm.15 Several studies have demonstrated that the distinction between a T1a and T1b is minimal in terms of prognosis in the absence of high risk pathological features or extrathyroidal extension.16,17 Currently, the ATA guidelines recommend AS for T1aN0 and potentially for T1bN0 low risk thyroid cancer.1
Patients with small papillary microcarcinomas that are intrathyroidal, lack aggressive cytopathology, and lack local invasion or clinically detectable metastases are candidate for AS.1 Various prospective studies have been conducted for AS of low-risk (T1aN0M0) PTMC since the 1990s demonstrating favorable outcomes that include a low rate of growth, rare regional or distal lymph node metastases, and low mortality.18,19,20,21 In a systematic review and meta-analysis, Cho et al., found the pooled proportion of tumor size enlargement (defined as 3 mm or more) occurring at 5 years was 5.3% (95% confidence interval (CI), 4.4-6.4%), and the pooled proportion of 5-year lymph node metastasis was only 1.6% (CI, 1.1-2.4%).22
While active surveillance makes sense from a population health perspective, it can be burdensome on patients and it does not address patient anxiety. Many patients who live in rural areas and are not prepared to commute to a large city center for regular surveillance. Cho et al. demonstrated the main reason for patients undergoing surgery at a later date instead of ongoing active surveillance (32-69%) was due to patient anxiety rather than disease progression.22 The key concerns from the AS group were the risks of surgery, the possibility of having to take thyroid hormone treatment, and the potential impact on quality of life, making thermal ablation an attractive option.
Indications for Radiofrequency Ablation
Low risk primary thyroid cancer
Currently, the recommendations for treatment with RFA in primary thyroid carcinoma are low risk papillary thyroid cancer patients who would be otherwise eligible for AS or refuse surgery.1,2,9,23, 24, 25, 26 The majority of studies have demonstrated the efficacy and safety of thermal ablation for low-risk papillary thyroid microcarcinoma (PTMC) as well as for smaller papillary thyroid carcinoma (PTC) less than 2 cm.23,27,28,29 In a long-term retrospective study, Cho et al. found complete disappearance rates of 98.8% at 24 months and 100% at 60 month follow-up after RFA of 84 PTMC’s.24 After more than five years of follow-up, there was no local progression, regional or distant metastases, delay in surgery or procedure related death found.
Careful evaluation by ultrasound is paramount to rule out aggressive sonographic characteristics that may prevent delay for patients who would be better served with surgery. The cytopathology should confirm classic variant of PTC without evidence of histological aggressiveness that is associated with the tall cell variant, hobnail variant, or the columnar cell variant.18 The tall cell variant has a higher rate of recurrence, poorer survival compared with the classical variant, and a BRAF mutation (associated with extrathyroidal extension and lymph node metastases) in up to 80% of these tumors.30,31 The hobnail variant and the columnar cell subtype are associated with frequent distant metastases (typically to the lung) and increased risk of tumor-related death.32,33 Other variants of papillary carcinoma such as the solid variant and diffuse sclerosing variant are also associated with a less favorable outcomes however the data is conflicting.1 The presence of TERT promoter and TP53 mutations are contraindications to the use of thermal ablation.9 Although the combination of BRAF and TERT promoter mutation is very rare, the two are associated with a poorer prognosis in PTC.34
Tumor location is also an important consideration. A more superficial location makes a tumor more amenable to RFA as there is more distance from the trachea and the recurrent laryngeal nerve. Tumors that abut the trachea carry a higher risk of invasion, particularly if no rim of normal thyroid tissue is observed.