Risk of Second Primary Malignancy after Surgery or Definitive Radiotherapy for Early-Stage Head and Neck Squamous Cell Carcinoma: A Population-based Study

Abstract

Background The primary treatment modalities for patients with early-stage head and neck squamous cell carcinoma (HNSCC) predominantly include surgical resection and definitive radiotherapy (RT). However, RT may increase the risk of second primary malignancy (SPM) in cancer patients. This study aimed to investigate the association between treatment modalities and SPM risk in early-stage HNSCC patients. Methods Data of 5-year survivors of early-stage (stage I-II, 7th AJCC staging manual) HNSCC from 2000 to 2020 was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized incidence ratio (SIR) and excess absolute risk (EAR) were used to assess SPM development externally. Relative risk (RR) was estimated to compare SPM risk within treatment groups. Fine-Gray's competing risk model was applied to estimate cumulative SPM incidence after the diagnosis of index early-stage HNSCC. Results The study included 8957 5-year survivors with early-stage HNSCC. Patients who received definitive RT had poorer long-term survival compared to those who underwent surgical resection. Surgical resection was associated with a lower SPM risk (RR = 0.89, 95% CI 0.80–0.99), particularly in patients with primary oropharyngeal squamous cell carcinoma (RR = 0.56, 95% CI 0.39–0.82). Differences in the risk of SPM development among subgroups based on clinical characteristics were not significant. Treatment modalities did not significantly affect SPM risk within each subgroup. Conclusions Surgical treatment in early-stage HNSCC patients was associated with better overall survival and a lower risk of SPM compared to definitive RT. SPM incidence and sites varied among different primary sites, emphasizing the importance of targeted long-term follow-up surveillance.