Discussion
With the accumulation of evidence regarding the excellent prognosis of
lrPTMC, active surveillance is becoming a viable
strategy.3,18 In this study, we aimed to provide tools
to optimize the risk stratification process, in order to allow
physicians to tailor the most suitable strategy according to the
patient’s and nodule’s specific characteristics.
Regional or distant metastases or other aggressive features such as
tracheal or recurrent laryngeal invasion are clear indications for
immediate
surgery.18However, a broader approach to facilitate decision on AS was suggested
for more complex cases, integrating sonography characteristics, tumor
location, patient’s demographics, comorbidities, and preferences, as
well as the medical team’s capabilities.19 Our model
adds to these factors input from BRAFV600Emolecular testing, one of the most common genetic etiologies in thyroid
cancer which was shown to be associated with aggressive
features.9,11,20
When considering the patient factors, patient-specific preferences and
quality of life implications play a major role. While surgery has
well-known risk and complication rates, it should be noted that AS
requires repeated ultrasounds and visits to the clinic which may pose a
burden to the patient and the health care system. In addition, AS may
also be accompanied by emotional stress and potential anxiety in the
face of uncertainty for some patients.6,21 The fear of
the ”C-word” was also found to be a factor in the
decision.22 The extent of this stress may be affected
by various factors, including the patient’s personal perspectives,
cultural norms, and social circumstances.23
We found that the first and most significant step in selecting the
optimal strategy is the patient’s attitude towards AS and surgery, which
is reflected by the utility he would assign for ”living with the tumor”
(AS) vs. ”going into surgery” (post-HT). This finding is supported by
the analysis of the results from two previously published
cost-effectiveness models comparing AS with hemithyroidectomy for
PTMC.17,24 These models have reached opposite
conclusions, while the only remarkable difference between the two was
the utility assigned to AS, thereby pointing out its major role. As no
specific data exist for AS in PTMCs, estimation was driven from similar
scenarios in other cancer types, mostly prostate, which resulted in a
wide range of variability.
Hence, it is a great challenge for the physician to integrate the
clinical features with the utility values for the individual patient in
order to design the best-personalized treatment strategy. Quality tools
to assist the physicians in establishing this value are currently
lacking and could have a great value in facilitating the patient-doctor
communication and the decision-making process.
Nodules features also play a key role in selecting treatment strategies.
In addition to the current known low-risk
criteria18,19 that are the basic requirements to
consider AS, our model incorporates the implication ofBRAFV600E testing in risk stratification. This
variant was found to be associated with tumor recurrent in PTMC cases,
suggesting a more aggressive tumor behavior. However, there is currently
yet to be tested in real-life studies and there is no evidence regarding
the association between prognosis and the variant in patients under AS.
The major limitation of this study is its design – computational
modeling rather than real-life patients. This type of model is commonly
accepted before implantation of new methods, where it allows primary
assessment of the potential benefits without is costs and risks. Our
positive finding now can encourage further investment of resources in
real-life studies.
As most of the data on molecular testing in PTMC focused onBRAFV600E , we have presented this variant’s
influence on the model outcomes. However, in real life, molecular
testing includes a wider profile of aggressive mutations, such as theTERT mutations. This information may give us a more precise
understanding of the tumor behavior and assist in further
decision-making.