A randomized phase III trial of preoperative chemoradiation followed by surgery (CR-S) versus surgery alone (S) for localized resectable cancer of the esophagus

Abstract

Purpose: To determine whether CR-S improves survival for resectable cancer of the esophagus. Method: Patients from 25 institutions in 3 countries randomized over a 70 month period - after stratification for histology, gender and institution. The neoadjuvant regimen (CT/RT) consisted of Cisplatin 80mg/m2 day 1 and 5FU 800mg/m2 days 2-5 combined with radiation therapy 35Gy in 15 fractions. Surgery was performed 4 -6 weeks after radiation was completed. Results: Median age was 62 yrs, (range 28 - 81). There were 206 males and 50 females. One hundred and fifty seven patients (61%) had adenocarcinoma (AC). Two hundred and five patients completed the intended protocol including the surgery. The toxicity of the CT/RT was mild and did not affect the morbidity of surgery or length of hospital stay. The overall treatment related mortality was 4.6%. Pathological complete response rate in the patients receiving CT/RT was 15.1 % ( SCC 26.3%, AC 9%). Median overall survival (OS) for CR-S therapy was 21.7 months and for S it was 18.5 months (p= 0.38). Relapse free (RF) and OS were identical in both arms for AC but for SCC there was a significant RF advantage to CR-S (p=0.04) which did not translate into an OS advantage (p=0.06). Conclusion: The findings are compatible with those from previous trials, indicating that the benefits of CT/RT are limited when surgical results are optimal.