Minimally Invasive Therapy Versus Open Radical Hysterectomy for Management of Early Stage Cervical Cancer

Study Overview
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Brief Summary
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Radical hysterectomy and pelvic lymph node dissection (+/- aortic lymph node dissection) is the standard treatment for early stage cervical cancer. And minimally invasive surgery has been successfully and safely demonstrated in the treatment of early stage cervical cancer. This study aims to compare total laparoscopic radical hysterectomy and total abdominal radical hysterectomy in terms of disease-free survival and overall survival. Rates and characteristics of recurrence, incidence of complications and morbidity, impact on quality of life and cost-effectiveness will also be determined.

Detailed Description
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Radical hysterectomy and pelvic lymph node dissection (+/- aortic lymph node dissection) is the standard treatment for early stage cervical cancer. Laparotomy has been the surgical method of choice for a considerable length of time. While it is an accepted effective treatment, laparotomy is highly invasive and is associated with increased risk of tissue trauma, intraoperative and postoperative complications, and longer hospital stay. Minimally invasive surgery has been successfully and safely demonstrated in the treatment of early stage cervical cancer. Retrospective studies have shown that oncologic outcomes in terms of recurrence rates and patterns of recurrence are similar in patients who had a laparoscopic or an open approach to radical hysterectomy. There is reduction of overall postoperative complications, treatment-related morbidity and length of hospital stay. However, there are two studies stating poorer survival of women treated by minimally invasive surgery. An epidemiologic study using two large US databases (National Cancer Database and Surveillance, Epidemiology, and End Results database) showed a reduction in overall survival of patients undergoing minimally invasive radical hysterectomy. Furthermore, in a prospective, multi-center, open-label randomized clinical trial, minimally invasive radical hysterectomy (both total laparoscopic and total robotic radical hysterectomy) was associated with significantly worse disease-free survival and overall survival compared to open abdominal radical hysterectomy among women with early stage cervical cancer. Recurrence rates were also higher in the minimally invasive group. This study aims to compare total laparoscopic radical hysterectomy and total abdominal radical hysterectomy in terms of disease-free survival and overall survival. Rates and characteristics of recurrence, incidence of complications and morbidity, impact on quality of life and cost-effectiveness will also be determined.

Official Title
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Minimally Invasive Therapy Versus Open Radical Hysterectomy (MITOR) for Management of Early Stage Cervical Cancer

Conditions
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Cancer of Cervix, Laparoscopic Surgery

Intervention / Treatment
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* Procedure: radical hysterectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically confirmed primary squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma of the uterine cervix Patients with histologically confirmed stage IAI (+) LVSI, IA2, IB1, IB2 and IIA1 disease (TNM and 2018 FIGO staging for carcinoma of the uterine cervix) Patients undergoing a Type II/Type III radical hysterectomy (Piver-Rutledge Classification) or Type B/Type C radical hysterectomy (Querleu-Morrow Classification) Patients with adequate bone marrow, renal and hepatic function using Standard International Units 4.1 WBC > 3.0 x 109 cells/L 4.2 Platelets > 100 x 109 cells/L 4.3 Creatinine < 2.0 mg/dL 4.4 Bilirubin < 1.5 x upper normal limit and AST/SGOT or ALT/SGPT < 3 x upper normal limit ECOG Performance Status of 0 or 1 Patients who have signed an approved Informed Consent Patients with a prior malignancy if > 5 years ago with no current evidence of disease Females aged 18 years or older Negative serum pregnancy test ≤ 30 days of surgery in premenopausal women and women < 2 years after the onset of menopause Exclusion Criteria: Patients with any histology other than squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma of the uterine cervix Stage IB3, IIA2-IV (TNM and 2018 FIGO staging for carcinoma of the uterine cervix) Patients with evidence of metastatic disease by conventional imaging studies (CT Scan, MRI or PET CT Scan), enlarged pelvic or aortic lymph nodes > 2cm, or histologically positive lymph nodes Patients with a history of pelvic or abdominal radiotherapy Uterine size larger than 12 cm in length Patients with contraindications to surgery or who are unfit for surgery with serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator)

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Laparoscopic radical hysterectomy<br> | Procedure: radical hysterectomy<br>* To compare disease-free survival and overall survival of patients with early stage cervical cancer undergoing total laparoscopic radical hysterectomy versus total abdominal radical hysterectomy<br>|
| Active Comparator: Laparotomic radical hysterectomy<br> | Procedure: radical hysterectomy<br>* To compare disease-free survival and overall survival of patients with early stage cervical cancer undergoing total laparoscopic radical hysterectomy versus total abdominal radical hysterectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-Free Survival | the time from randomization to disease recurrence or death from cervical cancer | 5 year | 
| Overall Survival | the time from randomization to disease recurrence or death from any cause | 5 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence Pattern | Recurrences will be described in detail and recorded according to date and location of first recurrence. The location can be designated as local, vault, pelvis or distal metastasis. | 5 years | 
| Intraoperative and Postoperative Complications | Intraoperative complications - hemorrhage; injury to bladder, ureter, bowel; vascular injury; nerve injury Perioperative complications (from post-surgery to discharge from hospital) - genitourinary (urinary tract infection, urinary retention), gastrointestinal (ileus), cardiac (myocardial infarction, atrial fibrillation), pulmonary (edema, atelectasis, pneumonia), renal and cerebrovascular morbidity. Wound and vault complications (infection, breakdown and dehiscence). Septicemia and thromboembolic complications (deep vein thrombosis and pulmonary embolism). Lymphocyst and abscess formation. Early postoperative complications (<4 weeks from surgery): Wound and vault complications (infection, dehiscence). Urinary retention, urinary incontinence. Lymphocyst, lymphedema, abscess formation, or fistula formation. Long term morbidity (4 weeks to 12 months from surgery): Urinary retention, urinary incontinence. lymphedema, incisional hernia formation, vaginal evisceration. | 1 year | 
| Impact on Quality of Life | Change in quality of life using Functional Assessment of Cancer Therapy Cervical (FACT-Cx) between baseline (pre-surgery) and 6 months after surgery. The FACT-CX comprises 42 items with 5 domains and a score range of 0-168. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radical hysterectomy, Cervical cancer, Laparotomy, Laparoscopy, Outcome