Delayed Surgical Intervention After Chemoradiotherapy in Esophageal Cancer: (DICE) Study

Background: Chemoradiotherapy (CRT) is a core component of multimodality treatment for locally advanced esophageal cancer. The timing of surgery following CRT may influence the probability of performing an oncological resection and the associated operative morbidity. Objective: To determine the impact of delayed surgical intervention following CRT on survival from esophageal cancer. Methods: This was an international, multi-center, cohort study, including patients from seventeen centers who received CRT followed by surgery between 2010-2020. In the main analysis patients were divided into four groups based upon the interval between chemoradiotherapy and surgery (0-50, 51-100, 101-200 and >200 d) to assess the impact upon 90-day mortality and 5-year overall survival (OS). Multivariable logistic and Cox regression provided hazard rations (HRs) with 95% confidence intervals (95%CI) adjusted for relevant patient, oncological and pathological confounding factors. Results: 2,867 patients who underwent esophagectomy after CRT were included. After adjustment for relevant confounders, prolonged interval following CRT was associated with an increased 90-day mortality compared to 0-50 days (reference): 51-100 days (HR=1.54, 95%CI 1.04-2.29), 101-200 days (HR=2.14, 95%CI 1.37-3.35) and >200 days (HR=3.06, 95%CI 1.64-5.69). Similarly, a poorer 5-year OS was also observed with prolonged interval following CRT compared to 0-50 days (reference): 101-200 days (HR=1.41, 95%CI 1.17-1.70) and >200 days (HR=1.64, 95%CI 1.24-2.17). Conclusion: Prolonged interval following CRT before esophagectomy is associated with increased 90-day mortality and poorer long-term survival. Further investigation is needed to understand the mechanism that underpins these adverse outcomes observed with a prolonged interval to surgery.