Second primary malignancy risk after thymic epithelial tumors: a Surveillance, Epidemiology, and End Results analysis integrating multiple primary-standardized incidence ratio and competing-risk models.

Background: Thymic epithelial tumors (TETs) are rare, but with improving survival, second primary malignancies (SPM) are an emerging concern. This study aimed to characterize the overall, site-specific, and latency-dependent risk of SPM after TETs and to identify clinical predictors using multiple primary-standardized incidence ratio and competing-risk models. Methods: Using Surveillance, Epidemiology, and End Results (SEER) 17 registries (2000-2022), we identified patients with microscopically confirmed TETs. Multiple primary-standardized incidence ratio (MP-SIR) analyses in SEER*Stat were used to compare observed SPM in TETs survivors with expected numbers based on age-, sex-, race- and calendar year-specific incidence rates in the general U.S. population. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated overall and stratified by histology, cancer site, and latency interval. Fine-Gray competing-risk models were used to assess clinical predictors of SPM. Results: Among 5,849 patients with TETs, 590 (10.1%) developed an SPM. The incidence rate of SPM among TETs survivors in our cohort was 2,034.6 per 100,000 person-years, far exceeding that of the general population (80.4 per 100,000 person-years). Significantly elevated SIRs were observed for SPM arising in the respiratory, endocrine, urinary, digestive, and lymphoid/hematopoietic systems. Age >60 years, thymoma histology, receipt of surgery, and absence of chemotherapy were each independently associated with a higher risk of SPM. Notably, patients who developed SPM had better overall survival than those who did not. Conclusions: TETs survivors have a clearly increased and persistent risk of SPM, with risk magnitude and patterns differing across histologic subtypes and organ sites.