Risk of second cancer in esophageal squamous cell carcinoma and adenocarcinoma survivors: a population-based analysis in SEER dataset

BACKGROUND: Previous studies have reported increased risk of second cancer in both esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC) survivors. This study aimed to examine the risk and influential factors of second cancer in ESCC and EAC patients. METHODS: This population-based cohort study included 7,297 ESCC patients and 11,812 EAC patients who were in 1992–2019 from the Surveillance, Epidemiology, and End Results (SEER) program in the United States. These patients were followed up until diagnosis of second cancer, death, or end of the study (December 31, 2019). We calculated standard incidence ratio (SIR) and 95% confidence interval (CI) of second cancer and performed competing-risk regression to estimate the subdistribution hazard ratios (sHR) comparing categories of patients’ characteristics. RESULTS: After a total of 49,509.38 person-years of follow-up, 431 (5.9%) ESCC patients and 636 (5.9%) EAC patients developed a second cancer. An overall increased risk of second cancer was observed in both ESCC patients (SIR: 1.66, 95% CI: 1.51–1.83) and EAC patients (SIR: 1.11, 95% CI: 1.02–1.20). ESCC patients were at increased risk of second malignancy in oral cavity and pharynx (SIR: 12.57, 95% CI: 9.87–15.79), stomach (SIR: 3.03, 95% CI: 1.77–4.85), nose and larynx (SIR: 4.79, 95% CI: 2.47–8.37), and lung and bronchus (SIR: 2.44, 95% CI: 1.96–2.99), but decreased risk of prostate cancer (SIR: 0.73, 95% CI: 0.52–0.99). EAC patients had increased risk of second malignancies in stomach (SIR: 4.41, 95% CI: 3.23–5.89), lung and bronchus (SIR: 1.26, 95% CI: 1.02–1.54), and kidney (SIR: 1.57, 95% CI: 1.05–2.25). The risk of second cancer was higher in female ESCC patients than in males (sHR: 1.34, 95% CI: 1.11–1.63) and decreased with more advanced tumor stage in both ESCC patients (sHR: 0.62, 95% CI: 0.50–0.76 for regional stage; sHR: 0.27, 95% CI: 0.20–0.36 for distant stage) and EAC patients (sHR: 0.47, 95% CI: 0.40–0.56 for regional stage; sHR: 0.10, 95% CI: 0.07–0.13 for distant stage). CONCLUSIONS: Both ESCC and EAC patients are at considerable risk of certain types of second cancer.