What is the Appropriate Timing for Surgery after Neoadjuvant Chemoradiation for Esophageal Cancer

Abstract

Background and Objective: The optimal interval between neoadjuvant chemoradiation (CRT) and surgery has not been elucidated for squamous esophageal cancer (ESC). The aim of this study is to evaluate the impact of this time interval on postoperative and long-term outcomes. Methods: A total of 107 patients with intrathoracic ESC treated with neoadjuvant CRT between 2002 and 2009 were analyzed from a prospectively collected database. Patients were divided into three groups based on the interval between completion of CRT and surgery: group A: <40 days (n=16); B: 41-80 days (n=60); and C: > 80 days (n=31). Survival was also compared by dividing these patients into two groups using the median interval (64 days) as the cutoff point: group A* (n=54) and B*(n=53). Intraoperative parameters, postoperative outcomes, pathological data and long-term survival were investigated. Results: The three groups were comparable in patient and tumor characteristics, intraoperative parameters, postoperative morbidity and mortality. Pathological analysis showed that the median number of lymph nodes harvested was comparable. All three groups had significant rate of downstaging [A: n=8 (50%), B: n=43 (71.7%), C: n=21 (67.7%)]. For group A, the rate of R0 resection was significantly lower than the other two groups [A: n=9 (56.3%), B: n=54 (90%), C: n=23 (74.2%), p=0.006]. The pathological complete response (pCR) rates were comparable [A: n=5(31.2%), B: n=21(35%), C:n=6(19.4%), p=0.301]. Overall 3-year survival were 73.4%, 66.7%, and 53.5% respectively, p=0.23. After R0 resection, group A had longer 3-year survival (100%) compared to group B (73%) & C (64.4%), (log-rank test: A vs B, p=0.04; A vs C, p=0.015; B vs C, p=0.315). Using the median interval (64 days) as the dividing point, the overall 3-year survivals of group A* and B* were 71.1% and 56.5%, respectively, p=0.081. If R0 was achieved, the 3-year survival of group A* and B* were 83.4% and 64.3%, p=0.023. With R0 resection, though statistically not significant, there was no tumor recurrence detected in group A, whereas 8 (14.8%) and 5 (21.7%) patients had tumor recurrence in group B and C during follow up, p=0.302. Conclusion: Interval between CRT and surgery did not affect postoperative morbidity and mortality. Although early surgery seemed to result in less R0 resection, overall survival was not compromised. In those with R0 resection, better survival was attained. Delayed surgery may compromise long-term survival.