Laparoscopy for Rectal Cancer: Is the Story Settled?

Recently, two large, multicenter prospective randomized controlled trials were published in the Journal of the American Medical Association regarding the comparison of the use of laparoscopic and open surgery to achieve an oncologically complete resection of rectal cancer in patients with locally advanced disease (stage II, IIIA, or IIIB) treated with neoadjuvant therapy. The American College of Surgeons Oncology Group (ACOSOG) Z6051 study was conducted across 35 institutions in the United States and Canada and enrolled 486 rectal cancer patients. Concurrently, a second trial called the Australasian Laparoscopic Cancer of the Rectum (ALaCaRT) trial enrolled 475 rectal cancer patients from 24 sites across Australia and New Zealand. Both trials used a composite endpoint assessed by histopathology consisting of a complete total mesorectal excision (TME), a negative circumferential resection margin (CRM), and a negative distal margin (DM). All three parameters needed to be satisfied in order for the resection to be deemed complete. These criteria have been shown previously to correlate with long-term outcomes. In the ACOSOG trial, complete resection was achieved in 81.7% of laparoscopic cases and 86.9% of open cases (P = .41 for noninferiority). Similarly, in the ALaCaRT trial, the primary outcome of a complete resection was achieved in 82% compared to 89% in the open surgery group (P = .38 for noninferiority). Despite a high proportion of complete resection in both the open and laparoscopic arms and a low conversion rate, both studies obviously concluded that the noninferiority endpoint was not met. These results were surprising considering previous multicenter prospective trials demonstrating the efficacy of laparoscopic surgery for colorectal cancers as well as several meta-analyses indicating equivalent oncologic success between laparoscopic and open surgery in the treatment of rectal cancer. Is there a way to reconcile these disparate findings? The safety and efficacy of laparoscopic surgery in the treatment of colorectal cancer were greatly influenced by the landmark Clinical Outcomes of Surgical Therapy (COST) trial, a noninferiority randomized controlled study carried out at 48 institutions comparing shortand long-term outcomes among 872 colon cancer patients who were randomized to undergo open or laparoscopically assisted colectomy. After a median of 4.4 years of follow-up, no significant difference was seen in the recurrence rate or overall survival between the two surgical techniques. With the effectiveness of laparoscopy for colon cancer well supported, the subsequent Conventional versus Laparoscopic Assisted Surgery in Patients with Colorectal Cancer (CLASICC) trial included both colon and rectal cancer patients in a prospective randomized controlled trial. This study was conducted in 27 centers in the United Kingdom from 1996 to 2002 and demonstrated no statistically significant differences in the overall and diseasefree survival between laparoscopic and open resection of colon or rectal cancer after 10 years of follow-up. Like the ACOSOG Z6051 and ALaCaRT studies, the CLASICC trial initially used surrogate short-term histopathologic endpoints in an attempt to predict long-term outcomes. In the short-term results of the CLASICC trial, an analysis of the subgroup of rectal cancer patients who received a low anterior resection (LAR) revealed a greater proportion of positive CRM in specimens from laparoscopic compared to open resection (12.1% versus 7.7%, P = .16), but this difference was not statistically significant. Because positive CRM has been associated with worse long-term outcomes in rectal cancer, the authors initially concluded that laparoscopic LAR for rectal cancer could be associated with a higher risk of local recurrence and cautioned against the use of laparoscopy for this type of resection. This conclusion was tempered when the 3-year results of the CLASICC trial found no difference in the incidence of local recurrence or OS among rectal cancer patients undergoing laparoscopic compared to open LAR. Furthermore, no difference in DFS or OS was seen in rectal cancer patients between laparoscopic and open APR at the 3-year mark. These results were echoed at 5 years and 10 years of follow-up. With the results of the CLASICC trial in mind, it becomes apparent that the findings of the ACOSOG Z6051 and ALaCaRT trials should be interpreted carefully. Specifically, the question remains whether the composite endpoint chosen for these studies will adequately predict long-term outcomes. When looking at CRM positivity alone, neither trial demonstrated a statistically significant difference between laparoscopic and open surgery, although a strong trend favoring open resection was noted in both studies. The ACOSOG trial noted positive CRM in 12.1% of laparoscopically resected specimens versus 7.7% of open resection specimens (P = . 11,