Influence of the second primary cancer on clinical outcomes of nasopharyngeal carcinoma following definitive chemoradiotherapy

Nasopharyngeal carcinoma (NPC) is a distinct type of head and neck cancer characterized by undifferentiated histopathological features and a notably high incidence in Taiwan and Southeastern China. Advances in NPC diagnosis and treatment have led to improved prognosis and long‑term survival rates. Compared with other head and neck cancers, NPC tends to occur at a younger age, and is associated with a relatively higher rate of second primary cancers (SPCs) that may develop during follow‑up. Therefore, investigating the risk of SPCs in a non‑metastatic NPC cohort treated with concurrent chemoradiotherapy (CCRT) is essential for developing tailored follow‑up strategies. Patients with pathologically confirmed NPC were retrospectively enrolled between January 2012 and December 2022. The primary outcome of this study was overall survival (OS). A total of 161 eligible patients were analyzed. During a median follow‑up period of 4.5 years, seven patients developed SPCs, yielding a crude incidence rate of 4.3%. The lung was the most common SPC site (42%, n=3). The median interval from NPC diagnosis to the first SPC was 2.7 years. Kaplan‑Meier analysis with the log‑rank test indicated that SPC development significantly affected OS (P=0.049). Using Firth's logistic penalized Cox regression, univariate analysis showed that the absence of SPCs [hazard ratio (HR)=0.27, 95% confidence interval (CI): 0.09‑0.86] was associated with favorable OS, whereas older age (≥65 years) (HR=3.66, 95% CI: 1.60‑8.40) was associated with worse OS. In the multivariate analysis, only older age (≥65 years) (HR=3.34, 95% CI: 1.43‑7.80) remained significantly associated with unfavorable OS. Post‑CCRT follow‑up for patients with NPC should include surveillance not only for recurrence but also for the potential development of SPCs.