A New Frontier in Papillary Thyroid Cancer Treatment

Natalia Genere, MD; Juan P. Brito, MD, MS


April 26, 2021

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A 73-year-old man with prostate cancer and hypertension came to see me for an incidental diagnosis of papillary thyroid microcarcinoma (PTMC). He had undergone fluorodeoxyglucose (FDG) PET with his oncology team because of a rising serum prostate-specific antigen (PSA) level. There were no concerning findings from the prostate cancer perspective, and the PSA level subsequently declined. However, a small FDG-avid thyroid nodule was incidentally discovered.

Ultrasound revealed a 7-mm highly suspicious thyroid nodule with no extrathyroidal extension and no suspicious lymph nodes. Cytology from a fine-needle biopsy of the lesion confirmed a diagnosis of papillary thyroid microcarcinoma. The patient was referred to me for further management.

This scenario of an incidentally discovered small papillary thyroid cancer is all too common. In the United States, the incidence of thyroid cancer increased 300% in the past four decades, with the largest increase noted in tumors ≤ 2 cm (annual percentage change, 6.8%) and in papillary thyroid cancer subtype (annual percentage change, 1.7%). However, mortality has stayed the same or minimally increased over this time, suggesting that overdiagnosis is the likely cause of the surge in thyroid cancer cases.

How Should We Manage PTMC?

In accordance with the American Thyroid Association guidelines and the American College of Radiology Thyroid Imaging, Reporting and Data System (TI-RADS), such a nodule could be safely observed without biopsy. However, performing a biopsy is not uncommon and speaks to the importance of implementing appropriate care process protocols to improve patient care.

For my patient, the biopsy was performed before being evaluated in the endocrinology clinic. But now that we have the biopsy information, what do we do with it? The answer used to be unanimous: surgically remove the cancer. However, in the past decade, rigorous research from Japan and Korea has changed this paradigm, bringing other options into the picture.

In the landmark study by Ito and colleagues, 1235 confirmed PTMCs were followed clinically for an average of 5 years (range, 1.5-19 years). Over the study period, 3.5% showed clinically significant progression and only 1.5% metastasized to regional lymph nodes; surgical intervention at the time of clinical change was adequate to prevent recurrences.

An important point to note from this study is that patients with suspicious lymph nodes or nodules close to the medial or posterior edge of the thyroid, or with concern for extrathyroidal extension, were excluded. Patients in the active surveillance protocol had comprehensive neck ultrasonography every 6-12 months. This study also identified that younger patients are more likely than their older counterparts to have clinically significant enlargement of PTMCs and to have regional metastatic disease.

On the basis of these studies, among others, the Japanese Association of Endocrine Surgery provided a consensus statement on best practices for active surveillance of PTMCs.

But What About in the United States?

There has been some uptake of active surveillance in the United States, but it has been isolated to a few tertiary care centers and progress has been slow. One major obstacle to implementation is inconsistent access to high-quality, comprehensive ultrasound imaging that would reliably assess for clinically significant changes in size or suspicious lymph nodes.

Thyroid sonography generally performed well when a standardized reporting system was used, but in practice, utilization of these structured reporting systems continues to be low internationally, and quality of ultrasound can be quite variable based on sonographer experience. We have experienced this to be true in patients coming for consultation for thyroid nodules with poor-quality or incomplete sonographic exams, which should not be used to decide whether a patient qualifies for active surveillance.

This issue may not be unique to the United States; we are unable to comment on care accessibility in Japan. What is certain, however, is that we must have close collaboration with a multidisciplinary team, including skilled and experienced neck sonographers, to offer active surveillance as an option for thyroid cancer.

Who Is a Good Candidate for Active Surveillance?

Active surveillance is an option for patients who have a confirmed subcentimeter papillary thyroid cancer without evidence of extrathyroidal extension and no suspicious lymph nodes. Tumors up to 2 cm can be considered for active surveillance, with the caveat that longitudinal data are less robust for papillary thyroid cancers between 1 cm and 2 cm.

Active surveillance may not be the right choice for a patient for a variety of reasons, including difficulty with coordination of active surveillance (eg, getting to regular visits, access to high-quality ultrasound), anxiety about the diagnosis, or expected duration of active surveillance. We tend to steer young, healthy patients away from active surveillance in some cases, given data suggesting a higher rate of progression in this population as well as the burden of a decades-long active surveillance regimen.

The patient's situation should drive clinical decision-making. For some patients, it may make sense to do active surveillance for a few years, and then opt for surgery at a later time. Active surveillance provides patients with the flexibility to deal with a low-risk cancer in the context of their values and preferences.

In our clinic, we use a shared decision-making approach when discussing management options for PTMCs, which take into account tumor characteristics, patient characteristics, and medical team experience and infrastructure (Figure). We review longitudinal data on the safety of active surveillance and the monitoring protocol, and we discuss how this approach is used in other types of cancers as well, such as prostate cancer.

Figure. Sample of the shared decision-making tool used to facilitate treatment conversations.

For our patient above, we decided that active surveillance was appropriate because of his age and comorbidities, nodule characteristics (small, without evidence of invasion), and his personal preferences to avoid surgery. He is currently doing well after 3 years, with no significant changes in his ultrasound. Our current protocol for active surveillance includes ultrasonography of the neck (with comprehensive lymph node evaluation) every 6 months for 2-3 years, followed by annual surveillance thereafter in most cases. This is consistent with the Japanese consensus statement.

The Future of Differentiated Thyroid Cancer

Our understanding of the natural history and behavior of small papillary thyroid cancers is evolving. These developments have paved new opportunities to deliver evidence-based care in a more individualized way. Active surveillance for PTMCs is an appealing option for thyroid cancer management in certain patient scenarios and when the clinical infrastructure allows for it.

With the Japanese expertise in active surveillance as a framework, we hope that more centers in the United States will offer this option in the future. The days of a one-size-fits-all approach to thyroid cancer have passed, and now we must learn how to apply these new techniques for the good of our patients.

Natalia Genere, MD, is an instructor in medicine at Washington University School of Medicine in St. Louis. Her clinical interests are in benign and malignant disorders of the thyroid. She has published in the areas of clinical decision-making in thyroid nodules and thyroid cancer epidemiology.

Juan P. Brito, MD, MS is the medical director of the Mayo Clinic Shared Decision Making National Resource Center. He is dedicated to improving the lives of patients with thyroid cancer by improving the care they receive.

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