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.