Outcomes of a 5-Year Active Surveillance Program in Bethesda IV-VI Thyroid Nodules

1. Overview Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland. To date, several clinicopathological characteristics have been identified that predict poor prognosis in patients with PTC, including advanced age, extrathyroidal and/or extranodal extension, lymph node metastasis and/or distant metastasis, and tumor size. ¹ Active surveillance in thyroid nodules has been proposed as an alternative to surgery in patients with indeterminate or suspicious nodules for malignancy on fine-needle aspiration cytology (Bethesda IV, V, and VI). Active surveillance involves the systematic and regular observation of nodules through imaging techniques and clinical examination to detect changes in size and ultrasonographic characteristics of the nodules.

The main advantage of active surveillance is that it can avoid thyroid surgery in selected patients, thereby reducing the rate of surgery-related complications. Several studies have shown that most Bethesda IV-VI thyroid nodules exhibit non-aggressive behavior, and many patients do not require surgery.

For example, Ito et al.¹ reported that 88% of patients with Bethesda V-VI thyroid nodules who underwent active surveillance did not require surgery during a 5-year follow-up. In addition, active surveillance has been associated with a reduction in the rate of surgery and, consequently, surgery-related complications.2 Another advantage of active surveillance is that it can be a cost-effective alternative compared to surgery. Thyroid surgery is an invasive procedure that can be expensive. On the other hand, it involves regular doctor visits and imaging tests, which are less costly than surgery. In a cost-effectiveness study, active surveillance was associated with a savings of USD $16,542 per patient compared to surgery.3 However, active surveillance also has some limitations and disadvantages. One limitation is that it requires long-term follow-up and a high level of patient compliance to be effective. Patients undergoing active surveillance must be closely monitored for changes in the nodules that may indicate the need for surgery. Additionally, some patients may experience anxiety or stress due to the uncertainty of not knowing whether they have cancer, or if confirmed, not understanding the behavior the cancer will take. 3,4 2. Problem Statement Thyroid nodules with a cytopathological diagnosis of Bethesda IV-VI represent a significant clinical challenge due to the possibility of malignancy and the implications this has for therapeutic management. The current standard recommendation includes thyroidectomy (partial or total); however, these interventions are not without risks and/or morbidity for the patient. Although active surveillance has been proposed as a conservative alternative, especially for nodules with suspicious characteristics and/or nodules with confirmed malignancy that meet certain criteria, there is still a lack of studies in the literature that systematically evaluate its efficacy and safety in our setting.

Active surveillance aims to avoid overtreatment by identifying and monitoring nodules with high-risk imaging or cytopathological characteristics, allowing for selective surgical intervention only when there is evidence of progression, such as nodule growth or the appearance of lymph node metastases. While preliminary studies on active surveillance in Bethesda V-VI nodules exist, the clinical and ultrasound behavior of patients managed with this strategy has not been sufficiently characterized, nor has its impact on reducing unnecessary surgical procedures been clearly determined. Therefore, a systematic evaluation of the evolution of Bethesda IV-VI thyroid nodules under an active surveillance program is essential.

This study aims to describe the initial clinical, imaging, and cytopathological characteristics, as well as the documentation of changes during follow-up, including the nodule growth rate, the appearance of lymph node metastases, and the need for conversion to surgery. The evidence generated could guide future clinical management, optimizing the balance between safety and the reduction of unnecessary surgical interventions.