The objective of the study by Janda and colleagues (known as the “LACE” trial) was to evaluate the equivalency of total laparoscopic hysterectomy (TLH) with staging versus the standard procedure, which is total abdominal hysterectomy (TAH) with staging, for surgical management of women with presumed low-risk, early-stage endometrial cancer.
2016 Update on cancer
Details of the study
This nonblinded, randomized controlled multicenter equivalency trial included 760 women from Australia, New Zealand, and Hong Kong undergoing surgical management of presumed stage I uterine endometrioid adenocarcinoma. All surgeries were performed or supervised by trained gynecologic oncologists. Pelvic lymph node sampling was required but omission was permitted for: morbid obesity, low risk of metastasis based on frozen section results, medically unfit status, or institutional guidelines prohibiting the procedure. Patients were excluded for preoperative nonendometrioid histology, suspected ultimate FIGO stage II–IV based on preoperative imaging, or uterine size greater than 10 weeks’ gestation.
The primary outcome was disease-free survival, defined as the time from surgery to the date of first recurrence, which included disease progression, development of a new primary malignancy, or death. Secondary outcomes included disease recurrence, patterns of recurrence, and overall survival. A 7% difference in disease-free survival at 4.5 years postoperatively was prespecified and determined based on previously published literature.1–4
By Kaplan-Meier estimates, disease-free survival at 4.5 years was 81.3% in the TAH group and 81.6% in the TLH group, a 0.3% difference. In addition, there were no differences noted in secondary outcomes, further supporting equivalency of the surgical modalities. The only significantly different surgical findings included decreased operative time in the TAH group and decreased lymph node dissection completion in the TLH group.
Study strengths and weaknesses
The largest previous trial of more than 2,000 patients examining the method of surgical management was the Gynecologic Oncology Group’s (GOG) noninferiority LAP2 trial.3 This trial has been used widely to promote a minimally invasive approach, but did not actually reach the prespecified statistical goals. The LACE trial, however, successfully reached its statistical targets and is now the largest randomized trial supporting an equivalence in oncologic outcomes.
It is important to recognize the limitations of the LACE trial in the current medical environment. The study population was a very specific group of low-risk women without high-risk histologic subtypes or even moderately enlarged uteri; many institutions would consider offering a minimally invasive approach to these women. In addition, this study did not include robotic minimally invasive surgery, which in many regions of the country is rapidly becoming accepted as the first choice procedure over traditional laparoscopy.5 Furthermore, the FIRES trial and others6–8 have demonstrated that utilizing a minimally invasive approach that includes sentinel lymph node identification and removal may be as diagnostic as a full dissection, adding considerations to surgical modality selection.
--Kathryn A. Mills, MD, and David G. Mutch, MD
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