The traditional approach to the management of differentiated thyroid cancer placed a premium on early detection and immediate intervention for both the primary disease lesion and for biochemical or structural evidence of persistent/recurrent disease. While this aggressive treatment strategy was viable and effective when our rather crude disease detection tools identified primarily large volume macroscopic disease, it is much less clear whether an aggressive approach to either very low risk thyroid cancer primaries or small volume persistent/recurrent disease that is only detected with highly sensitive imaging tools and blood tests is beneficial to patients. Multiple studies now demonstrate that small volume disease in carefully selected patients (both in the primary setting and in the persistent/recurrent disease setting) progresses very slowly in the vast majority of patients and is often not “cured” with additional surgery or radioactive iodine. Furthermore, some of our well meaning treatments may be associated risks that are greater than the potential harm that could be caused by small volume disease. We have reached a point where our highly sensitive detection tools are identifying small volume disease that is very unlikely to cause any harm.
In this lecture, we will re-evaluate what we think we know about the natural history of small volume primary thyroid cancers (papillary microcarcinomas) and small volume minimal residual disease (biochemical incomplete and/or structural incomplete). We will question the clinical benefit, effectiveness, and toxicity of additional therapies aimed at destroying all residual disease and describe a clinical management paradigm in which clinically important disease is identified and appropriately treated while small volume disease that is unlikely to cause immediate harm is followed with active surveillance utilizing a deferred therapeutic management approach.
Screening and autopsy studies indicate that asymptomatic papillary microcarcinomas are present in at least 5-10% of the United States adult population ( representing nearly 16 million people with un-diagnosed thyroid cancer). Despite this huge pool of subclinical cases, the prevalence of thyroid cancer in United States is only 0.5 million patients indicating that <3% of this subclinical reservoir has been detected and diagnosed. However, the current management paradigm of aggressive disease detection using US guided fine needle aspiration is resulting in a dramatic increase in the identification and therapy of very low risk thyroid cancers.
Interestingly, data from our Japanese colleagues indicates that the vast majority of these subclinical thyroid cancer foci progress either slowly or not while under observation with serial ultrasound examinations. Importantly, even the small number of patients that demonstrated disease progression while under active surveillance were effectively treated with thyroid surgery indicating that a delayed surgical management approach in properly selected patients had no impact on disease specific survival.
In light of the very low disease specific mortality associated with papillary microcarcinomas, the lack of proven benefit of thyroid surgery, and the potential for side effects and complications from thyroidectomy, we are obligated to carefully consider alternative management strategies. The 2015 American Thyroid Association thyroid cancer management guidelines will state that while surgery is generally recommended for biopsy proven thyroid cancer, an active surveillance management approach “can be considered” as an alternative to immediate surgery in patients with very low risk tumors. Furthermore, the 2015 ATA guidelines strongly discourage FNA of asymptomatic sub-centimeter thyroid nodules, even if ultrasonographically suspicious, endorsing serial ultrasonographic follow-up with cytology evaluation recommended only if there is evidence of disease progression.