Comparing the Efficacy of Surgery Staging and Image Staging of Locally Advanced Cervical Cancer

Study Overview
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Brief Summary
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The study is a domestic multicenter, prospective, non-randomized controlled concurrent trial. It will be assessed whether surgery staging on locally advanced cervical cancer is superior to image staging for improving progression-free survival and overall survival.

Detailed Description
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All eligible patients will be divided into the following two treatment groups nonrandomly. Image staging group: standard chemoradiation (Pelvic EBRT/Extended-field EBRT + concurrent platinum-containing chemotherapy+brachytherapy). Surgery staging group: open/minimally invasive para-aortic lymph node dissection followed by concurrent chemoradiation. (Level of lymph node dissection: At least the inferior mesenteric artery. Chemoradiation will be conducted within 28 days postoperatively.)

Official Title
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Non-randomized Concurrent Controlled Trial of Surgery Staging or Image Staging of Locally Advanced Cervical Cancer

Conditions
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Locally Advanced Cervical Cancer

Intervention / Treatment
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* Radiation: Concurrent chemoradiation
* Procedure: Open/minimally invasive para-aortic lymph node dissection followed by concurrent chemoradiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patients with good compliance, voluntarily signed the informed consent form and participated in the study. Histopathology: squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma Stage (FIGO2018): IB3, IIA2, IIB-IVA; ECOG score: 0   1; The expected survival >6 months; The result of a pregnancy test (serum or urine) within seven days must be negative for women of childbearing age, who must take contraception during the trial. Exclusion Criteria: Activity or uncontrol severe infection; Liver cirrhosis or other decompensated liver disease; A history of immune deficiency, including HIV positive or a congenital immunodeficiency disease; Chronic renal insufficiency or renal failure; Other malignancies were diagnosed within five years or needed treatments; Myocardial infarction, severe arrhythmia and congestive heart failure with grade ≥2 (New York heart association); The CT/MRI/PET/CT show that the para-aortic lymph nodes are positive; A history of pelvic artery embolization; A history of pelvic radiotherapy; A history of partial hysterectomy or radical hysterectomy; A history of severe allergic reaction to platinum drugs; The drugs for the treatment of concomitant disease seriously impaired liver or kidney function, such as tuberculosis; Patients who cannot understand the research regimen and refuse to sign the informed consent form; Other concomitant diseases or special conditions seriously endanger the patient's health or interfere with the trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a non-randomized controlled concurrent trial. According to the patients' voluntary choice, they are enrolled on the surgery staging group or image staging group. All patients are evaluated by CT(≥32 slices) or MRI(≥1.5T) or PET/CT. The criteria for positive pelvic or para-aortic lymph nodes (one of the following): ① CT or MRI show more than one positive lymph node with a short diameter ≥ 15mm; ② PET/CT shows more than one positive lymph node with SUV ≥ 2.5; ③ If CT or MRI show positive lymph node with a short diameter between 10mm and 15mm, PET / CT should further verify that it is a positive lymph node with SUV ≥ 2.5.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Image staging group<br>Standard chemoradiation (Pelvic EBRT/Extended-field EBRT + concurrent platinum-containing chemotherapy + brachytherapy). | Radiation: Concurrent chemoradiation<br>* Standard concurrent chemoradiation: A point/HCR-CTV D90 ≥80Gy (+20%) by using IMRT or TOMO technics. Patients with image-positive common iliac lymph nodes or para-aortic lymph nodes receive extended-field EBRT. Brachytherapy should begin after 15-20F external radiotherapy. A radiation dose for the image-positive nodes can range from 55Gy to 60Gy. Five cycles of concurrent platinum-containing chemotherapy (Cisplatin 40mg/m2 q1w or Carboplatin AUC=2 q1w, Window period one week) and CCRT should be completed within 56 days. CCRT one week later, if the cervix biopsy shows residual tumour and/or imaging (CT/MRI/PET/CT) indicates that there are still positive lymph nodes in the pelvic and abdominal cavity, three cycles of adjuvant chemotherapy (TP: Paclitaxel 135mg/m2, Cisplatin 50mg/m2, q3w or TC: Paclitaxel 135mg/m2, Carboplatin AUC=4, q3W; Window period 2 weeks) ± brachytherapy will be performed (A point/HR-CTV D90 ≤ 96Gy).<br>|
| Experimental: Surgery staging group<br>Open/minimally invasive para-aortic lymph node dissection followed by chemoradiation (Pelvic EBRT/Extended-field EBRT + concurrent platinum-containing chemotherapy + brachytherapy). | Procedure: Open/minimally invasive para-aortic lymph node dissection followed by concurrent chemoradiation<br>* Open/minimally invasive para-aortic lymph node dissection followed by concurrent chemoradiation. (height of lymph node dissection: At least the inferior mesenteric artery. Chemoradiation should be performed postoperatively within 28 days.) The chemoradiation is consistent with the image staging group, except for extended-field EBRT determined by pathological positive para-aortic lymph nodes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression-free survival | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | 3-year and 5-year Overall Survival | 3 years and 5 years | 
| Complication | Some conditions caused by surgery or chemoradiation. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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surgery staging, image staging, Locally advanced cervical cancer, PFS