Risk of second primary malignancies after definitive treatment for esophageal cancer: A competing risk analysis

Esophageal cancer is associated with synchronous or metachronous cancer at other primary sites. However, few studies have evaluated the second malignancies after the treatment of esophageal cancer. The present study aimed to clarify the frequency of and risk factors for the second malignancies after definitive therapy for esophageal cancer.

We included patients with esophageal cancer who received definitive therapy between 2000 and 2010. Exclusion criteria were synchronous cancer or a past history of cancer. Standardized incidence rate (SIR) was calculated using age- and sex-specific incidence rates from the cancer registry data. To conduct risk analyses, we used the competing risk regression model, which defined death and the development of second malignancies as competing risks.

A total of 758 patients were included, with 131 second malignancies occurring in 106 patients (14%), over a median follow-up of 3.7 years. Cumulative incidences of second malignancies after 3, 5, and 8 years were 4.0%, 7.6%, and 13.8%, respectively. The risk of second malignancy was significantly elevated [SIR = 1.83, 95% confidence interval (CI): 1.50-2.22]. The most common sites of primary tumor were the head and neck (20%), followed by the lung (17%), stomach (16%), colon and rectum (11%), and urinary tract (9%). Risk analyses revealed that age ≥ 65 years [subdistribution hazard ratio (sHR): 1.51, 95% CI: 1.01-2.24, vs age < 65] and clinical stages 0-I (sHR: 2.48, 95% CI: 1.46-4.22, vs stage III and IV) and II (sHR: 2.10, 95% CI: 1.23-3.58, vs stage III and IV) were significantly associated with second malignancies.

Compared with the general population, an increased incidence of second malignancies was observed in the patients with esophageal cancer in the present study even after definitive treatment. Careful follow-up is required, especially in patients at a higher risk of second malignancies.