Development of Second Primary Malignancies in Long- term Survivors of Unresectable Esophageal Cancer

Background/Aim: The recent advent of immunotherapy has improved long-term survival in patients with unresectable esophageal cancer. However, second primary malignancies (SPMs) are expected to develop in these patients. We investigated the incidence of SPMs in patients with unresectable advanced esophageal cancer. Patients and Methods: We retrospectively reviewed the records of patients with unresectable esophageal cancer, including those with locally advanced and metastatic disease, who were treated at the Kindai University Hospital between 2016 and 2022. The incidence of SPMs was determined among long-term survivors. The cumulative incidence of SPMs was estimated using the Gray subdistribution method, treating death as a competing risk. Results: Among the 211 patients with unresectable esophageal cancer, 45 (21%) met the criteria for long-term survival. Five (11%) were diagnosed with SPMs after a median follow-up of 3.7 years. The cumulative incidences of SPMs after 3, 5, and 8 years were 7, 10, and 14%, respectively. The types of SPMs included diffuse large B-cell lymphoma and urothelial, lung, prostate, and thyroid cancers. All SPMs were cured with definitive treatment, and no deaths were attributed to them. Conclusion: long-term survivors had a measurable rate of SPMs. This highlights the importance of post-treatment surveillance for SPMs.