Surgical Resection After Neoadjuvant Chemoradiation for Oesophageal Adenocarcinoma: What is the Optimal Timing?

Objectives: The purpose of this study was to determine the optimal timing of surgical resection of oesophageal adenocarcinoma following neoadjuvant chemoradiotherapy (nCRT).

Methods: nCRT before resection of oesophageal adenocarcinoma yields improved overall and progression-free survival. Despite the wide acceptance of tri-modal therapy, the optimal timing of surgical resection after nCRT is not well defined and existing studies are limited. Adults with Stage II/III oesophageal adenocarcinoma undergoing nCRT before surgery were identified from the National Cancer Database. Multivariable analysis using restricted cubic splines was used to identify an inflection point in clinical outcomes as a function of time between nCRT and surgery, dividing the cohort into short- and long-interval treatment groups, which were then compared. Adjusted rates of survival and margin status were compared between groups using multivariable analysis.

Results: Among 2444 patients, restricted cubic splines identified an inflection point at 56 days, dividing our cohort into 1533 short-interval and 911 long-interval patients. Long-interval patients had a higher adjusted incidence of pathologic downstaging (odds ratio 1.38, confidence interval 1.02-1.85, P = 0.04) but no difference in margin positivity compared with short-interval patients (odds ratio 0.91, confidence interval 0.56-1.47, P = 0.69). Worse overall survival was noted in the long-interval subgroup (hazard ratio 1.44, confidence interval 1.22-1.71, P < 0.001), but 30-day postoperative mortality was not statistically different (odds ratio 1.56, confidence interval 0.9-2.72, P = 0.12).

Conclusions: Restricted cubic splines provides an objective mechanism to more accurately delineate optimum timing between nCRT and surgical resection. A time interval of 56 days represents an interval where increased pathologic downstaging is balanced by decreased overall survival.