Introduction
The incidence of thyroid cancer is growing in recent years, with an upsurge in the detection of microcarcinomas, defined as tumors < 1 cm in diameter. The abundant availability and continuous advances in imaging modality, mainly sonography, have contributed to the incidental identification of such tumors.1
Low-risk papillary thyroid microcarcinomas (PTMCs) were demonstrated to be less aggressive than larger tumors, to have low recurrence rates, and to carry a good prognosis with less than a 1% mortality rate.1,2Patients under active surveillance (AS) had similar survivals rates, and for those who eventually needed surgery, deferring surgery did not affect the chances for complete remission.3 That has led to a shifting trend in the management of PTMCs from traditional surgical treatment to AS in selected cases.2,4–6 The American Thyroid Association (ATA) guideline7 states that the AS management approach can be considered for very low-risk papillary microcarcinomas, e.g. without clinically evident metastases or local invasion and no convincing cytologic evidence of aggressive disease. Other studies found a correlation between tumor aggressiveness and the location of the tumor; peripheral tumors and tumors which are attached to the trachea or located in the course of the recurrent laryngeal nerve are considered to express more aggressive behavior. These tumors were regarded as unsuitable for AS.8
Given the overall good prognosis of PTMCs and the increasing evidence of the benefits of AS, an accurate risk stratification process would be a valuable addition to the diagnostic workup.
In the past decade, molecular testing of thyroid nodules has rapidly evolved. BRAF point mutation at codon 600 (BRAFV600E ) is the most common alteration that is found in 40-70% of papillary thyroid cancers.BRAFV600E is strongly associated with more aggressive behavior of the tumor. It was also shown to be a predictor for aggressive features in studies and meta-analyses focusing on PTMC.9–13 In these reports,BRAFV600E positive nodules had a higher likelihood for recurrence.9,10 Following this evidence, it has been suggested to useBRAFV600E testing for risk stratification, while BRAFV600E- negative PTMC will be eligible for AS.10 However, to date there is no real-life data testing this hypothesis nor data on the use ofBRAFV600E pre-operatively for PTMC. In order to test its utility, we developed this stimulated model. Decision tree models are used to compare treatment strategies using computed data from previously published sources rather than an actual patient’s cohort. The model results are based on chosen outcomes, such as cost, effectiveness, and quality of life. AS requires a high level of adherence from the patient. The patient’s perception of his condition and his cooperation can highly influence the final decision. Therefore, we chose to perform this model from the patient’s perspective, defining the optimal outcome as the strategy that will maximize quality of life.