Chemotherapy followed by surgery versus surgery alone in patients with resectable oesophageal squamous cell carcinoma: long-term results of a randomized controlled trial

Abstract

Background: This is a randomized, controlled trial of preoperative chemotherapy in patients undergoing surgery for oesophageal squamous cell carcinoma (OSCC). Patients were allocated to chemotherapy, consisting of 2-4 cycles of cisplatin and etoposide, followed by surgery (CS group) or surgery alone (S group). Initial results reported only in abstract form in 1997, demonstrated an advantage for overall survival in the CS group. The results of this trial have been updated and discussed in the timeframe in which this study was performed.

Methods: This trial recruited 169 patients with OSCC, 85 patients assigned to preoperative chemotherapy and 84 patients underwent immediate surgery. The primary study endpoint was overall survival (OS), secondary endpoints were disease free survival (DFS) and pattern of failure. Survival has been determined from Kaplan-Meier curves and treatment comparisons made with the log-rank test.

Results: There were 148 deaths, 71 in the CS and 77 in the S group. Median OS time was 16 months in the CS group compared with 12 months in the S group; 2-year survival rates were 42% and 30%; and 5-year survival rates were 26% and 17%, respectively. Intention to treat analysis showed a significant overall survival benefit for patients in the CS group (P = 0.03, by the log-rank test; hazard ratio [HR] 0.71; 95%CI 0.51-0.98). DFS (from landmark time of 6 months after date of randomisation) was also better in the CS-group than in the S group (P = 0.02, by the log-rank test; HR 0.72; 95%CI 0.52-1.0). No difference in failure pattern was observed between both treatment arms.

Conclusions: Preoperative chemotherapy with a combination of etoposide and cisplatin significantly improved overall survival in patients with OSCC.

Figure 1

CONSORT Flow-diagram: random assignment, and compliance to the allocated treatment. CTX, chemotherapy

Figure 2

Overall and disease free survival. A) Overall survival of all allocated patients. The distribution curves represent the results of an intention-to-treat survival analysis involving all patients. Patients who received preoperative chemotherapy had a median survival of 16 months; in comparison, patients who underwent only surgery had a median survival of 12 months (P = 0.03 by the log-rank test). B) Disease-free survival of all patients from a landmark time of 6 months after date of randomisation (P = 0.02 by the log-rank test).

Figure 3

Survival by characteristics at randomisation and post-treatment. Centre of each square indicates hazard ratio, and area of square the amount of information. Lines on either side indicate 95 CI.