Completion of FLOT Therapy, Regardless of Tumor Regression, Significantly Improves Overall Survival in Patients with Esophageal Adenocarcinoma

SIMPLE SUMMARY: Multimodal therapy concepts, including surgery and systemic therapy, are the mainstay in the treatment of esophageal adenocarcinoma. Despite the technical advances in the surgical field and the widespread use of chemoradiation therapy, the prognosis and overall survival for esophageal cancer remains poor. Therapy with a continuous infusion of 5-FU, leucovorin, oxaliplatin, and docetaxel (FLOT protocol) has been shown to improve the overall survival for patients with esophageal adenocarcinoma. However, uncertainty exists as to whether patients with poor tumor responses should complete the chemotherapy following surgery. The aim of our study was to analyze the effect of neoadjuvant and adjuvant FLOT therapy on the outcomes of patients following an esophagectomy for adenocarcinoma, with the focus on the tumor regression grading and the completion of the systemic therapy. We showed that the completion of the systemic therapy, regardless of the tumor regression grading, improved the outcomes of patients with esophageal adenocarcinoma. Subgroup analyses further showed that complications from chemotherapy reduced the overall survival, while surgical complications did not. ABSTRACT: Esophageal cancer is the eighth most common cancer worldwide, with poor prognosis and high mortality. The combination of surgery and systemic therapy provide the best chances for long-term survival. The purpose of this study was to analyze the impact of the FLOT protocol on the overall survival of patients following surgery for esophageal adenocarcinoma, with a focus on the patients who did not benefit in terms of pathological remission from the neoadjuvant therapy. A retrospective analysis of all the patients who underwent esophagectomies from 2012 to 2017 for locally advanced adenocarcinomas of the esophagus at a tertiary medical center was performed. The results show that the completion of systemic therapy, regardless of the tumor regression grading, had a significant positive impact on the overall survival. The patients with complete regression and complete systemic therapy showed the best outcomes. Anastomotic insufficiency did not negatively impact the long-term survival, while complications of the systemic therapy led to significantly reduced overall survival. We conclude that adjuvant systemic therapy should, when possible, always be completed, regardless of the tumor regression, following an esophagectomy.