Brief Title
2D Versus 3D Radical Laparoscopic Hysterectomy for Endometrial Cancer: a Prospective Randomized Trial
Official Title
Prospective Randomized Trial on 2D Versus 3D Laparoscopic Total Laparoscopic Hysterectomy With Pelvic Lymphadenectomy for the Treatment of Endometrial Cancer FIGO Stage IB-II
Brief Summary
This prospective randomized pilot study is aimed to verify if the operative time of a total
laparoscopical hysterectomy (TLH) with pelvic lymphadenectomy for endometrial cancer FIGO
stage IB-II could be reduced using 3D laparoscopy versus standard laparoscopy
Detailed Description
The standard treatment for early-stage endometrial cancer is surgery. Surgical procedures
include washing for cytology, total extrafascial hysterectomy and bilateral
salpinges-oophorectomy. Although the therapeutic value of routine pelvic and para-aortic
lymphadenectomy is debated, staging information is a critical determinant of adjuvant therapy
for most gynecologic oncologists.
Type-1 endometrial cancer spread is limited to the pelvic nodes in most cases. If there are
positive lymph nodes, those around the obturator nerve and around the external and common
iliac vessels are more likely to be involved than those in the presacral area. Isolated
involvement of the para-aortic nodes is rare. Complete excision of the nodes located around
the iliac vessels and above the obturator nerve allows identification of 90% of node-positive
patients.
The decision on whether to undertake lymphadenectomy should not be based on palpation of the
nodal area, because less than 10% of patients with nodal metastases have grossly enlarged
nodes.
Patients with endometrioid cancer, grade 1-2 with deep myometrial invasion and any grade 3
endometrioid endometrial cancer have at least a 5% risk of having positive pelvic lymph
nodes. In our current treatment protocol, these patients undergo complete pelvic
lymphadenectomy. Laparotomy may be indicated in endometrial cancer patients presenting with
grossly positive pelvic nodes, grossly positive adnexal metastasis, or serosal infiltration.
Although the complication rate of a simple hysterectomy with bilateral salpinges-oophorectomy
is not very high, over 70% new cases of endometrial cancer are diagnosed in post-menopausal
women, commonly associated with medical co-morbidities, such as diabetes, hypertension and
obesity. Abdominal surgery therefore exposes them to an increased risk of complications.
Vaginal hysterectomy has been suggested as an attractive alternative to abdominal surgery for
these patients, but this approach does not allow exploration of the abdominal cavity,
peritoneal washing, and lymph-node dissection. Laparoscopic-assisted vaginal hysterectomy or
total laparoscopic hysterectomy overcome the previous limitations.
In 1993, Childers et al first proposed laparoscopy as an option for early-stage endometrial
cancer. Despite its recognized benefits, many surgeons found this approach difficult for
routine use such that relatively few centers offered laparoscopic hysterectomy and
lymphadenectomy for a majority of their patients.
From those first reports there have been 12 major reports on the use of laparoscopy, often
comparing to series of similar patients staged by laparotomy. Clear advantages, such as the
reduction of peri-operative complications, the shorter hospital stay and the earlier
recovery, have been confirmed in each series. Failure to complete the staging procedure by
laparoscopy ranges between 5 and 35% of the patients, most frequently due to obesity of the
patients. In reality in 2005 some researchers have suggested that laparoscopic surgery is
safe in obese or elderly patients with endometrial cancer too.
Moreover, this approach does not seem to modify the incidence of recurrence and overall
patient survival . The big randomized trials planned to study differences in morbidity and
survival between laparoscopy or laparotomy in endometrial cancer are the GOG LAP-2 study, the
Dutch study from Bijen and Mourits, and the Australian study LACE. Unfortunately none of
these three randomised trials have yet reported survival data, but only on health-related
issues and complications. In the GOG study, patients with clinical stage I to IIA uterine
cancer were randomly assigned to laparoscopy (n = 1,696) or open laparotomy (n = 920),
including hysterectomy, salpinges-oophorectomy, pelvic cytology, and pelvic and para-aortic
lymphadenectomy. Laparoscopy resulted in fewer postoperative moderate or severe adverse
events, a shorter hospital stay, and a longer operative time than did laparotomy. The median
operative time for the open laparotomy arm was 130 minutes (range 102-167 minutes), and for
the laparoscopy arm, it was 204 minutes (rang 160-252 minutes; P < .001).
In the Dutch study the major and minor complication rates were the same in the group of
patients treated with laparoscopy compared with laparotomy. However, TLH was associated with
less blood loss, less use of pain medication, a shorter hospital stay, and a longer operative
time than with TAH. The median duration of surgery was 115 minutes in the TLH group, (range
35-267) and 71 minutes (range 31-239) in the TAH group. The difference with the GOG study is
probably due to the fact that the patients in the Netherlands only underwent a hysterectomy
and bilateral salpinges-oophorectomy and not a complete surgical staging including pelvic and
para-aortic lymphadenectomy.
In the Australian LACE study patients with stage I endometrioid adenocarcinoma were randomly
assigned to TLH (n=190) or TAH (n=142). Surgeons were required to perform pelvic node (with
or without) para-aortic lymph-node dissection as part of the treatment in both groups.
Operating time was significantly longer in the TLH group (138 minutes [SD 43]) than in the
TAH group (109 minutes [34]; p=0•001).
Health-related outcome was reported in all three trials. Better physical functioning, body
image, reduced pain, and an earlier resumption of work over the 6-week post-laparoscopy
period was reported in the GOG and the Dutch study than in the laparotomy patients, but these
differences disappeared 6 months after surgery. In the Australian study, quality of life was
still improved 6 months after surgery.
In conclusion, laparoscopic treatment of endometrial cancer clinically confined to the uterus
is associated with less pain, shorter hospital stay, faster recovery, and better quality of
life at least 3 months post surgery, but with a longer operative time than with laparotomy.
Another recent single institution Italian trial randomized patients with clinical stage I
endometrial cancer to receive TLH (n=81) or TAH (n=78) with bilateral salpinges-oophorectomy
and bilateral pelvic lymphadenectomy. Para-aortic lymphadenectomy was performed in selected
cases. The mean operative time was 123 minutes ± 29 (95% CI 111-198) in the LPT group and 136
minutes ± 31 (95% CI 118- 181) in the LPS group (P<0.01). These operative times match closely
with our experience by both laparotomy and laparoscopy, using conventional bipolar
electrosurgery.
Shortening the operative time of laparoscopy could further increase the benefits of the
laparoscopic approach, especially in obese patients. Overweight (defined as body-mass index
[BMI] of at least 25 kg/m2) infect is an important risk factor present in almost 50% of women
with endometrial cancer.
Since these patients are characterised by several systemic physiopathological alterations,
the perioperative management may present some problems, mainly related to their respiratory
system (obstructive sleep apnea, airway intubation and atelectasis). Obstructive sleep
apnea-hypopnea syndrome (OSA) occurs in up to 70% of morbidly obese patients undergoing
surgery being OSA a known risk factor for adverse perioperative outcomes.
Shortening the operative time could reduce these perioperative complications and the
postoperative pain. This could translate in fewer days of hospitalization and than lower
incidence of hospital infections and lower costs for the health care system.
This prospective randomized pilot study is aimed to verify if the operative time of a TLH
with pelvic lymphadenectomy for endometrial cancer FIGO stage IB-II could be reduced using 3D
laparoscopy (Olympus Medical Systems Corp) vs standard laparoscopy .
Secondary endpoints of this comparison are incidence of intra- or postoperative complications
(Cardiac, Respiratory, Neurological, Gastrointestinal, Renal, Fever, Wound or other
Infection, Lymphocele), estimated blood loss, days of hospitalization and costs for the
health care system.
Study Type
Interventional
Primary Outcome
Operative time for laparoscopic total hysterectomy with pelvic lymphadenectomy
Secondary Outcome
number of participants with intra or post operative complications
Condition
Endometrial Cancer
Intervention
3D Laparoscopy
Study Arms / Comparison Groups
3D Laparoscopy
Description: Laparoscopic total hysterectomy with pelvic lymphadenectomy are performed with 3D Laparoscopic technology. A 10 mm port is inserted at the umbilicus for the telescope. Once pneumoperitoneum (12 mmHg) is achieved, intra-abdominal visualization will be obtained with a 0° high-definition 3D telescope. Two additional 5 mm ports are placed under direct visualization. One more 5- mm trocar is inserted in the right mid abdomen at the level of the umbilicus. The instruments used include bipolar grasper, monopolar scissors, monopolar hook, various graspers and a suction irrigation system
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Procedure
Estimated Enrollment
36
Start Date
October 2014
Completion Date
March 2015
Primary Completion Date
March 2015
Eligibility Criteria
Inclusion/Exclusion Criteria:
- Age ≤ 75 years
- Patient's informed consent
- American Society of Anesthesiologists: < class III or IV
- No actual pregnancies or P.I.D.
- No previous major abdominal surgical procedures
- Endometrial cancer FIGO stages IB-II
- Endometrioid histotype
- No previous radiotherapy on pelvic fields
- No uterine size larger than conform 10 weeks gestation
Gender
Female
Ages
N/A - 75 Years
Accepts Healthy Volunteers
No
Contacts
, ,
Location Countries
Italy
Location Countries
Italy
Administrative Informations
NCT ID
NCT02320565
Organization ID
2D versus 3D Endometrium
Responsible Party
Principal Investigator
Study Sponsor
Catholic University of the Sacred Heart
Collaborators
Fagotti, Anna, M.D.
Study Sponsor
, ,
Verification Date
June 2015