This prospective, multi-institutional randomized trial sought to assess whether laparoscopic surgical treatment and staging were noninferior to open laparotomy, in terms of time to recurrence, for the surgical staging of uterine cancer. The a priori statistical boundaries for noninferiority, based on the assumption of a 15% recurrence rate with laparotomy, were not reached. However, the absolute percentage difference in recurrence rates between the two treatment arms at 3 years was 1.14% (90% lower bound, −1.278; 95% upper bound, 3.996). This trial previously confirmed the feasibility and improved short-term surgical safety profile associated with laparoscopic staging for uterine cancer when compared with the same procedures undertaken via laparotomy.11
The 5-year OS of 84.8% in both arms is excellent for this population, with 13.6% demonstrating histologic evidence of metastatic disease (stages III and IV) including: 9% with positive lymph node metastasis, 2.4% with adnexal metastasis, and 2.6% with intraperitoneal spread of tumor. There is controversy worldwide regarding the survival benefit of comprehensive staging.18,19
However, as morbidity and cost associated with these procedures decrease, the added information results in individualized treatment and improvement in the overall quality of cancer care in the United States.
Improved follow-up in the initial postsurgical period of 3 years would have strengthened the study and enhanced its ability to achieve a more definitive finding, partially because of the late addition of the long-term end point, approximately 23% of patients had fewer than 3 years of follow-up. However, the fact that this study did not demonstrate statistical noninferiority as originally planned should be considered together with the fact that the initial assumption of a 15% recurrence rate with laparotomy resulted in establishment of noninferiority boundaries that were not met when actual recurrence rates were substantially lower. This, along with the resulting finding that the estimated difference in recurrence rates at 3 years was only 1.14% (90% lower bound, −1.278; 95% upper bound, 3.996), should be considered as strong evidence that laparoscopy may be an acceptable alternative to the more invasive laparotomy. The importance of demonstrating that laparoscopic staging does not adversely affect survival in patients with uterine cancer cannot be overstated. This clinical trial should alleviate concerns about missing metastatic disease or laparoscopic surgery altering recurrence rates or patterns of recurrence. Thorough surgical staging and histologic evaluation of expected metastatic sites were performed in this trial, and the differences observed were not clinically or statistically different. Evaluating the appropriateness of using laparoscopy in low-risk patients (ie, those with grades 1 to 2 endometrioid tumors), but not in those with high-risk histologic cell types, was not a study end point. This concern was examined, and we observed no significant differences in treatment effect related to histologic cell type or nuclear grading of endometrioid cell types. Because this study was not adequately powered to assess differences in recurrence rates within any subgroups, these observations warrant further investigation. Our experience suggests that neither serous papillary histology nor grade 3 endometrioid cancers involve a higher failure rate from laparoscopy because of poor detection of intraperitoneal disease or high left para-aortic lymph nodes. The concern that using laparoscopy could result in new sites of recurrent disease at the trocar sites was investigated. The low rate of port site recurrences (0.24%), three fourths of which were identified in patients with metastatic disease, has now been systematically documented and is reassuring.
These results do not demonstrate a survival decrement from laparoscopy, which allows patients and surgeons comfort in choosing the less morbid procedure. The conversion to laparotomy when adequate surgical staging cannot be completed laparoscopically allows for completion of surgical staging without compromising the patient. The results of this trial cannot be generalized to the use of laparoscopic hysterectomy without lymphadenectomy, because thorough surgical staging was required in both arms of this trial, and conversion was required when lymphadenectomy could not be completed using laparoscopy. Improved surgical training and technology may make minimally invasive surgery safer and improve success rates in the increasingly more common obese population. Two other major prospective clinical trials in the Netherlands and Australia evaluating minimally invasive treatment of endometrial cancer should not be compared to this trial because of their exclusion of nonendometrioid cell types and the comprehensive staging requirement for all of the participants in this trial.20,21
These laparoscopic surgery trials included only endometrioid histology and required only hysterectomy and bilateral salpingoophorectomy,20
and the LACE (Laparoscopic Approach to Cancer of the Endometrium) trial in Austrailia excluded nonendometrioid cell types, did not require lymphadenectomy (only recommended this), and did not mandate conversion to laparotomy for completion of staging.21
Examination of a large variety of pathologic subsets (cell type, grade, node status, stage) did not reveal any evidence of a particular subgroup that should not be treated with laparoscopy. Endometrial cancer is an ideal cancer for minimally invasive surgery. Combined with the previously published results from this study, patients treated by laparoscopy had a superior QOL through the first 6 postoperative weeks when compared with those treated by laparotomy, with fewer complications, less pain, faster recovery, and significantly reduced length of hospital stay without compromising OS.11,12
This study demonstrates that comprehensive surgical staging of endometrial cancer can be performed laparoscopically with relatively small differences in recurrence rates (estimated difference at 3 years, 1.14%; 90% lower bound, −1.278; 95% upper bound, 3.996). These results, combined with previous findings from this study of improved QOL and decreased complications associated with laparoscopy, are reassuring to patients and allow surgeons to reasonably suggest this method as a means to surgically treat and stage patients with presumed early-stage uterine cancers.