Uterine Manipulator Versus no Uterine Manipulator in Endometrial Cancer Trial

Study Overview
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Brief Summary
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Minimally invasive surgery is the recommended approach in endometrial cancer (EC) patients based on the results of two randomized controlled trials, given its advantages without compromised oncologic outcomes. The uterine manipulator is commonly used in benign and malignant pathologies to perform a laparoscopic or robotic hysterectomy. However, although regularly used, the uterine manipulator adoption in EC is a controversial technical aspect due to the raised concerns regarding the possible risk of disruption of the tumor mass, the spread of malignant cells, and seeding of the disease, particularly at the level of the vaginal cuff or spread of tumor cells, with increased risk of recurrence and death due to EC. On that basis, given that hysterectomy without a uterine manipulator is feasible, only a randomized controlled trial comparing oncologic outcomes in EC patients after use versus not use of the uterine manipulator will be able to provide high-quality evidence to answer this critical question and allow or exclude the use of a uterine manipulator during minimally invasive hysterectomy for EC.

Official Title
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Randomized Controlled Trial on the Oncologic Outcomes of Use Versus Not Use of the Uterine Manipulator in the Surgical Treatment of Apparent Uterine-confined Endometrial Carcinoma

Conditions
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Endometrial Neoplasms

Intervention / Treatment
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* Device: Uterine manipulator use


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Endometrial Cancer of any histology (including carcinosarcoma) and grade Planned surgical treatment including hysterectomy and bilateral salpingo-oophorectomy (ovarian preservation in selected patients is not an exclusion criterion) Age ≥ 18 years No preoperative evidence of extrauterine disease (Clinical stage IIIA, IIIB) No preoperative evidence of suspicious lymph nodes (Clinical stage IIIC) No preoperative evidence of distant metastasis (Clinical stage IV) Approved and signed informed consent Exclusion Criteria: Neoadjuvant therapy Synchronous or previous (< 5 years) invasive cancer, not including non-melanoma skin cancer Fertility preservation World Health Organization performance score > 2 Uterine sarcoma Previous pelvic/abdominal radiotherapy, hormone therapy for cancer (< 5 years), chemotherapy (< 5 years), pelvic or paraaortic lymphadenectomy, or retroperitoneal surgery Inadequate bone marrow function (white blood cells <3·0×109/L, platelets <100×109/L) Inadequate liver function (bilirubin >1.5×upper normal limit [UNL], aspartate aminotransferase, and alanine aminotransferase >2.5 × UNL) Inadequate kidney function (creatinine clearance < 60 mL per min calculated according to Cockcroft-Gault 10 or < 50 mL per min Ethylenediaminetetraacetic acid clearance) Intraoperative evidence of stage IV disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter, parallel arms, open-label, randomized controlled trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Total hysterectomy with a uterine manipulator<br>Total hysterectomy with bilateral salpingo-oophorectomy performed with the use of a uterine manipulator during surgery. | Device: Uterine manipulator use<br>* After peritoneal washing, the uterine manipulator will be inserted into the uterus to assist in the procedure of total hysterectomy.<br>|
| No Intervention: Total hysterectomy without a uterine manipulator<br>Total hysterectomy with bilateral salpingo-oophorectomy performed without the use of a uterine manipulator during surgery. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free survival | Any recurrence or death related to endometrial cancer (EC) or treatment | Each follow-up visit, up to 4 years from the day of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cause-specific survival | Any death related to endometrial cancer (EC) or treatment | Each follow-up visit, up to 4 years from the day of surgery | 
| Overall survival | Any death for any cause | Each follow-up visit, up to 4 years from the day of surgery | 
| Site-specific recurrence-free survival | Any recurrence per site of first recurrence | Each follow-up visit, up to 4 years from the day of surgery | 
| Operative time | Time between first incision and skin closure | Day of surgery | 
| Intraoperative blood loss | Total blood aspirate during the surgical procedure | Day of surgery | 
| 30-day post-surgical morbidity | Perioperative (intraoperative and postoperative) complications graded based on the Clavien-Dindo classification | 30 days after surgery | 
| Lymphovascular space invasion | Presence of lymphovascular space invasion at definitive pathology | Day of surgery | 
| Peritoneal cytology | Presence of positive peritoneal cytology at definitive pathology | Day of surgery | 
| Quality of life indexes | The Functional Assessment of Cancer Therapy - General (FACT-G) - A 27-item questionnaire designed to measure four domains of Health-Related Quality of Life in cancer patients: Physical, social, emotional, and functional well-being. Score range 0-108. The higher the score, the better the Quality of Life. | Each follow-up visit, up to 4 years from the day of surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endometrial Neoplasms, Uterine manipulator, Laparoscopic hysterectomy, Recurrence-free survival, Cause-specific survival, Overall survival, Oncologic outcomes