Trends in Survival and Factors Associated with Survival in Primary Thyroid Lymphoma: A SEER-Based Analysis (1975–2021)

Background: Primary thyroid lymphoma (PTL) is a rare malignancy, comprising less than 5% of all thyroid cancers and about 2.5% of lymphomas. Historically, treatment with surgery and radiation yielded poor outcomes. The advent of combined chemotherapy and radiation has improved survival, but long-term trends and prognostic factors remain underexplored. This study aimed to characterize the clinical and demographic features of PTL, evaluate changes in survival over time, and identify factors independently associated with survival. Methods: A retrospective cohort study was conducted using Surveillance, Epidemiology, and End Results data from PTL patients aged ≥20 years, diagnosed between 1975 and 2021. Variables analyzed included age, sex, race/ethnicity, lymphoma subtype, stage, and treatment modality. Survival outcomes were estimated using Kaplan-Meier curves, and Cox proportional hazards models were used to identify factors associated with survival. Treatment was categorized as chemotherapy plus radiation (with or without surgery), chemotherapy alone, radiation alone, or no treatment. Results: A total of 2465 patients were included; 76% (n = 1,874) were diagnosed from 2001 to 2021. Median age at diagnosis was 67 years (interquartile range [IQR]: 56-77); 69.9% (n = 1723) were female, and 88.8% (n = 2189) were White. The most common subtype was diffuse large B-cell lymphoma (62.5%, n = 1540). Median follow-up was 83 months (IQR: 24-156). Median overall survival (OS) was 150 months, with 1-, 5-, and 10-year OS rates of 84.9%, 72.9%, and 57.7%, respectively. Disease-specific survival (DSS) rates at the same time points were 89.1%, 83.7%, and 80.5%. Survival significantly improved for patients diagnosed after 2000 (p < 0.001). Variables associated with poorer DSS survival included age ≥70 years (hazard ratio [HR] = 5.77; confidence interval [CI] 2.71-12.32, p < 0.001), regional metastatic disease (HR = 1.45; CI 1.04-2.02; p = 0.03) and distant metastatic disease (HR = 1.53; CI 1.17-1.99; p = 0.002). The highest 10-year DSS (86.6%) was seen in those receiving combined chemotherapy and radiation, outperforming chemotherapy alone (77.2%), radiation alone (77.0%), and no treatment (68.2%). Conclusion: PTL survival has significantly improved in recent decades, which may reflect both advances in treatment, particularly the combined use of chemotherapy and radiation, and shifts in disease presentation, including earlier diagnosis and changes in stage distribution.