A retrospective study on clinical and survival differences of head and neck versus other second primary malignancies in nasopharyngeal carcinoma survivors

Background Nasopharyngeal carcinoma (NPC) survivors face elevated risks of second primary malignancies (SPM); however, disparities between head and neck (HN-SPM) and non-head and neck (non-HN-SPM) are incompletely characterized. Methods This retrospective study analyzed 232 NPC survivors with metachronous SPMs (HN-SPM: n = 107; non-HN-SPM: n = 125) to compare their clinicopathological features, survival, and prognostic factors. Results HN-SPM patients were younger at NPC diagnosis and SPM onset, with longer latency. Non-HN-SPM exhibited higher smoking rates and better functional status. Pathologically, sarcomas dominated HN-SPM, whereas epithelial carcinomas prevailed in non-HN-SPM. HN-SPM underwent more surgery; non-HN-SPM received more chemotherapy. Non-HN-SPM exhibited significantly superior post-SPM overall survival compared to HN-SPM (median survival: 37.0 vs. 21.9 months, P = 0.010), with anatomical site emerging as an independent prognostic factor (HR = 0.504, P < 0.001). Advanced TNM stages of NPC and SPM were adverse factors in both groups. Surgical resection (HR = 0.262, P < 0.001) and curative intent (HR = 0.276, P < 0.001) protected HN-SPM; curative intent also protected non-HN-SPM (HR = 0.466, P = 0.003). Conclusion These findings provide evidence that anatomical site is a critical determinant of survival disparities in NPC survivors; distinct pathologies underpin this disparity and treatment responses, necessitating site-specific management.