Effect of Laparoscopic-Assisted Resection vs Open Resection of Stage II or III Rectal Cancer on Pathologic Outcomes: The ACOSOG Z6051 Randomized Clinical Trial

Abstract

Importance: 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.

Trial registration: clinicaltrials.gov Identifier: NCT00726622.

Figure. Flow of Patients Through the ACOSOG Z6051 Randomized Clinical Trial

Data on assessment of eligibility were not collected. Of the 486 patients randomized, 5 patients’ data could not be used in any analysis (including demographics). Of these 5 patients 1 was allocated to receive the laparoscopic-assisted resection and 4 were allocated to receive the open rectal resection. The patient allocated to the laparoscopic-assisted resection refused to participate after randomization and refused to have any data used. This patient did not receive surgery. The 4 patients allocated to open rectal resection did not receive proper consent; hence, no data could be used. Of those 4 patients, 3 went on to receive the allocated intervention per protocol. ^aPatients found to be ineligible after randomization (n = 10): Pregnancy test not conducted before neoadjuvant therapy (n = 3), no transrectal ultrasound/magnetic resonance imaging (TRUS/MRI) conducted before the start of neoadjuvant therapy (n = 2), no computed tomography (CT) scan of the abdomen and pelvis before neoadjuvant therapy (n = 1), liver metastasis (n = 1), liver metastasis and stage I (n = 2), and lower lobe metastasis (n = 1). ^bOne patient from the laparoscopic arm and 4 patients from the open resection arm are not shown in Table 1 because of patient refusal or improper consent. ^cPatients found to be ineligible after randomization (n = 18): Consent after registration (n = 2), consent after registration and CT scan of the abdomen and pelvis after neoadjuvant therapy and TRUS/MRI not conducted (n = 1), consent after registration and stage I (n = 1), CT scan of the abdomen and pelvis after neoadjuvant therapy (n = 2), metastatic adenocarcinoma (n = 1), pregnancy test not conducted (n = 3), pregnancy test not conducted and body mass index higher than 34 (n = 1), severe dysplasia (n = 1), stage I (n = 1), TRUS/MRI not conducted (n = 4), and TRUS/MRI not conducted and stage I (n = 1).