Laparoscopic Approach to Cervical Cancer

Study Overview
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Brief Summary
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The goal of this clinical research study is to compare the long-term outcomes of different surgical methods for the treatment of cervical cancer. The long-term outcome of a total abdominal radical hysterectomy (TARH) will be compared against laparoscopy. In this study, the laparoscopy will be done with or without robotic technology.

Detailed Description
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Primary Objective: To compare disease-free survival amongst patients who undergo a total laparoscopic (TLRH) or robotic radical hysterectomy (TRRH) verses those who undergo a total abdominal radical hysterectomy (TARH) for early stage cervical cancer. Secondary Objectives: Compare patterns of recurrence between arms. Compare treatment-associated morbidity within 6 months from surgery. Compare the cost effectiveness of TLRH/TRRH versus TARH Compare the impact on Quality of Life (QOL) between arms. Assess pelvic floor function Compare overall survival between arms Determine the feasibility of sentinel lymph node biopsy in this group of patients RATIONALE FOR STUDY DESIGN Total abdominal radical hysterectomy (TARH) and pelvic lymph node dissection (± aortic lymph node dissection ± postoperative [chemo-] radiotherapy) is the current standard treatment for early cervical cancer. While this is an accepted effective treatment, a laparotomy is highly invasive, visibly scarring and is associated with tissue trauma, blood loss and a significant risk of wound and infectious adverse events . Additionally, radical hysterectomy by laparotomy is associated with an average hospital stay of approximately 5 to 7 days and an average recovery period (from surgery) of 5 to 6 weeks. Laparoscopic techniques have been demonstrated to be feasible and safe with previous retrospective studies on TLH showing encouraging results . In a number of retrospective and prospective, non-controlled series the incidence of treatment-related morbidity was less in patients who had a laparoscopic hysterectomy compared to patients who underwent a TAH . Retrospective data suggest that the recurrence rate and patterns of recurrence are similar in patients who had a laparoscopic or an open approach . Treatment recommendations ideally are based on prospective, randomized trials comparing the current standard technique (TARH) with the proposed better technique (TLRH). However, there are currently no prospective studies available which directly compare TLRH against the standard treatment of TARH in regards to disease-free or overall survival. The proposed clinical trial will be biphasic. The primary outcome variable in stage 1 will be feasibility of recruitment as determined by overall trial recruitment. Following completion of Stage 1, the data of this study will become the basis for assessing recurrence and disease-free survival in the Stage 2 design. RATIONALE FOR THE QUALITY OF LIFE Retrospective studies suggest equivalency between the laparoscopic and open approaches to radical hysterectomy in regards to surgical specimens obtained and likely disease-free and overall survivals . Thus, quality of life could be seen as one of the most significant factors in recommending one approach over the other and therefore an extremely important endpoint for this protocol. In the GOG LAP-2 protocol , a trial evaluating a comparison between hysterectomy by laparotomy or laparoscopy, the investigators found equivalency adequacy of the two surgical approaches however a significant difference in short term quality of life favoring laparoscopy. As expected, patients who underwent laparoscopy had a faster return to baseline functioning compared with those patients who had undergone laparotomy which translated into improved short-term quality of life. By 6 months, however, patients in both cohorts were reporting equivalent quality of life parameters. Quality of life surveys employed with this Phase III clinical trial will encompass important endpoints such as postoperative pain and related symptoms using the MD Anderson Symptom Assessment Index (MDSAI), as well as cancer specific Functional Assessment of Cancer Therapy (FACT-Cx) and the general 12-Item Short-Form Health Survey (SF-12). RATIONALE FOR LYMPHATIC MAPPING Published experience with the techniques for lymphatic mapping and sentinel lymph node detection in women with cervical cancer has been very limited. To date, no single study has enrolled more than 100 patients undergoing lymphatic mapping as part of their surgical treatment for cervical cancer. In fact, the majority of studies report on less than 50 patients. In addition, this procedure has not yet been shown to be viable in a multi-institutional setting. The limitations of previously published reports are important as these techniques are associated with a significantly high learning curve with early procedures less successful than later ones. This study will provide us the opportunity to enroll large numbers of patients for validation of intraoperative lymphatic mapping in women with cervical cancer in an international, multi-institutional setting.

Official Title
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A Phase III Randomized Clinical Trial of Laparoscopic or Robotic Radical Hysterectomy Versus Abdominal Radical Hysterectomy in Patients With Early Stage Cervical Cancer

Conditions
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Cervical Cancer

Intervention / Treatment
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* Procedure: Total Abdominal Radical Hysterectomy
* Procedure: Total Laparoscopic or Robotic Radical Hysterectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed primary adenocarcinoma, squamous cell carcinoma or adenosquamous carcinoma of the uterine cervix; Patients with Histologically confirmed stage IA1 (with lymph vascular invasion), stage IA2, or stage IB1 disease Patients undergoing either a Type II or III radical hysterectomy (Piver Classification) Patients with adequate bone marrow, renal and hepatic function: ECOG Performance Status of 0 or 1. Patient must be suitable candidates for surgery. Patients who have signed an approved Informed Consent Patients with a prior malignancy allowed if > 5 years ago with no current evidence of disease Females, aged 18 years or older Negative serum pregnancy test within <30 days of surgery in pre-menopausal women and women < 2 years after the onset of menopause Exclusion Criteria: Any histology other than adenocarcinoma, squamous cell carcinoma or adenosquamous carcinoma of the uterine cervix; Tumor size greater than 4 cm; FIGO stage II-IV; Patients with a history of pelvic or abdominal radiotherapy; Patients who are pregnant; Patients with contraindications to surgery; Patients with evidence of metastatic disease by conventional imaging studies, enlarged pelvic or aortic lymph nodes > 2cm; or histologically positive lymph nodes Unfit for Surgery: serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator); Patients unable to withstand prolonged lithotomy and steep Trendelenburg position Patient compliance and geographic proximity that do not allow adequate follow-up

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 |
| --- | --- |
| Active Comparator: 1<br>Total Abdominal Radical Hysterectomy | Procedure: Total Abdominal Radical Hysterectomy<br>* In a radical hysterectomy the uterus, the upper one to two centimetres of the vagina and the soft tissues around the cervix are excised.<br>* Other names: Open radical hysterectomy;|
| Experimental: 2<br>Total Laparoscopic or Robotic Radical Hysterectomy | Procedure: Total Laparoscopic or Robotic Radical Hysterectomy<br>* In a radical hysterectomy the uterus, the upper one to two centimetres of the vagina and the soft tissues around the cervix are excised.<br>* Other names: Keyhole radical hysterectomy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival | Compare treatment equivalence | 5 years from surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patterns of recurrence | date and localization of 1st recurrence as confirmed histologically - Compare patterns between groups | 5 years from surgery | 
| Costs | Compare costs between groups | 6 months from surgery | 
| Quality of life Questionnaires | Compare QoL between groups | 6 months from surgery | 
| Pelvic Floor Distress Inventory Questionnaire | Compare PFDI between groups | 5 years from surgery | 
| Overall survival | Compare between groups | 5 years from surgery | 
| Feasibility of sentinel lymph node biopsy | Compare between groups | Intra-operatively | 
| Intra-operative, peri-operative, post-operative and long term treatment related morbidity | Compare these between groups | 6 months from surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cervix, Cervical, Cancer, Carcinoma, Radical hysterectomy, Hysterectomy, Laparoscopy, Laparoscopic, Robotic, Squamous Cell, Adenosquamous, Adenocarcinoma, Lymphatic Mapping, IOLM, SPECT, Sentinel Node, Uterine cervix