Over 10 years ago, we welcomed a new approach to cancer surgery when the 2004 COST trial demonstrated the benefits of laparoscopic compared with open surgery for colon cancer. This randomized trial of 872 patients showed improved perioperative recovery with laparoscopic colectomy without compromising long-term oncologic outcomes.¹ As a result of this and other studies, oncologic surgeons have tried to push the envelope and expand the indications for minimally invasive surgery, including in rectal cancer.

Mixed Results

Research to date, however, indicates that the benefits of laparoscopic over open surgery for rectal cancer remain mixed. The recently reported ACOSOG Z6051 and ALaCaRT trials,^2,3 summarized in this issue of The ASCO Post, suggested laparoscopy as possibly inferior to open surgery. ACOSOG Z6051 and ALaCaRT are both well-designed studies involving highly proficient rectal cancer surgeons. Participating surgeons were very experienced in both open and laparoscopic surgery, and the study groups required specific surgeon credentialing.

In both studies, the primary outcome difference did not meet statistical significance. However, based on their predetermined statistical criteria, laparoscopy failed to show noninferiority compared with an open approach with regard to pathologic assessment. Both studies concluded that their findings do not provide sufficient evidence to support the routine use of laparoscopic surgery.

Other similar trials, with long-term follow-up, comparing laparoscopy with open surgery have not found the same results. The COREAN trial randomized 340 neoadjuvantly treated patients to open vs laparoscopic surgery.⁴ Their short-term and recent long-term follow up showed no difference in long-term outcome or quality of oncologic resection (ie, circumferential radial margin, completeness of total mesorectal excision, lymph node evaluation, and complication rate).

Recently, results of the COLOR II trial were reported in The New England Journal of Medicine.⁵ A total of 1,044 patients with rectal cancer were randomized to both surgical approaches. At 3 years, there was no difference in locoregional recurrence, disease-free survival, or overall survival. Laparoscopy actually showed better outcomes with regard to circumferential margins in lower rectal tumors. It will be interesting to see whether failure to meet noninferiority in the ACOSOG Z6051 and ALaCaRT studies will correlate with short- and long-term differences in oncologic outcomes.

Laparoscopy vs Open Surgery

Rectal cancer surgery is challenging, even when performed with traditional open methods. Both tumor and patient-related factors can bring important technical challenges. The dark, narrow, and confined bony pelvis limits the working space for dissection and visualization. Tumors and nodal disease may extend radially and may compromise the mesorectal envelope, placing the circumferential margin at risk. This dissection must also account for critical pelvic and sacral vessels and nerves that, if injured, can lead to significant intraoperative blood loss and permanent urinary
and/or sexual dysfunction.

An intact mesorectum and a negative (circumferential) margin resection are associated with the lowest rates of locoregional recurrence and are considered important prognostic factors (and markers of surgical quality) in rectal cancer. Their importance is such that both the ALaCaRT and ACOSOG Z6051 studies used these factors to determine their primary outcomes. Notably, they may also be the factors most influenced by the limitations of laparoscopy. Standard rigid, in-line laparoscopic instruments are limited by their ergonomics within the deep pelvis; they can be restricted by the amount of traction and countertraction needed for optimal visualization of the total mesorectal excision plane and are devoid of wrist motion, which would be helpful to clean the circumferential mesorectum before distal rectal transection.

Other Techniques

Therefore, other techniques have been developed to try to improve on the limitations of laparoscopic total mesorectal excision. The robotic platform has gained popularity, especially in rectal cancer surgery, for these reasons. High-definition, three-dimensional optics, stable instruments, along with varying degrees of wrist motion, may make up for laparoscopic limitations. Of note, in the ACOSOG Z6051 trial, 14.2% of patients in the laparoscopic arm underwent robotic surgery; unfortunately, the outcomes of this subgroup have not been reported. Robotics was excluded in the ALaCaRT study.

Preliminary data from the ROLARR trial showed no significant difference between laparoscopic and robotic surgery regarding conversion to open and circumferential margin positivity; however, there was a trend toward improved outcomes with robotics for the most challenging patients (ie, male, obese, and those with low tumors).

Another minimally invasive procedure, transanal total mesorectal excision, is also gaining momentum in this field. Lacy and colleagues recently published their success using this technique in 140 patients.⁶ It involved a two-step approach: laparoscopic mobilization of the splenic flexure and start of the abdominal total mesorectal excision from above, and a transanal approach using a minimally invasive surgery platform dissection from below, for total mesorectal excision completion. This approach allows for clear distinction of the distal margin and improved visualization of the total mesorectal excision dissection in the deep pelvis. With the results of the ACOSOG Z6051 and ALaCaRT trials, these techniques will likely be critically evaluated further as minimally invasive options.

Clinical Implications

There is no question that laparoscopic total mesorectal excision is difficult to perform and comes with a steep learning curve. Both the ACOSOG Z6051 and ALaCaRT studies increase our awareness of the complexities and technical challenges of laparoscopy for rectal cancer. Clinical trials such as these often involve academic clinicians with exceptional expertise and likely do not represent the skill set of the average general surgeon. Thus, even minor differences in outcomes between surgical approaches noted in these trials may become magnified on a national level.

However, we should pause before we conclude that laparoscopy is inferior to open surgery for all rectal cancer. As mentioned previously, studies with long-term follow-up are not in agreement with these results, and some studies actually show superiority of minimally invasive approaches in short-term and oncologic outcomes. Some patients (and tumors) will be at varying risk for incomplete total mesorectal excision and margin positivity.

I eagerly await a more-detailed analysis (or meta-analysis) of these studies to determine which factors or surgical approaches lead to the best outcomes. Such data may help assess patient risk and guide surgeons to offer the best procedure appropriate to the patient and the disease. Laparoscopic, robotic, transanal, and open approaches may all have a place in the management of rectal cancer. Cost, training, proficiency, and credentialing remain important aspects of surgical care, and they cannot be stressed enough for rectal cancer surgery. ■

Disclosure: Dr. Nurkin reported no potential conflicts of interest.

References

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

2. 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 314:1346-1355, 2015.

3. Stevenson AR, 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 314:1356-1363, 2015.

4. 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, randomised controlled trial. Lancet Oncol 15:767-774, 2014.

5. Bonjer HJ, Deijen CL, Abis GA, et al: A randomized trial of laparoscopic versus open surgery for rectal cancer. N Engl J Med 372:1324-1332, 2015.

6. Lacy AM, Tasende MM, Delgado S, et al: Transanal total mesorectal excision for rectal cancer: Outcomes after 140 patients. J Am Coll Surg 221:415-423, 2015.