Dynamic Risk Group Analysis and Staging for Differentiated Thyroid Cancer

Introduction

A defined set of clinical factors and pathologic characteristics have been used in different staging systems (e.g., Tumor, Node, and Metastases [TNM] with American Joint Committee on Cancer [AJCC]; metastasis, age, completeness of resection, invasion, and size [MACIS]; age, metastasis, extent, and size [AMES]; and age, gender, extent, and size [AGES]) to predict the risk of death in differentiated thyroid cancer. The most important of these include age of the patient at diagnosis, histology, size of the tumor, completeness of resection, and the presence of metastases at presentation. However, in clinical practice a comprehensive initial risk stratification requires review of all available data that is obtained up to 4 months after initial diagnosis and treatment ( Table 24.1 ). Integration of all of these factors allows for an initial estimation of both the risk of death and importantly also the risk of recurrence.

Although each of the major staging systems use risk stratification with respect to disease-specific mortality, they are much less effective at predicting risk of recurrence. For this reason the American Thyroid Association (ATA) endorses a three-tiered system that better predicts risk of recurrence and that can be combined with other staging systems to provide a more comprehensive initial estimate of the risk of death and recurrence for each patient. Unfortunately, these staging systems fail to adequately incorporate the effect of initial therapy (other than completeness of resection). Because the effect of initial therapies is likely to have a major impact on the final outcome of patients, failure to incorporate the effect of initial therapy may result in an inappropriately low estimate of risk in the few “low-risk” patients who do not respond to initial therapy or an inappropriately high estimate of risk in the few “high-risk” patients who have an excellent response to initial therapy.

But more importantly, the current staging systems which classify patients at the time of initial presentation are static and do not change over time. In clinical care our risk estimates clearly change over time depending on the response to therapy and biological behavior of each tumor for individual patients, and this risk stratification process should be dynamic. For example a “low-risk” patient who develops a rapidly rising thyroglobulin (Tg) level or new pulmonary nodules would forever be classified as “low risk” based on initial staging when, in reality, the patient is now at increasing risk of developing structurally identifiable progressive disease and may be at increased risk of death from thyroid cancer by virtue of these new clinical findings. It is both the failure to account for the effect of initial therapy and the static nature of our current staging systems that result in the relative inability of these staging systems to guide long-term follow-up recommendations.

The importance of accurate, ongoing risk stratification cannot be overemphasized. The most important clinical aspects of patient care are based on an assessment of individualized risk; therefore implementation of the ATA guidelines into clinical practice requires a thorough understanding of the risk of death as well as of the risk of recurrence for each individual patient we evaluate and treat. This chapter provides an updated guideline on how to practically apply and integrate an initial staging system with the ATA Risk Stratification system, a separate postoperative clinicopathologic system that better predicts recurrence, and the ATA Response to Therapy system, an ongoing reassessment of the patient that incorporates clinical information as it becomes available.

Initial Risk Stratification

Although initial risk stratification using the current staging systems has some limitations, it provides a starting point for initial management recommendations and forms the basis of ongoing risk stratification. The updated ATA guidelines on the management of thyroid cancer and thyroid nodules recommend using both (1) the AJCC TNM system to estimate the risk of death from thyroid cancer and (2) the ATA Risk Stratification system, a separate postoperative clinicopathologic staging system to improve the ability to predict recurrence and to plan follow-up for patients with differentiated thyroid cancer ( Box 24.1 ).