Phase III Trial of Minimally Invasive vs Open Abdominal Radical Hysterectomy in Early Cervical Cancer
In a phase III trial (Laparoscopic Approach to Cervical Cancer [LACC]) reported in The New England Journal of Medicine, Ramirez et al found that minimally invasive radical hysterectomy was associated with poorer disease-free and overall survival vs open abdominal radical hysterectomy in women with early-stage cervical cancer.
Study Details
In the trial, 631 women with stage IA1 (lymphovascular invasion), IA2, or IB1 cervical cancer and histologic subtypes of squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma from 33 centers worldwide were randomly assigned between June 2008 and June 2017 to undergo minimally invasive surgery (n = 319) or open surgery (n = 312). Among patients in the minimally invasive surgery group, 84.4% underwent laparoscopy and 15.6% underwent robot-assisted surgery. Patients had a mean age of 46.0 years; 91.9% had stage IB1 disease; and the groups were similar at baseline for histologic subtypes, rate of lymphovascular invasion, rate of parametrial and lymph node involvement, tumor size, tumor grade, and use of adjuvant therapy. The primary outcome measure was rate of disease-free survival at 4.5 years; noninferiority was to be claimed if the lower boundary of the two-sided 95% confidence interval (CI) of the between-group difference (minimally invasive surgery minus open surgery) was greater than −7.2 percentage points.
Disease-Free Survival
At the time of analysis, 59.7% of patients had reached the 4.5-year time point (median follow-up = 2.5 years). The trial did not reach its final intended enrollment, due to a safety alert from the data and safety monitoring committee based on observation of higher rates of recurrence and death in the minimally invasive surgery group.
The rate of disease-free survival at 4.5 years was 86.0% with minimally invasive surgery vs 96.5% with open surgery, a difference of −10.6 percentage points, with a 95% CI of −16.4 to −4.7; since the lower boundary of the CI included the noninferiority margin of −7.2 percentage points, noninferiority was not declared (P = .87 for noninferiority).
On superiority testing using proportional hazards models, minimally invasive surgery was associated with significantly poorer disease-free survival vs open surgery on unadjusted analysis (3-year rate = 91.2% vs 97.1%, hazard ratio [HR] = 3.74, P = .002). In analysis adjusting for age, body mass index, disease stage, lymphovascular invasion, lymph node involvement, and Eastern Cooperative Oncology Group performance status, the HR was 4.39 (P < .001). Minimally invasive surgery was also associated with a lower rate of overall survival (3-year rate = 93.8% vs 99.0%, HR = 6.00, 95% CI = 1.77–20.30), increased risk of death from cervical cancer (3-year rate = 4.4% vs 0.6%, HR = 6.56, 95% CI = 1.48–29.00), and increased risk of locoregional recurrence (3-year rate of locoregional recurrence–free survival = 94.3% vs 98.3%, HR = 4.26, 95% CI = 1.44–12.60).
The investigators concluded, “In this trial, minimally invasive radical hysterectomy was associated with lower rates of disease-free survival and overall survival than open abdominal radical hysterectomy among women with early-stage cervical cancer.”
The study was funded by The University of Texas MD Anderson Cancer Center and Medtronic.
Disclosure: See study authors’ full disclosures at nejm.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
