BackgroundDifferentiated thyroid cancer (DTC) survivors are at increased risk of developing nonsynchronous second primary malignancy (NSPM). This study aims to examine possible risk factors leading to occurrence of NSPM as well as risk factors leading to NSPM-related death in patients with DTC.MethodsOf the 1,106 patients with DTC managed at our institution, 92 (8.3%) patients developed NSPM and 40 (3.6%) patients died of NSPM. All causes of death were confirmed by medical record, autopsy report or death certificate. Clinicopathological variables were compared between those without NSPM and with NSPM as well as between those who died of NSPM and did not die of NSPM. Significant variables on univariate analysis were entered into a Cox proportional hazards model.ResultsThe median latency period from diagnosis of DTC to NSPM was 142.7 (range 16.8–511.0) months. For occurrence of NSPM, age at DTC diagnosis ≥50 years old [relative risk (RR) = 2.35], cumulative radioactive iodine (RAI) activity 3.0–8.9 GBq (RR = 2.38), and external local radiotherapy (ERT) (RR = 1.95) were significant risk factors. For NSPM-related death, age at DTC diagnosis ≥50 years old (RR = 3.32) and nonbreast cancer (RR = 5.76) were significant risk factors.ConclusionsNSPM accounted for 18.7% of all deaths in DTC, but mortality was high (43.5%). Age at DTC diagnosis ≥50 years old, cumulative RAI activity 3.0–8.9 GBq, and ERT were significant risk factors for occurrence of NSPM, whereas age at DTC diagnosis ≥50 years old and the diagnosis of nonbreast cancer were significant risk factors for NSPM-related death.