Malignant Neoplasm of Descending Colon Clinical Trial
Official title:
Randomized Controlled Trial to Evaluate Laparoscopic Versus Open Surgery in Transverse and Descending Colon Cancer Patients
The long-term results of several large-scale prospective randomized trials that compared laparoscopic-assisted and open colectomy for colon cancer were published in the past decade. The oncologic outcomes were nearly similar in patients who underwent laparoscopic or open surgery. In Japan, the Japan Clinical Oncology Group (JCOG) conducted a randomized trial to compare oncological outcomes between patients who underwent laparoscopic or open surgery for advanced colon cancer and recto-sigmoid cancer. However, the exclusion criterion were concerning tumor site in transverse and descending colon. The reason of exclusion was that laparoscopic procedure was difficult in transverse and descending colon cancers. However, laparoscopic surgery for transverse and descending colon cancer was performed clinically. We conducted a randomized trial that compared laparoscopic surgery and conventional open surgery in in transverse and descending colon cancer. The purpose of the present study was to clarify the safety and feasibility of laparoscopic surgery on in transverse and descending colon cancer patients.
Patients
- This was a randomized controlled trial conducted at a single institute, which was
Yokohama City University Medical Center (Japan).
- 80 patients who had transverse colon or descending colon cancer were randomly allocated
to receive laparoscopic surgery or conventional open surgery.
Surgical procedures
- All surgical procedures were performed by one specialized colorectal treatment team.
The laparoscopic surgeries were performed by a surgeon who passed the skill
accreditation system for laparoscopic gastroenterological surgery was established by
the Japanese Society for Endoscopic Surgery (JSES), and all open surgeries were
performed under the supervision of these skillful surgeons.
- All operations were performed according to the standard radical cure procedure
described in the seventh edition of the Japanese General Rules for Clinical and
Pathological Studies on Cancer of the Colon, Rectum and Anus. That is, intestinal
excision with lymph node dissection that separated the feeding blood vessel at its
origin was performed in all surgical procedures. Patients who underwent palliative
partial excision were not included.
- In the laparoscopic surgery, a medial-to-lateral approach was performed in all
patients.
- In the conventional open surgery, the first procedure was done in lateral approach. The
reconstruction techniques were the same as those used in laparoscopic surgery.
Randomization - To balance the operative backgrounds between the laparoscopic and the
conventional open surgery groups, the patients were stratified by the tumor location
(transverse colon, descending colon).
Adjuvant therapy
- When the pathological stage was diagnosed as stage 3 by histological examination of the
resected specimen, adjuvant chemotherapy was done with oral fluoropyrimidine
anti-cancer drug.
- Neither radiation therapy nor preoperative chemotherapy was given to any patient.
Preoperative chemo-radiotherapy even for rectal cancer is not yet standard treatment in
Japan.
Assessment parameters
- The preoperative parameters
- Operative assessment parameters
- Postoperative assessment parameters An early postoperative complication was defined as
a complication that occurred between the finish of the operation and postoperative day
30. A late postoperative complication was defined as a complication that occurred after
postoperative day 30. The terminologies of complications were classified according to
the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, and grading was
done by Classification of Surgical Complication.
- The pathological results were recorded according to the 7th edition of the Japanese
General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and
Anus and 7th edition of primary tumor, regional nodes, metastasis (TNM) classification.
Circumferential margin involvement was defined as exposure of a cancer cell at the
vertical dissection surface on histological examination.
- Quality of life (QOL) scores. The QOL score was measured using the 36-item Short Form
Health Survey (SF-36) version 2.0. It is a tool that measures health-related QOL
(HRQOL) according to an inclusive standard and not a disease-specific standard. The
SF-36 is composed of 36 questions. The score is expressed numerically by the provided
scoring algorithm. SF-36 questionnaires were sent to the patients at one month, 6
months and one year after the surgery by postal mail. A return envelope was enclosed
with the SF-36 questionnaire, and the patient sent it back to the research secretariat
by postal mail. A questionnaire on the defecation situation and wound pain besides the
SF-36 was added all three times. The question of when complete rehabilitation occurred
was added in the questionnaire at one year.
Follow-up schedule
- The follow-up schedule was as follows according to stage. Patients with stages 0 and I
were followed up with outpatient examinations including tumor marker measurements, and
chest, abdominal and pelvic computed tomography (CT) once a year for five years. Patients
with stage 2 and 3a were examined by CT and tumor marker measurements every six months for
the first two years. These examinations were done once a year from the third year to the
fifth year. Patients with stage 3b and 3c were examined by CT and tumor marker measurements
every four months for the first two years, and every six months from the third year to the
fifth year.
Statistical analysis
- The primary endpoint was early complication rate.
- The secondary endpoints were 5-recurrence-free survival, 5-year overall survival,
length of postoperative hospital stay, and HRQOL score. To evaluate whether a
difference in the operative procedure influences survival including death due to
another disease, a comparison of overall survival has meaning. Early complication rate,
length of postoperative hospital stay and HRQOL score were added to the secondary
endpoints because these parameters had a possibility of becoming grounds of selection
of the operation method if there were no differences in overall survival and
recurrence-free survival.
- A sample size of 74 patients was assured to achieve a power of more than 70% to detect
a difference between the groups using a two-sided Chi-squared test with type I error
rate equal to 0.2, when the true complication rates were 20% and 40% for the
laparoscopic and open surgeries, respectively. The dropouts were considered and the
number of accumulation targets was assumed to be 80 patients.
- For continuous variables, data are presented as means ± standard deviation (SD). For
categorical variables, data are presented as frequencies and percentages (%).
Comparison of the endpoints was based on intention-to-treat principle, that is, the
patients who switched to another group during surgery were treated as members of the
allocated group. The Chi-squared test was applied to evaluate the significance of
differences in proportions, and t-test was used to evaluate the significance of
differences in continuous variables. A p-value of less than 0.05 was considered to be
statistically significant.
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Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment