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Simple Summary  Papillary thyroid cancer (PTC) is the most common subtypes of thyroid malignancy, and its distant metastasis (DM) is linked with higher mortality. We sought to study the consequences of different distant metastasis sites on the survival of PTC patients to better understand their association with survival outcomes, which will help clinicians to develop tailored treatment plans. Our results showed that metastasis to specific organs appear to affect prognosis. The 5-year survival rate was 6% and 12% for patients with brain and liver metastases, respectively. This was markedly lower than that in cohorts with bone (25%) and liver (21%) metastasis. Risk factors that significantly influence overall survival were male gender, multiple organ involvement, and brain metastasis. Therefore, we should take into consideration of such discrepancy when making treatment strategies.    Abstract  Introduction—heterogeneity in clinical outcomes and survival was observed in patients with papillary thyroid cancer (PTC) and distant metastases. Here, we investigated the effect of distant metastases sites on survival in PTC patients. Methods—patients with a diagnosis of PTC and known metastases were identified using the Surveillance, Epidemiology, and End Results database (1975–2016). Univariate and multivariate Cox regression analyses were performed to analyze the effect of distant metastases sites on thyroid cancer-specific survival (TCSS) and overall survival (OS). Results—from 89,694 PTC patients, 1819 (2%) developed distant metastasis at the initial diagnosis, of whom 26.3% presented with the multiple-organ disease. The most common metastatic sites were lung (53.4%), followed by bone (28.1%), liver (8.3%), and brain (4.7%). In metastatic patients, thyroid cancer-specific death accounted for 73.2%. Kaplan–Meier curves showed decreased OS in patients with metastases to the brain (median OS = 5 months) and liver (median OS = 6 months) compared to lung (median OS = 10 months) and bone (median OS = 23 months). Moreover, multiple organ metastasis had a higher mortality rate (67.4%) compared to single organ metastasis (51.2%,  p  < 0.001). Using multivariate analysis, risk factors that significantly influence TCSS and OS were male gender (HR = 1.86, 95% CI = 1.17–2.94,  p  < 0.001, and HR = 1.90, 95% CI = 1.40–2.57,  p =  0.009), higher tumor grade (HR = 7.31, 95% CI = 2.13–25.0,  p  < 0.001 and HR = 4.76, 95% CI = 3.93–5.76,  p  < 0.001), multiple organ involvement (HR = 6.52, 95% CI = 1.50–28.39,  p  = 0.026 and HR = 5.08, 95% CI = 1.21–21.30,  p  = 0.013), and brain metastasis (HR = 1.82, 95% CI = 1.15–2.89,  p  < 0.001 and HR = 4.21, 95% CI = 2.20–8.07,  p  = 0.010). Conclusion—the pattern of distant metastatic organ involvement was associated with variability in OS in PTC. Multi-organ metastasis and brain involvement are associated with lower survival rates in PTC. Knowledge of the patterns of distant metastasis is crucial to personalize the treatment and follow-up strategies.

Site-Specific Metastasis and Survival in Papillary Thyroid Cancer: The Importance of Brain and Multi-Organ Disease