The Prognostic Impact of Preoperative and Postoperative Chemoradiation in Clinical Stage II and III Esophageal Squamous Cell Carcinomas

While preoperative chemoradiation followed by surgery (pre-OP CRT) has been widely applied in the treatment of patients with esophageal cancer, some studies have shown a survival benefit of postoperative chemoradiation (post-OP CRT). The optimal combination of multimodality therapy and the sequence of surgery and chemoradiation for esophageal cancer remain to be investigated. A total of 1385 patients with clinical stage II and III esophageal squamous cell carcinoma (ESCC) were included. On the basis of the sequence of surgery and chemoradiation, the patients were grouped as follows: preoperative chemoradiation followed by surgery (pre-OP CRT+S), surgery alone (S), and surgery followed by postoperative chemoradiation (S+post-OP CRT). Propensity score matching analysis was used to identify 78 well-balanced patients in each group for outcome comparison.In all, 753, 339, and 293 patients were in the pre-OP CRT+S, S, and S+post-OP CRT groups, respectively. Before matching, no differences were observed in the overall survival among the patients in these 3 groups (P = 0.422). After matching, both the pre-OP CRT+S and S+post-OP CRT groups were significantly associated with a better survival compared with the S group (pre-OP CRT+S vs. S: P < 0.001; S+post-OP CRT vs. S: P = 0.005). In contrast, the survival was similar between the pre-OP CRT+S and S+post-OP CRT groups (P = 0.544). In the subgroup analysis, patients with clinical T3/4 stage tumors or those with a tumor size greater than 5 cm were more likely to demonstrate an overall survival benefit from pre-OP CRT compared with post-OP CRT. Both pre-OP CRT and post-OP CRT demonstrated a survival benefit compared with surgery alone, which indicates the importance of trimodality therapy in patients with clinical stage II/III ESCC. However, no survival difference was observed among patients in the pre-OP CRT+S and S+post-OP CRT groups, which suggests that the sequence of surgery and chemoradiation may be irrelevant to the outcome.