Risk patterns of subsequent primary cancers following esophagectomy in early-stage thoracic esophageal squamous cell cancer patients

Aims and Background: Subsequent primary cancers (SPCs) have been demonstrated to be the major causes of death among patients with thoracic esophageal squamous cell cancer (ESCC) negative for lymph node involvement. We designed this study to investigate clinical characteristics and risk patterns of SPCs following esophagectomy in patients with early-stage thoracic ESCC. Methods: We retrospectively analyzed clinical factors in 512 patients with early-stage thoracic ESCC collected from 3 independent hospitals over a 10-year interval. Results: The overall standard incidence rate (SIR) of SPCs was 3.84 (95% confidence interval 2.98-4.95). The most common SPCs were head and neck cancers, lung cancer, and stomach cancer. The risk patterns of SPCs varied across organs. A 3-phase risk pattern with a U-shaped curve between 2 rising phases was seen for head and neck cancers, while for the other cancers, the risk patterns all displayed as an approximately linear upward trend. It was further noted that sex, smoking habits, and cancer histories among first-degree relatives were 3 significant independent risk factors in the development of SPCs. Conclusions: We observed significant associations between early-stage ESCC and SPCs arising from anatomically adjacent sites. The different risk patterns of SPCs indicated that follow-up strategies should be established accordingly in different organs at different times, with particularly close follow-up for head and neck cancers in the first 5 years and beyond 15 years after diagnosis of ESCC.