Survival Prognostication in Patients with Differentiated Thyroid Cancer and Distant Metastases: A SEER Population-Based Study

Abstract

Background: For patients with thyroid cancer, distant metastasis is a significant predictor of poor outcome. Since distant metastasis occurs in less than 10% of patients with differentiated thyroid cancer, correlates of survival in this vulnerable patient population remain understudied. This study aimed to identify prognostic groups among patients with differentiated thyroid cancer and distant metastases and to determine the role of, and interactions between, patient and tumor characteristics in determining survival. Methods: We identified adult patients diagnosed with differentiated thyroid cancer with distant metastases from the U.S. SEER-17 cancer registry (2010-2019). Analyses were performed using Cox proportional hazards regression, survival trees, and random survival forest. Relative importance of patient and tumor factors important for disease-specific and overall survival was assessed based on the random survival forest analyses. Results: Cohort consisted of 2411 patients with differentiated thyroid cancer with distant metastases followed for a median of 62 months. Most common histopathologic subtype (86.0%) was papillary thyroid cancer, and the most common sites of distant metastasis were the lungs (33.7%) and bone (18.9%). Cox proportional hazards model illustrated significant associations between survival and the following: patient age (p < 0.001), tumor size (p < 0.01), and site of distant metastasis (p < 0.05). Survival tree analyses identified three distinct prognostic groups based on disease-specific survival (DSS) (5-year survival of the prognostic groups was 92%, 64%, and 41%; p < 0.001) and four distinct prognostic groups based on overall survival (OS) (5-year survival of the prognostic groups was 96%, 84%, 57%, and 31%; p < 0.001). The first split in the survival trees for DSS and OS was by age at diagnosis (≤57 years vs. ≥58 years) with subsequent splits based on presence/absence of lung metastases, tumor size (≤4 cm vs. >4 cm), and patient age. A total of 558 patients (23.1%) died from thyroid cancer, and 757 patients (31.4%) died from all causes during the study period. Conclusions: This study identifies distinct prognostic groups for patients with differentiated thyroid cancer with distant metastases and highlights the importance of patient age, lung metastases, and tumor size for determining both disease-specific and overall survival. These findings inform risk stratification and treatment decision-making in this understudied patient population.

Keywords: disease-specific survival; lung metastases; overall survival; thyroid cancer.

FIG. 1.

Disease-Specific Survival (DSS) Prognostication in Patients with Differentiated Thyroid Cancer and Distant Metastases. The first split in the tree was by age ≤57 years versus ≥58 years. All subsequent splits were based on presence/absence of lung metastases, age at diagnosis, and tumor size. There are three distinct prognostic groups. For each terminal group, we report the five-year DSS rate (5YR), the 95% confidence interval (in parentheses), the total number of patients in that terminal group (N), and the crude number of patients who died from thyroid cancer in that terminal group (D).

FIG. 2.

Kaplan–Meier curve illustrating the disease-specific survival for each of the three distinct prognostic groups of patients with differentiated thyroid cancer and distant metastases identified by survival tree analysis. Five-year survival in group I was 92% compared with 64% and 41% in groups II and III, respectively.

FIG. 3.

Overall Survival (OS) Prognostication in Patients with Differentiated Thyroid Cancer and Distant Metastases. The first split in the tree was by age ≤57 years versus ≥58 years. All subsequent splits were based on presence/absence of lung metastases, age at diagnosis, and tumor size. There are four distinct prognostic groups. For each terminal group, we report the five-year OS rate (5YR), the 95% confidence interval (in parentheses), the total number of patients in that terminal group (N), and the crude number of patients who died from any cause in that terminal group (D).

FIG. 4.

Kaplan–Meier curve illustrating the overall survival for each of the four distinct prognostic groups of patients with differentiated thyroid cancer and distant metastases identified by survival tree analysis. Five-year survival in group I was 96% compared with 84%, 57%, and 31% in groups II, III, and IV, respectively.