Laparoscopic versus conventional open surgery in T4 rectal cancer: A case-control study.

BACKGROUND: Laparoscopic surgery (LAS) for T4 rectal cancer (RC) is still controversial. This study aims to compare LAS with conventional open surgery in patients with T4 RC. PATIENTS AND METHODS: Patients undergoing laparoscopic or open curative resection for T4 RC from January 2010 to September 2014 in our hospital were enrolled. Patients' clinicopathological characteristics and survival outcomes were collected and compared. All statistical analysis was performed using SPSS 22.0.
RESULTS: A total of 125 patients (39 open, 86 LAS) were included in this study finally. The baseline information between the two groups were comparable except that LAS group had a more anterior resection (P = 0.012) and less combined resection (P = 0.003). The results demonstrated that patients in LAS group had less blood loss (P < 0.001), smaller incision length (P < 0.001), faster time to first soft diet (P = 0.010) and less incidence of post-operative complications, although it was not significantly different (P = 0.063). In addition, the operative time was also comparable (P = 0.140) and the conversion rate was low (2/86). The 3-year overall survival (OS) was 71.8%, 79.1% in open, LAS group respectively and the 3-year disease-free survival (DFS) was 66.7%, 68.6% in open, laparoscopic group, respectively. The Kaplan curves demonstrated that there was no significant difference between the two groups in OS (P = 0.981) or DFS (P = 0.900).
CONCLUSIONS: LAS is safe and feasible in selected patients with T4 RC. It can achieve a better perioperative outcomes, and the long-time survival is not inferior to open surgery. Prospective studies should be conducted in the future to reduce the selection bias.

INTRODUCTION

Rectal cancer (RC) has a high incidence and death rate worldwide.[1] In China, RC is also one of the most common carcinomas which have added great burden to society.[2] Although the management for RC has made great progress in the past decades including chemoradiotherapy,[34] targeted therapy[56] and even immune therapy,[78] radical resection is still regarded as the best choice to strive for the cure and better survival outcomes.[910]

Surgical techniques also got rapid development in the past century.[11] For different tumour location, there are various surgical approaches for RC.[12] Besides, in recent years, advanced laparoscopic techniques have been widely used in abdominal surgery, especially in gastrointestinal surgery.[13] Previous studies have reported that laparoscopy surgery (LAS) was safe and feasibility in colon cancer.[14] Although there were some controversies about the use of laparoscopic techniques in RC,[12] several recent studies also demonstrated that LAS was safe and also not inferior to open surgery in long survival outcomes.[15]

T4 invasion which means tumour invades to serosa or adjacent organ is a risk factor for bad prognosis in colorectal cancer.[16] Radical resection might be more difficult and had more demands for surgeons and techniques in T4 tumours. Hence, some studies indicated that LAS might be not suitable in T4 colorectal cancer.[17] However, some previous articles and meta-analysis indicated that LAS was also safe and feasible in T4 colon cancer.[1819] In the deep pelvic cavity, rectum had a more complex anatomic relation with surrounding structures so T4 RC might be more complex than T4 colon cancer in the local region. Up to now, just a very few studies have compared LAS with open surgery in T4 RC, and the sample size was small, and results were not consistent.[2021] Hence, the safety and feasibility of LAS in T4 RC remain unclear. Thus, we conducted this study to compare LAS with open surgery for T4 RC in short- and long-time outcomes.

PATIENTS AND METHODS

Patients

We retrospectively reviewed the prospective colorectal cancer database of the department of gastrointestinal surgery in our hospital. Patients undergoing resection for T4 RC from January 2010 to September 2014 were enroled in this study. All the patients were operated by one experienced surgeon (author Ziqiang Wang). The inclusion criteria were as follows: (1) confirmed diagnosis of RC by biopsy; (2) surgical procedure was open or laparoscopy and (3) the depth of tumour invasion was T4 (including T4a and T4b). The exclusion criteria were as follows: (1) benign disease such as inflammatory bowel disease; (2) multiple cancers in gastrointestinal tract and (3) emergency surgery. Ethical approval was not necessary because this was a retrospective study.

Assessment parameters

Patient demographics and clinicopathological characteristics were collected, including gender, age, body mass index (BMI), the American Society of Anesthesiologists (ASA) class, pre-treatment carcinoembryonic antigen (CEA) level, tumour location, surgical procedure, R0 resection rate, combined organ resection, neoadjuvant therapy and adjuvant therapy. Operative parameters (including operative time, incision length and estimated blood loss), post-operative recovery, complication, reoperation, mortality and oncologic outcomes which included T stage, N stage, tumour, node, metastasis (TNM) stages, differentiation, tumour size, retrieved lymph nodes, positive lymph nodes, vascular invasion, perineural invasion, positive circumferential resection margin (CRM) and positive distal resection margin (DRM) were also recorded. All the time of post-operative recovery such as time to first flatus was recorded from the finish of surgery. Long-term endpoints were overall survival (OS) and disease-free survival (DFS).

Follow-up

All patients were followed up regularly at 3, 6, 12, 24, 36, 48 and 60 months after surgery. Contrast-enhanced computed tomography (CT) scan of the abdomen and chest were done every half year, and colonoscopy was done per year. Routine blood test and tumour biomarker were performed every time. When it was necessary, biopsy and positron emission tomography–CT would be added.

Statistical analysis

Data were stored and updated in our institutional databases. Continuous variables were expressed as median (range) and non-parametric Mann–Whitney U-test or independent-sample t-test was induced for analysis. Ranked data were also analysed by non-parametric test. Categorical variables were showed as a number and percentage and analysed by Chi-Square or Fisher's exact tests. Kaplan–Meier survival curves were used for cancer-specific outcome analysis, and cox-regression was used for multivariable analysis. P ≤ 0.05 was deemed to be statistically significant. All statistical analysis was performed using SPSS version 22.0 (SPSS, Inc., Chicago, IL).

RESULTS

Patient characteristics

A total of 125 patients undergoing resection for T4 RC from January 2010 to September 2014 were enroled in this study. Among them, 39 patients (males 16 and females 23) received conventional open surgery and 89 patients (males 51 and females 35) received LAS. There was no significant difference between the two groups in terms of gender (P = 0.058), age (P = 0.421), BMI (P = 0.253), ASA score (P = 0.272), CEA level (P = 0.929), tumour location (P = 0.541), R0 resection rate (P = 0.107), neoadjuvant therapy (P = 0.076) or adjuvant therapy (P = 0.684). We also found that open group had more combined organ resection (P=0.003) and less surgical approach of anterior resection (P=0.012) [Table 1].

Table 1

Patients’ baseline information

When it came to operative outcomes, LAS had comparable operative time with open surgery (P = 0.141). What's more, we also observed that LAS had significantly less blood loss (P < 0.001) and a smaller length of incision (P < 0.001) than open surgery. There was one patient received intraoperative blood transfusion in both two groups (P = 1.000). Two patients in LAS group converted to open surgery because of local invasion and technique difficulty. As for post-operative recovery, when compared with open surgery, LAS showed less time to first soft diet (P = 0.010) through the two groups were comparable in gastric tube retaining time (P = 0.532), time to first flatus (P = 0.056), time to first liquid diet (P = 0.122), oxygen inhalation time (P = 0.329), catheter retaining time (P = 0.667), hospital days (P = 0.939) and post-operative hospital days (P = 0.946). In addition, although there was no significant difference, we still observed patients in LAS group had a lower incidence of post-operative complication. There was one incidence of reoperation in LAS group due to anastomotic leakage. There was no incidence of post-operative mortality in both groups [Table 2].

Table 2

Operative and postoperative information

Except for that LAS group had more T4a invasion (P = 0.001) and less incidence of positive CRM (P = 0.044), there was no significant difference in other pathological outcomes including N stage (P = 0.329), TNM stage (P = 0.689), differentiation degree (P = 0.206), tumour size (P = 0.423), retrieved lymph node (P = 0.265), vascular invasion (P = 0.915), perineural invasion (P = 0.818) and positive DRM (P = 0.096) [Table 3].

Table 3

Pathological outcomes

Survival outcomes

The median follow-up time was 48 months. The 3-year OS was 71.8%, 79.1% in open, LAS group, respectively and the 3-year DFS was 66.7%, 68.6% in open, laparoscopic group, respectively. The Kaplan curves demonstrated that there was no significant difference between the two groups in OS (P = 0.981) or DFS (P = 0.900) [Figure 1].

Figure 1

LAS versus open surgery for OS (a), DFS (b). LAS: Laparoscopic surgery, OS: Overall survival, DFS: Disease-free survival

DISCUSSION

The application of laparoscopic techniques in T4 colorectal cancer surgery has obtained more and more attention in recent years.[19] In our study, we enrolled 125 patients undergoing resection for T4 RC to compared laparoscopic surgery (LAS) with conventional open surgery. We found that patients undergoing LAS had less blood loss, smaller incision length and the operative time was not significantly different. Besides, we also found that patients in LAS group had faster post-operative recovery and less incidence of post-operative complication. As for survival outcomes, LAS was also not inferior to open surgery.

Previous literatures have demonstrated that T4 invasion was a high-risk factor for the recurrence of colorectal cancer.[17] So for T4 cancer, the requirement for surgical quality should be even higher. Sometimes, surgeons need to resect one to several adjacent organs to reach the effect of R0 resection.[22] Conventionally, some surgeons thought that the narrow pelvic cavity could be a limitation to the use of laparoscopic techniques in rectal surgery.[12] In fact, most concerns were that the limited exposure might lead to residual tumour tissue and would affect the survival outcomes, especially in T4 stage 15. However, we cannot deny that laparoscopic techniques actually have some advantages including less pain, post-operative complication and faster post-operative recovery from which patients can benefit a lot.[23] After several decades’ development, laparoscopic techniques have been advanced greatly, and many shortcomings have been overcome.[1424] What's more, surgeons’ experience accumulation and progress in learning-curve can make them more skilful when operating LAS. In recent years, some articles reported that the long-time survival outcome of LAS was not inferior to open surgery for RC.[15]

Once in a long time, LAS needs much more duration time than open surgery.[25] However, in recent years, more and more articles reported that LAS had comparable operative time in colorectal cancer when compared with open surgery.[1526] Our result was consistent with it. We think the most important reason is the increasing experience and familiarity of laparoscopic skills. In this study, all patients were operated by Professor Ziqiang Wang, one of the surgeons who earliest performed LAS in China. Although electrocoagulation equipment has been widely used in surgery,[27] we still observed that LAS group had less blood loss than the open group. This might because the magnifying view in LAS can help the surgeon recognise the small blood vessels and reduce the incidence of injury.[25] Besides, the advantages of LAS on post-operative complication were also observed in our study. Although there was no significant difference in hospital days, we think this might be affected by some individuals who had a longer hospital day.

Whether LAS or open surgery, surgeons will follow the surgical principle to resect tumour tissue as much as possible.[28] Hence, in our study, the two groups were similar in retrieved lymph node, R0 resection rate and combined resection. These factors will influence the survival outcomes directly.[29] Thus we also observed that both OS and DFS in laparoscopy group were not inferior to open group.

Unfortunately, this was a retrospective study. A prospective randomised study is still needed to compare laparoscopic and open surgery for T4 RC in the future.

CONCLUSIONS

LAS is safe and feasible in selected patients with T4 RC. It can reduce intraoperative blood loss and incision length while the operative time was comparable. The conversion rate was low. It can also faster the post-operative recovery and reduce post-operative complication. Besides, the OS and DFS are also not inferior to open group. Prospective studies should be conducted in the future to reduce the selection bias.

Financial support and sponsorship

This work was supported by the Science and Technology Support Program of the Science and Technology Department of Sichuan Province (Grant numbers: 2016SZ0043).

Conflicts of interest

There are no conflicts of interest.