ACOSOG Z6051
Effect of Laparoscopic-Assisted Resection vs Open Resection of Stage II or III Rectal Cancer on Pathologic Outcomes: The ACOSOG Z6051 Randomized Clinical Trial
Phase 3N = 486NCT00726622
- Population
- Patients with clinical stage II or III rectal cancer within 12 cm of the anal verge, randomised after neoadjuvant therapy
- Design
- Multicentre, balanced, non-inferiority randomised trial (October 2008 to September 2013) by credentialed surgeons at 35 institutions in the United States and Canada. 486 patients with clinical stage II or III rectal cancer within 12 cm of the anal verge were randomised after completion of neoadjuvant therapy to laparoscopic or open resection. Primary outcome: composite of circumferential radial margin greater than 1 mm, distal margin without tumour and completeness of total mesorectal excision, with a 6% non-inferiority margin. The 2-year disease-free survival and recurrence analyses were secondary endpoints that were not powered and assessed for superiority.
- Primary endpoint
- Successful resection (pathological composite)
- Arms
- Open resection (control, n = 243): Open proctectomy
- Laparoscopic-assisted resection (experimental, n = 243): Laparoscopic-assisted proctectomy
- People
- Fleshman J, senior author Nelson H
Δ Successful resection (pathological composite)−5.2 pointsΔ 24-month DFS−3.7 pointsΔ Locoregional recurrence after rectal surgery+0.1 points
Show the numbers
| Endpoint | Analysis | Laparoscopic-assisted resection | Open resection | Effect |
|---|---|---|---|---|
| Successful resection (pathological composite)Evaluable patients (240 laparoscopic, 222 open) of the 486 enrolledComposite: circumferential radial margin greater than 1 mm, distal margin without tumour and completeness of total mesorectal excision | primaryFleshman 2015 | 81.7% (76.8–86.6%) | 86.9% (82.5–91.4%) | P=0.41Difference -5.3% (1-sided 95% CI -10.8% to infinity); P for non-inferiority 0.41 against a 6% non-inferiority margin. The abstract states that the result did not support non-inferiority. Other findings, laparoscopic vs open: negative circumferential radial margin 87.9% vs 92.3% (P = .11); distal margin negative in more than 98% of patients (P = .91); conversion to open resection occurred in 11.3% of patients per the abstract (the full text says it was required for 11% of the laparoscopic-arm patients); mean operative time 266.2 vs 220.6 minutes. |
| DFS462 evaluable patients (240 laparoscopic, 222 open) of 486 randomised; secondary endpoint, not poweredDisease-free survival at 2 years (secondary endpoint) | long term-updatemedian follow-up 47.9 monthsFleshman 2019 | 79.5% at 2 y (74.4–84.9%) | 83.2% at 2 y (78.3–88.3%) | Median follow-up 47.9 months. |
| Locoregional recurrence after rectal surgery462 evaluable patients (240 laparoscopic, 222 open); secondary endpoint, not poweredProportion of evaluable patients with a local or regional recurrence as of the analysis (no landmark time). Table 1 of the full text lists local recurrences in 5 laparoscopic and 4 open patients and regional recurrences in 6 and 6, which together give the 4.6% and 4.5% of the abstract. | long term-updatemedian follow-up 47.9 monthsFleshman 2019 | 4.6% | 4.5% | Distant recurrence 14.6% laparoscopic and 16.7% open. Disease-free survival was impacted by unsuccessful resection (hazard ratio 1.87, 95% CI 1.21 to 2.91). |
| Endpoint | Analysis | Laparoscopic-assisted resection | Open resection | Effect |
|---|---|---|---|---|
| Successful resection (pathological composite)Evaluable patients (240 laparoscopic, 222 open) of the 486 enrolledComposite: circumferential radial margin greater than 1 mm, distal margin without tumour and completeness of total mesorectal excision | primaryFleshman 2015 | 81.7% (76.8–86.6%) | 86.9% (82.5–91.4%) | P=0.41Difference -5.3% (1-sided 95% CI -10.8% to infinity); P for non-inferiority 0.41 against a 6% non-inferiority margin. The abstract states that the result did not support non-inferiority. Other findings, laparoscopic vs open: negative circumferential radial margin 87.9% vs 92.3% (P = .11); distal margin negative in more than 98% of patients (P = .91); conversion to open resection occurred in 11.3% of patients per the abstract (the full text says it was required for 11% of the laparoscopic-arm patients); mean operative time 266.2 vs 220.6 minutes. |
| DFS462 evaluable patients (240 laparoscopic, 222 open) of 486 randomised; secondary endpoint, not poweredDisease-free survival at 2 years (secondary endpoint) | long term-updatemedian follow-up 47.9 monthsFleshman 2019 | 79.5% at 2 y (74.4–84.9%) | 83.2% at 2 y (78.3–88.3%) | Median follow-up 47.9 months. |
| Locoregional recurrence after rectal surgery462 evaluable patients (240 laparoscopic, 222 open); secondary endpoint, not poweredProportion of evaluable patients with a local or regional recurrence as of the analysis (no landmark time). Table 1 of the full text lists local recurrences in 5 laparoscopic and 4 open patients and regional recurrences in 6 and 6, which together give the 4.6% and 4.5% of the abstract. | long term-updatemedian follow-up 47.9 monthsFleshman 2019 | 4.6% | 4.5% | Distant recurrence 14.6% laparoscopic and 16.7% open. Disease-free survival was impacted by unsuccessful resection (hazard ratio 1.87, 95% CI 1.21 to 2.91). |
Appears in
Sources
Fleshman J, Branda M, Sargent DJ, Boller AM, George V, Abbas M, 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):1346-55.
Fleshman J, Branda ME, Sargent DJ, Boller AM, George VV, Abbas MA, et al. Disease-free Survival and Local Recurrence for Laparoscopic Resection Compared With Open Resection of Stage II to III Rectal Cancer: Follow-up Results of the ACOSOG Z6051 Randomized Controlled Trial. Ann Surg. 2019;269(4):589-595.