The ACOSOG Z6051 Randomized Clinical Trial
Evidence about the efficacy of laparoscopic resection of rectal cancer is incomplete, particularly for patients with more advanced-stage disease.
Objective: To determine whether laparoscopic resection is noninferior to open resection, as determined by gross pathologic and histologic evaluation of the resected proctectomy specimen.
Design, Setting, and Participants: A multicenter, balanced, noninferiority, randomized trial enrolled patients between October 2008 and September 2013. The trial was conducted by credentialed surgeons from 35 institutions in the United States and Canada. A total of 486 patients with clinical stage II or III rectal cancer within 12 cm of the anal verge were randomized after completion of neoadjuvant therapy to laparoscopic or open resection.
Interventions: Standard laparoscopic and open approaches were performed by the credentialed surgeons.
Main Outcomes and Measures: The primary outcome assessing efficacy was a composite of circumferential radial margin greater than 1 mm, distal margin without tumor, and completeness of total mesorectal excision. A 6% noninferiority margin was chosen according to clinical relevance estimation.
Results: Two hundred forty patients with laparoscopic resection and 222 with open resection were evaluable for analysis of the 486 enrolled. Successful resection occurred in 81.7% of laparoscopic resection cases (95% CI, 76.8%-86.6%) and 86.9% of open resection cases (95% CI, 82.5%-91.4%) and did not support noninferiority (difference, −5.3%; 1-sided 95% CI, −10.8% to ∞; P for noninferiority = .41). Patients underwent low anterior resection (76.7%) or abdominoperineal resection (23.3%). Conversion to open resection occurred in 11.3% of patients. Operative time was significantly longer for laparoscopic resection (mean, 266.2 vs 220.6 minutes; mean difference, 45.5 minutes; 95% CI, 27.7-63.4; P < .001). Length of stay (7.3 vs 7.0 days; mean difference, 0.3 days; 95% CI, −0.6 to 1.1), readmission within 30 days (3.3% vs 4.1%; difference, −0.7%; 95% CI, −4.2% to 2.7%), and severe complications (22.5% vs 22.1%; difference, 0.4%; 95% CI, −4.2% to 2.7%) did not differ significantly. Quality of the total mesorectal excision specimen in 462 operated and analyzed surgeries was complete (77%) and nearly complete (16.5%) in 93.5% of the cases. Negative circumferential radial margin was observed in 90% of the overall group (87.9% laparoscopic resection and 92.3% open resection; P = .11). Distal margin result was negative in more than 98% of patients irrespective of type of surgery (P = .91).
Conclusions and Relevance: Among patients with stage II or III rectal cancer, the use of laparoscopic resection compared with open resection failed to meet the criterion for noninferiority for pathologic outcomes. Pending clinical oncologic outcomes, the findings do not support the use of laparoscopic resection in these patients.
JAMA. 2015;314(13):1346-1355. doi:10.1001/jama.2015.10529. Trial Registration clinicaltrials.gov Identifier: NCT00726622
Authors: James Fleshman, MD1; Megan Branda, MS2; Daniel J. Sargent, PhD2; Anne Marie Boller, MD3; Virgilio George, MD4; Maher Abbas, MD5; Walter R. Peters Jr, MD6; Dipen Maun, MD7; George Chang, MD8; Alan Herline, MD9; Alessandro Fichera, MD10; Matthew Mutch, MD11; Steven Wexner, MD12; Mark Whiteford, MD13; John Marks, MD14; Elisa Birnbaum, MD11; David Margolin, MD15; David Larson, MD2; Peter Marcello, MD16; Mitchell Posner, MD10; Thomas Read, MD16; John Monson, MD17; Sherry M. Wren, MD18; Peter W. T. Pisters, MD8; Heidi Nelson, MD19
Author Affiliations:
1Baylor University Medical Center, Dallas, Texas
2Alliance Statistics and Data Center, Mayo Clinic, Rochester, Minnesota
3Northwestern University, Feinberg School of Medicine, Chicago, Illinois
4Indiana University School of Medicine, Indianapolis
5Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
6Boone Hospital Center, Columbia, Missouri
7Franciscan St. Francis Health, Indianapolis, Indiana
8MD Anderson Cancer Center, Houston, Texas
9Vanderbilt University School of Medicine, Nashville, Tennessee
10University of Chicago, Chicago, Illinois
11Washington University, St Louis, Missouri
12Cleveland Clinic–Weston, Weston, Florida
13The Oregon Clinic, Oregon Health & Science University, Portland
14Lankenau Hospital, Wynnewood, Pennsylvania
15Ochsner Clinic, New Orleans, Louisiana
16Lahey Clinic, Burlington, Massachusetts
17University of Rochester, Rochester, New York
18Stanford University, Palo Alto, California
19Mayo Clinic