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.