Incidence of second primary malignancies in patients with esophageal cancer: a comprehensive review

Background: Development of a second primary malignancy (SPM) after an index esophageal cancer is fairly rare, primarily due to decreased survival in patients with esophageal cancer. However, with advances in early detection and therapy, the number of long-term survivors is increasing, as is the incidence of SPMs in this population. Scope: We review herein the published literature on the incidence of SPMs after an index esophageal cancer as well as its associated risk factors, prognosis and surveillance. We discuss predisposing factors that may contribute to the development of SPMs, epidemiology and attempts at chemoprevention. Findings: Data from population-based studies, retrospective reviews and case reports indicate an increased risk of SPMs in patients with esophageal cancer with reported incidence rates between 8.3 and 27.1%. Index esophageal squamous cell carcinomas have a higher association with other tobacco-related cancers such as those of the head and neck and lung. They have also shown an association with second primary cancers of the breast, stomach, thyroid, and kidney. Individuals with esophageal adenocarcinomas are at a higher risk of developing second cancers of the stomach, oropharynx and lung/bronchus. Other primary cancer sites involved include the kidney, colorectum and pancreas. Common risk factors including lifestyle and genetic alterations may explain the increased incidence of second primary cancers in this patient population. Conclusions: Risk of developing a second malignancy should be anticipated after curative treatment of esophageal cancer, and raises concerns for optimal surveillance and therapy of these patients. Recent literature suggests similar survival rates in esophageal cancer patients with and without SPMs. With the increasing incidence of SPMs in subjects with esophageal cancer, there may be benefit to close screening for and aggressive therapy of SPMs. However, further studies are needed to elucidate optimal management strategies.