After the Clinical Outcomes of Surgical Therapy (COST) trial demonstrated that laparoscopic resection was an acceptable alternative to open resection for colon cancer, the next issue for oncologic surgeons was determining the role of laparoscopic surgery in treating rectal cancer.1 Since the results of the COST trial could not be extrapolated to rectal surgery, the American College of Surgeons Oncology Group (ACOSOG) conducted the Z6051 randomized controlled non-inferiority trial comparing laparoscopic and open resection of rectal cancer.
The Z6051 trial
The results of the Z6051 trial were recently published in the Journal of the American Medical Association.2 This study enrolled 486 patients with rectal cancer from 46 credentialed surgeons working at 35 institutions. The primary outcome was a composite success of the operation involving completeness of the total mesorectal excision (TME), negative circumferential resection margin (CRM), and negative distal margin (DM). The composite operative success rate was 81.7 percent for the laparoscopic group and 86.9 percent in the open group. This difference did not support the primary hypothesis that laparoscopic resection of the rectum was non-inferior to open resection of the rectum for stage II and III rectal cancer within 12 cm of the anal verge and treated with neoadjuvant therapy in patients with a body mass index of less than 35.
The surgeons involved in the study are considered experts in laparoscopic surgery based on their participation in the COST trial or their submission of operative reports and videos of laparoscopic colectomies for central review. All of the participating surgeons were credentialed for laparoscopic and open rectal resection before participating in the trial with the submission and review of videos from participants’ operations. Reviewers were looking for the following:
- High ligation of the inferior mesenteric artery
- Mobilization of the splenic flexure, high ligation of the inferior mesenteric vein
- Dissection in the pelvis in the areolar tissue plane just outside the mesenteric envelope of the rectum that contains the lymphatics and fat of the rectum
- Transection of the rectum at a level to provide a clear distal margin in a right angle direction across the mesenteric fat
The pathology specimen was assessed in a standardized manner after the pathologists met to agree on methodology in order to provide CRM distance from the closest tumor invasion, completeness of the TME specimen based on the intactness of the mesenteric envelope, and DM negativity. Photo documentation of the TME specimen and video audit of the procedure served as quality control mechanisms throughout the study (see photo). The laparoscopic group showed TME complete or near complete, negative CRM and negative DM in 92.1 percent, 87.9 percent, and 98 percent, respectively, versus the open group rates of 95.1 percent, 92.3 percent, and 98 percent, respectively. The local recurrence and survival rates are still pending and will provide additional outcomes measures to assess laparoscopic rectal resection.
Implications for the future
What do these findings mean for minimally invasive treatment of rectal cancer in the future? There are several key points to consider in discussing this question.
First, the participants were all motivated, expert surgeons functioning in a well-monitored and quality-controlled trial, using standardized operative techniques within their individual practice technique, treating the most difficult rectal cancer patients (curable, irradiated cancers within 12 cm of the anal verge, 50 percent in the low rectum), and applying a strict definition of laparoscopy (dissection in the pelvis by instrumentation under pneumoperitoneum). If these individuals could not achieve non-inferior results on the pathologic oncology outcomes compared with open surgery, it is unlikely that anyone else could.
It may be necessary to rethink the appropriate candidate for laparoscopic rectal surgery. Use of this procedure may need to be limited to the upper rectal lesions and the smallest tumors in the widest pelvis to ensure perfect excision of the mesorectum. It is important to remember that incomplete TME and positive CRM increase the risk of local recurrence of rectal cancer. It may be more appropriate to use the hybrid laparoscopic technique to achieve high ligation of the vessels and mobilization of the splenic flexure and limit the size of the lower abdominal incision to perform the pelvic dissection. This combines the minimally invasive benefits in the upper abdomen and the standard open approach to the pelvic dissection.
Another possibility is to use the robotic approach for the pelvic dissection since in-line, wristed instruments should improve the access to the low pelvis and reduce the chances of an incomplete TME. Only 34 patients in the study were operated on using a robot, so the conclusions regarding the robotic capabilities are limited by a small sample size. Preliminary data from other studies comparing robotic with laparoscopic approaches suggest equivalence between the two modalities. But do these data indicate that the robot can compensate for the laparoscopic deficiencies, or is it still putting the patient at risk?
It also is possible that a combined transanal TME and laparoscopic anterior resection as mentioned earlier for the hybrid open/laparoscopic approach may be able to overcome the difficulty with distal resection in the low pelvis. The transanal approach can be performed using transanal endoscopic microdissection, transanal minimally invasive surgery, or standard transanal excision techniques. The learning curve and generalizability for these two approaches—robotic and combined minimally invasive/ transanal—are as yet unknown.
Furthermore, as the ACS rolls out the new Rectal Cancer Program through the Commission on Cancer (CoC), the use of strict audit through the multidisciplinary team approach will become mandatory in institutions seeking CoC accreditation. This audit will provide a ready-made registry that will allow us, as concerned surgeons, to document our true success rate in the management of rectal cancer regardless of the approach used. It is anticipated that these ACS Rectal Program institutions will be reviewed in conjunction with the routine CoC accreditation survey. This process clearly has implications for which institutions will be performing rectal cancer in the future, and this study has raised the bar for surgeons to perform self-audit as we move forward.
The Z6051 trial has introduced several new concepts into the surgical trial arena including the following:
- Credentialing of surgeons based on video review and prior participation in surgical trials
- Use of pathologic oncology outcomes (TME, CRM, and DM) combined in a composite to determine operative success
- Use of a pathologic oncology outcome as a surrogate for long-term indicators of success (survival and recurrence)
- Use of photodocumentation of the surgical specimen as a means of quality control for the surgeons in the study
- Standardization of pathologic evaluation and surgical technique
- Definition of the rectum as 12 cm above the anal verge
- Distribution of the protocol to the Australian GI Trials Group for the Australasian Laparoscopic Cancer of the Rectum (ALaCART) study3 and the Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) study trial group4 to enable meta-analysis of the results in the future
The participants in this trial, both patients and surgeons, are to be congratulated for their contributions to the successful completion of this major study, which has led investigators to ask even more questions.
- Clinical outcomes of surgical therapy study group. A comparison of laparoscopically assisted and open colectomy for colon cancer. N Engl J Med. 2004;350(20):2050-2059.
- Fleshman J, Branda M, Sargent DJ, et al. Effect of laparoscopic-assisted resection vs open resection of stage II or III rectal cancer on pathologic outcomes: The ACOSOG Z6051 randomized clinical trial. JAMA. 2015;314(13):1346-1355.
- Stevenson ARL, Solomon MJ, Lumley JW, et al. Effect of laparoscopic-assisted resection vs open resection on pathological outcomes in rectal cancer: The ALaCaRT randomized clinical trial. JAMA. 2015;314(13):1356-1363.
- Jeong SY, Park JW, Nam BH, et al. Open versus laparoscopic surgery for mid-rectal or low-rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): Survival outcomes of an open-label, non-inferiority, randomized controlled trial. Lancet Oncol. 2014;15(7):767-774.