Increased risk of second primary tumours in patients with oesophageal squamous cell carcinoma: a nationwide study in a Western population

Background: Patients with primary oesophageal squamous cell carcinoma are at risk of developing multiple primary tumours in the upper aero digestive tract. To date, most studies are performed in the Asian population. We aimed to evaluate the risk of multiple primary tumours in the upper aero digestive tract and stomach in patients with oesophageal squamous cell carcinoma in a Western population. Methods: We performed a nationwide, retrospective cohort study in collaboration with the Netherlands Cancer Registry. Patients with primary oesophageal squamous cell carcinoma, diagnosed between 2000 and 2016, were included. Primary endpoints were synchronous and metachronous multiple primary tumour risk. Results: The cohort consisted of 9058 patients, diagnosed with oesophageal squamous cell carcinoma (male: 57.3%, median age 67 years). In 476 patients (5.3%), 545 multiple primary tumours have been diagnosed. Most of them were located in the head and neck region (49.5%). Among all multiple primary tumours, 329 (60.4%) were diagnosed synchronously (<6 months after oesophageal squamous cell carcinoma diagnosis) and 216 (39.6%) metachronously (6 months). Patients with oesophageal squamous cell carcinoma had a significantly increased risk of both synchronous (standardised incidence ratio 10.95, 99% confidence interval 9.40–12.53) and metachronous multiple primary tumours (standardised incidence ratio 4.36, 99% confidence interval 3.56–5.10), compared to the general population. The median interval to metachronous second primary tumour diagnosis was 3.0 years (interquartile range 1.8–5.9). Conclusion: Approximately one in 20 patients with primary oesophageal squamous cell carcinoma have a second primary tumour in the upper aero digestive tract or stomach, either at the time of oesophageal squamous cell carcinoma diagnosis or at a later stage. As second primary tumours occur at an increased risk compared to the general population, prospective studies are necessary to investigate the yield and survival benefit of screening for second primary tumours in patients with oesophageal squamous cell carcinoma.