ALaCaRT
Effect of Laparoscopic-Assisted Resection vs Open Resection on Pathological Outcomes in Rectal Cancer: The ALaCaRT Randomized Clinical Trial (Australasian Laparoscopic Cancer of the Rectum)
Phase 3N = 475
- Population
- Patients with T1-T3 rectal adenocarcinoma less than 15 cm from the anal verge
- Design
- Randomised, non-inferiority, phase 3 trial (March 2010 to November 2014) in which 26 accredited surgeons at 24 sites in Australia and New Zealand randomised 475 patients with T1-T3 rectal adenocarcinoma less than 15 cm from the anal verge to open or laparoscopic-assisted resection. Primary end point: a composite indicating an adequate resection (complete total mesorectal excision, circumferential margin of at least 1 mm and distal margin of at least 1 mm) with a non-inferiority boundary of -8%; pathologists used standardised reporting and were blinded to the surgical approach. Registered at the Australian New Zealand Clinical Trials Registry (ACTRN12609000663257); no NCT number.
- Primary endpoint
- Successful resection (pathological composite)
- Arms
- Open resection (control, n = 237): Open laparotomy and rectal resection
- Laparoscopic-assisted resection (experimental, n = 238): Laparoscopic-assisted rectal resection
- People
- Stevenson AR, ALaCaRT Investigators
Δ Successful resection (pathological composite)−7 pointsΔ 24-month Locoregional recurrence after rectal surgery+2.3 pointsΔ 24-month DFS−2 pointsΔ 24-month OS+1 points
Show the numbers
| Endpoint | Analysis | Laparoscopic-assisted resection | Open resection | Effect |
|---|---|---|---|---|
| Successful resection (pathological composite)Intention-to-treat population of the full text: 238 laparoscopic and 235 open patients (two open-arm patients were excluded after randomisation: one sigmoid tumour more than 15 cm from the anal verge, one without protocol surgery)Composite: complete total mesorectal excision, clear circumferential margin (1 mm or more) and clear distal margin (1 mm or more) | primaryStevenson 2015 | 82% | 89% | P=0.38Risk difference -7.0% (95% CI -12.4% to infinity); P = .38 for non-inferiority against a boundary of -8%. The percentages are 194/238 and 208/235 (group sizes in Table 2 of the full text). Non-inferiority was not established (the authors' conclusion). Components, laparoscopic vs open: clear circumferential margin 222 (93%) vs 228 (97%), risk difference -3.7% (95% CI -7.6% to 0.1%), P = .06; clear distal margin 236 (99%) vs 234 (99%), P = .67; complete total mesorectal excision 206 (87%) vs 216 (92%), P = .06. Conversion from laparoscopic to open surgery 9%. |
| Locoregional recurrence after rectal surgery450 patients (95%) without metastases at baseline (225 laparoscopic, 225 open); secondary-endpoint analysisCumulative incidence of locoregional recurrence at 2 years (secondary endpoint) | long term-updatemedian follow-up 3.2 yearsStevenson 2019 | 5.4% at 2 y | 3.1% at 2 y | Difference 2.3% (95% CI -1.5% to 6.1%); hazard ratio 1.7 (95% CI 0.74 to 3.9); the abstract does not label its direction (above 1 where laparoscopic recurrence is higher, consistent with laparoscopic relative to open). Median follow-up 3.2 years (range 0.1 to 5.4 years). The authors state that confidence intervals included potentially clinically important differences favouring open resection. |
| DFS450 patients (95%) without metastases at baseline (225 laparoscopic, 225 open); secondary-endpoint analysisDisease-free survival at 2 years (secondary endpoint) | long term-updateStevenson 2019 | 80% at 2 y | 82% at 2 y | P=0.41Difference 2.0% (95% CI -9.3% to 5.4%), as printed without a sign: the interval is centred near -2.0, consistent with laparoscopic minus open (80% vs 82%); hazard ratio for recurrence or death 1.17 (95% CI 0.81 to 1.68); after adjustment for baseline factors 1.07 (95% CI 0.7 to 1.6). |
| OS450 patients (95%) without metastases at baseline (225 laparoscopic, 225 open); secondary-endpoint analysisOverall survival at 2 years (secondary endpoint) | long term-updateStevenson 2019 | 94% at 2 y | 93% at 2 y | Difference 0.9% (95% CI -3.6% to 5.4%). |
| Endpoint | Analysis | Laparoscopic-assisted resection | Open resection | Effect |
|---|---|---|---|---|
| Successful resection (pathological composite)Intention-to-treat population of the full text: 238 laparoscopic and 235 open patients (two open-arm patients were excluded after randomisation: one sigmoid tumour more than 15 cm from the anal verge, one without protocol surgery)Composite: complete total mesorectal excision, clear circumferential margin (1 mm or more) and clear distal margin (1 mm or more) | primaryStevenson 2015 | 82% | 89% | P=0.38Risk difference -7.0% (95% CI -12.4% to infinity); P = .38 for non-inferiority against a boundary of -8%. The percentages are 194/238 and 208/235 (group sizes in Table 2 of the full text). Non-inferiority was not established (the authors' conclusion). Components, laparoscopic vs open: clear circumferential margin 222 (93%) vs 228 (97%), risk difference -3.7% (95% CI -7.6% to 0.1%), P = .06; clear distal margin 236 (99%) vs 234 (99%), P = .67; complete total mesorectal excision 206 (87%) vs 216 (92%), P = .06. Conversion from laparoscopic to open surgery 9%. |
| Locoregional recurrence after rectal surgery450 patients (95%) without metastases at baseline (225 laparoscopic, 225 open); secondary-endpoint analysisCumulative incidence of locoregional recurrence at 2 years (secondary endpoint) | long term-updatemedian follow-up 3.2 yearsStevenson 2019 | 5.4% at 2 y | 3.1% at 2 y | Difference 2.3% (95% CI -1.5% to 6.1%); hazard ratio 1.7 (95% CI 0.74 to 3.9); the abstract does not label its direction (above 1 where laparoscopic recurrence is higher, consistent with laparoscopic relative to open). Median follow-up 3.2 years (range 0.1 to 5.4 years). The authors state that confidence intervals included potentially clinically important differences favouring open resection. |
| DFS450 patients (95%) without metastases at baseline (225 laparoscopic, 225 open); secondary-endpoint analysisDisease-free survival at 2 years (secondary endpoint) | long term-updateStevenson 2019 | 80% at 2 y | 82% at 2 y | P=0.41Difference 2.0% (95% CI -9.3% to 5.4%), as printed without a sign: the interval is centred near -2.0, consistent with laparoscopic minus open (80% vs 82%); hazard ratio for recurrence or death 1.17 (95% CI 0.81 to 1.68); after adjustment for baseline factors 1.07 (95% CI 0.7 to 1.6). |
| OS450 patients (95%) without metastases at baseline (225 laparoscopic, 225 open); secondary-endpoint analysisOverall survival at 2 years (secondary endpoint) | long term-updateStevenson 2019 | 94% at 2 y | 93% at 2 y | Difference 0.9% (95% CI -3.6% to 5.4%). |
Appears in
Sources
Stevenson AR, Solomon MJ, Lumley JW, Hewett P, Clouston AD, Gebski VJ, et al. Effect of Laparoscopic-Assisted Resection vs Open Resection on Pathological Outcomes in Rectal Cancer: The ALaCaRT Randomized Clinical Trial. JAMA. 2015;314(13):1356-63.
Stevenson ARL, Solomon MJ, Brown CSB, Lumley JW, Hewett P, Clouston AD, et al. Disease-free Survival and Local Recurrence After Laparoscopic-assisted Resection or Open Resection for Rectal Cancer: The Australasian Laparoscopic Cancer of the Rectum Randomized Clinical Trial. Ann Surg. 2019;269(4):596-602.