Different Clinicopathologic Features Predispose to Different Patterns of Distant Metastasis With Heterogeneous Short-Term Prognosis in Patients With Differentiated Thyroid Cancer

Li-Cheng Tan; Nai-Si Huang; Peng-Cheng Yu; Pei-Zhen Han; Wan-Lin Liu; Zhong-Wu Lu; Rong-Liang Shi; Xiao Shi; Yu Wang; Qing-Hai Ji; Ning Qu; Wen-Jun Wei; Yu-Long Wang


Clin Endocrinol. 2022;96(3):402-412. 

In This Article

Abstract and Introduction


Background: Limited studies have focused on the associated clinicopathologic features and short-term prognostic impacts of metastatic patterns at initial diagnosis in differentiated thyroid cancer (DTC).

Methods: Overall, 530 individuals with distant DTC diagnosed between 2010 and 2014 were identified from Surveillance, Epidemiology, and End Results (SEER) database. Multinomial logistic regression model was used to assess the clinicopathologic factors influencing the pattern of distant metastasis. Kaplan–Meier method and multivariable Cox regression were used to estimate the short-term effects of metastatic patterns on overall (OS) and thyroid cancer-specific survival (TCSS).

Results: Fifty, 111, 263, 59 and 47 patients presented with distant lymph node (LN)-only, bone-only, lung-only, bone plus lung, and liver and/or brain metastases (Mets), respectively. Regional lymph node metastasis (LNM) and follicular histotype were the only confirmed risk factors for distant LN-only Mets and bone-only Mets, respectively. Larger tumour size, extrathyroidal extension (ETE) and papillary histotype were associated with lung-only Mets. Synchronous bone and lung Mets were more likely to occur in older patients. In addition, patients with distant LN-only Mets had hardly any negative effect on OS and TCSS, whereas those with synchronous bone and lung or liver/brain Mets predicted unfavourable short-term outcomes, regardless of whether they received total thyroidectomy and radioisotopes.

Conclusions: Different clinicopathologic factors predispose to different patterns of metastases with profound short-term survival differences among DTC patients. Our findings may help to determine effective pretreatment screening for aggressive metastatic patterns at initial diagnosis, and thus to provide additional treatment or access of clinical trials for these patients.


Thyroid cancer is the most common malignancy affecting the endocrine glands, which have increased substantially over the past decades. In the United States, the incidence of thyroid cancer has increased 3.6% annually from 1974 to 2013, regardless of sex, race and age groups.[1]

Although differentiated thyroid cancer (DTC) is always associated with a favourable survival, distant metastasis is known to be an adverse prognostic factor. Distant metastasis in DTC could be divided into two scenarios: distant metastasis at first diagnosis and distant metastasis discovered during follow-up after the initial treatment.[2] For the first scenario, the frequency of DTC patients with initial distant metastasis ranges from 1% to 9% and long-term survival ranges from 31% to 50%.[2,3] However, there is a significant increase of distant papillary thyroid cancer (PTC) of 2.4% per year, and the incidence-based mortality increased 2.9% per year for distant PTC and 1.1% per year for overall PTC.[1] The most frequent sites of metastasis are lung and bone.[4]

Several studies have been conducted on distant metastatic DTC patients. Machens et al.[5] found that extrathyroidal extension (ETE) and lymph node metastasis were independent predictive factors for distant metastasis. Sampson et al.[3] noted that the prognosis of distant metastatic DTC patients was associated with age, site of metastasis, histology, and iodine avidity. Goffredo et al.[6] summarized the data in the Surveillance, Epidemiology, and End Results (SEER) database, and showed 2.2% DTC cases were diagnosed with distant metastasis at first presentation, and the survival has not improved over the past two decades.

Nevertheless, with variable treatment information and follow-up, there is still limited information regarding impact of different metastatic patterns on survival of DTC patients; and the associated factors of specific pattern of metastasis remain indistinct. In this study, we aim to explore the relationship among clinicopathological features, patterns of metastatic DTC, and prognosis based on SEER program, which is the largest population-based and publicly available cancer database. We explore the risk factors and survival of different metastatic patterns in DTC patients for the first time, which would help us to understand the metastatic paradigm in DTC as well as improve screening and treatment strategies in these patients.