Laporoscopic Surgery for Colorectal Cancer

Abstract & commentary

Synopsis: A European multi-institutional trial compared outcome in terms of three-year disease-free and overall survival for patients with colon cancer who had resection either by laparoscopic approach or laparotomy. Although there were minor differences observed, these and other secondary outcomes were comparable, and the authors conclude that laparoscopic surgery should be implemented more widely for colon cancer resection.

Source: Buunen M, et al. Survival after laparoscopic surgery versus open surgery for colon cancer: long-term outcome of a randomized clinical trial. Lancet Oncology. 2009;10:44-52.

Surgery remains the only curative option for colon cancer, and traditionally this has entailed tumor resection through large abdominal incisions. However, since the introduction of laparoscopic approaches, there has been increased interest in applying this technique to colon tumor resection. There is evidence that laparoscopic colectomy is associated with less morbidity and improved convalescence,1-4 but early concerns regarding local tumor recurrence5 have raised lingering questions regarding the safety of laparoscopy for cancer surgery.

Buunen et al now present findings from the colon cancer laparoscopic or open resection (COLOR) trial, the aim of which was to compare three-year disease-free survival and overall survival after laparoscopic and open resection of solitary colon cancer. The trial was conducted at 29 sites throughout Europe over a six-year period (1997-2003). Patients with a solitary cancer of the right or left colon and a body mass index < 30 kg/m2 were randomly assigned to either laparoscopic or open surgery as curative treatment in a carefully controlled effort to prove the hypothesis that laparoscopic colon tumor resection was not inferior to laparotomy. Disease-free survival at three years after surgery was the primary outcome, with a prespecified non-inferiority boundary at 7% difference between the groups. Secondary outcomes were short-term morbidity and mortality, number of positive resection margins, local recurrence, port-site or wound-site recurrence, and blood loss during surgery. Neither patients nor healthcare providers were blinded to patient groupings. Analysis was intention-to-treat.

During the recruitment period, 1,248 patients were randomly assigned to either open surgery (n = 621) or laparoscopic surgery (n = 627). Of these, 172 were excluded after randomization, mainly because of the presence of distant metastases or benign disease, leaving 1,076 patients eligible for analysis (542 assigned open surgery and 534 assigned laparoscopic surgery). Of those assigned to laparoscopic surgery, 102 (19%) were converted to open resection either before or during the procedure because of initial operative findings precluding effective laparoscopic resection. With regard to analysis, converted procedures were considered in the laparoscopic group as warranted by the 'intent-to-treat' principle of the study design.

Median follow-up was 53 months (range 0.03-60). Positive resection margins, number of lymph nodes removed, and morbidity and mortality were similar in both groups. The combined three-year disease-free survival for all stages was 74.2% (95% CI 70.4-78.0) in the laparoscopic group and 76.2% (72.6-79.8) in the open surgery group (p = 0.70 by log-rank test); the difference in disease-free survival after three years was 2.0% (95% CI -3.2 to 7.2). The hazard ratio (HR) for disease-free survival (open vs. laparoscopic surgery) was 0.92 (95% CI 0.74-1.15). The combined three-year overall survival for all stages was 81.8% (78.4-85.1) in the laparoscopic group and 84.2% (81.1-87.3) in the open-surgery group (p = 0.45 by log-rank test); the difference in overall survival after three years was 2.4% (95% CI -2.1 to 7.0; HR 0.95 [0.74-1.22]).

The data were insufficient to rule out a difference in disease-free survival at three years in favor of open colectomy because the upper limit of the 95% CI for the difference just exceeded the predetermined non-inferiority boundary of 7%. However, the difference in disease-free survival between groups was small, overall survival met criteria for non-inferiority, and there were no significant differences in the adequacy of resection, as indicated by the comparability in tumor-free margins and number of lymph nodes resected. Nor was there any difference in operative morbidity or mortality. Tumor recurrence in the abdominal wall was noted in seven of 534 (1.3%) in the laparoscopy group and in two of 542 who had been assigned to open colectomy (p = 0.09). In the laparoscopic group, five of the seven local recurrences occurred at the trocar site; two were at the extraction site. In total, however, only three local recurrences occurred as the only manifestation of recurrent disease (two in the laparoscopy group and one in the open group).

Commentary

There have been similar trials comparing laparoscopic and open colon cancer resection in recent years, and a recent meta-analysis, which incorporated data from three other large trials and the first 520 patients of the COLOR trial, concluded that disease-free survival (at three years) and overall survival for stages I-III colon cancer patients did not differ between treatment groups.

The COLOR trial adds impetus to the movement to more widely applied laparoscopic techniques. However, certain reservations persist and need to be addressed. In this trial, patients with a BMI of > 30 kg/m2 were excluded, primarily because at the time of study initiation, there was limited experience with this procedure in obese patients. Nonetheless, obesity is an established risk factor for colon cancer,6 and it remains to be established if comparable results will be achieved in this increasing segment of the population. Furthermore, the 19% pre- and intraoperative conversion rates need to be addressed. Will improved preoperative imaging studies allow for a more accurate assessment of which patients are appropriate for laparoscopic resection? Finally, broad application of the procedure will require additional training and experience for practicing surgeons. Although the COLOR trial included 29 hospitals, all surgical teams were experienced (a minimum of 20 laparoscopically assisted colectomies), and their techniques recorded and reviewed, before they were allowed to participate in the trial. Until this type of experience is achieved in the community, expectations of 'non-inferiority' of the laparoscopic approach might not be what is observed.

References

1. A comparison of laparoscopically assisted and open colectomy for colon cancer. N Engl J Med. 2004;350: 2050-2059.

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

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

4. Veldkamp R, et al. Laparoscopic surgery versus open surgery for colon cancer: short-term outcomes of a randomised trial. Lancet Oncol. 2005;6:477-484.

5. Berends FJ, et al. Subcutaneous metastases after laparoscopic colectomy. Lancet. 1994;344:58.

6. Nock NL, et al. Associations between obesity and changes in adult BMI over time and colon cancer risk. Obesity. 2008;16:1099-1104.