Trial Information

Randomized Controlled Trial to Evaluate Laparoscopic Versus Open Surgery in Elderly Colorectal Cancer Patients Who Were 75 Years Old or Over

Patients

- This was a randomized controlled trial conducted at a single institute, which was
Yokohama City University Medical Center (Japan).

- 200 patients were age of 75 years old or over 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 (right colon, left
colon and rectum).

- A transverse colon cancer was allocated to the right colon group, and a rectosigmoid
cancer was allocated to the rectum group.

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 1
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 3-year recurrence-free survival.

- The secondary endpoints were overall survival, early complication rate, length of
postoperative hospital stay, and HRQOL score.

- A sample size of 200 patients was assured to achieve a power of more than 80% to detect
a difference between the groups using a two-sided Chi-squared test with type I error
rate equal to 0.05, when the true complication rates were 20% and 40% for the
laparoscopic and open surgeries, respectively.

- 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.