Trial Information

Background :

Esophageal carcinoma is an aggressive disease with a poor prognosis. Surgical resection with
radical lymphadenectomy remains the basic method of management of this malignancy. The
international Society for Diseases of the Esophagus has classified the extent of
lymphadenectomy as standard, extended, total, and three-field lymphadenectomy. However,
lymph node metastases can be present as regional metastasis, skip metastasis and distant
metastasis, the optimal extent of lymphadenectomy remains controversial by now. Three-filed
lymphadenectomy was criticized for higher surgical risks, but have the merits of removing
all potential positive nodes and reducing the local recurrence. The purpose of this study is
to conduct a large scale prospective randomized Phase Ⅲ clinical trial to test that based on
the long-term outcomes(overall survival and disease free survival )and postoperative
short-term outcomes(mortality, morbidity),whether one extent of lymphadenectomy is superior
than the other approach or not.

Objectives:

1. To compare overall survival after three-field lymphadenectomy and two-field
lymphadenectomy

2. To compare locoregional recurrence, disease free survival after three-field
lymphadenectomy and two-field lymphadenectomy

3. To compare postoperative morbidity and mortality in the two groups

4. To evaluate short and long term quality of life after the two procedures Design:
Prospective randomized controlled Setting: Fudan University Cancer Center, Shanghai,
China. Patients and methods : All patients with biopsy proven carcinoma of the middle
or lower third of the esophagus presenting to our hospital will be considered for the
study.

Staging investigations will be standard and will include

1. Computed Tomography (CT) scans in all patients

2. Esophagogastroscopy

3. Barium swallow

4. Endoscopic Ultrasonography (EUS) wherever possible

5. PET-CT scan wherever possible

Randomization:

Block randomization will be done using a computer generated sheet. Randomization will be
performed 3 days to 1 week before the operation.

All surgeries will be performed under general anesthesia with epidural analgesia. The
surgery will be either performed by or under the direct supervision of consultant thoracic
surgeons with experience in esophageal surgery. Operative time, blood loss, blood product
replacement and all intraoperative details will be recorded in the proforma. Patients will
be shifted postoperatively to the intensive care unit (ICU) for observation and subsequently
to the recovery or high dependency ward once stabilized. Postoperative details including
period of postoperative ventilation, hemorrhage, pulmonary and cardiac complications,
arrhythmias, thoracic duct leak, anastomotic leak, wound infection and recurrent laryngeal
nerve paresis or palsy will be recorded. Postoperative mortality will be defined as 30-day
mortality plus death before discharge after surgery. The total duration of ICU stay and
hospital stay will also be recorded.

Follow up:

Patients will be followed up three monthly for the first two years and six monthly for the
third to fifth years and annually thereafter. A detailed history and clinical examination
and CT scan, barium swallow and ultrasound will be done routinely on every follow up.

Data management: All collected data will be entered into a statistical software package for
subsequent analysis

Main research variables:

Primary end point: Disease free survival in the two arms

Secondary endpoints:

1. Overall survival

2. Locoregional recurrence

3. Postoperative morbidity and mortality

4. Quality of life : assessed with EORTC QLQ-C30 scale and EORTC QLQ- OES18 scale.