Determination of the risk of developing secondary primary malignancy and the factors increasing this risk in patients with differentiated thyroid cancer

The aim of this study was to determine the risk of developing secondary primary malignancy (SPM) in patients with differentiated thyroid carcinoma (DTC) and to identify potential risk factors associated with SPM development. A total of 2,364 patients who were histopathologically diagnosed with thyroid malignant neoplasm between 2010 and 2022 were retrospectively reviewed. After applying the predefined exclusion criteria, 67 patients who developed SPM constituted the study group, while 250 patients randomly selected from 2,297 DTC patients without SPM comprised the control group. Both groups were analyzed in terms of demographic, clinical, and histopathological characteristics, as well as radioactive iodine (RAI) therapy, cumulative activity, and survival outcomes. Survival analysis was performed using the Kaplan–Meier method, and prognostic factors were evaluated by multivariate logistic and Cox regression analyses. A p-value of <0.05 was considered statistically significant. According to the results, the incidence of SPM was calculated as 2.83%. There was no significant difference in SPM development between patients who received RAI therapy and those who did not (p>0.05). The mean total RAI dose administered was lower in patients who developed SPM compared to those without SPM. Neither RAI dose nor cumulative activity was significantly associated with SPM development. No significant differences were found between the groups in terms of tumor size, tumor number, lymph node metastasis, lymphovascular invasion, or extrathyroidal extension. The presence of distant metastasis was more frequent in the SPM group but did not reach statistical significance (p=0.059). Multivariate analyses revealed that SPM development was an independent adverse prognostic factor for overall survival (p<0.0001). In addition, advanced age, male gender, higher TNM stage, and the presence of distant metastasis were also identified as independent factors negatively affecting survival. In conclusion, it was determined that low and medium doses of RAI therapy did not increase the likelihood of SPM development in DTC patients. Survival was found to be associated with clinical and prognostic parameters such as age, disease stage, and the presence of additional malignancies.