Risk Stratification in Differentiated Thyroid Cancer: From Detection to Final Follow-Up

Abstract

Context: Modern management of differentiated thyroid cancer requires individualized care plans that tailor the intensity of therapy and follow-up to the estimated risks of recurrence and disease-specific mortality.

Design: This summary is based on the authors' knowledge and extensive clinical experience, supplemented by review of published review articles, thyroid cancer management guidelines, published staging systems, and original articles identified through a PubMed search, which included terms such as risk stratification, staging, clinical outcomes, and differentiated thyroid cancer.

Main outcome measures: In the past, risk stratification in differentiated thyroid cancer usually referred to a static estimate of disease-specific mortality that was based on a small set of clinicopathological features available within a few weeks of completing initial therapy (thyroidectomy, with or without radioactive iodine). Today, risk stratification is a dynamic, active process used to predict the appropriateness for minimalistic initial therapy, disease-specific mortality, risk of recurrence, and the most likely response to initial therapy. Rather than being a static prediction available only after initial therapy, modern risk stratification is a dynamic, iterative process that begins as soon as a suspicious nodule is detected and continues through final follow-up.

Conclusions: Dynamic risk assessment should be used to guide all aspects of thyroid cancer management, beginning before a definitive diagnosis is made and continuing through the final follow-up visit.

Figure 1.

Risk stratification in thyroid cancer is best viewed as a dynamic, iterative, active process that begins in the peri-diagnostic period and extends through final follow-up. AJCC, American Joint Committee on Cancer; ATA, American Thyroid Association.

Figure 2.

Highly sensitive detection tools often detect small-volume disease that may or may not require action. Key factors that differentiate actionable from non-actionable findings include tumor volume, location, growth rate, symptoms, and patient preference.

Figure 3.

Peri-diagnostic risk stratification considers medical team characteristics, imaging/clinical findings, and patient characteristics to classify patients as ideal, appropriate, or inappropriate for a minimalistic initial management approach.

Figure 4.

A simplified approach to AJCC staging in differentiated thyroid cancer, emphasizing the critical decision nodes, which include age at diagnosis, distant metastasis, and gross extrathyroidal extensions.

Figure 5.

As described in the ATA guidelines, individualized risk stratification is best visualized as a “continuum of risk” rather than as three discrete risk categories that predict the risk of structural disease recurrence. [Adapted with permission from Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1–133.]

Figure 6.

The 2015 ATA guidelines expanded the inclusion criteria for ATA low-risk and ATA high-risk disease categories as described in this table. [Adapted with permission from Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1–133.]

Figure 7.

Definitions, clinical outcomes, and management implications of the ATA response to therapy categories. NED denotes a patient as having no evidence of disease at final follow-up. Tg value cutoffs used in the definition of excellent, biochemical, and incomplete response categories assume the absence of anti-Tg antibodies. [Adapted with permission from Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26(1):1–133.]