Sentinel Lymph Node Biopsy Versus Pelvic Lymphadenectomy in Early-stage Cervical Cancer (PHENIX/CSEM 010)

Study Overview
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Brief Summary
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The diagnostic value of sentinel lymph node biopsy in early-stage cervical cancer has been well studied. However, there were no randomized controlled study on comparing the long-term outcomes of sentinel lymph node biopsy and conventional procedure. The investigators perform a phase III, randomized controlled trial to determine whether pelvic lymphadenectomy can be replaced by sentinel lymph node biopsy in surgical treatment for patients with early-stage cervical cancer.

Detailed Description
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This study comprises two parts: PHENIX-I: To compare the outcomes of managements with and without pelvic lymphadenectomy for patients with negative sentinel lymph node; PHENIX-II: To compare the outcomes of managements with and without pelvic lymphadenectomy for patients with positive sentinel lymph node. Patients with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage IA1 (lymphovascular space involvement), IA2, IB1, and IB2 cervical cancer are eligible for our study. The tumor diameter should be less than 3cm. Sentinel lymph node biopsy will be performed at the beginning of operations. After pathological examination of frozen section, patients will be assigned to PHENIX-I or PHENIX-II study according to their status of sentinel nodes. In both parts of this trail, patients have equal chance to be randomly assigned to experimental arms (radical hysterectomy only) and reference arms (radical hysterectomy and pelvic lymphadenectomy).Adjuvant treatments will be planned according to postoperative pathological factors. The primary objective is disease-free survival at 3 years for PHENIX-I and 2 years for PHENIX-II. The secondary end points are overall survival, long-term outcome of sentinel lymph node biopsy and the quality of life.

Official Title
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Sentinel Lymph Node Biopsy Versus Pelvic Lymphadenectomy in Early-stage Cervical Cancer (PHENIX/CSEM 010)

Conditions
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Cervical Cancer, Surgery, Quality of Life

Intervention / Treatment
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* Procedure: no systematic pelvic lymphadenectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with newly histologically confirmed cervical carcinoma Histopathology squamous carcinoma, adenocarcinoma or adeno-squamous carcinoma Original clinical stage must be FIGO (2018) stage IA1 (lymphovascular space involvement), IA2, IB1, and IB2 No suspected node should be found on imaging examination (RESIST 1.1) Age between 18-65 Patients must give signed informed consent P.S status: 0-1 Estimated survival time > 3 months Tumor diameter ≤ 3 cm Exclusion Criteria: The presence of uncontrolled life-threatening illness Receiving other ways of anti-cancer therapy Investigator consider the patients can't finish the whole study With normal liver function test (ALT、AST>2.5×ULN) With normal renal function test (Creatinine>1.5×ULN) WBC<4,000/mm3 or PLT<100,000/mm The whole cervix has been occupied by tumor and there is no normal surface left for tracer injection History of severe heart disease or deep venous thrombosis; 4) Presence or history of other malignant disease Gestation or perinatal period Intention to fertility preservation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Arm 1<br>patients with negative sentinel nodes confirmed by pathological examination of frozen section will be randomly assigned to Arm 1 or Arm 2 Arm 1: patients undergo radical hysterectomy±salpingo-oophorectomy (no systematic pelvic lymphadenectomy) Arm 2: patients undergo radical hysterectomy±salpingo-oophorectomy+pelvic lymph node dissection | Procedure: no systematic pelvic lymphadenectomy<br>* systematic pelvic lymphadenectomy is omitted in surgical treatment<br>|
| No Intervention: Arm 2<br>patients with negative sentinel nodes confirmed by pathological examination of frozen section will be randomly assigned to Arm 1 or Arm 2 Arm 1: patients undergo radical hysterectomy±salpingo-oophorectomy (no systematic pelvic lymphadenectomy) Arm 2: patients undergo radical hysterectomy±salpingo-oophorectomy+pelvic lymph node dissection | |
| Experimental: Arm 3<br>patients with positive sentinel nodes confirmed by pathological examination of frozen section will be randomly assigned to Arm 3 or Arm 4 Arm 3: patients undergo radical hysterectomy±salpingo-oophorectomy (no systematic pelvic lymphadenectomy) Arm 4: patients undergo radical hysterectomy±salpingo-oophorectomy+pelvic lymph node dissection | Procedure: no systematic pelvic lymphadenectomy<br>* systematic pelvic lymphadenectomy is omitted in surgical treatment<br>|
| No Intervention: Arm 4<br>patients with positive sentinel nodes confirmed by pathological examination of frozen section will be randomly assigned to Arm 3 or Arm 4 Arm 3: patients undergo radical hysterectomy±salpingo-oophorectomy (no systematic pelvic lymphadenectomy) Arm 4: patients undergo radical hysterectomy±salpingo-oophorectomy+pelvic lymph node dissection | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival in PHENIX-I |  | 3 years | 
| Disease free survival in PHENIX-II |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Surgical morbidity |  | 3 years | 
| Rate of retroperitoneal node recurrence |  | 3 years | 
| Overall survival |  | 5 years | 
| Patients' quality of life |  | 5 years | 
| Performance of SLN detection |  | 3 years | 
| Diagnostic accuracy of frozen section examination |  | 3 years | 
| Anatomic distribution of SLNs |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sentinel lymph node, pelvic lymphadenectomy, cervical carcinoma, surgery, radiotherapy