Background
Phase III RCT (LACC Trial). 631 patients with stage IA1 (with LVSI), IA2, or IB1 cervical cancer (squamous, adenocarcinoma, or adenosquamous histology). Randomized 1:1 at 33 centers in 11 countries. Designed as a noninferiority trial to determine whether minimally invasive radical hysterectomy (laparoscopic or robotic) was equivalent to open abdominal radical hysterectomy.
Interventions and follow up
Arm A: Minimally invasive radical hysterectomy (laparoscopic or robotic-assisted) + pelvic lymph node dissectio
Arm B: Open abdominal radical hysterectomy + pelvic lymph node dissectio
Primary endpoint: Disease-free survival at 4.5 years (noninferiority margin: −7.2 percentage points)
mFollow up: Median ~3 year
Arm B: Open abdominal radical hysterectomy + pelvic lymph node dissectio
Primary endpoint: Disease-free survival at 4.5 years (noninferiority margin: −7.2 percentage points)
mFollow up: Median ~3 year
Results
DFS at 4.5 years: 86.0% MIS vs 96.5% open; difference −10.6 percentage points (95% CI −16.4 to −4.7) — noninferiority NOT met
3-year DFS: 91.2% MIS vs 97.1% open; HR for recurrence 3.74 (95% CI 1.63–8.58)
3-year OS: 93.8% MIS vs 99.0% open; HR for death 6.00 (95% CI 1.48–24.4)
Local recurrence: 4.4% MIS vs 0.6% open
3-year DFS: 91.2% MIS vs 97.1% open; HR for recurrence 3.74 (95% CI 1.63–8.58)
3-year OS: 93.8% MIS vs 99.0% open; HR for death 6.00 (95% CI 1.48–24.4)
Local recurrence: 4.4% MIS vs 0.6% open
Adverse events
Main adverse events: No significant difference in perioperative safety. Intraoperative complications: 6.9% MIS vs 6.4% open. Postoperative complications were similar across arms. The harm was oncologic, not surgical — MIS produced significantly higher rates of locoregional recurrence and death despite comparable perioperative safety profiles.
Conclusions
Minimally invasive radical hysterectomy was significantly inferior to open abdominal radical hysterectomy for early-stage cervical cancer, with substantially higher recurrence rates and worse overall survival. This landmark trial fundamentally changed surgical practice, leading to a major shift away from laparoscopic and robotic radical hysterectomy as standard of care for cervical cancer.
Key Limitations
Key Limitations: The trial was stopped early due to emerging safety signals, which may have limited power for secondary endpoints. The mechanism for inferior outcomes with MIS remains debated — proposed explanations include uterine manipulator use causing tumor dissemination, CO2 pneumoperitoneum effects, and colpotomy technique. Subsequent retrospective analyses and the parallel Surveillance, Epidemiology, and End Results (SEER) study confirmed the survival decrement with MIS in real-world practice. Implementation of modified MIS techniques (avoiding manipulator, contained colpotomy) is being evaluated in ongoing trials (SUCCOR-2).
Clinical Context
The LACC trial was practice-changing, reversing the global trend toward minimally invasive radical hysterectomy in cervical cancer. Prior to LACC, MIS had been widely adopted based on observational data and perceived perioperative advantages. After LACC, NCCN, ESGO, and SGO guidelines updated recommendations to state that open surgery is the preferred approach for radical hysterectomy in cervical cancer. Concurrent retrospective SEER analysis confirmed an increase in mortality associated with MIS adoption. The LACC findings have prompted investigation into whether tumor-containment modifications can recapture the benefits of MIS while restoring oncologic equivalence.
References
References: Ramirez PT et al, N Engl J Med 2018 (LACC Trial)