Effectiveness and Safety of Laparoscopic Resection Versus Open Surgery in Patients with Rectal Cancer: A Randomized,Controlled Trial from China

Abstract

Background:

The long-term survival and safety of laparoscopic surgery in patients with rectal cancer remain unclear. The aim of this trial was to assess the efficacy and safety of laparoscopic surgery for treatment of rectal cancer.

Methods:

We undertook a randomized, controlled trial in 343 patients with rectal cancer between May 2004 and April 2008. One hundred sixty-nine patients were randomly assigned to laparoscopic surgery and 174 patients to open surgery. The main endpoint was 3-year survival. Data were analyzed according to the intention-to-treat principle.

Results:

Laparoscopic surgery was associated with earlier recovery of bowel movement compared with open surgery. The average time to first discharge, bowel movement, resumption of fluid intake, and activity out of bed in laparoscopic surgery were shorter by 0.63, 0.32, 0.33, and 0.63 day, respectively (P < .001). The incidences of postoperative morbidities such as infectious complications, anastomotic leakage, anastomotic stenosis, and deep vein thrombosis have no differences. No differences were found in the comparison of long-term survival.

Interpretation:

Laparoscopic surgery for rectal cancer is as safe and effective as open surgery in terms of oncology outcomes. Long-term survival for patients with rectal cancer undergoing laparoscopic surgery were similar to those undergoing conventional open surgery, thus supporting the continued use of laparoscopic surgery in Chinese patients with rectal cancer.

Introduction

Rectal cancer is one of the common digestive tract tumors, and the disease incidence rate rises by 2% per year continually in China. Surgical operation is the first-choice method to treat rectal cancer. In 1991, Jacobs introduced for the first time the laparoscopic technology in colorectal cancer surgical operation,¹ which is considered a milestone-like progress in colorectal cancer treatment. Until now, the application of laparoscopic techniques in colorectal cancer has lasted for more than a decade. For the past few years, the practical effectiveness of laparoscopic surgery for colorectal cancer has been conspicuously enhanced because of the improvement of instruments and technique. Although laparoscopic colorectal resection has some merits such as tiny injury and superior cosmesis, as a kind of therapy for malignant tumor, the safety of surgery (radical care or not), postoperative short-term outcomes, and the cancer-related long-term survival remain the focus of attention. There were several large-scale, randomized, controlled trials comparing laparoscopic and open surgery for colorectal cancer to evaluate the feasibility of laparoscopic surgery. The radical resection of laparoscopic surgery for colorectal cancer was confirmed.^2–4 National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (Version 2010) pointed out explicitly that the colon cancer laparoscopic surgery may be the conventional application in clinic; however, the rectal cancer laparoscopic surgery is not recommended outside of a clinical trial.^5,6

The trial was designed to evaluate the clinical effectiveness and safety of laparoscopic surgery for Chinese patients with rectal cancer by comparing with open surgery.

Materials and Methods

Patients

Between May 2004 and April 2008, we undertook a randomized, controlled trial comparing laparoscopic resection with conventional open surgery in 343 patients with rectal cancer meeting the selection criteria. Inclusion criteria were as follows: (1) rectal cancer patients diagnosed by pathologic examination; (2) written informed consent was obtained. Exclusion criteria were as follows: (1) liver or lung metastases assessed by computed tomography, magnetic resonance imaging, or ultrasonography; (2) body mass index (BMI) of >30 kg/m²; (3) acute intestinal obstruction; (4) serious infection; (5) previous abdominal surgery; (6) patients had received neoadjuvant chemotherapy. All the operations were done by the same surgeon team. Randomization was done on the day before surgery through sealed opaque envelopes containing surgical method. The study was approved by the institutional ethics research committee.

No differences existed in the preoperative examination measures and preparation of intestinal tract between the two groups. Radicality principles of malignant tumor and total mesorectal excision were followed strictly during the operation. Resection modalities included lower anterior resection (LAR) and abdominoperineal resection. Indication of each resection modality was not different between the two groups. After the operation, patients were requested abrosia and no drinking for 2–3 days until first discharge. During the period, gastrointestinal decompression and parenteral alimentation were performed. Liquid diet could be taken by patients who had evacuated, if no abdominal distention was observed, and semiliquid diet could be taken soon after. Low-residue diet could be taken till 2 weeks after the surgery. The patients were encouraged to be out of bed as soon as possible if their strength allowed.

Primary and secondary outcomes

The primary endpoint of the trail was 3-year survival. Secondary endpoints were number of lymph nodes removed, length of specimen, distance between inferior border of tumor and incised margin in LAR operation, time to first discharge, bowel movement and fluid intake, infectious complications, anastomotic leakage, anastomotic stenosis, deep vein thrombosis, and 1-year survival.

Follow-up

Patients were assessed for complications at the time of hospital discharge by a single reviewer who was unaware of patients' treatment assignments. Follow-up visits were at 1 and 3 months after surgery, then every 3 months for the first 2 years, and every 6 months afterward, including physical examination, abdominal and pelvic part ultrasonography, chest radiography, examination of alimentary tract tumor markers, and colonofiberscope examination. Confirmation of recurrence required imaging or pathological evaluation.

Statistical analysis

We compared the differences of categorical data using χ² test or Fisher's exact test and of continuous data using two-sample t-test. Kaplan–Meier curve was used to estimate the distribution of survival, and the log-rank test was used to compare survival between the two groups. All hypothesis tests were at the 0.05 significance levels (two-sided). Statistical analyses were performed using SPSS version 13.0. Data were analyzed according to the intention-to-treat principle.

Results

Characteristics of the patients and tumors

One hundred sixty-nine patients were randomly assigned to receive laparoscopic surgery and 174 patients to conventional open surgery. One patient in the laparoscopic surgery group was converted to open surgery because of severe ankylenteron (bowel adherence) (Fig. 1). There were no differences in the baseline characteristics such as gender, age, BMI, TNM (topography, lymph node, metastasis) stage, and resection modality between the two treatment arms (Table 1).

FIG. 1.

Trial profile.

Table 1.

Baseline Characteristics

	Laparoscopic surgery (n = 169)	Open surgery (n = 174)	P value
Median ± SD (year)	57.34 ± 14.13	57.36 ± 13.08	.990
Male	104	92	.127
BMI (kg/m²)	21.45	22.31	.223
T1-2N0M0	9	7	.616
T3-4N0M0	72	84	.329
TxN1-2M0	88	83	.450
APR	83	70	.065
LAR	86	104	.051

BMI, body mass index; APR, abdominoperineal resection; LAR, lower anterior resection.

Data associated with surgical intervention and morbidity

Duration of surgery in the laparoscopic group was significantly longer than that in the open surgery group by 19.5 minutes. The percentages of patients who needed blood transfusion in the two groups were not different. The tumor size, number of lymph nodes removed, length of specimen, and distance between inferior border of tumor and incised margin were similar in both groups. The average time to first discharge, bowel movement and fluid intake, and time to first activity out of bed in the laparoscopic surgery group were shorter by 0.63, 0.32, 0.33, and 0.63 day, respectively (P < .001) (Table 2).

Table 2.

Data Associated with Surgical Intervention and Morbidity

	Laparoscopic surgery (n = 169)	Open surgery (n = 174)	P value
Duration of surgery (minutes)	138.08 ± 23.79	118.53 ± 21.989	.000
Number of patients who needed blood transfusion	4	8	.380
Number of lymph nodes removed	7.05 ± 5.05	7.44 ± 4.89	.469
Length of specimen (cm)	19.11 ± 2.20	18.97 ± 2.25	.574
Tumor size (cm)	4.26 ± 1.301	4.17 ± 1.288	.530
Distance between the inferior border of tumor and the incised margin in LAR operation (cm)	3.22 ± 0.738	3.03 ± 0.684	.154
First activity out of bed (day)	3.50 ± 0.832	4.13 ± 0.983	.000
First discharge (day)	2.96 ± 0.889	3.28 ± 0.780	.000
APR	2.98 ± 0.826	3.19 ± 0.778	.104
LAR	2.95 ± 0.961	3.35 ± 0.785	.002
First bowel movement (day)	3.90 ± 0.850	4.24 ± 0.788	.000
APR	3.86 ± 0.857	4.07 ± 0.739	.100
LAR	3.93 ± 0.852	4.34 ± 0.808	.001
First resuming of fluid intake (day)	5.71 ± 1.716	6.34 ± 1.618	.001
APR	5.49 ± 1.735	6.03 ± 1.592	.031
LAR	5.95 ± 1.681	6.78 ± 1.573	.002

Postoperative complications

There were no significant differences between the groups in the rates of postoperative complications, including infectious complications, anastomotic leakage, anastomotic stenosis, deep vein thrombosis, and death (Table 3).

Table 3.

Postoperative Complications

	Laparoscopic surgery (n = 169)	Open surgery (n = 174)	P value
Infection	14	12	.686
Wound infection	9	8
Abdominal abscess	2	1
Respiratory tract	2	2
Urinary tract	1	1	.215
Anastomotic leakage	4	6	.751
Bowel obstruction	1	2	.545
Deep vein thrombosis	0	1	.867
Anastomotic stenosis	0	0	.991
Death within 30 days after surgery	0	0	.991

Long-term survival

Two subjects from each group were lost to follow-up. The median length of follow-up was 44 months (range: 1–72). There was no evidence to support a difference in 1-, 2-, and 3-year survival between the two groups. No port site or wound metastasis was seen in the laparoscopic surgery group thus far (Table 4, Fig. 2).

FIG. 2.

Survival curve.

Table 4.

Long-Term Endpoints

	Laparoscopic surgery	Open surgery
1-year survival	94.0%	95.3%
2-year survival	82.6%	91.2%
3-year survival	76.0%	82.8%
Port site or wound metastasis	0	0

Discussion

Whether a new surgery technology can be promoted in clinic needs to be evaluated from six aspects, namely, technical feasibility, repeatability, security, effect, cost–benefit analysis, and whether the technique can become the gold standard. The technical feasibility and repeatability of laparoscopic surgery have not been questioned. But, in the decade of its development and promotion, dispute on the security, clinical effect, and especially the long-term effectiveness has not stopped.

The patients' characteristics such as gender, age, BMI, TNM stage, and resection modality equilibrated between the laparoscopic surgery group and the open surgery group, and thus, a comparable baseline was established for comparison of the other data. From the data of WHO, the world standard BMI ranges from 18.5 to 24.9 kg/m². It was defined as overweight when the BMI exceeded 25.0 kg/m² but was lower than 30 kg/m². However, the optimal BMI range of Chinese people was from 20.0 to 22.0 kg/m², and overweight was defined as ranging from 24.0 to 28.0 kg/m². The median BMI of patients in the trial were ecumenic in Chinese people. The most apparent improvement of laparoscopic surgery for colorectal cancer compared with open surgery was its tiny wound: minimal intervention to the bowels, blood vessels, and nerves, application of ultrasound knife in the laparoscopic surgery for colorectal cancer, decrease in blood loss, and fewer transfusions required during the operation. The fact that laparoscopic surgery causes tiny injury was acknowledged extensively and thus laparoscopic surgery has become the basic surgery method of nonmalignant abdominal tract disease. The trial data adequately proved the dominance of laparoscopic surgery for rectal cancer. The average time to first discharge, bowel movement and fluid intake, and time to first activity out of bed in the laparoscopic surgery group were shorter than that of the open surgery group.

Laparoscopic surgery had more large space for operation and a specific magnifying video of laparoscopy, so that broader visual field was supplied to the operator, the anatomic structure was more easily identified, the tissue diastem was more easily captured, and scavenging boundary and extent were identified clearly. As long as tumor-free principles were strictly followed by the operator during the operation, the curative resection could be reached unquestionably by laparoscopic surgery theoretically. No differences were found in the length of specimen, tumor positive of incisal edge, and number of lymph nodes removed between laparoscopic and open surgeries for colorectal cancer in several trials previously reported.^2,7 In the trial, length of specimen, tumor size, distance between inferior border of tumor and incised margin in LAR operation, and number of lymph nodes removed were not different significantly, and the result proved that laparoscopic surgery for rectal cancer could reach a radical resection. However, it was regretful that the radiation margin was not detected in the pathology analysis. Laparoscopy has microsurgery features such as superordinary illumination equipments, megascopic operative visual field, and simultaneous limitations such as stereoscopic vision loss, loss of finger-touch sensation, and strictly relying on equipment and instruments. The difficulty of laparoscopic surgery was obviously raised and demands on surgeon's technique were accordingly increased. Thus, it was apprehensible and construable that the duration of laparoscopic surgery was much longer than that of open surgery. Of course, more experiences with laparoscopic surgery would lead to shorter operation time.

Braga et al.⁸ reported that laparoscopic surgery for colorectal cancer caused a similar rate of complications to that of open surgery. Lacy et al.⁹ and Frasson et al.¹⁰ reported that the postoperative total rate of complications of laparoscopic surgery for colorectal cancer decreased when compared with open surgery. The comparison of infectious complications, anastomotic leak, anastomotic stenosis, deep vein thrombosis, and death within 30 days after surgery between the laparoscopic surgery group and the open surgery group demonstrated that laparoscopic surgery was safe and feasible. The incident of complications in laparoscopic surgery was definitely related to the operator's experience and learning curve.¹¹ For the purpose of reducing the incidence of morbidity maximally, we should combine the perfect technique of open surgery, skilled laparoscopic technique, careful dissection according to tumor-free principle during the operation, and careful supervision after operation.

Port site or wound metastasis was a focus point of the dispute of laparoscopic surgery. Original literature reported that laparoscopic surgery for colorectal cancer could lead to high incidence of port site or wound metastasis⁸ and this has been a reason that laparoscopic surgery for colorectal cancer has frequently been in question in the clinical application. The follow-up period has been 1–72 months at present in our trial, and no port site or wound metastasis has yet occurred. As a kind of therapy for malignant tumor, the cancer-related long-term survival is still a main focus for patients and surgeons. At the time of analysis, the follow-up data of the trial confirmed that the technique of laparoscopic surgery could reach radical resection in the therapy of rectal cancer. No differences were found in the comparison of long-term survival.

In summary, our study indicates that laparoscopic surgery for rectal cancer was as safe and effective as open surgery in terms of oncology outcomes. Moreover, laparoscopic surgery reduced the patients' pain and hospital stay. Thus, this surgical approach can be used in Chinese patients with rectal cancer.

Footnotes

Acknowledgments

The authors thank all the friends who had helped during the study, Professor Gui-feng Liu from the Statistics Research Institute of Shanxi Medical University for her helpful suggestions and instructions, and Yan Wang from Shanxi Medical University for her direction in the use of statistic software.

Disclosure Statement

No competing financial interests exist.

References

Jacobs

, Vere ja

, Goldstein

. Minimally invasive colon resection. Surg Laparosc Endosc Percutan Tech, 1991; 1:144–150.

The Clinical Outcomes of Surgical Therapy Study Group. A comparison of laparoscopically assisted and open colectomy for colon cancer. N Engl J Med, 2004; 350:2050–2059.

Guillou

, Quirke

, Thorpe

et al. Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): Multicentle, randomized controlled trial. Lancet, 2005; 365:1718–1726.

Veldkamp

, Kuhry

, Hop

et al. Laparoscopic surgery versus open surgery for colon cancer: Short-term outcomes of a randomized trial. Lancet Oncol, 2005; 6:477–484.

NCCN Clinical Practice Guideline in Oncology, Colon Cancer, V.2. 2010. National Comprehensive Cancer Network, updated Feb. 8, 2010 2010 February 15 www.nccn.org/professionals/physician_gls/PDF/colon.pdf.

NCCN Clinical Practice Guideline in Oncology, Rectal Cancer, V.2. 2010. National Comprehensive Cancer Network, updated Feb. 8, 2010 2010 February 15 www.nccn.org/professionals/physician_gls/PDF/rectal.pdf.

Bouvet

, Mansfield

, Skibber

et al. Clinical, pathologic, and economic parameters of laparoscopic colon resection for cancer. Am J Surg, 1998; 176:554–558.

Braga

, Frasson

, Vignali

et al. Laparoscopic vs. open colectomy in cancer patients: Long-term complications, quality of life, and survival. Dis Colon Rectum, 2005; 48:2217–2223.

Lacy

, Garcia-Valdecasas

, Delgado

et al. Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: A randomised trial. Lancet, 2002; 359:2224–2229.

10.

Frasson

, Braga

, Vignali

et al. Laparoscopic-assisted versus open surgery for colorectal cancer: Postoperative morbidity in a single center randomized trial. Minerva Chir, 2006; 61:283–292.

11.

Paraskeva

, Aziz

, Darzi

. Laparoscopic surgery for colon cancer. Surg Clin North Am, 2005; 85:49–60.