Left thoraco-abdominal approach (LT) compared with abdominal and transhiatal approach (AT) for cardia or sub-cardia cancer. Results of a surgical randomized controlled trial (JCOG9502)

Abstract

4000 Background: It has long been controversial whether LT is superior to AT for two subtypes of esophago-gastric junctional (EGJ) tumors, true cardia (TC) and sub-cardia (SC) cancer. In many reports LT showed better survival but with increased morbidity. To evaluate the superiority of LT over AT, we conducted a RCT. Methods: Eligibility criteria included histologically proven adenocarcinoma, clinical T2–4 with esophageal invasion of 3 cm or less, 75 or younger age, no distant metastasis, sufficient organ functions for both procedures. Linitis plastica and stump cancer were excluded. Eligible patients were randomly assigned to either LT or AT before surgery. After curative surgery no adjuvant treatment was permitted until recurrence. Lymph nodes dissection included D2 dissection, left para-aortic nodes above renal vein for both arms but thorough or limited lower mediastinal dissection for LT and AT. The primary endpoint was overall survival. Postoperative morbidity, mortality and symptom scores were also evaluated. Projected sample size was 250 for alpha error one-sided 0.1, beta error 0.2 detecting 10% increase of 5-year survival. Results: The first planned interim analysis was performed at 12/03 using the information of 165 patients randomized between 07/95 and 10/03. The information time was 28%, O'Brien-Fleming type alpha-spending function was used. One patient died post-operatively after LT but none after AT. Higher morbidity was observed after LT as expected. The 3- and 5-year survival rates were 62% and 49% in the ATarm and 55% and 36% in the LT arm, respectively. Hazard ratio was 1.37 (95%CI: 0.84, 2.22) in favor of AT. One-sided stratified log-rank p was 0.93 (two-sided p 0.14). Conditional power that survival of LT would be significantly superior to that of AT at the end of the trial was estimated as 3.65%. The study was terminated immediately as JCOG Data and Safety Monitoring Committee recommended. Conclusions: This RCT demonstrated that LT has no survival benefit over AT for TC or SC with esophageal invasion of 3 cm or less. They should be treated by AT. No significant financial relationships to disclose.