The "revolutionary change" brought about by laparoscopic surgery for gastrointestinal tract cancers might stop at the rectum, according to two major randomized clinical trials that compared the minimally invasive surgery with traditional open resection.
The studies were published in the October 6 issue of JAMA.
Both trials — the ACOSOG Z6051 trial conducted in North America and the ALaCaRT trial conducted in Oceania — failed to establish the noninferiority of laparoscopic rectal cancer surgery.
However, longer-term clinical outcomes might yet trump these early pathologic results in rectal cancer.
Follow-up results from both trials "may show that long-term oncologic outcomes (e.g., local recurrence and survival) are not compromised by a laparoscopic approach," write Scott Strong, MD, and Nathaniel Soper, MD, from Northwestern University in Chicago, in an accompanying editorial.
The rectal cancer data are a bit of a surprise, because in colon cancer, multiple international trials have demonstrated that laparoscopic surgery is noninferior to open resection in terms of safety and survival.
In the ACOSOG Z6051 trial, the result "was not the anticipated outcome," say the authors, led by James Fleshman, MD, from the Baylor University Medical Center in Dallas. "This group of highly motivated, credentialed, expert laparoscopic rectal surgeons was ideal to test this hypothesis."
But in fact, there have been concerns all along about the "applicability of minimally invasive surgery to rectal cancer," because of its complexity and the limitations of in-line rigid instruments in the curved extremes of the pelvis, say the authors of the ALaCaRT trial, led by Andrew Stevenson, MB BS, from the University of Queensland in Brisbane, Australia.
But the ALaCaRT authors point out that advances in laparoscopic technology during the 1990s led to revolutionary change in the surgical management of diseases of the colon and rectum.
Ultimately, more large randomized trials of rectal cancer are needed to fully establish the newer technique, they note.
Details of Study Results
ACOSOG Z6051 involved 462 evaluable patients with stage II or III rectal cancer treated at 35 centers in Canada and the United States from 2008 to 2013. All of the participants received neoadjuvant therapy.
The primary outcome of successful resection was a composite of circumferential radial margin (CRM) greater than 1 mm, distal margin without tumor, and completeness of total mesorectal excision (TME). The noninferiority margin was 6%.
The rate of successful resection was similar in the laparoscopic and open resection groups (81.7% vs 86.9%), and did not support the noninferiority of the newer approach (difference, −5.3%; P = .41 for noninferiority).
Mean operative time was significantly longer with laparoscopic resection than with open resection (266.2 vs 220.6 minutes; P < .001).
There was no significant difference between laparoscopic and open resection for length of stay (7.3 vs 7.0 days), readmission within 30 days (3.3% vs 4.1%), or severe complications (22.5% vs 22.1%).
Conversion to open resection occurred in 11.3% of the laparoscopic patients.
"Pending clinical oncologic outcomes, the findings do not support the use of laparoscopic resection in these patients," the ACOSOG Z6051 team notes, referring to eventual efficacy data on disease-free survival, rate of local recurrence, and other measures.
ALaCaRT involved 475 patients with T1 to T3 rectal cancer less than 15 cm from the anal verge who were treated at 24 sites in Australia and New Zealand from 2010 to 2014. Half of the patients received preoperative radiotherapy.
Successful resection was the primary outcome, defined as complete TME, a clear circumferential margin (1 mm), and a clear distal resection margin (1 mm). The noninferiority margin was 8%.
The rate of successful resection was similar for the 194 patients who underwent laparoscopic resection and the 208 patients who underwent open resection (82.0% vs 89.0%; risk difference, −7.0%; P = .38 for noninferiority).
The conversion rate from laparoscopic to open surgery was 9%.
"These findings do not provide sufficient evidence for the routine use of laparoscopic surgery," conclude the authors. As in the ACOSOG Z6051 trial, longer follow-up of recurrence and survival is currently being collected.
More Trials Add Perspective
In their editorial, Drs Strong and Soper do not explicitly agree with the conclusion arrived at by both teams — that laparoscopic surgery in rectal cancer is not ready for prime time.
Instead, they say that these two trials "have set a standard for surgeons performing these complex operations and the surgical expertise that must be ensured when conducting randomized clinical trials." This is a reference to the high-quality screening that the trials conducted before admitting centers and surgeons to the trials.
They also emphasize the need to wait for long-term oncologic outcomes from both trials, which could yet provide an endorsement of the newer approach.
They point out that two randomized trials have already investigated laparoscopic surgery for rectal cancer: COREAN from South Korea and COLOR II from Europe. And in both these trials, the results show that laparoscopic surgery had "slightly favorable outcomes" compared with open resection.
In COREAN, patients had clinical stage II or III rectal cancer, and in COLOR II, patients had stage I to III rectal cancer, but all patients underwent laparoscopic or open proctectomy (removal of the rectum) after neoadjuvant chemoradiotherapy.
In the COREAN trial, results for laparoscopic and open proctectomy were comparable for complete TME and the achievement of uninvolved CRM (>1 mm) (Lancet Oncol. 2014;15:767-774). Furthermore, 3-year local recurrence rates were comparable in the two groups (2.6% vs 4.9%), and disease-free and overall survival rates were similar.
Similarly, in the COLOR II trial, results for laparoscopic and open proctectomy were comparable for complete TME, the achievement of uninvolved CRM (≥2 mm), and operative morbidity and mortality rates (Lancet Oncol. 2013;14:210-218). In addition, 3-year local recurrence rates were 5.0% in both groups, and disease-free and overall survival rates were similar.
Until longer-term results emerge from ACOSOG Z6051 and ALaCaRT, "surgeons need to continue to refine the conduct of the operation and determine the causes for an incomplete TME or inadequate CRM," the editorialists write.
ACOSOG Z6051 was sponsored by the American College of Surgeons and the National Cancer Institute. Some of the authors report relationships with medical device makers, including one with financial ties to Intuitive Surgical Inc., the manufacturer of the only surgical robotic system commercially available for minimally invasive rectal cancer surgery. ALaCaRT was supported by the Colorectal Surgical Society of Australia and New Zealand Foundation and the National Health and Medical Research Council. The authors have disclosed no relevant financial relationships.
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