Minimal extrathyroidal extension affects the prognosis of differentiated thyroid cancer: Is there a need for change in the AJCC classification system?

Zeming Liu,Sichao Chen,Min Wang,Haifeng Feng,Liang Guo,Ling Zhou,Di Hu,Yihui Huang,Chao Zhang,Danyang Chen,Wei Wei,Wei Zhou,Wen Zeng,Scott M Langevin

doi:10.1371/journal.pone.0218171

Abstract

Minimal extrathyroidal extension (ETE) is defined as tumor cells extending to the sternothyroid muscle or perithyroidal soft tissue. However, there is controversy regarding whether the magnitude of ETE (minimal or gross) should be considered in assigning a precise TNM stage to patients with thyroid cancer in the seventh/eighth editions of the AJCC system. The present study evaluated Surveillance, Epidemiology, and End Results data from 107,114 patients with differentiated thyroid cancer (2004–2013) to determine whether the magnitude of ETE (thyroid confinement, minimal, or gross) influenced the ability to predict cancer-specific survival (CSS) and overall survival (OS). Patient mortality was evaluated using Cox proportional hazards regression analyses and Kaplan-Meier analyses with log-rank tests. The cancer-specific mortality rates per 1,000 person-years were 1.407 for the thyroid confinement group (95% CI: 1.288–1.536), 5.133 for the minimal ETE group (95% CI: 4.301–6.124), and 29.735 for the gross ETE group (95% CI: 28.147–31.412). Relative to the thyroid confinement group, patients with minimal ETE and gross ETE had significantly poorer CSS and OS in the univariate and multivariate analyses (both P<0.001). After propensity-score matching according to age, sex, and race, we found that thyroid confinement was associated with better CSS and OS rates than minimal ETE (P<0.001) and gross ETE (P<0.001). These results from a population-based cohort provide a reference for precise personalized treatment and management of patients with minimal ETE. Furthermore, it may be prudent to revisit the magnitude of ETE as advocated by the AJCC and currently used for treatment recommendation by the American Thyroid Association.

Highlights

The incidence of thyroid cancer has generally been increasing during recent decades, the mortality rate has steadily declined [1]
Some patients have a high risk of recurrence or even death from papillary and follicular thyroid carcinomas [3], with specific clinicopathological features being associated with progression and a dire prognosis even after extensive surgery, radioactive iodine (RAI) ablation therapy, and thyroid-stimulating hormone suppression [4]
There remains controversy regarding whether the magnitude of ETE should be considered in assigning a precise TNM stage to patients with thyroid cancer, and further studies are needed to determine the impact of ignoring minimal ETE and only considering gross ETE when assigning a T status

Summary

Introduction

The incidence of thyroid cancer has generally been increasing during recent decades, the mortality rate has steadily declined [1]. Well-established clinicopathological indicators must be used to predict patient prognosis and select treatment for differentiated thyroid carcinoma. Previous research has indicated that appropriate treatment for thyroid cancer should be selected based on the precise TNM stage [4,5,6]. In this context, minimal extrathyroidal extension (ETE) is defined as tumor cells extending to the sternothyroid muscle or perithyroidal soft tissue [7]. The sixth edition of the UICC system defined T3 disease as a tumor with a greatest dimension of >4 cm or any tumor with minimal ETE, while T4a disease was defined as tumors extending beyond the thyroid capsule and with invasion of the subcutaneous soft tissue, larynx, trachea, esophagus, or recurrent laryngeal nerve [10]. The present study evaluated Surveillance, Epidemiology, and End Results (SEER) data to determine whether the magnitude of ETE influenced the ability to predict cancer-specific survival (CSS) and overall survival (OS) among patients with differentiated thyroid cancer

Methods

Results

Conclusion