Active Surveillance Is Not Surgery: Rethinking Disease Progression in PTMC
- Carlos E Costa Almeida
- 17 de jul.
- 5 min de leitura
Current guidelines for papillary thyroid cancer management recognize active surveillance as an alternative to surgery for selected patients with low-risk papillary thyroid microcarcinoma (PTMC). However, because papillary thyroid carcinoma has traditionally been regarded as a surgical disease, many patients find it difficult to accept active surveillance—essentially, the absence of immediate intervention—as an appropriate strategy for managing cancer. In Portugal, at least, the word cancer carries a particularly negative connotation and is often perceived as belonging to the “dark side” of medicine. Nevertheless, by avoiding surgery, active surveillance spares patients the potential complications of an operation for a disease that is highly indolent and associated with an excellent prognosis.
In Korea, the increasing prevalence of thyroid microcarcinoma has been attributed by some authors to the widespread use of ultrasound, together with easy access to medical care. However, easy access to healthcare should not be regarded as the problem. Instead, the key questions are why these patients undergo thyroid ultrasound in the first place and, more importantly, why fine-needle aspiration (FNA) is performed for thyroid nodules measuring less than 1 cm. Patients are not consumers, and physicians should request diagnostic tests and perform surgical procedures only when supported by appropriate clinical indications based on the patient's symptoms and clinical evaluation, rather than in response to patient demand alone.
A recent study by Dr. Eun Kyung Lee and colleagues, published in Thyroid in 2022, investigated the progression of papillary thyroid microcarcinoma (PTMC) during active surveillance (AS) and the factors associated with disease progression. The authors acknowledge that AS is an accepted management option for patients with low-risk PTMC. However, the risk factors for disease progression remain incompletely understood, with younger age (<40 years) being the only factor consistently associated with progression. Whether other factors, such as tumor size, calcifications, Graves' disease, multifocality, and a family history of thyroid cancer, are associated with disease progression remains to be established.
The authors conducted a multicentre, non-randomized prospective study that enrolled patients older than 18 years with low-risk PTMC (no extrathyroidal extension (ETE), no lymph node metástases (LNM), and no distant metastases) confirmed by FNA or core needle biopsy. A total of 706 patients were assigned to active surveillance (AS), whereas 387 underwent immediate surgery (iOP). We must highlight that in the AS group, patients were older and with smaller tumors (p<0.001).
The authors defined progression in the following way:
Size increase ≥3mm in at least one dimension or ≥2mm in at least two dimensions;
New ETE or adjacent organ involvement
Lymph node metastases (LNM)
During a mean follow-up of 44.9 months (3.7 years), the overall disease progression rate was 9.6% (68 patients). Tumor enlargement occurred in 8.1% of patients, lymph node metastasis (LNM) developed in 1.3%, and extrathyroidal extension (ETE) in 0.4%. The cumulative progression rates at 2 and 5 years were 5.3% and 14.2%, respectively. Interestingly, patients who developed disease progression due to new ETE showed neither tumor enlargement nor clinical signs suggestive of progression, such as voice changes or vocal cord palsy. Furthermore, one patient experienced a reduction in tumor size during AS but subsequently developed new LNM. In my view, these findings highlight that the absence of tumor growth does not necessarily indicate disease stability. This observation is particularly relevant in daily clinical practice, where tumor size stability is often considered reassuring, leading clinicians to conclude that the disease remains under control.
During active surveillance, 11 patients were diagnosed with a new thyroid cancer by fine-needle aspiration (FNA) after a mean follow-up of 14.1 months. Notably, 10 of these newly diagnosed cancers arose in pre-existing thyroid nodules that had initially appeared benign on ultrasound but subsequently developed suspicious sonographic features. Once again, these findings emphasize the importance of continued surveillance of other thyroid nodules, even when they are considered benign at the initial evaluation.
Dr. Eun Kyung Lee and colleagues concluded that the progression rate observed in their cohort was higher than that reported in previous studies. One possible explanation is the definition of disease progression adopted in their study, which included a tumor size increase of at least 2 × 2 mm. This criterion is more sensitive for detecting progression than the definitions used in most previous studies, which typically consider only an increase of ≥3 mm in a single dimension. This leads the authors to state that more studies are necessary to define progression criteria in PTMC. Interestingly, among patients who remained on active surveillance despite meeting the criteria for progression, disease appeared to stabilize after an increase of approximately 3 mm in maximum tumor diameter or a 50% increase in tumor volume. These findings raise the question of whether surgery should be recommended immediately at the first sign of disease progression. Furthermore, some authors have suggested that surgery should be offered once a PTMC reaches 13 mm during active surveillance. Overall, additional studies are needed to provide robust evidence and establish clear recommendations regarding the optimal timing of surgery after disease progression.
Finally, this study identified age <30 years (also a predictor of earlier disease progression), male sex, and tumor size ≥6 mm as factors associated with PTMC progression.
In conclusion, this study suggests that the progression rate of PTMC during active surveillance may be higher than that reported in previous studies. In this context, greater caution may be warranted when considering active surveillance for younger patients and for men. It is important to remember that surgery and active surveillance are fundamentally different approaches. Surgery treats the disease by removing the cancer, whereas active surveillance does not provide treatment but instead relies on careful monitoring of the tumor's behavior to defer surgery until there is evidence of progression.
Once a cancer has been diagnosed—even an indolent, low-risk one—it can be difficult for patients to understand the concept of active surveillance: "You have cancer, but we are only going to monitor it until it grows or spreads." A natural response from a patient is, "Why not remove it before it grows or metastasizes?" This raises a fundamental question: Why perform an FNA on a thyroid micronodule in the first place?
As we all know, many thyroid nodules are likely being overdiagnosed and, consequently, overtreated. Many patients would live their entire lives with these microcarcinomas without experiencing symptoms or disease-related morbidity, and without the anxiety associated with a cancer diagnosis.
Link to article:
Dr. Carlos Eduardo Costa Almeida
General Surgeon
Comentários